Mr. C, age 30, with schizoaffective disorder, bipolar type, Cannabis abuse, and nicotine dependence, has been enrolled in a Program of Assertive Community Treatment (PACT) for approximately 5 years. He presents to the PACT clinic for follow-up with his psychiatrist. Mr. C reports dizziness, lightheadedness, blurred vision, and nausea worsening over the last few days, and he appears drowsy and hypoactive. He does not report any chest pain, abdominal pain, swelling, cold extremities, shortness of breath, vomiting, diarrhea, or blood loss. Mr. C admits he has eaten only once daily for several weeks because of delusional ideation that he is responsible for others suffering from anorexia nervosa.

His medical history includes gastroesophageal reflux disease. Mr. C’s medication regimen for the past year included total daily oral doses of benztropine, 2 mg, divalproex extended-release, 1,000 mg, fluphenazine, 15 mg, and gabapentin, 300 mg. He also receives IM fluphenazine decanoate, 50 mg every 2 weeks; lithium, 600 mg/d, was added to his regimen 5 months ago. Vital signs include temperature 97°F, weight 162 lb, height 69 inches, blood pressure 105/64 mm Hg, heart rate (HR) 46 beats per minute (bpm), and respirations 18 breaths per minute.

Because of Mr. C’s complaints, appearance, and low HR, the psychiatrist calls emergency medical services (EMS). Although the paramedics recommend emergency transport to the hospital, Mr. C refuses. The psychiatrist instructs Mr. C to stop taking lithium because of suspected lithium-induced bradycardia and a concern that he may be more susceptible to lithium toxicity with prolonged anorexia nervosa. When nursing staff evaluate Mr. C the next day, his vitals are HR 60 bpm, respirations 20 breaths per minute, and blood pressure 124/81 mm Hg; his dizziness, blurred vision, lightheadedness, and nausea are resolved.

Bradycardia is defined as a HR <60 bpm; however, symptoms may not occur until the HR is <50 bpm. Symptoms include fatigue, dizziness, lightheadedness, chest pain, shortness of breath, and syncope. The incidence of bradycardia during lithium treatment is unknown; it is considered a rare but serious adverse effect. A literature review reveals several case reports of bradycardia with lithium treatment,^2-4 including symptomatic bradycardia after a single dose of lithium.⁵ Other possible causes of bradycardia include anorexia nervosa, hypothermia, hypothyroidism, hypoxia, infection, stroke, acute myocardial infarction, sedative or opiate use, increased vagal tone with exercise conditioning, and other medications including fluphenazine.⁶

Mr. C’s symptoms may have been assumed to be secondary to several possible causes, including bradycardia, dehydration from poor oral intake, lithium toxicity, or an undiagnosed medical condition. The combination of nausea, dizziness, anorexia nervosa, blurred vision, and lightheadedness in a patient receiving lithium would certainly trigger a clinician’s concern for lithium toxicity, but he (she) may not be aware of the risk of bradycardia as an adverse effect of lithium. Because Mr. C refused hospital transportation by EMS, discontinuing lithium appears to have been the safest option. Laboratory studies from the day after Mr. C presented to the clinic appeared to lessen the probability that lithium toxicity, hypothyroidism, valproate toxicity, type 2 diabetes mellitus, or infection had caused Mr. C’s symptoms.

Although psychiatrists may be vigilant about monitoring for signs and symptoms of toxicity with lithium use by utilizing regular laboratory studies, they may not be as vigilant with monitoring vital signs at every patient visit (Table). This case demonstrates the importance of regular vital sign measurements to be able to detect this rare but serious adverse effect.

Mr. C, age 30, with schizoaffective disorder, bipolar type, Cannabis abuse, and nicotine dependence, has been enrolled in a Program of Assertive Community Treatment (PACT) for approximately 5 years. He presents to the PACT clinic for follow-up with his psychiatrist. Mr. C reports dizziness, lightheadedness, blurred vision, and nausea worsening over the last few days, and he appears drowsy and hypoactive. He does not report any chest pain, abdominal pain, swelling, cold extremities, shortness of breath, vomiting, diarrhea, or blood loss. Mr. C admits he has eaten only once daily for several weeks because of delusional ideation that he is responsible for others suffering from anorexia nervosa.

His medical history includes gastroesophageal reflux disease. Mr. C’s medication regimen for the past year included total daily oral doses of benztropine, 2 mg, divalproex extended-release, 1,000 mg, fluphenazine, 15 mg, and gabapentin, 300 mg. He also receives IM fluphenazine decanoate, 50 mg every 2 weeks; lithium, 600 mg/d, was added to his regimen 5 months ago. Vital signs include temperature 97°F, weight 162 lb, height 69 inches, blood pressure 105/64 mm Hg, heart rate (HR) 46 beats per minute (bpm), and respirations 18 breaths per minute.

Because of Mr. C’s complaints, appearance, and low HR, the psychiatrist calls emergency medical services (EMS). Although the paramedics recommend emergency transport to the hospital, Mr. C refuses. The psychiatrist instructs Mr. C to stop taking lithium because of suspected lithium-induced bradycardia and a concern that he may be more susceptible to lithium toxicity with prolonged anorexia nervosa. When nursing staff evaluate Mr. C the next day, his vitals are HR 60 bpm, respirations 20 breaths per minute, and blood pressure 124/81 mm Hg; his dizziness, blurred vision, lightheadedness, and nausea are resolved.

Bradycardia is defined as a HR <60 bpm; however, symptoms may not occur until the HR is <50 bpm. Symptoms include fatigue, dizziness, lightheadedness, chest pain, shortness of breath, and syncope. The incidence of bradycardia during lithium treatment is unknown; it is considered a rare but serious adverse effect. A literature review reveals several case reports of bradycardia with lithium treatment,^2-4 including symptomatic bradycardia after a single dose of lithium.⁵ Other possible causes of bradycardia include anorexia nervosa, hypothermia, hypothyroidism, hypoxia, infection, stroke, acute myocardial infarction, sedative or opiate use, increased vagal tone with exercise conditioning, and other medications including fluphenazine.⁶

Mr. C’s symptoms may have been assumed to be secondary to several possible causes, including bradycardia, dehydration from poor oral intake, lithium toxicity, or an undiagnosed medical condition. The combination of nausea, dizziness, anorexia nervosa, blurred vision, and lightheadedness in a patient receiving lithium would certainly trigger a clinician’s concern for lithium toxicity, but he (she) may not be aware of the risk of bradycardia as an adverse effect of lithium. Because Mr. C refused hospital transportation by EMS, discontinuing lithium appears to have been the safest option. Laboratory studies from the day after Mr. C presented to the clinic appeared to lessen the probability that lithium toxicity, hypothyroidism, valproate toxicity, type 2 diabetes mellitus, or infection had caused Mr. C’s symptoms.

Although psychiatrists may be vigilant about monitoring for signs and symptoms of toxicity with lithium use by utilizing regular laboratory studies, they may not be as vigilant with monitoring vital signs at every patient visit (Table). This case demonstrates the importance of regular vital sign measurements to be able to detect this rare but serious adverse effect.

Mr. C, age 30, with schizoaffective disorder, bipolar type, Cannabis abuse, and nicotine dependence, has been enrolled in a Program of Assertive Community Treatment (PACT) for approximately 5 years. He presents to the PACT clinic for follow-up with his psychiatrist. Mr. C reports dizziness, lightheadedness, blurred vision, and nausea worsening over the last few days, and he appears drowsy and hypoactive. He does not report any chest pain, abdominal pain, swelling, cold extremities, shortness of breath, vomiting, diarrhea, or blood loss. Mr. C admits he has eaten only once daily for several weeks because of delusional ideation that he is responsible for others suffering from anorexia nervosa.

His medical history includes gastroesophageal reflux disease. Mr. C’s medication regimen for the past year included total daily oral doses of benztropine, 2 mg, divalproex extended-release, 1,000 mg, fluphenazine, 15 mg, and gabapentin, 300 mg. He also receives IM fluphenazine decanoate, 50 mg every 2 weeks; lithium, 600 mg/d, was added to his regimen 5 months ago. Vital signs include temperature 97°F, weight 162 lb, height 69 inches, blood pressure 105/64 mm Hg, heart rate (HR) 46 beats per minute (bpm), and respirations 18 breaths per minute.

Because of Mr. C’s complaints, appearance, and low HR, the psychiatrist calls emergency medical services (EMS). Although the paramedics recommend emergency transport to the hospital, Mr. C refuses. The psychiatrist instructs Mr. C to stop taking lithium because of suspected lithium-induced bradycardia and a concern that he may be more susceptible to lithium toxicity with prolonged anorexia nervosa. When nursing staff evaluate Mr. C the next day, his vitals are HR 60 bpm, respirations 20 breaths per minute, and blood pressure 124/81 mm Hg; his dizziness, blurred vision, lightheadedness, and nausea are resolved.

Bradycardia is defined as a HR <60 bpm; however, symptoms may not occur until the HR is <50 bpm. Symptoms include fatigue, dizziness, lightheadedness, chest pain, shortness of breath, and syncope. The incidence of bradycardia during lithium treatment is unknown; it is considered a rare but serious adverse effect. A literature review reveals several case reports of bradycardia with lithium treatment,^2-4 including symptomatic bradycardia after a single dose of lithium.⁵ Other possible causes of bradycardia include anorexia nervosa, hypothermia, hypothyroidism, hypoxia, infection, stroke, acute myocardial infarction, sedative or opiate use, increased vagal tone with exercise conditioning, and other medications including fluphenazine.⁶

Mr. C’s symptoms may have been assumed to be secondary to several possible causes, including bradycardia, dehydration from poor oral intake, lithium toxicity, or an undiagnosed medical condition. The combination of nausea, dizziness, anorexia nervosa, blurred vision, and lightheadedness in a patient receiving lithium would certainly trigger a clinician’s concern for lithium toxicity, but he (she) may not be aware of the risk of bradycardia as an adverse effect of lithium. Because Mr. C refused hospital transportation by EMS, discontinuing lithium appears to have been the safest option. Laboratory studies from the day after Mr. C presented to the clinic appeared to lessen the probability that lithium toxicity, hypothyroidism, valproate toxicity, type 2 diabetes mellitus, or infection had caused Mr. C’s symptoms.

Although psychiatrists may be vigilant about monitoring for signs and symptoms of toxicity with lithium use by utilizing regular laboratory studies, they may not be as vigilant with monitoring vital signs at every patient visit (Table). This case demonstrates the importance of regular vital sign measurements to be able to detect this rare but serious adverse effect.

CASE Grieving, delusional

Mr. M, age 51, is brought to the emergency department (ED) because of new-onset delusions and decreased self-care over the last 2 weeks following the sudden death of his wife. He has become expansive and grandiose, with pressured speech, increased energy, and markedly reduced sleep. Mr. M is preoccupied with the idea that he is “the first to survive a human reboot process” and says that his and his wife’s bodies and brains had been “split apart.” Mr. M has limited his food and fluid intake and lost 15 lb within the past 2 to 3 weeks.

Mr. M has no history of any affective, psychotic, or other major mental disorders or treatment. He reports that he has regularly used Cannabis over the last 10 years, and a few years ago, he started occasionally using nitrous oxide (N₂O). He says that in the week following his wife’s death, he used N₂O almost daily and in copious amounts. In an attempt to “self-anesthetize” himself after his wife’s funeral, he isolated himself in his bedroom and used escalating amounts of Cannabis and N₂O, while continually working on a book about their life together.

At first, Mr. M shows little emotion and describes his situation as “interesting and fascinating.” He mentions that he thinks he might have been “psychotic” the week after his wife’s death, but he shows no sustained insight and immediately relapses into psychotic thinking. Over several hours in the ED, he is tearful and sad about his wife’s death. Mr. M recalls a similar experience of grief after his mother died when he was a teenager, but at that time he did not abuse substances or have psychotic symptoms. He is fully alert, fully oriented, and has no significant deficits of attention or memory.

[polldaddy:9859135]

The authors’ observations

Grief was a precipitating event, but by itself grief cannot explain psychosis. Psychotic depression is a possibility, but Mr. M’s psychotic features are incongruent with his mood. Mania would be a diagnosis of exclusion. Mr. M had no prior history of major affective illness. Mr. M was abusing Cannabis, which might independently contribute to psychosis¹; however, he had been using it recreationally for 10 years without psychiatric problems. N₂O, however, can cause symptoms consistent with Mr. M’s presentation.

[polldaddy:9859140]

EVALUATION Laboratory tests

Mr. M’s physical examination is notable only for an elevated blood pressure of 196/120 mm Hg. Neurologic examination is normal. Toxicology is positive for cannabinoids and negative for amphetamines, cocaine, opiates, and phencyclidine. Chemistries are normal except for a potassium of 3.4 mEq/L (reference range, 3.7 to 5.2 mEq/L) and a blood urine nitrogen of 25 mg/dL (reference range, 6 to 20 mg/dL), which are consistent with reduced food and fluid intake. Mr. M shows no signs of anemia. Hematocrit is 42% and mean corpuscular volume is 90 fL. Syphilis screen is negative; a head CT scan is unremarkable.

The authors’ observations

N₂O, also known as “laughing gas,” is routinely used by dentists and pediatric anesthesiologists, and has other medical uses. Some studies have examined an adjunctive use of N₂O for pain control in the ED and during colonoscopies.^3,4

In the 2013 U.S. National Survey on Drug Use and Health, 16% of respondents reported lifetime illicit use of N₂O.^5,6 It is readily available in tanks used in medicine and industry and in small dispensers called “whippits” that can be legally purchased. Acute effects of N₂O include euphoric mood, numbness, feeling of warmth, dizziness, and auditory hallucinations.⁷ The anesthetic effects of N₂O are linked to endogenous release of opiates, and recent research links its anxiolytic activity to the facilitation of GABAergic inhibitory and N-methyl-d-aspartic acid (NMDA)-mediated transmission.⁸ Abuse of N₂O has been the presumptive cause of death in 29 cases.⁹

TREATMENT Supplementation

Mr. M is diagnosed with substance-induced psychotic disorder. His symptoms were precipitated by an acute increase in N₂O use, which has been shown to cause vitamin B₁₂ deficiency, which we consider was likely a primary contributor to his presentation. Other potential contributing factors are premorbid hyperthymic temperament, a possible propensity to psychotic thinking under stress, the sudden death of his wife, acute grief, the potentiating role of Cannabis, dehydration, and general malnutrition. The death of a loved one is associated with an increased risk of developing substance use disorders.²⁷

During a 15-day psychiatric hospitalization, Mr. M is given olanzapine, increased to 15 mg/d and oral vitamin B₁₂, 1,000 mcg/d for 4 days, then IM cyanocobalamin for 7 days. Mr. M’s symptoms steadily improve, with normalization of sleep and near-total resolution of delusions. On hospital Day 14, his vitamin B₁₂ levels are within normal limits (844 pg/mL). At discharge, Mr. M shows residual mild grandiosity, with limited insight into his illness and what caused it, but frank delusional ideation has clearly receded. He still shows some signs of grief. Mr. M is advised to stop using Cannabis and N₂O and about the potential consequences of continued use.

The authors’ observations

For patients with vitamin B₁₂ deficiency, guidelines from the National Health Service in the United Kingdom and the British Society for Haematology recommend treatment with IM hydroxocobalamin, 1,000 IU, 3 times weekly, for 2 weeks.^21,28 For patients with neurologic symptoms, the British National Foundation recommends treatment with IM hydroxocobalamin, 1,000 IU, on alternative days until there is no further improvement.²¹

This case is a reminder for clinicians to screen for inhalant use, specifically N₂O, which can precipitate vitamin B₁₂ deficiency with psychiatric symptoms as the only presenting concern. Clinicians should consider measuring vitamin B₁₂ levels in psychiatric patients at risk of deficiency of this nutrient, including older adults, vegetarians, and those with alimentary disorders.^29,30 Dietary sources of vitamin B₁₂ include meat, milk, egg, fish, and shellfish.³¹ The body can store a total of 2 to 5 mg of vitamin B₁₂; thus, it takes 2 to 5 years to develop vitamin B₁₂ deficiency from malabsorption and can take as long as 20 years to develop vitamin B₁₂ deficiency from vegetarianism.³² However, by chemically inactivating vitamin B₁₂, N₂O causes a rapid functional deficiency, as was seen in our patient.

OUTCOME Improved insight

At a 1-week follow-up appointment with a psychiatrist, Mr. M has no evident psychotic symptoms. He reports that he has not used Cannabis or N₂O, and he discontinues olanzapine following this visit. Two weeks later, Mr. M shows no psychotic or affective symptoms other than grief, which is appropriately expressed. His insight has improved. He commits to not using Cannabis, N₂O, or any other illicit substances. Mr. M is referred back to his long-standing primary care provider with the understanding that if any psychiatric symptoms recur he will see a psychiatrist again.

CASE Grieving, delusional

Mr. M, age 51, is brought to the emergency department (ED) because of new-onset delusions and decreased self-care over the last 2 weeks following the sudden death of his wife. He has become expansive and grandiose, with pressured speech, increased energy, and markedly reduced sleep. Mr. M is preoccupied with the idea that he is “the first to survive a human reboot process” and says that his and his wife’s bodies and brains had been “split apart.” Mr. M has limited his food and fluid intake and lost 15 lb within the past 2 to 3 weeks.

Mr. M has no history of any affective, psychotic, or other major mental disorders or treatment. He reports that he has regularly used Cannabis over the last 10 years, and a few years ago, he started occasionally using nitrous oxide (N₂O). He says that in the week following his wife’s death, he used N₂O almost daily and in copious amounts. In an attempt to “self-anesthetize” himself after his wife’s funeral, he isolated himself in his bedroom and used escalating amounts of Cannabis and N₂O, while continually working on a book about their life together.

At first, Mr. M shows little emotion and describes his situation as “interesting and fascinating.” He mentions that he thinks he might have been “psychotic” the week after his wife’s death, but he shows no sustained insight and immediately relapses into psychotic thinking. Over several hours in the ED, he is tearful and sad about his wife’s death. Mr. M recalls a similar experience of grief after his mother died when he was a teenager, but at that time he did not abuse substances or have psychotic symptoms. He is fully alert, fully oriented, and has no significant deficits of attention or memory.

[polldaddy:9859135]

The authors’ observations

Grief was a precipitating event, but by itself grief cannot explain psychosis. Psychotic depression is a possibility, but Mr. M’s psychotic features are incongruent with his mood. Mania would be a diagnosis of exclusion. Mr. M had no prior history of major affective illness. Mr. M was abusing Cannabis, which might independently contribute to psychosis¹; however, he had been using it recreationally for 10 years without psychiatric problems. N₂O, however, can cause symptoms consistent with Mr. M’s presentation.

[polldaddy:9859140]

EVALUATION Laboratory tests

Mr. M’s physical examination is notable only for an elevated blood pressure of 196/120 mm Hg. Neurologic examination is normal. Toxicology is positive for cannabinoids and negative for amphetamines, cocaine, opiates, and phencyclidine. Chemistries are normal except for a potassium of 3.4 mEq/L (reference range, 3.7 to 5.2 mEq/L) and a blood urine nitrogen of 25 mg/dL (reference range, 6 to 20 mg/dL), which are consistent with reduced food and fluid intake. Mr. M shows no signs of anemia. Hematocrit is 42% and mean corpuscular volume is 90 fL. Syphilis screen is negative; a head CT scan is unremarkable.

The authors’ observations

N₂O, also known as “laughing gas,” is routinely used by dentists and pediatric anesthesiologists, and has other medical uses. Some studies have examined an adjunctive use of N₂O for pain control in the ED and during colonoscopies.^3,4

In the 2013 U.S. National Survey on Drug Use and Health, 16% of respondents reported lifetime illicit use of N₂O.^5,6 It is readily available in tanks used in medicine and industry and in small dispensers called “whippits” that can be legally purchased. Acute effects of N₂O include euphoric mood, numbness, feeling of warmth, dizziness, and auditory hallucinations.⁷ The anesthetic effects of N₂O are linked to endogenous release of opiates, and recent research links its anxiolytic activity to the facilitation of GABAergic inhibitory and N-methyl-d-aspartic acid (NMDA)-mediated transmission.⁸ Abuse of N₂O has been the presumptive cause of death in 29 cases.⁹

TREATMENT Supplementation

Mr. M is diagnosed with substance-induced psychotic disorder. His symptoms were precipitated by an acute increase in N₂O use, which has been shown to cause vitamin B₁₂ deficiency, which we consider was likely a primary contributor to his presentation. Other potential contributing factors are premorbid hyperthymic temperament, a possible propensity to psychotic thinking under stress, the sudden death of his wife, acute grief, the potentiating role of Cannabis, dehydration, and general malnutrition. The death of a loved one is associated with an increased risk of developing substance use disorders.²⁷

During a 15-day psychiatric hospitalization, Mr. M is given olanzapine, increased to 15 mg/d and oral vitamin B₁₂, 1,000 mcg/d for 4 days, then IM cyanocobalamin for 7 days. Mr. M’s symptoms steadily improve, with normalization of sleep and near-total resolution of delusions. On hospital Day 14, his vitamin B₁₂ levels are within normal limits (844 pg/mL). At discharge, Mr. M shows residual mild grandiosity, with limited insight into his illness and what caused it, but frank delusional ideation has clearly receded. He still shows some signs of grief. Mr. M is advised to stop using Cannabis and N₂O and about the potential consequences of continued use.

The authors’ observations

For patients with vitamin B₁₂ deficiency, guidelines from the National Health Service in the United Kingdom and the British Society for Haematology recommend treatment with IM hydroxocobalamin, 1,000 IU, 3 times weekly, for 2 weeks.^21,28 For patients with neurologic symptoms, the British National Foundation recommends treatment with IM hydroxocobalamin, 1,000 IU, on alternative days until there is no further improvement.²¹

This case is a reminder for clinicians to screen for inhalant use, specifically N₂O, which can precipitate vitamin B₁₂ deficiency with psychiatric symptoms as the only presenting concern. Clinicians should consider measuring vitamin B₁₂ levels in psychiatric patients at risk of deficiency of this nutrient, including older adults, vegetarians, and those with alimentary disorders.^29,30 Dietary sources of vitamin B₁₂ include meat, milk, egg, fish, and shellfish.³¹ The body can store a total of 2 to 5 mg of vitamin B₁₂; thus, it takes 2 to 5 years to develop vitamin B₁₂ deficiency from malabsorption and can take as long as 20 years to develop vitamin B₁₂ deficiency from vegetarianism.³² However, by chemically inactivating vitamin B₁₂, N₂O causes a rapid functional deficiency, as was seen in our patient.

OUTCOME Improved insight

At a 1-week follow-up appointment with a psychiatrist, Mr. M has no evident psychotic symptoms. He reports that he has not used Cannabis or N₂O, and he discontinues olanzapine following this visit. Two weeks later, Mr. M shows no psychotic or affective symptoms other than grief, which is appropriately expressed. His insight has improved. He commits to not using Cannabis, N₂O, or any other illicit substances. Mr. M is referred back to his long-standing primary care provider with the understanding that if any psychiatric symptoms recur he will see a psychiatrist again.

CASE Grieving, delusional

Mr. M, age 51, is brought to the emergency department (ED) because of new-onset delusions and decreased self-care over the last 2 weeks following the sudden death of his wife. He has become expansive and grandiose, with pressured speech, increased energy, and markedly reduced sleep. Mr. M is preoccupied with the idea that he is “the first to survive a human reboot process” and says that his and his wife’s bodies and brains had been “split apart.” Mr. M has limited his food and fluid intake and lost 15 lb within the past 2 to 3 weeks.

Mr. M has no history of any affective, psychotic, or other major mental disorders or treatment. He reports that he has regularly used Cannabis over the last 10 years, and a few years ago, he started occasionally using nitrous oxide (N₂O). He says that in the week following his wife’s death, he used N₂O almost daily and in copious amounts. In an attempt to “self-anesthetize” himself after his wife’s funeral, he isolated himself in his bedroom and used escalating amounts of Cannabis and N₂O, while continually working on a book about their life together.

At first, Mr. M shows little emotion and describes his situation as “interesting and fascinating.” He mentions that he thinks he might have been “psychotic” the week after his wife’s death, but he shows no sustained insight and immediately relapses into psychotic thinking. Over several hours in the ED, he is tearful and sad about his wife’s death. Mr. M recalls a similar experience of grief after his mother died when he was a teenager, but at that time he did not abuse substances or have psychotic symptoms. He is fully alert, fully oriented, and has no significant deficits of attention or memory.

[polldaddy:9859135]

The authors’ observations

Grief was a precipitating event, but by itself grief cannot explain psychosis. Psychotic depression is a possibility, but Mr. M’s psychotic features are incongruent with his mood. Mania would be a diagnosis of exclusion. Mr. M had no prior history of major affective illness. Mr. M was abusing Cannabis, which might independently contribute to psychosis¹; however, he had been using it recreationally for 10 years without psychiatric problems. N₂O, however, can cause symptoms consistent with Mr. M’s presentation.

[polldaddy:9859140]

EVALUATION Laboratory tests

Mr. M’s physical examination is notable only for an elevated blood pressure of 196/120 mm Hg. Neurologic examination is normal. Toxicology is positive for cannabinoids and negative for amphetamines, cocaine, opiates, and phencyclidine. Chemistries are normal except for a potassium of 3.4 mEq/L (reference range, 3.7 to 5.2 mEq/L) and a blood urine nitrogen of 25 mg/dL (reference range, 6 to 20 mg/dL), which are consistent with reduced food and fluid intake. Mr. M shows no signs of anemia. Hematocrit is 42% and mean corpuscular volume is 90 fL. Syphilis screen is negative; a head CT scan is unremarkable.

The authors’ observations

N₂O, also known as “laughing gas,” is routinely used by dentists and pediatric anesthesiologists, and has other medical uses. Some studies have examined an adjunctive use of N₂O for pain control in the ED and during colonoscopies.^3,4

In the 2013 U.S. National Survey on Drug Use and Health, 16% of respondents reported lifetime illicit use of N₂O.^5,6 It is readily available in tanks used in medicine and industry and in small dispensers called “whippits” that can be legally purchased. Acute effects of N₂O include euphoric mood, numbness, feeling of warmth, dizziness, and auditory hallucinations.⁷ The anesthetic effects of N₂O are linked to endogenous release of opiates, and recent research links its anxiolytic activity to the facilitation of GABAergic inhibitory and N-methyl-d-aspartic acid (NMDA)-mediated transmission.⁸ Abuse of N₂O has been the presumptive cause of death in 29 cases.⁹

TREATMENT Supplementation

Mr. M is diagnosed with substance-induced psychotic disorder. His symptoms were precipitated by an acute increase in N₂O use, which has been shown to cause vitamin B₁₂ deficiency, which we consider was likely a primary contributor to his presentation. Other potential contributing factors are premorbid hyperthymic temperament, a possible propensity to psychotic thinking under stress, the sudden death of his wife, acute grief, the potentiating role of Cannabis, dehydration, and general malnutrition. The death of a loved one is associated with an increased risk of developing substance use disorders.²⁷

During a 15-day psychiatric hospitalization, Mr. M is given olanzapine, increased to 15 mg/d and oral vitamin B₁₂, 1,000 mcg/d for 4 days, then IM cyanocobalamin for 7 days. Mr. M’s symptoms steadily improve, with normalization of sleep and near-total resolution of delusions. On hospital Day 14, his vitamin B₁₂ levels are within normal limits (844 pg/mL). At discharge, Mr. M shows residual mild grandiosity, with limited insight into his illness and what caused it, but frank delusional ideation has clearly receded. He still shows some signs of grief. Mr. M is advised to stop using Cannabis and N₂O and about the potential consequences of continued use.

The authors’ observations

For patients with vitamin B₁₂ deficiency, guidelines from the National Health Service in the United Kingdom and the British Society for Haematology recommend treatment with IM hydroxocobalamin, 1,000 IU, 3 times weekly, for 2 weeks.^21,28 For patients with neurologic symptoms, the British National Foundation recommends treatment with IM hydroxocobalamin, 1,000 IU, on alternative days until there is no further improvement.²¹

This case is a reminder for clinicians to screen for inhalant use, specifically N₂O, which can precipitate vitamin B₁₂ deficiency with psychiatric symptoms as the only presenting concern. Clinicians should consider measuring vitamin B₁₂ levels in psychiatric patients at risk of deficiency of this nutrient, including older adults, vegetarians, and those with alimentary disorders.^29,30 Dietary sources of vitamin B₁₂ include meat, milk, egg, fish, and shellfish.³¹ The body can store a total of 2 to 5 mg of vitamin B₁₂; thus, it takes 2 to 5 years to develop vitamin B₁₂ deficiency from malabsorption and can take as long as 20 years to develop vitamin B₁₂ deficiency from vegetarianism.³² However, by chemically inactivating vitamin B₁₂, N₂O causes a rapid functional deficiency, as was seen in our patient.

OUTCOME Improved insight

At a 1-week follow-up appointment with a psychiatrist, Mr. M has no evident psychotic symptoms. He reports that he has not used Cannabis or N₂O, and he discontinues olanzapine following this visit. Two weeks later, Mr. M shows no psychotic or affective symptoms other than grief, which is appropriately expressed. His insight has improved. He commits to not using Cannabis, N₂O, or any other illicit substances. Mr. M is referred back to his long-standing primary care provider with the understanding that if any psychiatric symptoms recur he will see a psychiatrist again.

As physicians, we are cognizant of the importance of patient-centered care, active listening, empathy, and patience—the so-called “hidden curriculum of medicine.”¹ However, our attempts to centralize these concepts may be overshadowed by the deeply rooted drive to treat and fix. At times, we are simply treating uncertainty, whether it be diagnostic uncertainty or the uncertainty arising from clinical responses and outcomes that are far from binary. Definitive actions, such as adding medications or altering dosages, may appear to both patients and physicians to be a step closer to a “cure.” However, watchful waiting, re-evaluation, and accepting uncertainty are the true skills of effective care.

Be savvy about psychopharmacology

Psychotropics can take weeks to months to reach their full potential, and have varying responses and adverse effects. Beware of changing regimens prematurely, and keep in mind basic, yet crucial, pharma­cokinetic concepts (eg, 4 to 5 half-lives to reach steady state, variations in metabolism). Receptor binding and dosing heuristics are notably common in psychiatry. Although such concepts are important to grasp, there is no one-size-fits-all rule. The brain simply does not possess the heart’s machine-like, linear functioning. Therefore, targeting individual parts (ie, receptors) will not equate to fixing the whole organ systematically or predictably.

Is the patient truly treatment-resistant?

Even the best treatment regimen has no clinical benefit if the patient cannot afford the prescription or does not take the medication. If cost is an impediment, switch from brand name drugs to generic formulations or to older medications in the same class. Before declaring the patient “treatment-resistant” and making medication changes, assess for compliance. This may require assistance from collateral informants. Ask family members to count the number of pills remaining in the bottle, and call the pharmacy to find out the last refill dates. If the patient exhibits a partial response to what should be a therapeutic dose, consider obtaining drug plasma levels to rule out rapid metabolism before deeming the medication trial a failure.²

Medications as liabilities

Overreliance on medications can result in the medications becoming liabilities. The polypharmacy problem is not unique to psychiatry.³ However, psychiatric patients may be more likely to inadvertently use medications in a maladaptive manner and disrupt the fundamental goals of long-term care. Avoid making medication adjustments in response to a patient’s life stressors and normative situational reactions. Doing so is a disservice to patients, because we are robbing them of chances to develop necessary coping skills and defenses. This can be overtly damaging in certain patient populations, such as those with borderline personality disorder, who may use medication adjustments as a crutch during crises.⁴

Treat the patient, not yourself

We physicians mean well in prescribing evidence-based treatments; however, if the symptoms or adverse effects are not bother­some or cause functional impairment, we risk losing sight of the patient’s goals in treatment and imposing our own instead. Displacing the treatment focus can alienate the patient, harm the therapeutic alliance, and result in “pill fatigue.” For example, we may be tempted to treat antipsychotic-induced tardive dyskinesia, even if the patient is not concerned about abnormal movements. Although we see this adverse effect as a secondary problem that necessitates treatment, from the patient’s perspective, taking additional medication may be a far greater burden. The patient’s perception of direct beneficial effects from medications is crucial not only for patient-oriented care but also for adherence.⁵

Change does not happen overnight

Picking a treatment option out of a lineup of choices, à la UWorld questions, does not always translate into patients agreeing with the suggested treatment, let alone the idea of receiving treatment at all. Motivational interviewing is our chance to shine in such situations and the reason why we are physicians, rather than answer-picking bots. Patients cannot change if they are not ready. However, we should be ready to roll with resistance while looking for signs of readiness to change. We must accept that it may take a week, a month, a year, or even longer for patients to align with our plan of action. The only futile decision is deeming our efforts as futile while discounting the benefits of incremental care.

As physicians, we are cognizant of the importance of patient-centered care, active listening, empathy, and patience—the so-called “hidden curriculum of medicine.”¹ However, our attempts to centralize these concepts may be overshadowed by the deeply rooted drive to treat and fix. At times, we are simply treating uncertainty, whether it be diagnostic uncertainty or the uncertainty arising from clinical responses and outcomes that are far from binary. Definitive actions, such as adding medications or altering dosages, may appear to both patients and physicians to be a step closer to a “cure.” However, watchful waiting, re-evaluation, and accepting uncertainty are the true skills of effective care.

Be savvy about psychopharmacology

Psychotropics can take weeks to months to reach their full potential, and have varying responses and adverse effects. Beware of changing regimens prematurely, and keep in mind basic, yet crucial, pharma­cokinetic concepts (eg, 4 to 5 half-lives to reach steady state, variations in metabolism). Receptor binding and dosing heuristics are notably common in psychiatry. Although such concepts are important to grasp, there is no one-size-fits-all rule. The brain simply does not possess the heart’s machine-like, linear functioning. Therefore, targeting individual parts (ie, receptors) will not equate to fixing the whole organ systematically or predictably.

Is the patient truly treatment-resistant?

Even the best treatment regimen has no clinical benefit if the patient cannot afford the prescription or does not take the medication. If cost is an impediment, switch from brand name drugs to generic formulations or to older medications in the same class. Before declaring the patient “treatment-resistant” and making medication changes, assess for compliance. This may require assistance from collateral informants. Ask family members to count the number of pills remaining in the bottle, and call the pharmacy to find out the last refill dates. If the patient exhibits a partial response to what should be a therapeutic dose, consider obtaining drug plasma levels to rule out rapid metabolism before deeming the medication trial a failure.²

Medications as liabilities

Overreliance on medications can result in the medications becoming liabilities. The polypharmacy problem is not unique to psychiatry.³ However, psychiatric patients may be more likely to inadvertently use medications in a maladaptive manner and disrupt the fundamental goals of long-term care. Avoid making medication adjustments in response to a patient’s life stressors and normative situational reactions. Doing so is a disservice to patients, because we are robbing them of chances to develop necessary coping skills and defenses. This can be overtly damaging in certain patient populations, such as those with borderline personality disorder, who may use medication adjustments as a crutch during crises.⁴

Treat the patient, not yourself

We physicians mean well in prescribing evidence-based treatments; however, if the symptoms or adverse effects are not bother­some or cause functional impairment, we risk losing sight of the patient’s goals in treatment and imposing our own instead. Displacing the treatment focus can alienate the patient, harm the therapeutic alliance, and result in “pill fatigue.” For example, we may be tempted to treat antipsychotic-induced tardive dyskinesia, even if the patient is not concerned about abnormal movements. Although we see this adverse effect as a secondary problem that necessitates treatment, from the patient’s perspective, taking additional medication may be a far greater burden. The patient’s perception of direct beneficial effects from medications is crucial not only for patient-oriented care but also for adherence.⁵

Change does not happen overnight

Picking a treatment option out of a lineup of choices, à la UWorld questions, does not always translate into patients agreeing with the suggested treatment, let alone the idea of receiving treatment at all. Motivational interviewing is our chance to shine in such situations and the reason why we are physicians, rather than answer-picking bots. Patients cannot change if they are not ready. However, we should be ready to roll with resistance while looking for signs of readiness to change. We must accept that it may take a week, a month, a year, or even longer for patients to align with our plan of action. The only futile decision is deeming our efforts as futile while discounting the benefits of incremental care.

As physicians, we are cognizant of the importance of patient-centered care, active listening, empathy, and patience—the so-called “hidden curriculum of medicine.”¹ However, our attempts to centralize these concepts may be overshadowed by the deeply rooted drive to treat and fix. At times, we are simply treating uncertainty, whether it be diagnostic uncertainty or the uncertainty arising from clinical responses and outcomes that are far from binary. Definitive actions, such as adding medications or altering dosages, may appear to both patients and physicians to be a step closer to a “cure.” However, watchful waiting, re-evaluation, and accepting uncertainty are the true skills of effective care.

Be savvy about psychopharmacology

Psychotropics can take weeks to months to reach their full potential, and have varying responses and adverse effects. Beware of changing regimens prematurely, and keep in mind basic, yet crucial, pharma­cokinetic concepts (eg, 4 to 5 half-lives to reach steady state, variations in metabolism). Receptor binding and dosing heuristics are notably common in psychiatry. Although such concepts are important to grasp, there is no one-size-fits-all rule. The brain simply does not possess the heart’s machine-like, linear functioning. Therefore, targeting individual parts (ie, receptors) will not equate to fixing the whole organ systematically or predictably.

Is the patient truly treatment-resistant?

Even the best treatment regimen has no clinical benefit if the patient cannot afford the prescription or does not take the medication. If cost is an impediment, switch from brand name drugs to generic formulations or to older medications in the same class. Before declaring the patient “treatment-resistant” and making medication changes, assess for compliance. This may require assistance from collateral informants. Ask family members to count the number of pills remaining in the bottle, and call the pharmacy to find out the last refill dates. If the patient exhibits a partial response to what should be a therapeutic dose, consider obtaining drug plasma levels to rule out rapid metabolism before deeming the medication trial a failure.²

Medications as liabilities

Overreliance on medications can result in the medications becoming liabilities. The polypharmacy problem is not unique to psychiatry.³ However, psychiatric patients may be more likely to inadvertently use medications in a maladaptive manner and disrupt the fundamental goals of long-term care. Avoid making medication adjustments in response to a patient’s life stressors and normative situational reactions. Doing so is a disservice to patients, because we are robbing them of chances to develop necessary coping skills and defenses. This can be overtly damaging in certain patient populations, such as those with borderline personality disorder, who may use medication adjustments as a crutch during crises.⁴

Treat the patient, not yourself

We physicians mean well in prescribing evidence-based treatments; however, if the symptoms or adverse effects are not bother­some or cause functional impairment, we risk losing sight of the patient’s goals in treatment and imposing our own instead. Displacing the treatment focus can alienate the patient, harm the therapeutic alliance, and result in “pill fatigue.” For example, we may be tempted to treat antipsychotic-induced tardive dyskinesia, even if the patient is not concerned about abnormal movements. Although we see this adverse effect as a secondary problem that necessitates treatment, from the patient’s perspective, taking additional medication may be a far greater burden. The patient’s perception of direct beneficial effects from medications is crucial not only for patient-oriented care but also for adherence.⁵

Change does not happen overnight

Picking a treatment option out of a lineup of choices, à la UWorld questions, does not always translate into patients agreeing with the suggested treatment, let alone the idea of receiving treatment at all. Motivational interviewing is our chance to shine in such situations and the reason why we are physicians, rather than answer-picking bots. Patients cannot change if they are not ready. However, we should be ready to roll with resistance while looking for signs of readiness to change. We must accept that it may take a week, a month, a year, or even longer for patients to align with our plan of action. The only futile decision is deeming our efforts as futile while discounting the benefits of incremental care.

Although the biological aspects of psychiatry are crucial, psychotherapy is an integral part of psychiatry. Unfortunately, the emphasis on psychotherapy training in psychiatry residency programs has declined compared with a decade or more ago. In an era of dwindling psychotherapy training and resources, the quality and type of psychotherapy training has become more variable. In addition to helping maintain the therapeutic alliance, nuanced psychotherapy by a trained professional can be transformational by helping patients to:

• process complex life events and emotions
• feel understood
• overcome psychological barriers to recovery
• enhance self-esteem.

For the therapist, effective psychotherapy usually involves warmth and empathy, active listening, an authentic and genuine positive regard for the patient and his (her) experiences. The therapist should also pay attention to her (his) own emotions and internal responses, as well as the patient’s, while having the perseverance to address and help the patient work through challenging aspects.

When providing psychotherapy for adult patients, consider these basic, but salient points that are often overlooked.

Refrain from making life decisions for patients, except in exceptional circumstances, such as in situations of abuse and other crises.¹ Telling an adult patient what to do about life decisions that he finds challenging fits more under life coaching than psychotherapy. Through therapy, patients should be helped in processing the pros and cons of certain decisions and in navigating the decision-making process to arrive at a decision that makes the most sense to them. Also, it’s not uncommon for thera­peutic relationships to rupture when therapists give advice such as suggesting that a patient divorce his spouse, date a certain individual, or have children.

There are many reasons why giving advice in psychotherapy is not recommended. Giving advice can be an impediment to the therapeutic process.² What is good advice for one patient may not be good for another. Therapists who give advice often do so from their own lens and perspective. This perspective may not only be different from the patient’s priorities and life circumstances, but the therapist also may have inadequate information about the patient’s situation,^1,2 which could lead to providing advice that could even harm the patient. In addition, providing advice might prevent a patient from gaining adequate agency or self-directedness while promoting an unhealthy dependence on the therapist and reinforcing the patient’s self-doubt or lack of confidence. In these cases, the patient may later resent the therapist for the advice.

Address the ‘here and now.’¹ Pay attention to immediate issues or themes that emerge, and address them with the patient gently and thoughtfully, as appropriate. Ignoring these may create risks of missing vital, underlying material that could reveal more of the patient’s inner world, as these themes can sometimes reflect other themes of the patient’s life outside of treatment.

Acknowledging and empathizing, when appropriate, are key initial steps that help decrease resistance and facilitate the therapeutic process.

Explore the affect. Paying attention to the patient’s emotional state is critical.³ This holds true for all types of psychotherapy. For example, if a patient suddenly becomes tearful when telling his story or describing recent events, this is usually a sign that the subject matter affects or holds value to the patient in a significant or meaningful way and should be further explored.

‘Meet the patient where they are.’ This doesn’t mean you should yield to the patient or give in to his demands. It implies that you should assess the patient’s readiness for a particular intervention and devise interventions from that standpoint, exploring the patient’s ambivalence, noticing resistance, and continuing to acknowledge and empathize with where the patient is in life or treatment. When utilized judiciously, this technique can help the therapist align with the patient, and help the patient move forward through resistance and ambivalence.

Be nonjudgmental and empathetic. Patients place trust in their therapists when they disclose thoughts or emotions that are sensitive, meaningful, or close to the heart. A nonjudgmental response helps the patient accept his experiences and emotions. Being empathetic requires putting oneself in another’s shoes; it does not mean agreeing with the patient. Of course, if you learn that your patient abused a child or an older adult, you are required to report it to the appropriate state agency. In addition, follow the duty to warn and protect in case of any other safety issues, as appropriate.

Do not assume. Open-ended questions and exploration are key. For example, a patient told her resident therapist that her father recently passed away. The therapist expressed to the patient how hard this must be for her. However, the patient said she was relieved by her father’s death, because he had been abusive to her for years. Because of the therapist’s comment, the patient doubted her own reaction and felt guilty for not being more upset about her father’s death.

Avoid over-identifying with your patient. If you find yourself over-identifying with a patient because you have a common background or life events, seek supervision. Over-identification not only can pose barriers to objectively identifying patterns and trends in the patient’s behavior or presentation but also can increase the risk of crossing boundaries or even minimizing the patient’s experience. Exercise caution if you find yourself wanting to be liked by your patient; this is a common mistake among beginning therapists.⁴

Seek supervision. If you are feeling angry, frustrated, indifferent, or overly attached toward a patient, recognize this countertransference and seek consultation or supervision from an experienced colleague or supervisor. These emotions can be valuable tools that shed light not only on the patient’s life and the session itself, but also help you identify any other factors, such as your own feelings or experiences, that might be contributing to these reactions.

Although the biological aspects of psychiatry are crucial, psychotherapy is an integral part of psychiatry. Unfortunately, the emphasis on psychotherapy training in psychiatry residency programs has declined compared with a decade or more ago. In an era of dwindling psychotherapy training and resources, the quality and type of psychotherapy training has become more variable. In addition to helping maintain the therapeutic alliance, nuanced psychotherapy by a trained professional can be transformational by helping patients to:

• process complex life events and emotions
• feel understood
• overcome psychological barriers to recovery
• enhance self-esteem.

For the therapist, effective psychotherapy usually involves warmth and empathy, active listening, an authentic and genuine positive regard for the patient and his (her) experiences. The therapist should also pay attention to her (his) own emotions and internal responses, as well as the patient’s, while having the perseverance to address and help the patient work through challenging aspects.

When providing psychotherapy for adult patients, consider these basic, but salient points that are often overlooked.

Refrain from making life decisions for patients, except in exceptional circumstances, such as in situations of abuse and other crises.¹ Telling an adult patient what to do about life decisions that he finds challenging fits more under life coaching than psychotherapy. Through therapy, patients should be helped in processing the pros and cons of certain decisions and in navigating the decision-making process to arrive at a decision that makes the most sense to them. Also, it’s not uncommon for thera­peutic relationships to rupture when therapists give advice such as suggesting that a patient divorce his spouse, date a certain individual, or have children.

There are many reasons why giving advice in psychotherapy is not recommended. Giving advice can be an impediment to the therapeutic process.² What is good advice for one patient may not be good for another. Therapists who give advice often do so from their own lens and perspective. This perspective may not only be different from the patient’s priorities and life circumstances, but the therapist also may have inadequate information about the patient’s situation,^1,2 which could lead to providing advice that could even harm the patient. In addition, providing advice might prevent a patient from gaining adequate agency or self-directedness while promoting an unhealthy dependence on the therapist and reinforcing the patient’s self-doubt or lack of confidence. In these cases, the patient may later resent the therapist for the advice.

Address the ‘here and now.’¹ Pay attention to immediate issues or themes that emerge, and address them with the patient gently and thoughtfully, as appropriate. Ignoring these may create risks of missing vital, underlying material that could reveal more of the patient’s inner world, as these themes can sometimes reflect other themes of the patient’s life outside of treatment.

Acknowledging and empathizing, when appropriate, are key initial steps that help decrease resistance and facilitate the therapeutic process.

Explore the affect. Paying attention to the patient’s emotional state is critical.³ This holds true for all types of psychotherapy. For example, if a patient suddenly becomes tearful when telling his story or describing recent events, this is usually a sign that the subject matter affects or holds value to the patient in a significant or meaningful way and should be further explored.

‘Meet the patient where they are.’ This doesn’t mean you should yield to the patient or give in to his demands. It implies that you should assess the patient’s readiness for a particular intervention and devise interventions from that standpoint, exploring the patient’s ambivalence, noticing resistance, and continuing to acknowledge and empathize with where the patient is in life or treatment. When utilized judiciously, this technique can help the therapist align with the patient, and help the patient move forward through resistance and ambivalence.

Be nonjudgmental and empathetic. Patients place trust in their therapists when they disclose thoughts or emotions that are sensitive, meaningful, or close to the heart. A nonjudgmental response helps the patient accept his experiences and emotions. Being empathetic requires putting oneself in another’s shoes; it does not mean agreeing with the patient. Of course, if you learn that your patient abused a child or an older adult, you are required to report it to the appropriate state agency. In addition, follow the duty to warn and protect in case of any other safety issues, as appropriate.

Do not assume. Open-ended questions and exploration are key. For example, a patient told her resident therapist that her father recently passed away. The therapist expressed to the patient how hard this must be for her. However, the patient said she was relieved by her father’s death, because he had been abusive to her for years. Because of the therapist’s comment, the patient doubted her own reaction and felt guilty for not being more upset about her father’s death.

Avoid over-identifying with your patient. If you find yourself over-identifying with a patient because you have a common background or life events, seek supervision. Over-identification not only can pose barriers to objectively identifying patterns and trends in the patient’s behavior or presentation but also can increase the risk of crossing boundaries or even minimizing the patient’s experience. Exercise caution if you find yourself wanting to be liked by your patient; this is a common mistake among beginning therapists.⁴

Seek supervision. If you are feeling angry, frustrated, indifferent, or overly attached toward a patient, recognize this countertransference and seek consultation or supervision from an experienced colleague or supervisor. These emotions can be valuable tools that shed light not only on the patient’s life and the session itself, but also help you identify any other factors, such as your own feelings or experiences, that might be contributing to these reactions.

Although the biological aspects of psychiatry are crucial, psychotherapy is an integral part of psychiatry. Unfortunately, the emphasis on psychotherapy training in psychiatry residency programs has declined compared with a decade or more ago. In an era of dwindling psychotherapy training and resources, the quality and type of psychotherapy training has become more variable. In addition to helping maintain the therapeutic alliance, nuanced psychotherapy by a trained professional can be transformational by helping patients to:

• process complex life events and emotions
• feel understood
• overcome psychological barriers to recovery
• enhance self-esteem.

For the therapist, effective psychotherapy usually involves warmth and empathy, active listening, an authentic and genuine positive regard for the patient and his (her) experiences. The therapist should also pay attention to her (his) own emotions and internal responses, as well as the patient’s, while having the perseverance to address and help the patient work through challenging aspects.

When providing psychotherapy for adult patients, consider these basic, but salient points that are often overlooked.

Refrain from making life decisions for patients, except in exceptional circumstances, such as in situations of abuse and other crises.¹ Telling an adult patient what to do about life decisions that he finds challenging fits more under life coaching than psychotherapy. Through therapy, patients should be helped in processing the pros and cons of certain decisions and in navigating the decision-making process to arrive at a decision that makes the most sense to them. Also, it’s not uncommon for thera­peutic relationships to rupture when therapists give advice such as suggesting that a patient divorce his spouse, date a certain individual, or have children.

There are many reasons why giving advice in psychotherapy is not recommended. Giving advice can be an impediment to the therapeutic process.² What is good advice for one patient may not be good for another. Therapists who give advice often do so from their own lens and perspective. This perspective may not only be different from the patient’s priorities and life circumstances, but the therapist also may have inadequate information about the patient’s situation,^1,2 which could lead to providing advice that could even harm the patient. In addition, providing advice might prevent a patient from gaining adequate agency or self-directedness while promoting an unhealthy dependence on the therapist and reinforcing the patient’s self-doubt or lack of confidence. In these cases, the patient may later resent the therapist for the advice.

Address the ‘here and now.’¹ Pay attention to immediate issues or themes that emerge, and address them with the patient gently and thoughtfully, as appropriate. Ignoring these may create risks of missing vital, underlying material that could reveal more of the patient’s inner world, as these themes can sometimes reflect other themes of the patient’s life outside of treatment.

Acknowledging and empathizing, when appropriate, are key initial steps that help decrease resistance and facilitate the therapeutic process.

Explore the affect. Paying attention to the patient’s emotional state is critical.³ This holds true for all types of psychotherapy. For example, if a patient suddenly becomes tearful when telling his story or describing recent events, this is usually a sign that the subject matter affects or holds value to the patient in a significant or meaningful way and should be further explored.

‘Meet the patient where they are.’ This doesn’t mean you should yield to the patient or give in to his demands. It implies that you should assess the patient’s readiness for a particular intervention and devise interventions from that standpoint, exploring the patient’s ambivalence, noticing resistance, and continuing to acknowledge and empathize with where the patient is in life or treatment. When utilized judiciously, this technique can help the therapist align with the patient, and help the patient move forward through resistance and ambivalence.

Be nonjudgmental and empathetic. Patients place trust in their therapists when they disclose thoughts or emotions that are sensitive, meaningful, or close to the heart. A nonjudgmental response helps the patient accept his experiences and emotions. Being empathetic requires putting oneself in another’s shoes; it does not mean agreeing with the patient. Of course, if you learn that your patient abused a child or an older adult, you are required to report it to the appropriate state agency. In addition, follow the duty to warn and protect in case of any other safety issues, as appropriate.

Do not assume. Open-ended questions and exploration are key. For example, a patient told her resident therapist that her father recently passed away. The therapist expressed to the patient how hard this must be for her. However, the patient said she was relieved by her father’s death, because he had been abusive to her for years. Because of the therapist’s comment, the patient doubted her own reaction and felt guilty for not being more upset about her father’s death.

Avoid over-identifying with your patient. If you find yourself over-identifying with a patient because you have a common background or life events, seek supervision. Over-identification not only can pose barriers to objectively identifying patterns and trends in the patient’s behavior or presentation but also can increase the risk of crossing boundaries or even minimizing the patient’s experience. Exercise caution if you find yourself wanting to be liked by your patient; this is a common mistake among beginning therapists.⁴

Seek supervision. If you are feeling angry, frustrated, indifferent, or overly attached toward a patient, recognize this countertransference and seek consultation or supervision from an experienced colleague or supervisor. These emotions can be valuable tools that shed light not only on the patient’s life and the session itself, but also help you identify any other factors, such as your own feelings or experiences, that might be contributing to these reactions.

Despite a lack of evidence, polypharmacy often is used to treat autism spectrum disorder (ASD),¹ while educational techniques are underutilized. Compared with the general population, children with ASD may be more prone to the adverse effects of the medications used to treat symptoms, such as antipsychotics and antidepressants.² Therefore, when addressing problem behaviors, such as tantrums, aggressiveness, or self-injury, in a patient with ASD, before prescribing a medication, consider the ABCs of these behaviors.³

Antecedents. What happened before the behavior occurred? Where and when did the behavior occur? Was the individual unable to get a desired tangible item, such as a preferred food, toy, or another object? Was the individual told complete a task that he (she) did not want to do? Did the individual see someone else getting attention?

Behaviors. What behavior(s) occurred after each antecedent?

Consequences. What happened after the behavior occurred? Did the caregiver give the individual the item he wanted? Was the individual able to get out of doing work that he did not want to do or become the center of attention?

Having parents document the ABCs is useful not only for finding out why a behavior occurred, but also for objectively determining if and how a medication is affecting the frequency of a behavior. Charts that parents can use to document ABC data are available online (eg, http://www.positively­autism.com/downloads/datasheet_abc.pdf). Once this data is collected, it can be used to implement appropriate interventions, which I describe as DEFG.

Differential reinforcement of other behaviors is a procedure that provides positive reinforcement for not engaging in a problem behavior or for staying on task. For example, use a token board to reward positive behaviors, with physical tokens or written marks. However, some patients require immediate reinforcement. I suggest that parents or caregivers carry small pieces of preferred food to give to the patient to reinforce positive behavior.

Exercise. A review of 18 studies reported that physical exercise, such as jogging, weight training, and bike riding, can help reduce problem behaviors in individuals with ASD.⁴ Among 64 participants with ASD, there was a decrease in aggression, stereotypy, off-task behavior, and elopement, and improvements in on-task and motor behavior such as playing catch.

Function. Refer to the ABCs to determine why a specific problem behavior is occurring. Each behavior can have 1 or multiple functions; therefore, develop a plan specific to the reason the patient engages in the behavior. For example, if the individual engages in a behavior to avoid a task, the parent or caregiver can give individual tokens that the individual can later exchange for a break, instead of engaging in the problem behavior to avoid the task. If a behavior appears to be done for attention, instruct the caregivers to provide frequent periods of attention when the individual engages in positive behaviors.

Go to the appropriate placement. By law, persons age ≤21 have the right to an education and to make meaningful progress. If a patient with ASD exhibits behaviors that interfere with learning, he is entitled to a placement that can provide intensive applied behavior analysis. If you feel that the child needs a different school, write an evaluation for the parent or guardian to submit to the school district and clearly outline the patient’s needs and requirements.

Despite a lack of evidence, polypharmacy often is used to treat autism spectrum disorder (ASD),¹ while educational techniques are underutilized. Compared with the general population, children with ASD may be more prone to the adverse effects of the medications used to treat symptoms, such as antipsychotics and antidepressants.² Therefore, when addressing problem behaviors, such as tantrums, aggressiveness, or self-injury, in a patient with ASD, before prescribing a medication, consider the ABCs of these behaviors.³

Antecedents. What happened before the behavior occurred? Where and when did the behavior occur? Was the individual unable to get a desired tangible item, such as a preferred food, toy, or another object? Was the individual told complete a task that he (she) did not want to do? Did the individual see someone else getting attention?

Behaviors. What behavior(s) occurred after each antecedent?

Consequences. What happened after the behavior occurred? Did the caregiver give the individual the item he wanted? Was the individual able to get out of doing work that he did not want to do or become the center of attention?

Having parents document the ABCs is useful not only for finding out why a behavior occurred, but also for objectively determining if and how a medication is affecting the frequency of a behavior. Charts that parents can use to document ABC data are available online (eg, http://www.positively­autism.com/downloads/datasheet_abc.pdf). Once this data is collected, it can be used to implement appropriate interventions, which I describe as DEFG.

Differential reinforcement of other behaviors is a procedure that provides positive reinforcement for not engaging in a problem behavior or for staying on task. For example, use a token board to reward positive behaviors, with physical tokens or written marks. However, some patients require immediate reinforcement. I suggest that parents or caregivers carry small pieces of preferred food to give to the patient to reinforce positive behavior.

Exercise. A review of 18 studies reported that physical exercise, such as jogging, weight training, and bike riding, can help reduce problem behaviors in individuals with ASD.⁴ Among 64 participants with ASD, there was a decrease in aggression, stereotypy, off-task behavior, and elopement, and improvements in on-task and motor behavior such as playing catch.

Function. Refer to the ABCs to determine why a specific problem behavior is occurring. Each behavior can have 1 or multiple functions; therefore, develop a plan specific to the reason the patient engages in the behavior. For example, if the individual engages in a behavior to avoid a task, the parent or caregiver can give individual tokens that the individual can later exchange for a break, instead of engaging in the problem behavior to avoid the task. If a behavior appears to be done for attention, instruct the caregivers to provide frequent periods of attention when the individual engages in positive behaviors.

Go to the appropriate placement. By law, persons age ≤21 have the right to an education and to make meaningful progress. If a patient with ASD exhibits behaviors that interfere with learning, he is entitled to a placement that can provide intensive applied behavior analysis. If you feel that the child needs a different school, write an evaluation for the parent or guardian to submit to the school district and clearly outline the patient’s needs and requirements.

Despite a lack of evidence, polypharmacy often is used to treat autism spectrum disorder (ASD),¹ while educational techniques are underutilized. Compared with the general population, children with ASD may be more prone to the adverse effects of the medications used to treat symptoms, such as antipsychotics and antidepressants.² Therefore, when addressing problem behaviors, such as tantrums, aggressiveness, or self-injury, in a patient with ASD, before prescribing a medication, consider the ABCs of these behaviors.³

Antecedents. What happened before the behavior occurred? Where and when did the behavior occur? Was the individual unable to get a desired tangible item, such as a preferred food, toy, or another object? Was the individual told complete a task that he (she) did not want to do? Did the individual see someone else getting attention?

Behaviors. What behavior(s) occurred after each antecedent?

Consequences. What happened after the behavior occurred? Did the caregiver give the individual the item he wanted? Was the individual able to get out of doing work that he did not want to do or become the center of attention?

Having parents document the ABCs is useful not only for finding out why a behavior occurred, but also for objectively determining if and how a medication is affecting the frequency of a behavior. Charts that parents can use to document ABC data are available online (eg, http://www.positively­autism.com/downloads/datasheet_abc.pdf). Once this data is collected, it can be used to implement appropriate interventions, which I describe as DEFG.

Differential reinforcement of other behaviors is a procedure that provides positive reinforcement for not engaging in a problem behavior or for staying on task. For example, use a token board to reward positive behaviors, with physical tokens or written marks. However, some patients require immediate reinforcement. I suggest that parents or caregivers carry small pieces of preferred food to give to the patient to reinforce positive behavior.

Exercise. A review of 18 studies reported that physical exercise, such as jogging, weight training, and bike riding, can help reduce problem behaviors in individuals with ASD.⁴ Among 64 participants with ASD, there was a decrease in aggression, stereotypy, off-task behavior, and elopement, and improvements in on-task and motor behavior such as playing catch.

Function. Refer to the ABCs to determine why a specific problem behavior is occurring. Each behavior can have 1 or multiple functions; therefore, develop a plan specific to the reason the patient engages in the behavior. For example, if the individual engages in a behavior to avoid a task, the parent or caregiver can give individual tokens that the individual can later exchange for a break, instead of engaging in the problem behavior to avoid the task. If a behavior appears to be done for attention, instruct the caregivers to provide frequent periods of attention when the individual engages in positive behaviors.

Go to the appropriate placement. By law, persons age ≤21 have the right to an education and to make meaningful progress. If a patient with ASD exhibits behaviors that interfere with learning, he is entitled to a placement that can provide intensive applied behavior analysis. If you feel that the child needs a different school, write an evaluation for the parent or guardian to submit to the school district and clearly outline the patient’s needs and requirements.

Most psychiatrists are required to sign an employment contract before taking a job, but few of us have received any training on reviewing such contracts. We often rely on coworkers and attorneys to navigate this process for us. However, the contract is crucial, because it outlines your employer’s clinical and administrative expectations for the position, and it gives you the opportunity to lay out what you want.¹ Because an employment contract is legally binding, you should thoroughly read it and look for clauses that may not work in your best interest. Although not a complete list, the following items should be reviewed before signing a contract.^1,2
 

Benefits. Make sure you are offered a reasonable salary, but balance the dollar amount with benefits such as:

• continuing medical education allowances
• educational loan forgiveness
• health/malpractice/disability insurance
• retirement benefits
• compensation for call schedule.

In some cases, there may be a delay before you are eligible to obtain certain benefits.

Work expectations. Many contracts state that the position is “full-time” or have other nonspecific parameters for work expectations. You should inquire about objective work parameters, such as duty hours, the average frequency of the current call schedule, timeframe for completing medical documentation, and penalties for not meeting clinical or administrative requirements, so you are not surprised by:

• working longer-than-planned shifts
• performing on-call duties
• working on days that you were not expecting
• having your credentialing status placed in jeopardy.

Some group practices allow for a half-day of no scheduled appointments with patients, so you can complete paperwork and return phone calls.

Noncompete clause. This restricts you from working within a certain geographic area or for a competing employer for a finite time period after the contract terminates or expires. A noncompete clause could restrict you from practicing within a large geographical area, especially if the job is located in a densely populated area. Some noncompete clauses do not include a temporal or geographic restriction, but can limit your ability to bring patients with you to a new practice or facility when the contract expires.

Malpractice insurance. Two types of malpractice insurance are occurrence and claims-made:

• Occurrence insurance protects you whenever an action is brought against you, even if the action is brought after the contract terminates or expires.
• Claims-made insurance provides coverage if the policy with the same insurer was in effect when the malpractice was committed and when the actual action was commenced.

Although claims-made insurance is less expensive, it can leave you without coverage should you leave your employer and no longer maintain the same insurance policy. Claims-made can be converted into occurrence through the purchase of a tail endorsement. If the employer does not offer you tail coverage, then it is your responsibility to pay for this insurance, which can be expensive.

Termination language. Every contract features a termination section that lists potential causes for terminating your employment. This list is usually not exhaustive, but it sets the framework for a realistic view of reasonable causes. Contracts also commonly contain provisions that permit termination “without cause” after notice of termination is provided. Although you could negotiate for more notice time, “without cause” clauses are unlikely to be removed from the contract.

Most psychiatrists are required to sign an employment contract before taking a job, but few of us have received any training on reviewing such contracts. We often rely on coworkers and attorneys to navigate this process for us. However, the contract is crucial, because it outlines your employer’s clinical and administrative expectations for the position, and it gives you the opportunity to lay out what you want.¹ Because an employment contract is legally binding, you should thoroughly read it and look for clauses that may not work in your best interest. Although not a complete list, the following items should be reviewed before signing a contract.^1,2
 

Benefits. Make sure you are offered a reasonable salary, but balance the dollar amount with benefits such as:

• continuing medical education allowances
• educational loan forgiveness
• health/malpractice/disability insurance
• retirement benefits
• compensation for call schedule.

In some cases, there may be a delay before you are eligible to obtain certain benefits.

Work expectations. Many contracts state that the position is “full-time” or have other nonspecific parameters for work expectations. You should inquire about objective work parameters, such as duty hours, the average frequency of the current call schedule, timeframe for completing medical documentation, and penalties for not meeting clinical or administrative requirements, so you are not surprised by:

• working longer-than-planned shifts
• performing on-call duties
• working on days that you were not expecting
• having your credentialing status placed in jeopardy.

Some group practices allow for a half-day of no scheduled appointments with patients, so you can complete paperwork and return phone calls.

Noncompete clause. This restricts you from working within a certain geographic area or for a competing employer for a finite time period after the contract terminates or expires. A noncompete clause could restrict you from practicing within a large geographical area, especially if the job is located in a densely populated area. Some noncompete clauses do not include a temporal or geographic restriction, but can limit your ability to bring patients with you to a new practice or facility when the contract expires.

Malpractice insurance. Two types of malpractice insurance are occurrence and claims-made:

• Occurrence insurance protects you whenever an action is brought against you, even if the action is brought after the contract terminates or expires.
• Claims-made insurance provides coverage if the policy with the same insurer was in effect when the malpractice was committed and when the actual action was commenced.

Although claims-made insurance is less expensive, it can leave you without coverage should you leave your employer and no longer maintain the same insurance policy. Claims-made can be converted into occurrence through the purchase of a tail endorsement. If the employer does not offer you tail coverage, then it is your responsibility to pay for this insurance, which can be expensive.

Termination language. Every contract features a termination section that lists potential causes for terminating your employment. This list is usually not exhaustive, but it sets the framework for a realistic view of reasonable causes. Contracts also commonly contain provisions that permit termination “without cause” after notice of termination is provided. Although you could negotiate for more notice time, “without cause” clauses are unlikely to be removed from the contract.

Most psychiatrists are required to sign an employment contract before taking a job, but few of us have received any training on reviewing such contracts. We often rely on coworkers and attorneys to navigate this process for us. However, the contract is crucial, because it outlines your employer’s clinical and administrative expectations for the position, and it gives you the opportunity to lay out what you want.¹ Because an employment contract is legally binding, you should thoroughly read it and look for clauses that may not work in your best interest. Although not a complete list, the following items should be reviewed before signing a contract.^1,2
 

Benefits. Make sure you are offered a reasonable salary, but balance the dollar amount with benefits such as:

• continuing medical education allowances
• educational loan forgiveness
• health/malpractice/disability insurance
• retirement benefits
• compensation for call schedule.

In some cases, there may be a delay before you are eligible to obtain certain benefits.

Work expectations. Many contracts state that the position is “full-time” or have other nonspecific parameters for work expectations. You should inquire about objective work parameters, such as duty hours, the average frequency of the current call schedule, timeframe for completing medical documentation, and penalties for not meeting clinical or administrative requirements, so you are not surprised by:

• working longer-than-planned shifts
• performing on-call duties
• working on days that you were not expecting
• having your credentialing status placed in jeopardy.

Some group practices allow for a half-day of no scheduled appointments with patients, so you can complete paperwork and return phone calls.

Noncompete clause. This restricts you from working within a certain geographic area or for a competing employer for a finite time period after the contract terminates or expires. A noncompete clause could restrict you from practicing within a large geographical area, especially if the job is located in a densely populated area. Some noncompete clauses do not include a temporal or geographic restriction, but can limit your ability to bring patients with you to a new practice or facility when the contract expires.

Malpractice insurance. Two types of malpractice insurance are occurrence and claims-made:

• Occurrence insurance protects you whenever an action is brought against you, even if the action is brought after the contract terminates or expires.
• Claims-made insurance provides coverage if the policy with the same insurer was in effect when the malpractice was committed and when the actual action was commenced.

Although claims-made insurance is less expensive, it can leave you without coverage should you leave your employer and no longer maintain the same insurance policy. Claims-made can be converted into occurrence through the purchase of a tail endorsement. If the employer does not offer you tail coverage, then it is your responsibility to pay for this insurance, which can be expensive.

Termination language. Every contract features a termination section that lists potential causes for terminating your employment. This list is usually not exhaustive, but it sets the framework for a realistic view of reasonable causes. Contracts also commonly contain provisions that permit termination “without cause” after notice of termination is provided. Although you could negotiate for more notice time, “without cause” clauses are unlikely to be removed from the contract.

Throughout my 40 years in private psychiatric practice, I have found some treatments for premenstrual syndrome (PMS) that were not mentioned in “Etiology of premenstrual dysphoric disorder: 5 interwoven pieces” (Evidence-Based Reviews, Current Psychiatry. September 2017, p. 20-28).

This started in 1972 when I was serving in the Army in Oklahoma. A 28-year-old woman with severe PMS had been treated by internal medicine, an OB/GYN, and endocrinology, all to no avail. Three days before her menses began, she would start driving north. When menses commenced, she would find herself in Nebraska and have to call her husband so he could wire her money to come back.

Through my evaluation, I found that she would gain 10 lb before her menses. I prescribed a diuretic and instructed her to start taking it when she began swelling and to stop taking it after her menses began. This alleviated all of her symptoms. If a woman gains more than 3 to 5 lb, her brain also will swell, along with everything else. Because the brain is encapsulated in the skull, the swelling puts pressure on the brain, which might have been the cause of these brief psychotic episodes.

If a woman who develops PMS does not experience significant weight gain, the first thing I try is vitamin B6, 100 mg/d, prior to menses. Vitamin B6 is a cofactor in the production of numerous neurotransmitters. I found that prescribing vitamin B6 would alleviate about 20% of PMS symptoms. If the patient has a personal or family history of affective disorder, I often try antidepressants prior to menses, which alleviate approximately another 20% of her symptoms. If none of the previous 3 factors are present, I often add a low dose of progesterone, which appears to help. If all else fails, I will try a low dose of lithium, 300 mg/d, before menses. This also seems to have some positive effect.

I have not written an article about these approaches to PMS, although I have discussed them with OB/GYNs, who never seem to follow these recommendations. Because I am not university-based, I have not been able to put these treatments to scientific scrutiny. It would be helpful to conduct clinical trials to attempt to substantiate my clinical findings.

Throughout my 40 years in private psychiatric practice, I have found some treatments for premenstrual syndrome (PMS) that were not mentioned in “Etiology of premenstrual dysphoric disorder: 5 interwoven pieces” (Evidence-Based Reviews, Current Psychiatry. September 2017, p. 20-28).

This started in 1972 when I was serving in the Army in Oklahoma. A 28-year-old woman with severe PMS had been treated by internal medicine, an OB/GYN, and endocrinology, all to no avail. Three days before her menses began, she would start driving north. When menses commenced, she would find herself in Nebraska and have to call her husband so he could wire her money to come back.

Through my evaluation, I found that she would gain 10 lb before her menses. I prescribed a diuretic and instructed her to start taking it when she began swelling and to stop taking it after her menses began. This alleviated all of her symptoms. If a woman gains more than 3 to 5 lb, her brain also will swell, along with everything else. Because the brain is encapsulated in the skull, the swelling puts pressure on the brain, which might have been the cause of these brief psychotic episodes.

If a woman who develops PMS does not experience significant weight gain, the first thing I try is vitamin B6, 100 mg/d, prior to menses. Vitamin B6 is a cofactor in the production of numerous neurotransmitters. I found that prescribing vitamin B6 would alleviate about 20% of PMS symptoms. If the patient has a personal or family history of affective disorder, I often try antidepressants prior to menses, which alleviate approximately another 20% of her symptoms. If none of the previous 3 factors are present, I often add a low dose of progesterone, which appears to help. If all else fails, I will try a low dose of lithium, 300 mg/d, before menses. This also seems to have some positive effect.

I have not written an article about these approaches to PMS, although I have discussed them with OB/GYNs, who never seem to follow these recommendations. Because I am not university-based, I have not been able to put these treatments to scientific scrutiny. It would be helpful to conduct clinical trials to attempt to substantiate my clinical findings.

Throughout my 40 years in private psychiatric practice, I have found some treatments for premenstrual syndrome (PMS) that were not mentioned in “Etiology of premenstrual dysphoric disorder: 5 interwoven pieces” (Evidence-Based Reviews, Current Psychiatry. September 2017, p. 20-28).

This started in 1972 when I was serving in the Army in Oklahoma. A 28-year-old woman with severe PMS had been treated by internal medicine, an OB/GYN, and endocrinology, all to no avail. Three days before her menses began, she would start driving north. When menses commenced, she would find herself in Nebraska and have to call her husband so he could wire her money to come back.

Through my evaluation, I found that she would gain 10 lb before her menses. I prescribed a diuretic and instructed her to start taking it when she began swelling and to stop taking it after her menses began. This alleviated all of her symptoms. If a woman gains more than 3 to 5 lb, her brain also will swell, along with everything else. Because the brain is encapsulated in the skull, the swelling puts pressure on the brain, which might have been the cause of these brief psychotic episodes.

If a woman who develops PMS does not experience significant weight gain, the first thing I try is vitamin B6, 100 mg/d, prior to menses. Vitamin B6 is a cofactor in the production of numerous neurotransmitters. I found that prescribing vitamin B6 would alleviate about 20% of PMS symptoms. If the patient has a personal or family history of affective disorder, I often try antidepressants prior to menses, which alleviate approximately another 20% of her symptoms. If none of the previous 3 factors are present, I often add a low dose of progesterone, which appears to help. If all else fails, I will try a low dose of lithium, 300 mg/d, before menses. This also seems to have some positive effect.

I have not written an article about these approaches to PMS, although I have discussed them with OB/GYNs, who never seem to follow these recommendations. Because I am not university-based, I have not been able to put these treatments to scientific scrutiny. It would be helpful to conduct clinical trials to attempt to substantiate my clinical findings.

CASE

A 68-year-old woman with a history of well-controlled hypertension and diabetes presents to the office for routine follow-up. She says she has adhered to her current medications, and her blood pressure and hemoglobin A1c remain at goal. At the close of the visit, she mentions that she is worried she may be developing dementia. She says she has been having difficulty finding the right word in conversation and needs to write things down more than she used to.

What might be causing this patient’s changes in cognition?

In primary care settings, when patients complain of memory loss, there is a 20% to 30% chance they will be found to have mild cognitive impairment (MCI) or some level of dementia.¹ Given the significant consequences of dementia, it’s important to maximize opportunities to distinguish those with age-related changes in cognition or reversible causes of memory loss from those who have irreversible pathologic changes.

Age-related changes in cognition

Changes in cognition associated with aging vary considerably among individuals and across domains of cognition. By their 7th decade, most people experience a decline in processing speed and working memory.² However, some individuals retain excellent function into their 80s and perform as well as younger adults.³

Changes long thought to be due to brain senescence may, in fact, be related to the effects of age-related medical conditions on the brain’s function.⁴ Consistent with this theory is the observation that cognitive changes tend to occur earlier in individuals with cardiovascular disease, diabetes, and cancer.² What constitutes a normal change depends on an individual’s baseline cognitive function, educational background, medical comorbidities, and the potential impact of sensory impairment on performance.

General cognitive trends with aging. Awareness of normal changes in an aging population is useful when assessing patients concerned about their memory. In general, an individual’s ability to maintain attention to a single task is preserved into late life. Ability to perform tasks requiring divided attention or attention-switching tends to decline.³ This has implications for driving, given the need to constantly switch one’s attention in response to the environment and the ability to sort relevant from irrelevant information.

Remote memory, semantic memory (factual information), and procedural memory (knowledge of skills and procedures) tend to remain intact with aging.⁴ Short-term memory (simple maintenance of information over a short period of time) shows little change with aging. However, working memory, which requires the manipulation of information in short-term memory, declines.

A simple demonstration of this is that performance on digit span testing tends to remain preserved (7±2), but digit span backwards declines. Holding digits in mind in the order they are received can be achieved through rehearsal. But to reverse the order requires reorganization of the information, and this ability declines with aging.³

An individual's ability to maintain attention to a single task is preserved into late life. Ability to perform tasks requiring divided attention or attention-switching tends to decline.

Prospective memory (remembering to do things in the future) often requires increased dependence on external aids, such as a to-do list.³ The capacity to learn and recall new information declines. Even when given repeated opportunity to practice, older adults demonstrate a slower learning curve and lower total amount learned.⁴ Therefore, it becomes easier relying on well-learned cognitive processes such as cooking a familiar meal or relying on previously used principles for decision making.²

Language comprehension and vocabulary remain stable over time. However, difficulty with spontaneous word finding—the “tip-of-the-tongue” phenomenon—tends to increase. In contrast to the dysnomia related to dementia, the word-finding difficulties with normal aging typically improve with cues, indicating that the problem is in retrieval of information rather than storage. Verbal fluency, the rate at which words from a single category can be produced, shows decline. This is particularly true in tests of semantic verbal fluency (name all the animals you can think of); phonemic fluency (words that start with a certain letter) tends to be preserved.⁴

Cognitive changes with aging typically do not interfere with an individual's ability to function independently.

Some studies using neurocognitive testing have suggested a decline in executive functioning. But, in general, aging has little impact on “real world” executive functions that are required for planning and executing tasks.⁴ On the whole, cognitive changes related to aging typically do not interfere with an individual’s ability to function independently.

Mild cognitive impairment/mild neurocognitive disorder

Originally conceived as a precursor to Alzheimer’s dementia,⁵ mild cognitive impairment (MCI) is a diagnosis that has evolved to describe a heterogeneous syndrome of abnormal cognition characterized by:^6-8

• a suspected change in cognition expressed by the patient, an acquaintance who knows the patient well, or a clinician;
• objectively measured impairment in one or more cognitive domains beyond what would be expected based on an individual’s age and educational background;
• preservation of functional abilities; and
• a lack of findings that would fulfill criteria for dementia.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V), this concept is identified as mild neurocognitive disorder, with the additional caveats that an individual’s cognitive deficits do not occur exclusively in the context of delirium and are not better explained by another mental disorder such as depression or schizophrenia.⁹

An accurate assessment of cognitive change is best measured against the individual’s baseline, which may necessitate the report of a reliable acquaintance. An assessment of functional abilities is also critical. Mild problems in performing complex functions (bill paying, shopping, etc) could be present and still allow a patient to meet the criteria for MCI. An individual may take more time, be less efficient, or make more errors than before; however, independence with minimal aid or assistance is preserved. It can be difficult to distinguish MCI from the effects of normal aging particularly on a single assessment, and serial evaluations can be beneficial.

MCI can be divided into 4 subtypes depending upon the cognitive domains affected (complex attention, executive function, learning and memory, language, visuospatial, social cognition):

1. Amnestic MCI single domain, if only memory is affected.
2. Amnestic MCI multiple domain, if memory and any other cognitive domains are affected.
3. Non-amnestic MCI single domain, if any other cognitive domain aside from memory is the only one affected.
4. Non-amnestic MCI multiple domain, if multiple domains other than memory are affected.

These distinctions may provide clues to the underlying cause of dysfunction and provide prognostic information regarding the risk of progression to dementia.^6,7

Prevalence estimates for MCI vary widely due to differences in definitions used and populations studied. The best estimate is 5% to 10% prevalence among those ages 65 to 69 years old, and 12% to 25% among those ages 80 to 84.¹⁰ Similarly, estimates of the rate of progression to dementia vary. Among MCI populations identified through referral sources such as memory centers, the rate of progression to dementia has been 10% to 15% per year.¹¹ In epidemiologic studies of general populations, the rate has been 6% to 10% per year.¹¹ The rate of development of dementia among normal subjects is 1% to 2% per year.⁵

Dementia/major neurocognitive disorder

The primary feature distinguishing MCI/mild neurocognitive disorder from dementia or major neurocognitive disorder is a patient’s functional status. The core clinical criteria for all-cause dementia are cognitive or neurobehavioral symptoms that: ¹²

• interfere with work or usual daily function,
• represent a change from the prior baseline function,
• are not explained by delirium or a psychiatric illness, and
• include detectable impairment in 2 cognitive domains.

Criteria outlined in the DSM-V for major neurocognitive disorder are essentially the same but describe the functional change criteria as cognitive changes that “interfere with independence in everyday activities.”⁹ The DSM-V elaborates: “at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications.”

Assessing functional status accurately in clinical practice typically requires the assistance of a collateral informant who knows the patient well. The Informant Questionnaire on Cognitive Decline in the Elderly (https://www.alz.org/documents_custom/shortiqcode_english.pdf) is one validated assessment tool that can be used for this purpose.¹³ With this self-administered form, the informant answers 16 questions regarding changes in the patient’s performance of different activities over the 10 years prior. Alternatively, a structured interview based on indices of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) as listed in TABLE 1 can be employed.^14,15

Review of the various causes of dementia is beyond the scope of this article, but a list of common diagnoses is presented in TABLE 2.

Dementia syndrome of depression (pseudodementia)

Elderly patients with depression commonly complain of memory impairment, and this interaction between depression and dementia has been investigated for decades. The term “pseudodementia” has been used since 1961 to describe signs of dementia in a patient with any psychiatric illness,¹⁶ but it has since been refined to apply solely to depression. The prevalence of depression among older adults varies depending on the population studied and how depression is defined. Approximately 2% to 3% of community-dwelling elders meet criteria for major depression, with 10% to 30% showing some symptoms of depression.^17,18

Twenty percent to 40% of elderly patients diagnosed with depression will have evidence of cognitive impairment.

Twenty percent to 40% of elderly patients diagnosed with depression will have evidence of cognitive impairment.^19-21 Most improve with antidepressive treatment, though evidence of cognitive impairment may continue for some.¹⁹

A broad range of cognitive deficits have been associated with depression. Most consistently described are deficits in processing speed,^22-25 attention,^26-28 and executive function.^22,25-29 Memory deficits can be apparent with tests of delayed recall, but recognition (the ability to identify items from a list) generally is preserved.^26,28-30

Distinguishing mild cognitive impairment from normal effects of aging may require serial evaluations following an initial assessment.

Distinguishing between pseudodementia and true dementia can be challenging. An increased severity of deficits, particularly with delayed recall, is more indicative of dementia.³¹ Additionally, on clock drawing tasks, individuals with depression perform more comparably to controls than do those with true dementia.³²

A 2013 meta-analysis reported a significant association of late-life depression with subsequent development of dementia, with an odds ratio (OR) of 1.85. The risk of subsequently developing vascular dementia (OR=2.52) was significantly higher than that for Alzheimer’s disease (OR=1.65). Individuals with evidence of reversible cognitive impairment at the time of diagnosis of depression seem to be particularly vulnerable, with dementia developing in 43% to 71%, compared with rates of 12% to 18% among elders diagnosed with depression but lacking signs of cognitive impairment.^20,21

Other causes of reversible dementia

A meta-analysis performed in 1988 found that 11% of cases of dementia were reversible.³³ However, an update using the same methodology in 2003 revealed the number had dropped to less than 1%.³⁴ In the latest meta-analysis, one of the authors’ leading hypotheses for the dramatic decline in apparent prevalence was a significant shift in the study population from the inpatient to outpatient setting. In studies of community-based populations used in the re-analysis, the reported prevalence of reversibility was near zero.³⁴

Metabolic abnormalities—most often B₁₂ deficiency and hypothyroidism—are commonly cited as potential causes of dementia. Four systematic reviews, including one conducted by the Cochrane Collaborative, concluded there is a lack of evidence that treating low vitamin B₁₂ in individuals with dementia improves cognition.^35,36 There is some evidence, though, of a time-limited window for successful treatment within 12 months of the onset of symptoms.^37,38 A study reviewing causes of dementia in nearly 3000 individuals found one case of reversible dementia attributable to hypothyroidism.³⁹ A subsequent review reached similar conclusions about the lack of data to support the notion that treatment of hypothyroidism reverses dementia.⁴⁰

Similarly, imaging for cerebral tumors, subdural hematomas, or normal-pressure hydrocephalus rarely identifies these as a cause of dementia.⁴¹ This is particularly true of unselected community-based populations, as there are typically signs or symptoms suggesting an intracranial pathology.

Numerous medications have been implicated in causing acute confusional states, and there is some evidence for their role in chronic confusion (TABLE 3).^42,43 In my experience, many who experience adverse effects on cognition with medications will also have an underlying neurodegenerative process, and symptoms do not completely resolve with withdrawal of the offending agent.

CASE

For more on healthy aging, listen to: "How much can we really do to slow cognitive decline," at: http://bit.ly/2ghoQKw.

Further assessment of the patient yielded a score of 29/30 on the Montreal Cognitive Assessment* and a zero on the Patient Health Questionnaire-2. Careful review of her daily function revealed no significant deficits in ADL or IADL performance, and her daughter confirmed that she had not observed any significant decline in her mother’s function. There was no significant family history of dementia. The patient was reassured that her cognitive changes were normal and age related.

Unfortunately, few data support specific interventions to reduce this patient’s risk of developing dementia. She was commended for keeping her blood pressure and blood sugar levels under control, thereby reducing her risk of vascular disease.

She and her daughter were directed to the Alzheimer’s Association Web site (alz.org) as a resource for information about signs and symptoms to watch for and for caregiving resources, should they be needed. She was briefly counseled to eliminate distractions to improve her ability to complete tasks and improve recall along with rehearsing or writing down information that she wished to retain.

Finally, she was counseled to remain physically, cognitively, and socially active as these are factors generally associated with healthy aging, have some evidence to support efficacy in reducing the risk of cognitive decline,^44,45 and are unlikely to be of harm.

*The Montreal Cognitive Assessment is a validated office-based tool for the evaluation of cognitive impairment that is highly sensitive for the detection of mild cognitive impairment.

CORRESPONDENCE
Ian M. Deutchki, MD, Professor of Family Medicine and Geriatrics, University of Rochester Medical Center, 777 S. Clinton Avenue, Rochester, NY 14620; [email protected].

CASE

A 68-year-old woman with a history of well-controlled hypertension and diabetes presents to the office for routine follow-up. She says she has adhered to her current medications, and her blood pressure and hemoglobin A1c remain at goal. At the close of the visit, she mentions that she is worried she may be developing dementia. She says she has been having difficulty finding the right word in conversation and needs to write things down more than she used to.

What might be causing this patient’s changes in cognition?

In primary care settings, when patients complain of memory loss, there is a 20% to 30% chance they will be found to have mild cognitive impairment (MCI) or some level of dementia.¹ Given the significant consequences of dementia, it’s important to maximize opportunities to distinguish those with age-related changes in cognition or reversible causes of memory loss from those who have irreversible pathologic changes.

Age-related changes in cognition

Changes in cognition associated with aging vary considerably among individuals and across domains of cognition. By their 7th decade, most people experience a decline in processing speed and working memory.² However, some individuals retain excellent function into their 80s and perform as well as younger adults.³

Changes long thought to be due to brain senescence may, in fact, be related to the effects of age-related medical conditions on the brain’s function.⁴ Consistent with this theory is the observation that cognitive changes tend to occur earlier in individuals with cardiovascular disease, diabetes, and cancer.² What constitutes a normal change depends on an individual’s baseline cognitive function, educational background, medical comorbidities, and the potential impact of sensory impairment on performance.

General cognitive trends with aging. Awareness of normal changes in an aging population is useful when assessing patients concerned about their memory. In general, an individual’s ability to maintain attention to a single task is preserved into late life. Ability to perform tasks requiring divided attention or attention-switching tends to decline.³ This has implications for driving, given the need to constantly switch one’s attention in response to the environment and the ability to sort relevant from irrelevant information.

Remote memory, semantic memory (factual information), and procedural memory (knowledge of skills and procedures) tend to remain intact with aging.⁴ Short-term memory (simple maintenance of information over a short period of time) shows little change with aging. However, working memory, which requires the manipulation of information in short-term memory, declines.

A simple demonstration of this is that performance on digit span testing tends to remain preserved (7±2), but digit span backwards declines. Holding digits in mind in the order they are received can be achieved through rehearsal. But to reverse the order requires reorganization of the information, and this ability declines with aging.³

An individual's ability to maintain attention to a single task is preserved into late life. Ability to perform tasks requiring divided attention or attention-switching tends to decline.

Prospective memory (remembering to do things in the future) often requires increased dependence on external aids, such as a to-do list.³ The capacity to learn and recall new information declines. Even when given repeated opportunity to practice, older adults demonstrate a slower learning curve and lower total amount learned.⁴ Therefore, it becomes easier relying on well-learned cognitive processes such as cooking a familiar meal or relying on previously used principles for decision making.²

Language comprehension and vocabulary remain stable over time. However, difficulty with spontaneous word finding—the “tip-of-the-tongue” phenomenon—tends to increase. In contrast to the dysnomia related to dementia, the word-finding difficulties with normal aging typically improve with cues, indicating that the problem is in retrieval of information rather than storage. Verbal fluency, the rate at which words from a single category can be produced, shows decline. This is particularly true in tests of semantic verbal fluency (name all the animals you can think of); phonemic fluency (words that start with a certain letter) tends to be preserved.⁴

Cognitive changes with aging typically do not interfere with an individual's ability to function independently.

Some studies using neurocognitive testing have suggested a decline in executive functioning. But, in general, aging has little impact on “real world” executive functions that are required for planning and executing tasks.⁴ On the whole, cognitive changes related to aging typically do not interfere with an individual’s ability to function independently.

Mild cognitive impairment/mild neurocognitive disorder

Originally conceived as a precursor to Alzheimer’s dementia,⁵ mild cognitive impairment (MCI) is a diagnosis that has evolved to describe a heterogeneous syndrome of abnormal cognition characterized by:^6-8

• a suspected change in cognition expressed by the patient, an acquaintance who knows the patient well, or a clinician;
• objectively measured impairment in one or more cognitive domains beyond what would be expected based on an individual’s age and educational background;
• preservation of functional abilities; and
• a lack of findings that would fulfill criteria for dementia.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V), this concept is identified as mild neurocognitive disorder, with the additional caveats that an individual’s cognitive deficits do not occur exclusively in the context of delirium and are not better explained by another mental disorder such as depression or schizophrenia.⁹

An accurate assessment of cognitive change is best measured against the individual’s baseline, which may necessitate the report of a reliable acquaintance. An assessment of functional abilities is also critical. Mild problems in performing complex functions (bill paying, shopping, etc) could be present and still allow a patient to meet the criteria for MCI. An individual may take more time, be less efficient, or make more errors than before; however, independence with minimal aid or assistance is preserved. It can be difficult to distinguish MCI from the effects of normal aging particularly on a single assessment, and serial evaluations can be beneficial.

MCI can be divided into 4 subtypes depending upon the cognitive domains affected (complex attention, executive function, learning and memory, language, visuospatial, social cognition):

1. Amnestic MCI single domain, if only memory is affected.
2. Amnestic MCI multiple domain, if memory and any other cognitive domains are affected.
3. Non-amnestic MCI single domain, if any other cognitive domain aside from memory is the only one affected.
4. Non-amnestic MCI multiple domain, if multiple domains other than memory are affected.

These distinctions may provide clues to the underlying cause of dysfunction and provide prognostic information regarding the risk of progression to dementia.^6,7

Prevalence estimates for MCI vary widely due to differences in definitions used and populations studied. The best estimate is 5% to 10% prevalence among those ages 65 to 69 years old, and 12% to 25% among those ages 80 to 84.¹⁰ Similarly, estimates of the rate of progression to dementia vary. Among MCI populations identified through referral sources such as memory centers, the rate of progression to dementia has been 10% to 15% per year.¹¹ In epidemiologic studies of general populations, the rate has been 6% to 10% per year.¹¹ The rate of development of dementia among normal subjects is 1% to 2% per year.⁵

Dementia/major neurocognitive disorder

The primary feature distinguishing MCI/mild neurocognitive disorder from dementia or major neurocognitive disorder is a patient’s functional status. The core clinical criteria for all-cause dementia are cognitive or neurobehavioral symptoms that: ¹²

• interfere with work or usual daily function,
• represent a change from the prior baseline function,
• are not explained by delirium or a psychiatric illness, and
• include detectable impairment in 2 cognitive domains.

Criteria outlined in the DSM-V for major neurocognitive disorder are essentially the same but describe the functional change criteria as cognitive changes that “interfere with independence in everyday activities.”⁹ The DSM-V elaborates: “at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications.”

Assessing functional status accurately in clinical practice typically requires the assistance of a collateral informant who knows the patient well. The Informant Questionnaire on Cognitive Decline in the Elderly (https://www.alz.org/documents_custom/shortiqcode_english.pdf) is one validated assessment tool that can be used for this purpose.¹³ With this self-administered form, the informant answers 16 questions regarding changes in the patient’s performance of different activities over the 10 years prior. Alternatively, a structured interview based on indices of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) as listed in TABLE 1 can be employed.^14,15

Review of the various causes of dementia is beyond the scope of this article, but a list of common diagnoses is presented in TABLE 2.

Dementia syndrome of depression (pseudodementia)

Elderly patients with depression commonly complain of memory impairment, and this interaction between depression and dementia has been investigated for decades. The term “pseudodementia” has been used since 1961 to describe signs of dementia in a patient with any psychiatric illness,¹⁶ but it has since been refined to apply solely to depression. The prevalence of depression among older adults varies depending on the population studied and how depression is defined. Approximately 2% to 3% of community-dwelling elders meet criteria for major depression, with 10% to 30% showing some symptoms of depression.^17,18

Twenty percent to 40% of elderly patients diagnosed with depression will have evidence of cognitive impairment.

Twenty percent to 40% of elderly patients diagnosed with depression will have evidence of cognitive impairment.^19-21 Most improve with antidepressive treatment, though evidence of cognitive impairment may continue for some.¹⁹

A broad range of cognitive deficits have been associated with depression. Most consistently described are deficits in processing speed,^22-25 attention,^26-28 and executive function.^22,25-29 Memory deficits can be apparent with tests of delayed recall, but recognition (the ability to identify items from a list) generally is preserved.^26,28-30

Distinguishing mild cognitive impairment from normal effects of aging may require serial evaluations following an initial assessment.

Distinguishing between pseudodementia and true dementia can be challenging. An increased severity of deficits, particularly with delayed recall, is more indicative of dementia.³¹ Additionally, on clock drawing tasks, individuals with depression perform more comparably to controls than do those with true dementia.³²

A 2013 meta-analysis reported a significant association of late-life depression with subsequent development of dementia, with an odds ratio (OR) of 1.85. The risk of subsequently developing vascular dementia (OR=2.52) was significantly higher than that for Alzheimer’s disease (OR=1.65). Individuals with evidence of reversible cognitive impairment at the time of diagnosis of depression seem to be particularly vulnerable, with dementia developing in 43% to 71%, compared with rates of 12% to 18% among elders diagnosed with depression but lacking signs of cognitive impairment.^20,21

Other causes of reversible dementia

A meta-analysis performed in 1988 found that 11% of cases of dementia were reversible.³³ However, an update using the same methodology in 2003 revealed the number had dropped to less than 1%.³⁴ In the latest meta-analysis, one of the authors’ leading hypotheses for the dramatic decline in apparent prevalence was a significant shift in the study population from the inpatient to outpatient setting. In studies of community-based populations used in the re-analysis, the reported prevalence of reversibility was near zero.³⁴

Metabolic abnormalities—most often B₁₂ deficiency and hypothyroidism—are commonly cited as potential causes of dementia. Four systematic reviews, including one conducted by the Cochrane Collaborative, concluded there is a lack of evidence that treating low vitamin B₁₂ in individuals with dementia improves cognition.^35,36 There is some evidence, though, of a time-limited window for successful treatment within 12 months of the onset of symptoms.^37,38 A study reviewing causes of dementia in nearly 3000 individuals found one case of reversible dementia attributable to hypothyroidism.³⁹ A subsequent review reached similar conclusions about the lack of data to support the notion that treatment of hypothyroidism reverses dementia.⁴⁰

Similarly, imaging for cerebral tumors, subdural hematomas, or normal-pressure hydrocephalus rarely identifies these as a cause of dementia.⁴¹ This is particularly true of unselected community-based populations, as there are typically signs or symptoms suggesting an intracranial pathology.

Numerous medications have been implicated in causing acute confusional states, and there is some evidence for their role in chronic confusion (TABLE 3).^42,43 In my experience, many who experience adverse effects on cognition with medications will also have an underlying neurodegenerative process, and symptoms do not completely resolve with withdrawal of the offending agent.

CASE

For more on healthy aging, listen to: "How much can we really do to slow cognitive decline," at: http://bit.ly/2ghoQKw.

Further assessment of the patient yielded a score of 29/30 on the Montreal Cognitive Assessment* and a zero on the Patient Health Questionnaire-2. Careful review of her daily function revealed no significant deficits in ADL or IADL performance, and her daughter confirmed that she had not observed any significant decline in her mother’s function. There was no significant family history of dementia. The patient was reassured that her cognitive changes were normal and age related.

Unfortunately, few data support specific interventions to reduce this patient’s risk of developing dementia. She was commended for keeping her blood pressure and blood sugar levels under control, thereby reducing her risk of vascular disease.

She and her daughter were directed to the Alzheimer’s Association Web site (alz.org) as a resource for information about signs and symptoms to watch for and for caregiving resources, should they be needed. She was briefly counseled to eliminate distractions to improve her ability to complete tasks and improve recall along with rehearsing or writing down information that she wished to retain.

Finally, she was counseled to remain physically, cognitively, and socially active as these are factors generally associated with healthy aging, have some evidence to support efficacy in reducing the risk of cognitive decline,^44,45 and are unlikely to be of harm.

*The Montreal Cognitive Assessment is a validated office-based tool for the evaluation of cognitive impairment that is highly sensitive for the detection of mild cognitive impairment.

CORRESPONDENCE
Ian M. Deutchki, MD, Professor of Family Medicine and Geriatrics, University of Rochester Medical Center, 777 S. Clinton Avenue, Rochester, NY 14620; [email protected].

CASE

A 68-year-old woman with a history of well-controlled hypertension and diabetes presents to the office for routine follow-up. She says she has adhered to her current medications, and her blood pressure and hemoglobin A1c remain at goal. At the close of the visit, she mentions that she is worried she may be developing dementia. She says she has been having difficulty finding the right word in conversation and needs to write things down more than she used to.

What might be causing this patient’s changes in cognition?

In primary care settings, when patients complain of memory loss, there is a 20% to 30% chance they will be found to have mild cognitive impairment (MCI) or some level of dementia.¹ Given the significant consequences of dementia, it’s important to maximize opportunities to distinguish those with age-related changes in cognition or reversible causes of memory loss from those who have irreversible pathologic changes.

Age-related changes in cognition

Changes in cognition associated with aging vary considerably among individuals and across domains of cognition. By their 7th decade, most people experience a decline in processing speed and working memory.² However, some individuals retain excellent function into their 80s and perform as well as younger adults.³

Changes long thought to be due to brain senescence may, in fact, be related to the effects of age-related medical conditions on the brain’s function.⁴ Consistent with this theory is the observation that cognitive changes tend to occur earlier in individuals with cardiovascular disease, diabetes, and cancer.² What constitutes a normal change depends on an individual’s baseline cognitive function, educational background, medical comorbidities, and the potential impact of sensory impairment on performance.

General cognitive trends with aging. Awareness of normal changes in an aging population is useful when assessing patients concerned about their memory. In general, an individual’s ability to maintain attention to a single task is preserved into late life. Ability to perform tasks requiring divided attention or attention-switching tends to decline.³ This has implications for driving, given the need to constantly switch one’s attention in response to the environment and the ability to sort relevant from irrelevant information.

Remote memory, semantic memory (factual information), and procedural memory (knowledge of skills and procedures) tend to remain intact with aging.⁴ Short-term memory (simple maintenance of information over a short period of time) shows little change with aging. However, working memory, which requires the manipulation of information in short-term memory, declines.

A simple demonstration of this is that performance on digit span testing tends to remain preserved (7±2), but digit span backwards declines. Holding digits in mind in the order they are received can be achieved through rehearsal. But to reverse the order requires reorganization of the information, and this ability declines with aging.³

An individual's ability to maintain attention to a single task is preserved into late life. Ability to perform tasks requiring divided attention or attention-switching tends to decline.

Prospective memory (remembering to do things in the future) often requires increased dependence on external aids, such as a to-do list.³ The capacity to learn and recall new information declines. Even when given repeated opportunity to practice, older adults demonstrate a slower learning curve and lower total amount learned.⁴ Therefore, it becomes easier relying on well-learned cognitive processes such as cooking a familiar meal or relying on previously used principles for decision making.²

Language comprehension and vocabulary remain stable over time. However, difficulty with spontaneous word finding—the “tip-of-the-tongue” phenomenon—tends to increase. In contrast to the dysnomia related to dementia, the word-finding difficulties with normal aging typically improve with cues, indicating that the problem is in retrieval of information rather than storage. Verbal fluency, the rate at which words from a single category can be produced, shows decline. This is particularly true in tests of semantic verbal fluency (name all the animals you can think of); phonemic fluency (words that start with a certain letter) tends to be preserved.⁴

Cognitive changes with aging typically do not interfere with an individual's ability to function independently.

Some studies using neurocognitive testing have suggested a decline in executive functioning. But, in general, aging has little impact on “real world” executive functions that are required for planning and executing tasks.⁴ On the whole, cognitive changes related to aging typically do not interfere with an individual’s ability to function independently.

Mild cognitive impairment/mild neurocognitive disorder

Originally conceived as a precursor to Alzheimer’s dementia,⁵ mild cognitive impairment (MCI) is a diagnosis that has evolved to describe a heterogeneous syndrome of abnormal cognition characterized by:^6-8

• a suspected change in cognition expressed by the patient, an acquaintance who knows the patient well, or a clinician;
• objectively measured impairment in one or more cognitive domains beyond what would be expected based on an individual’s age and educational background;
• preservation of functional abilities; and
• a lack of findings that would fulfill criteria for dementia.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V), this concept is identified as mild neurocognitive disorder, with the additional caveats that an individual’s cognitive deficits do not occur exclusively in the context of delirium and are not better explained by another mental disorder such as depression or schizophrenia.⁹

An accurate assessment of cognitive change is best measured against the individual’s baseline, which may necessitate the report of a reliable acquaintance. An assessment of functional abilities is also critical. Mild problems in performing complex functions (bill paying, shopping, etc) could be present and still allow a patient to meet the criteria for MCI. An individual may take more time, be less efficient, or make more errors than before; however, independence with minimal aid or assistance is preserved. It can be difficult to distinguish MCI from the effects of normal aging particularly on a single assessment, and serial evaluations can be beneficial.

MCI can be divided into 4 subtypes depending upon the cognitive domains affected (complex attention, executive function, learning and memory, language, visuospatial, social cognition):

1. Amnestic MCI single domain, if only memory is affected.
2. Amnestic MCI multiple domain, if memory and any other cognitive domains are affected.
3. Non-amnestic MCI single domain, if any other cognitive domain aside from memory is the only one affected.
4. Non-amnestic MCI multiple domain, if multiple domains other than memory are affected.

These distinctions may provide clues to the underlying cause of dysfunction and provide prognostic information regarding the risk of progression to dementia.^6,7

Prevalence estimates for MCI vary widely due to differences in definitions used and populations studied. The best estimate is 5% to 10% prevalence among those ages 65 to 69 years old, and 12% to 25% among those ages 80 to 84.¹⁰ Similarly, estimates of the rate of progression to dementia vary. Among MCI populations identified through referral sources such as memory centers, the rate of progression to dementia has been 10% to 15% per year.¹¹ In epidemiologic studies of general populations, the rate has been 6% to 10% per year.¹¹ The rate of development of dementia among normal subjects is 1% to 2% per year.⁵

Dementia/major neurocognitive disorder

The primary feature distinguishing MCI/mild neurocognitive disorder from dementia or major neurocognitive disorder is a patient’s functional status. The core clinical criteria for all-cause dementia are cognitive or neurobehavioral symptoms that: ¹²

• interfere with work or usual daily function,
• represent a change from the prior baseline function,
• are not explained by delirium or a psychiatric illness, and
• include detectable impairment in 2 cognitive domains.

Criteria outlined in the DSM-V for major neurocognitive disorder are essentially the same but describe the functional change criteria as cognitive changes that “interfere with independence in everyday activities.”⁹ The DSM-V elaborates: “at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications.”

Assessing functional status accurately in clinical practice typically requires the assistance of a collateral informant who knows the patient well. The Informant Questionnaire on Cognitive Decline in the Elderly (https://www.alz.org/documents_custom/shortiqcode_english.pdf) is one validated assessment tool that can be used for this purpose.¹³ With this self-administered form, the informant answers 16 questions regarding changes in the patient’s performance of different activities over the 10 years prior. Alternatively, a structured interview based on indices of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) as listed in TABLE 1 can be employed.^14,15

Review of the various causes of dementia is beyond the scope of this article, but a list of common diagnoses is presented in TABLE 2.

Dementia syndrome of depression (pseudodementia)

Elderly patients with depression commonly complain of memory impairment, and this interaction between depression and dementia has been investigated for decades. The term “pseudodementia” has been used since 1961 to describe signs of dementia in a patient with any psychiatric illness,¹⁶ but it has since been refined to apply solely to depression. The prevalence of depression among older adults varies depending on the population studied and how depression is defined. Approximately 2% to 3% of community-dwelling elders meet criteria for major depression, with 10% to 30% showing some symptoms of depression.^17,18

Twenty percent to 40% of elderly patients diagnosed with depression will have evidence of cognitive impairment.

Twenty percent to 40% of elderly patients diagnosed with depression will have evidence of cognitive impairment.^19-21 Most improve with antidepressive treatment, though evidence of cognitive impairment may continue for some.¹⁹

A broad range of cognitive deficits have been associated with depression. Most consistently described are deficits in processing speed,^22-25 attention,^26-28 and executive function.^22,25-29 Memory deficits can be apparent with tests of delayed recall, but recognition (the ability to identify items from a list) generally is preserved.^26,28-30

Distinguishing mild cognitive impairment from normal effects of aging may require serial evaluations following an initial assessment.

Distinguishing between pseudodementia and true dementia can be challenging. An increased severity of deficits, particularly with delayed recall, is more indicative of dementia.³¹ Additionally, on clock drawing tasks, individuals with depression perform more comparably to controls than do those with true dementia.³²

A 2013 meta-analysis reported a significant association of late-life depression with subsequent development of dementia, with an odds ratio (OR) of 1.85. The risk of subsequently developing vascular dementia (OR=2.52) was significantly higher than that for Alzheimer’s disease (OR=1.65). Individuals with evidence of reversible cognitive impairment at the time of diagnosis of depression seem to be particularly vulnerable, with dementia developing in 43% to 71%, compared with rates of 12% to 18% among elders diagnosed with depression but lacking signs of cognitive impairment.^20,21

Other causes of reversible dementia

A meta-analysis performed in 1988 found that 11% of cases of dementia were reversible.³³ However, an update using the same methodology in 2003 revealed the number had dropped to less than 1%.³⁴ In the latest meta-analysis, one of the authors’ leading hypotheses for the dramatic decline in apparent prevalence was a significant shift in the study population from the inpatient to outpatient setting. In studies of community-based populations used in the re-analysis, the reported prevalence of reversibility was near zero.³⁴

Metabolic abnormalities—most often B₁₂ deficiency and hypothyroidism—are commonly cited as potential causes of dementia. Four systematic reviews, including one conducted by the Cochrane Collaborative, concluded there is a lack of evidence that treating low vitamin B₁₂ in individuals with dementia improves cognition.^35,36 There is some evidence, though, of a time-limited window for successful treatment within 12 months of the onset of symptoms.^37,38 A study reviewing causes of dementia in nearly 3000 individuals found one case of reversible dementia attributable to hypothyroidism.³⁹ A subsequent review reached similar conclusions about the lack of data to support the notion that treatment of hypothyroidism reverses dementia.⁴⁰

Similarly, imaging for cerebral tumors, subdural hematomas, or normal-pressure hydrocephalus rarely identifies these as a cause of dementia.⁴¹ This is particularly true of unselected community-based populations, as there are typically signs or symptoms suggesting an intracranial pathology.

Numerous medications have been implicated in causing acute confusional states, and there is some evidence for their role in chronic confusion (TABLE 3).^42,43 In my experience, many who experience adverse effects on cognition with medications will also have an underlying neurodegenerative process, and symptoms do not completely resolve with withdrawal of the offending agent.

CASE

For more on healthy aging, listen to: "How much can we really do to slow cognitive decline," at: http://bit.ly/2ghoQKw.

Further assessment of the patient yielded a score of 29/30 on the Montreal Cognitive Assessment* and a zero on the Patient Health Questionnaire-2. Careful review of her daily function revealed no significant deficits in ADL or IADL performance, and her daughter confirmed that she had not observed any significant decline in her mother’s function. There was no significant family history of dementia. The patient was reassured that her cognitive changes were normal and age related.

Unfortunately, few data support specific interventions to reduce this patient’s risk of developing dementia. She was commended for keeping her blood pressure and blood sugar levels under control, thereby reducing her risk of vascular disease.

She and her daughter were directed to the Alzheimer’s Association Web site (alz.org) as a resource for information about signs and symptoms to watch for and for caregiving resources, should they be needed. She was briefly counseled to eliminate distractions to improve her ability to complete tasks and improve recall along with rehearsing or writing down information that she wished to retain.

Finally, she was counseled to remain physically, cognitively, and socially active as these are factors generally associated with healthy aging, have some evidence to support efficacy in reducing the risk of cognitive decline,^44,45 and are unlikely to be of harm.

*The Montreal Cognitive Assessment is a validated office-based tool for the evaluation of cognitive impairment that is highly sensitive for the detection of mild cognitive impairment.

CORRESPONDENCE
Ian M. Deutchki, MD, Professor of Family Medicine and Geriatrics, University of Rochester Medical Center, 777 S. Clinton Avenue, Rochester, NY 14620; [email protected].