Nazem Bassil, MD

Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/how-anxiety-presents-differently-in.html#comments

Although anxiety disorders are common at all ages, there is a misconception that their prevalence drastically declines with age. For this reason anxiety disorders often are underdiagnosed and undertreated in geriatric patients, especially when the clinical presentation of these disorders in older patients differs from that seen in younger adults.

In older persons, anxiety symptoms often overlap with medical conditions such as hyperthyroidism and geriatric patients tend to express anxiety symptoms as medical or somatic problems such as pain rather than as psychological distress.¹ As a result, older adults often seek treatment for depressive or anxiety symptoms from their primary care physician instead of a psychiatrist. Unfortunately, primary care physicians often miss psychiatric illness, including anxiety disorders, in geriatric patients.

Anxiety may be a symptom of an underlying psychiatric disturbance, secondary to a general medical condition, or induced by dietary substances, substances of abuse, or medications. Late-life anxiety often is comorbid with major depressive disorder (MDD) ( Box ) and other psychological stressors as older adults recognize declining cognitive and physical functioning.² Anxiety disorders commonly begin in early adulthood, tend to be chronic and interspersed with remissions and relapses, and usually continue into old age.³ In generalized anxiety disorder (GAD), there is a bimodal distribution of onset; approximately two-thirds of patients experience onset between the late teens and late 20s and one-third develop the disorder for the first time after age 50.³

Prevalence rates for anxiety disorders among older adults (age ≥55) range from 3. 5% to 10. 2%.⁴ These rates are slightly lower than those for younger adults.⁵ Among older adults, presence of a 12-month anxiety disorder was associated with female sex, lower education, being unmarried, and having ≥3 or more chronic conditions.⁶

Box

Anxiety and disability risk

Anxiety disorders affect geriatric patients more profoundly than their younger counterparts. Persons age ≥65 who have an anxiety disorder are 3 to 10 times more likely to be hospitalized than younger individuals.¹ Anxiety is associated with high rates of medically unexplained symptoms, increased use of health care resources, chronic medical illness, low levels of physical health-related quality of life, and physical disability.^7,8

Anxiety symptoms may predict progressing physical disability among older women and reduced ability to perform activities of daily living over 1 year.⁹ Anxious geriatric patients are less independent and increase the burden on family and caregivers.¹⁰ Anxiety disorders are associated with lower compliance with medical treatment, which could worsen chronic medical conditions and increase the risk for nursing home admission.¹¹ Anxious older adults report decreased life satisfaction, memory impairment, poorer self perception of health, and increased loneliness.¹²

Generalized anxiety disorder

Although GAD is the most common anxiety disorder among geriatric patients, with a prevalence of 0. 7% to 9%,¹³ it remains underdiagnosed and undertreated.¹⁴ In a cross-sectional observational study of 439 adults age ≥55 with lifetime GAD, approximately one-half experienced onset after age 50.¹⁵ Late onset is associated with more frequent hypertension and a poorer health-related quality of life than early onset.¹⁵

Compared with younger individuals, older persons with GAD have a greater variety of worry topics, including memory loss, medical illnesses, and fear of falls,¹⁶ but worry less about the future and work than younger patients. This type of anxiety is largely situational and temporary, and often accompanies comorbid medical problems (Table 1) .

Obsessive-compulsive disorder

A study comparing older (age ≥60) and younger obsessive-compulsive disorder (OCD) patients found that the clinical presentation of the disorder does not substantially differ between age groups; however, geriatric patients had fewer concerns about symmetry, needing to know, and counting rituals. Handwashing and fear of having sinned were more common.¹⁷

OCD is fairly uncommon in geriatric patients. Prevalence rates decrease with age, ranging between 0% and 0. 8% among persons age ≥60.¹⁸ OCD seldom begins in late life; most geriatric patients with OCD have had symptoms for decades. By late life, most individuals with OCD improve, although they may continue to experience clinical or subclinical symptoms.¹⁹ However, 1 report found a second peak of incidence of OCD in women age ≥65.²⁰ Case reports of late-onset OCD have found evidence of cerebral lesions, often in the basal ganglia, which suggests a possible neurodegenerative pathophysiology.²¹

Table 1

DSM-IV-TR criteria for generalized anxiety disorder

Posttraumatic stress disorder

Untreated posttraumatic stress disorder (PTSD) often is assumed to be a chronic disorder. Recollections of past trauma may lead to new PTSD symptoms in older patients. Neurodegeneration of memory pathways and cognitive impairment associated with Alzheimer‘s disease or vascular or alcohol-related dementia may disinhibit PTSD symptoms in patients whose PTSD was fairly well controlled.²²

Life events associated with aging—death of a spouse, financial and physical decline, chronic pain, or diminished cognitive coping resources—may precipitate or revive PTSD symptoms associated with earlier exposure to severe psychological trauma.²³ These life changes also may precipitate socalled delayed PTSD, when symptoms relating to past traumatic experiences present for the first time. Geriatric patients may be more likely than younger persons to deny their PTSD symptoms if their cultural background emphasizes stoicism and fortitude.²⁴

Phobias

Specific phobias. The prevalence of specific phobias drops dramatically in late life, although older patients might underreport symptoms. Many older persons are afraid of falling. Approximately 60% of older adults with a history of falling—and 30% of older individuals with no such history— report this fear. Fear of falling is more prevalent in women and increases with age.^25,26 This fear may be a protective response to a real threat that prevents older persons from attempting high-risk activities, but it also can cause patients to restrict their activities, which can result in decreased social, physical, or cognitive functioning and loss of in-dependence.²⁵

Social phobias (social anxiety disorder).

Among older adults, common social phobias include eating food around strangers, and—especially in men—being unable to urinate in public bathrooms. In a cross-sectional observational study, social anxiety disorder (SAD) was more common among older persons who reported stressful life events, such as death of a spouse.²⁷ MDD, specific phobia, and personality disorder are associated with SAD in geriatric patients.²⁷ Prevalence rates of SAD appear to slightly decrease with age, although the condition remains common in geriatric patients—5% of older adults report lifetime prevalence—and its presentation is similar to that seen in younger adults.²⁷

Agoraphobia. In older persons the prevalence of agoraphobia is 0. 6%.²⁸ Most cases are of early onset but the condition can present de novo following a stroke or other medical event and can inhibit activities needed for successful rehabilitation. Agoraphobia can present within the context of panic attacks as is seen in younger adults but most geriatric patients with agoraphobia do not have concurrent panic disorder. This phobia is more common in women, widowed or divorced individuals, patients with chronic health conditions, and those with comorbid psychiatric disorders.²⁹

Panic disorder

Panic disorder (PD) rarely starts for the first time after age 60, and most late-onset panic attacks are associated with medical and psychiatric comorbidities. PD tends to be less severe in older individuals than in younger adults.³⁰ Recent stressful life events or losses can predict onset and maintenance of PD. Older patients may present with panic symptoms, such as shortness of breath, dizziness, or trembling, that overlap with age-related medical conditions. PD may be prevalent in older patients with chest pain and no evidence of coronary artery disease.³¹ Panic symptoms that are secondary to underlying medical conditions, such as chronic obstructive pulmonary disease exacerbation, usually wax and wane.³²

Treatment

Treatment for anxiety disorders in geriatric patients may involve a combination of psychotherapy, pharmacotherapy, and complementary and alternative therapies. Treatment may be complicated if patients have ≥1 anxiety disorder or suffer from comorbid depression, substance abuse, or medical problems. As is seen with younger adults, the course of anxiety disorders in older patients waxes and wanes, but most disorders are unlikely to remit completely.³³ Aging may influence the effects of psychotropic medications in older patients. Increased distribution and decreased metabolism and clearance of medications results in higher medication plasma levels and longer elimination half-lives. Medication compliance in older patients may be complicated by:

• older patients’ sensitivity to anticho-linergic side effects
• coexisting medical illnesses
• polypharmacy, particularly in institutionalized settings
• sensory and cognitive deficits.³⁴

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) generally are safe and produce fewer side effects compared with tricyclic antidepressants (TCAs), especially in geriatric patients. SSRIs and SNRIs may be useful for GAD, PD, OCD, and PTSD in older patients.³⁵ TCAs can effectively treat anxiety symptoms but may be cardiotoxic and their anticholinergic properties can lead to serious side effects. Benzodiazepines often are used for acute or short-term anxiety management, but chronic use in geriatric patients can cause cognitive impairment, falls, and other serious side effects. Buspirone may be beneficial for GAD but is not effective for PD.³⁶ The drug is well tolerated in older persons, but may take 2 to 4 weeks to be effective ( Table 2 ).³⁵

Pharmacotherapy for anxiety disorders in geriatric patients often is used in conjunction with psychotherapy. Psychotherapeutic approaches include cognitive-behavioral therapy (CBT), exposure therapy, dialectical behavioral therapy, and interpersonal therapy. Increasing evidence supports the effectiveness of psychotherapy in treating anxiety disorders in younger adults as well as in older patients, often in combination with pharmacotherapy.³⁷ In older patients with GAD, CBT is associated with a greater improvement in worry severity, depressive symptoms, and overall mental health compared with usual care.³⁸

In addition to traditional pharmacotherapy, complementary and alternative therapies often are used for late-life anxiety. These therapies include biofeedback, progressive relaxation, acupuncture, yoga, massage therapy, art, music, or dance therapy, meditation, prayer, and spiritual counseling.

Table 2

Pharmacotherapy for anxiety disorders in older adults

Related Resources

• Wetherell JL, Lenze EJ, Stanley MA. Evidence-based treatment of geriatric anxiety disorders. Psychiatr Clin North Am. 2005; 28(4): 871-896, ix.
• Lenze EJ, Wetherell JL. Anxiety disorders. In: Blazer DG, Steffens DC, eds. The American Psychiatric Publishing textbook of geriatric psychiatry. Arlington, VA: American Psychiatric Publishing, Inc; 2009: 333-345.

Drug Brand Name

• Buspirone • BuSpar

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/how-anxiety-presents-differently-in.html#comments

Although anxiety disorders are common at all ages, there is a misconception that their prevalence drastically declines with age. For this reason anxiety disorders often are underdiagnosed and undertreated in geriatric patients, especially when the clinical presentation of these disorders in older patients differs from that seen in younger adults.

In older persons, anxiety symptoms often overlap with medical conditions such as hyperthyroidism and geriatric patients tend to express anxiety symptoms as medical or somatic problems such as pain rather than as psychological distress.¹ As a result, older adults often seek treatment for depressive or anxiety symptoms from their primary care physician instead of a psychiatrist. Unfortunately, primary care physicians often miss psychiatric illness, including anxiety disorders, in geriatric patients.

Anxiety may be a symptom of an underlying psychiatric disturbance, secondary to a general medical condition, or induced by dietary substances, substances of abuse, or medications. Late-life anxiety often is comorbid with major depressive disorder (MDD) ( Box ) and other psychological stressors as older adults recognize declining cognitive and physical functioning.² Anxiety disorders commonly begin in early adulthood, tend to be chronic and interspersed with remissions and relapses, and usually continue into old age.³ In generalized anxiety disorder (GAD), there is a bimodal distribution of onset; approximately two-thirds of patients experience onset between the late teens and late 20s and one-third develop the disorder for the first time after age 50.³

Prevalence rates for anxiety disorders among older adults (age ≥55) range from 3. 5% to 10. 2%.⁴ These rates are slightly lower than those for younger adults.⁵ Among older adults, presence of a 12-month anxiety disorder was associated with female sex, lower education, being unmarried, and having ≥3 or more chronic conditions.⁶

Box

Anxiety and disability risk

Anxiety disorders affect geriatric patients more profoundly than their younger counterparts. Persons age ≥65 who have an anxiety disorder are 3 to 10 times more likely to be hospitalized than younger individuals.¹ Anxiety is associated with high rates of medically unexplained symptoms, increased use of health care resources, chronic medical illness, low levels of physical health-related quality of life, and physical disability.^7,8

Anxiety symptoms may predict progressing physical disability among older women and reduced ability to perform activities of daily living over 1 year.⁹ Anxious geriatric patients are less independent and increase the burden on family and caregivers.¹⁰ Anxiety disorders are associated with lower compliance with medical treatment, which could worsen chronic medical conditions and increase the risk for nursing home admission.¹¹ Anxious older adults report decreased life satisfaction, memory impairment, poorer self perception of health, and increased loneliness.¹²

Generalized anxiety disorder

Although GAD is the most common anxiety disorder among geriatric patients, with a prevalence of 0. 7% to 9%,¹³ it remains underdiagnosed and undertreated.¹⁴ In a cross-sectional observational study of 439 adults age ≥55 with lifetime GAD, approximately one-half experienced onset after age 50.¹⁵ Late onset is associated with more frequent hypertension and a poorer health-related quality of life than early onset.¹⁵

Compared with younger individuals, older persons with GAD have a greater variety of worry topics, including memory loss, medical illnesses, and fear of falls,¹⁶ but worry less about the future and work than younger patients. This type of anxiety is largely situational and temporary, and often accompanies comorbid medical problems (Table 1) .

Obsessive-compulsive disorder

A study comparing older (age ≥60) and younger obsessive-compulsive disorder (OCD) patients found that the clinical presentation of the disorder does not substantially differ between age groups; however, geriatric patients had fewer concerns about symmetry, needing to know, and counting rituals. Handwashing and fear of having sinned were more common.¹⁷

OCD is fairly uncommon in geriatric patients. Prevalence rates decrease with age, ranging between 0% and 0. 8% among persons age ≥60.¹⁸ OCD seldom begins in late life; most geriatric patients with OCD have had symptoms for decades. By late life, most individuals with OCD improve, although they may continue to experience clinical or subclinical symptoms.¹⁹ However, 1 report found a second peak of incidence of OCD in women age ≥65.²⁰ Case reports of late-onset OCD have found evidence of cerebral lesions, often in the basal ganglia, which suggests a possible neurodegenerative pathophysiology.²¹

Table 1

DSM-IV-TR criteria for generalized anxiety disorder

Posttraumatic stress disorder

Untreated posttraumatic stress disorder (PTSD) often is assumed to be a chronic disorder. Recollections of past trauma may lead to new PTSD symptoms in older patients. Neurodegeneration of memory pathways and cognitive impairment associated with Alzheimer‘s disease or vascular or alcohol-related dementia may disinhibit PTSD symptoms in patients whose PTSD was fairly well controlled.²²

Life events associated with aging—death of a spouse, financial and physical decline, chronic pain, or diminished cognitive coping resources—may precipitate or revive PTSD symptoms associated with earlier exposure to severe psychological trauma.²³ These life changes also may precipitate socalled delayed PTSD, when symptoms relating to past traumatic experiences present for the first time. Geriatric patients may be more likely than younger persons to deny their PTSD symptoms if their cultural background emphasizes stoicism and fortitude.²⁴

Phobias

Specific phobias. The prevalence of specific phobias drops dramatically in late life, although older patients might underreport symptoms. Many older persons are afraid of falling. Approximately 60% of older adults with a history of falling—and 30% of older individuals with no such history— report this fear. Fear of falling is more prevalent in women and increases with age.^25,26 This fear may be a protective response to a real threat that prevents older persons from attempting high-risk activities, but it also can cause patients to restrict their activities, which can result in decreased social, physical, or cognitive functioning and loss of in-dependence.²⁵

Social phobias (social anxiety disorder).

Among older adults, common social phobias include eating food around strangers, and—especially in men—being unable to urinate in public bathrooms. In a cross-sectional observational study, social anxiety disorder (SAD) was more common among older persons who reported stressful life events, such as death of a spouse.²⁷ MDD, specific phobia, and personality disorder are associated with SAD in geriatric patients.²⁷ Prevalence rates of SAD appear to slightly decrease with age, although the condition remains common in geriatric patients—5% of older adults report lifetime prevalence—and its presentation is similar to that seen in younger adults.²⁷

Agoraphobia. In older persons the prevalence of agoraphobia is 0. 6%.²⁸ Most cases are of early onset but the condition can present de novo following a stroke or other medical event and can inhibit activities needed for successful rehabilitation. Agoraphobia can present within the context of panic attacks as is seen in younger adults but most geriatric patients with agoraphobia do not have concurrent panic disorder. This phobia is more common in women, widowed or divorced individuals, patients with chronic health conditions, and those with comorbid psychiatric disorders.²⁹

Panic disorder

Panic disorder (PD) rarely starts for the first time after age 60, and most late-onset panic attacks are associated with medical and psychiatric comorbidities. PD tends to be less severe in older individuals than in younger adults.³⁰ Recent stressful life events or losses can predict onset and maintenance of PD. Older patients may present with panic symptoms, such as shortness of breath, dizziness, or trembling, that overlap with age-related medical conditions. PD may be prevalent in older patients with chest pain and no evidence of coronary artery disease.³¹ Panic symptoms that are secondary to underlying medical conditions, such as chronic obstructive pulmonary disease exacerbation, usually wax and wane.³²

Treatment

Treatment for anxiety disorders in geriatric patients may involve a combination of psychotherapy, pharmacotherapy, and complementary and alternative therapies. Treatment may be complicated if patients have ≥1 anxiety disorder or suffer from comorbid depression, substance abuse, or medical problems. As is seen with younger adults, the course of anxiety disorders in older patients waxes and wanes, but most disorders are unlikely to remit completely.³³ Aging may influence the effects of psychotropic medications in older patients. Increased distribution and decreased metabolism and clearance of medications results in higher medication plasma levels and longer elimination half-lives. Medication compliance in older patients may be complicated by:

• older patients’ sensitivity to anticho-linergic side effects
• coexisting medical illnesses
• polypharmacy, particularly in institutionalized settings
• sensory and cognitive deficits.³⁴

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) generally are safe and produce fewer side effects compared with tricyclic antidepressants (TCAs), especially in geriatric patients. SSRIs and SNRIs may be useful for GAD, PD, OCD, and PTSD in older patients.³⁵ TCAs can effectively treat anxiety symptoms but may be cardiotoxic and their anticholinergic properties can lead to serious side effects. Benzodiazepines often are used for acute or short-term anxiety management, but chronic use in geriatric patients can cause cognitive impairment, falls, and other serious side effects. Buspirone may be beneficial for GAD but is not effective for PD.³⁶ The drug is well tolerated in older persons, but may take 2 to 4 weeks to be effective ( Table 2 ).³⁵

Pharmacotherapy for anxiety disorders in geriatric patients often is used in conjunction with psychotherapy. Psychotherapeutic approaches include cognitive-behavioral therapy (CBT), exposure therapy, dialectical behavioral therapy, and interpersonal therapy. Increasing evidence supports the effectiveness of psychotherapy in treating anxiety disorders in younger adults as well as in older patients, often in combination with pharmacotherapy.³⁷ In older patients with GAD, CBT is associated with a greater improvement in worry severity, depressive symptoms, and overall mental health compared with usual care.³⁸

In addition to traditional pharmacotherapy, complementary and alternative therapies often are used for late-life anxiety. These therapies include biofeedback, progressive relaxation, acupuncture, yoga, massage therapy, art, music, or dance therapy, meditation, prayer, and spiritual counseling.

Table 2

Pharmacotherapy for anxiety disorders in older adults

Related Resources

• Wetherell JL, Lenze EJ, Stanley MA. Evidence-based treatment of geriatric anxiety disorders. Psychiatr Clin North Am. 2005; 28(4): 871-896, ix.
• Lenze EJ, Wetherell JL. Anxiety disorders. In: Blazer DG, Steffens DC, eds. The American Psychiatric Publishing textbook of geriatric psychiatry. Arlington, VA: American Psychiatric Publishing, Inc; 2009: 333-345.

Drug Brand Name

• Buspirone • BuSpar

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Discuss this article at http://currentpsychiatry.blogspot.com/2011/03/how-anxiety-presents-differently-in.html#comments

Although anxiety disorders are common at all ages, there is a misconception that their prevalence drastically declines with age. For this reason anxiety disorders often are underdiagnosed and undertreated in geriatric patients, especially when the clinical presentation of these disorders in older patients differs from that seen in younger adults.

In older persons, anxiety symptoms often overlap with medical conditions such as hyperthyroidism and geriatric patients tend to express anxiety symptoms as medical or somatic problems such as pain rather than as psychological distress.¹ As a result, older adults often seek treatment for depressive or anxiety symptoms from their primary care physician instead of a psychiatrist. Unfortunately, primary care physicians often miss psychiatric illness, including anxiety disorders, in geriatric patients.

Anxiety may be a symptom of an underlying psychiatric disturbance, secondary to a general medical condition, or induced by dietary substances, substances of abuse, or medications. Late-life anxiety often is comorbid with major depressive disorder (MDD) ( Box ) and other psychological stressors as older adults recognize declining cognitive and physical functioning.² Anxiety disorders commonly begin in early adulthood, tend to be chronic and interspersed with remissions and relapses, and usually continue into old age.³ In generalized anxiety disorder (GAD), there is a bimodal distribution of onset; approximately two-thirds of patients experience onset between the late teens and late 20s and one-third develop the disorder for the first time after age 50.³

Prevalence rates for anxiety disorders among older adults (age ≥55) range from 3. 5% to 10. 2%.⁴ These rates are slightly lower than those for younger adults.⁵ Among older adults, presence of a 12-month anxiety disorder was associated with female sex, lower education, being unmarried, and having ≥3 or more chronic conditions.⁶

Box

Anxiety and disability risk

Anxiety disorders affect geriatric patients more profoundly than their younger counterparts. Persons age ≥65 who have an anxiety disorder are 3 to 10 times more likely to be hospitalized than younger individuals.¹ Anxiety is associated with high rates of medically unexplained symptoms, increased use of health care resources, chronic medical illness, low levels of physical health-related quality of life, and physical disability.^7,8

Anxiety symptoms may predict progressing physical disability among older women and reduced ability to perform activities of daily living over 1 year.⁹ Anxious geriatric patients are less independent and increase the burden on family and caregivers.¹⁰ Anxiety disorders are associated with lower compliance with medical treatment, which could worsen chronic medical conditions and increase the risk for nursing home admission.¹¹ Anxious older adults report decreased life satisfaction, memory impairment, poorer self perception of health, and increased loneliness.¹²

Generalized anxiety disorder

Although GAD is the most common anxiety disorder among geriatric patients, with a prevalence of 0. 7% to 9%,¹³ it remains underdiagnosed and undertreated.¹⁴ In a cross-sectional observational study of 439 adults age ≥55 with lifetime GAD, approximately one-half experienced onset after age 50.¹⁵ Late onset is associated with more frequent hypertension and a poorer health-related quality of life than early onset.¹⁵

Compared with younger individuals, older persons with GAD have a greater variety of worry topics, including memory loss, medical illnesses, and fear of falls,¹⁶ but worry less about the future and work than younger patients. This type of anxiety is largely situational and temporary, and often accompanies comorbid medical problems (Table 1) .

Obsessive-compulsive disorder

A study comparing older (age ≥60) and younger obsessive-compulsive disorder (OCD) patients found that the clinical presentation of the disorder does not substantially differ between age groups; however, geriatric patients had fewer concerns about symmetry, needing to know, and counting rituals. Handwashing and fear of having sinned were more common.¹⁷

OCD is fairly uncommon in geriatric patients. Prevalence rates decrease with age, ranging between 0% and 0. 8% among persons age ≥60.¹⁸ OCD seldom begins in late life; most geriatric patients with OCD have had symptoms for decades. By late life, most individuals with OCD improve, although they may continue to experience clinical or subclinical symptoms.¹⁹ However, 1 report found a second peak of incidence of OCD in women age ≥65.²⁰ Case reports of late-onset OCD have found evidence of cerebral lesions, often in the basal ganglia, which suggests a possible neurodegenerative pathophysiology.²¹

Table 1

DSM-IV-TR criteria for generalized anxiety disorder

Posttraumatic stress disorder

Untreated posttraumatic stress disorder (PTSD) often is assumed to be a chronic disorder. Recollections of past trauma may lead to new PTSD symptoms in older patients. Neurodegeneration of memory pathways and cognitive impairment associated with Alzheimer‘s disease or vascular or alcohol-related dementia may disinhibit PTSD symptoms in patients whose PTSD was fairly well controlled.²²

Life events associated with aging—death of a spouse, financial and physical decline, chronic pain, or diminished cognitive coping resources—may precipitate or revive PTSD symptoms associated with earlier exposure to severe psychological trauma.²³ These life changes also may precipitate socalled delayed PTSD, when symptoms relating to past traumatic experiences present for the first time. Geriatric patients may be more likely than younger persons to deny their PTSD symptoms if their cultural background emphasizes stoicism and fortitude.²⁴

Phobias

Specific phobias. The prevalence of specific phobias drops dramatically in late life, although older patients might underreport symptoms. Many older persons are afraid of falling. Approximately 60% of older adults with a history of falling—and 30% of older individuals with no such history— report this fear. Fear of falling is more prevalent in women and increases with age.^25,26 This fear may be a protective response to a real threat that prevents older persons from attempting high-risk activities, but it also can cause patients to restrict their activities, which can result in decreased social, physical, or cognitive functioning and loss of in-dependence.²⁵

Social phobias (social anxiety disorder).

Among older adults, common social phobias include eating food around strangers, and—especially in men—being unable to urinate in public bathrooms. In a cross-sectional observational study, social anxiety disorder (SAD) was more common among older persons who reported stressful life events, such as death of a spouse.²⁷ MDD, specific phobia, and personality disorder are associated with SAD in geriatric patients.²⁷ Prevalence rates of SAD appear to slightly decrease with age, although the condition remains common in geriatric patients—5% of older adults report lifetime prevalence—and its presentation is similar to that seen in younger adults.²⁷

Agoraphobia. In older persons the prevalence of agoraphobia is 0. 6%.²⁸ Most cases are of early onset but the condition can present de novo following a stroke or other medical event and can inhibit activities needed for successful rehabilitation. Agoraphobia can present within the context of panic attacks as is seen in younger adults but most geriatric patients with agoraphobia do not have concurrent panic disorder. This phobia is more common in women, widowed or divorced individuals, patients with chronic health conditions, and those with comorbid psychiatric disorders.²⁹

Panic disorder

Panic disorder (PD) rarely starts for the first time after age 60, and most late-onset panic attacks are associated with medical and psychiatric comorbidities. PD tends to be less severe in older individuals than in younger adults.³⁰ Recent stressful life events or losses can predict onset and maintenance of PD. Older patients may present with panic symptoms, such as shortness of breath, dizziness, or trembling, that overlap with age-related medical conditions. PD may be prevalent in older patients with chest pain and no evidence of coronary artery disease.³¹ Panic symptoms that are secondary to underlying medical conditions, such as chronic obstructive pulmonary disease exacerbation, usually wax and wane.³²

Treatment

Treatment for anxiety disorders in geriatric patients may involve a combination of psychotherapy, pharmacotherapy, and complementary and alternative therapies. Treatment may be complicated if patients have ≥1 anxiety disorder or suffer from comorbid depression, substance abuse, or medical problems. As is seen with younger adults, the course of anxiety disorders in older patients waxes and wanes, but most disorders are unlikely to remit completely.³³ Aging may influence the effects of psychotropic medications in older patients. Increased distribution and decreased metabolism and clearance of medications results in higher medication plasma levels and longer elimination half-lives. Medication compliance in older patients may be complicated by:

• older patients’ sensitivity to anticho-linergic side effects
• coexisting medical illnesses
• polypharmacy, particularly in institutionalized settings
• sensory and cognitive deficits.³⁴

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) generally are safe and produce fewer side effects compared with tricyclic antidepressants (TCAs), especially in geriatric patients. SSRIs and SNRIs may be useful for GAD, PD, OCD, and PTSD in older patients.³⁵ TCAs can effectively treat anxiety symptoms but may be cardiotoxic and their anticholinergic properties can lead to serious side effects. Benzodiazepines often are used for acute or short-term anxiety management, but chronic use in geriatric patients can cause cognitive impairment, falls, and other serious side effects. Buspirone may be beneficial for GAD but is not effective for PD.³⁶ The drug is well tolerated in older persons, but may take 2 to 4 weeks to be effective ( Table 2 ).³⁵

Pharmacotherapy for anxiety disorders in geriatric patients often is used in conjunction with psychotherapy. Psychotherapeutic approaches include cognitive-behavioral therapy (CBT), exposure therapy, dialectical behavioral therapy, and interpersonal therapy. Increasing evidence supports the effectiveness of psychotherapy in treating anxiety disorders in younger adults as well as in older patients, often in combination with pharmacotherapy.³⁷ In older patients with GAD, CBT is associated with a greater improvement in worry severity, depressive symptoms, and overall mental health compared with usual care.³⁸

In addition to traditional pharmacotherapy, complementary and alternative therapies often are used for late-life anxiety. These therapies include biofeedback, progressive relaxation, acupuncture, yoga, massage therapy, art, music, or dance therapy, meditation, prayer, and spiritual counseling.

Table 2

Pharmacotherapy for anxiety disorders in older adults

Related Resources

• Wetherell JL, Lenze EJ, Stanley MA. Evidence-based treatment of geriatric anxiety disorders. Psychiatr Clin North Am. 2005; 28(4): 871-896, ix.
• Lenze EJ, Wetherell JL. Anxiety disorders. In: Blazer DG, Steffens DC, eds. The American Psychiatric Publishing textbook of geriatric psychiatry. Arlington, VA: American Psychiatric Publishing, Inc; 2009: 333-345.

Drug Brand Name

• Buspirone • BuSpar

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Discuss this article

Pharmacologic treatments for Alzheimer’s disease (AD) may improve symptoms but have not been shown to prevent AD onset. Primary prevention therefore remains the goal. Although preventing AD by managing risk factors such as age or genetics is beyond our control (Box 1), we can do something about other factors.

This article summarizes the findings of many studies that address AD prevention and includes an online-only bibliography for readers seeking an in-depth review. The evidence does not support a firm recommendation for any specific form of primary prevention and has revealed hazards associated with estrogen therapy and nonsteroidal anti-inflammatory drugs (Box 2). Most important, it suggests that you could reduce your patients’ risk of developing AD by routinely supporting their mental, physical, and social health.

The potential benefits of modifying an individual’s AD risk factors likely will depend on his or her genetic makeup, environment, and lifestyle. Even so, counseling patients to exercise more and improve their diets—such as by eating more fish, fruits, and vegetables and less saturated fat—might help protect the brain. Your ongoing efforts to manage hypertension, hypercholesterolemia, and diabetes also may reduce their AD risk.

Box 1

Box 2

Cardiovascular risk factors

The risk of developing AD or vascular dementia appears to be increased by conditions that damage the heart or blood vessels. Recent evidence suggests that successfully managing cardiovascular risk factors may decrease the likelihood of dementia in later life.

Hypertension is associated with a higher risk of AD and all-cause dementia. Curiously, some studies have shown that low blood pressure also increases dementia risk, suggesting a U-shaped relationship between blood pressure and cognitive decline. Systolic hypertension in midlife may be associated with dementia 20 years later.

One might assume that antihypertensive therapy would help prevent dementia, but the data are conflicting. The Systolic Hypertension in Europe (SYST-EUR) study¹ showed a 53% reduction in vascular dementia or mixed dementia among patients receiving antihypertensive medication and a 60% reduction in AD. Similarly, the PROGRESS² clinical trial of prevention of recurrent stroke by antihypertensive treatment reported a 34% reduction in a composite measure of cognitive impairment and dementia. On the other hand, cognitive function neither improved nor worsened in the Hypertension in the Very Elderly Trial (HYVET-COG),³ whether patients received blood pressure treatment or placebo.

Hyperlipidemia. Lipid metabolism likely is an important pathway in amyloid beta-protein deposition, tau phosphorylation, and disruption of synaptic plasticity and neurodegenerative endpoints. Cognitive decline and incident dementia have been associated with higher dietary intake of saturated fats, partially hydrogenated unsaturated fatty acids (trans fats), and cholesterol. Not all studies have found this association, however. This could be because serum cholesterol levels may decrease in early dementia, limiting the ability to detect an effect of hypercholesterolemia on dementia risk when measurements are made later in life.

Using statins (3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors) to treat hypercholesterolemia has been hypothesized to impede large vessel atherosclerosis and its consequences and to trigger metabolic effects in the brain related to AD pathogenesis. Mechanisms by which statins might help prevent dementia include:

• a direct association between amyloid processing and cholesterol in the brain
• an indirect effect by decreasing the risk of stroke, as even small cerebral infarcts worsen AD severity.

Nonrandomized epidemiologic studies such as the Cardiovascular Health Study⁴ and MRC/BHF Heart Protection Study⁵ suggested that statin treatment might reduce the incidence of dementia, the degree of age-related cognitive decline, and AD’s neuropathologic burden. Large, randomized, controlled trials have not supported these observations, however. Statins failed to reduce the incidence of dementia in:

• the Heart Protection Study, testing simvastatin for 5 years in 20,536 subjects age 40 to 80⁵
• the 3-year Preventive Study of Pravastatin in the Elderly at Risk (PROSPER) of 5,800 subjects.⁶

Similarly, patients receiving adjunctive atorvastatin or placebo showed no significant differences in cognition assessments after 72 weeks in the Lipitor’s Effect in Alzheimer’s Dementia (LEADe) study. This trial enrolled 640 subjects age 50 to 90 with mild-to-moderate dementia who were treated with donepezil.⁷ A recent Cochrane review concluded that high serum cholesterol may contribute to the development of AD and vascular dementia, but lowering cholesterol levels with statins does not prevent these problems.⁸

Diabetes mellitus. Diabetes and cognitive decline are closely associated. Diabetes is associated with a 50% to 100% increase in risk of AD and dementia overall and a 100% to 150% increased risk of vascular dementia. The mechanism by which diabetes increases dementia risk is uncertain but does not appear to be mediated entirely through vascular disease. High and low insulin levels may increase the risk of dementia, independent of diabetes and blood glucose. Increased peripheral insulin levels are associated with reduced brain atrophy and cognitive impairment in patients with early AD, suggesting a role for insulin signaling in AD pathophysiology. A possible relationship between insulin and beta amyloid metabolism is being studied.

Elevated postprandial plasma glucose has been associated with accelerated declines in cognitive performance.⁹ An inverse correlation has been noted between some cognitive measures and hemoglobin A1C levels.¹⁰ It is not clear that treating diabetes reduces the risk of dementia. In addition, in the prospective, population-based Rotterdam study, elderly patients with type 2 diabetes treated with insulin had the highest incidence of dementia.¹¹

Tobacco smoke directly affects neuronal function, integrity, and survival. Chronic smoking has been linked to decreased global cerebral blood flow, accelerated cerebral atrophy, and ventricular enlargement.

Some studies suggest an increased risk of dementia in middle-aged and elderly smokers, possibly through a cerebrovascular mechanism such as stroke. Other studies found no association between smoking and dementia risk, and 1 suggested that nicotine may protect against AD by reducing senile plaque formation. Any protective effect of smoking would be offset by increased risks of lung cancer, chronic obstructive pulmonary disease, and vascular dementia.

The apolipoprotein E epsilon 4 (APOE e4) gene may explain, at least in part, the conflicting results of these studies. In 2 population-based cohorts,^12,13 smoking was associated with memory decline in patients without, but not with, the APOE e4 genotype.

Dietary factors

Antioxidants. The brains of patients with AD contain elevated levels of endogenous antioxidants. In vitro studies show exogenous antioxidants can reduce the toxicity of beta-amyloid in brain tissue of persons with AD. These findings have led to interest in assessing the role of dietary antioxidants such as vitamins E and C for AD prevention.

High-dose alpha-tocopherol (vitamin E, 2,000 IU/d) may slow disease progression in patients with AD, but this association is not consistently found. Furthermore, a meta-analysis of 19 randomized controlled trials (RCTs) totaling >135,000 patients found an association between vitamin E doses >400 IU/d and increased all-cause mortality.¹⁴ High-dose vitamin E supplementation for primary or secondary prevention of AD may be dangerous and is not recommended.

The lack of consistent efficacy data for vitamin C in preventing or treating AD may discourage its routine use for this purpose.¹⁵

Homocysteine is a risk factor for stroke and heart disease. It also could play a role in vascular dementia through its association with large- and small-vessel disease.

Low folate and hyperhomocysteinemia have been associated with dementia or cognitive impairment, although a cause-effect relationship is not clear. In non-demented elderly populations, plasma homocysteine is inversely associated with poor performance in tests of global cognitive function, particularly in measures of psychomotor speed.

In a recent double-blind RCT, folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age, especially information processing and sensorimotor speed.¹⁶ No other good evidence, however, has shown that homocysteine-lowering therapy using folic acid or other vitamin B supplements improves cognitive function or prevents cognitive decline.

Fish and omega-3 fatty acids. High total fat, saturated fat, and total cholesterol intake increases the risk for incident dementia. In epidemiologic studies, low omega-3 fatty acid serum levels have been linked to increased dementia risk.

Fish consumption may be beneficial in reducing the risk of dementia or cognitive decline. A prospective study of 815 elderly persons found 60% less risk of developing AD in those who ate ≥1 fish meal per week, compared with those who rarely or never ate fish.¹⁷ In the Framingham study, individuals who at baseline were in the top quartile of docosahexaenoic acid consumption had lower dementia rates over 9 years of follow-up.¹⁸ Results from cross-sectional and longitudinal studies have been inconsistent; some have shown that high intake of n-3 polyunsaturated fatty acids is associated with less cognitive decline,¹⁹ whereas others have not.²⁰

Although we cannot offer unequivocal advice regarding seafood or omega-3 fatty acid intake for primary prevention of dementia without evidence from RCTs, these uncontrolled studies show promise.

Mediterranean diet (MeDi) components include abundant fruits and vegetables, fish or shellfish at least twice weekly, very limited red meat, olive oil or canola oil instead of butter or margarine, tree nuts such as walnuts or pecans, red wine in moderation, and using herbs and spices instead of salt to season food. High adherence to the MeDi has been associated with a significantly lower risk for incident AD. The MeDi may affect the risk of developing AD²¹ as well as subsequent disease course, with a possible dose-response relationship in lower mortality.²²

Eating fruits and vegetables has been associated with improved cognitive performance²² and decreased incident dementia in elderly subjects.¹⁸

Alcohol. A U-shaped relationship exists between alcohol consumption and dementia risk. High alcohol intake is associated with clinical problem drinking and alcoholism and can lead to cognitive decline. Conversely, moderate wine consumption (250 to 500 mL/d) may be protective—compared with more or less than this amount—and is associated with approximately 50% less risk of dementia.

Alcohol use may increase the risk of dementia in persons carrying the APOE e4 allele, according to the population-based Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study from Sweden.²³ After an average 21 years of follow-up of 1,449 individuals, researchers found that environmental factors—such as physical inactivity, dietary fat intake, alcohol consumption, and smoking at midlife—were associated with an increased risk of dementia at age 65 to 79 in APOE e4 carriers compared with noncarriers. The study also found that physical inactivity, dietary fat intake, and smoking at midlife increase AD risk, especially among APOE e4 carriers.

In the absence of evidence from RCTs, we cannot recommend alcohol to reduce the risk of AD.

Lifestyle and activity

Three components of lifestyle—social, mental, and physical activity—are inversely associated with the risk for dementia, AD, and cognitive impairment.

Physical exercise has been thought to enhance brain neurotrophic factor and modify apoptosis. Exercise can deter stroke and microvascular disease and improve regional cerebral blood flow. In the Cardiovascular Health Study, participants who expended the highest quartile of energy had a lower risk of all-cause dementia and AD compared with participants who expended the lowest quartile of energy.²⁴

Mental and social activity. Epidemiologic studies have shown associations between higher educational achievement and other socioeconomic factors and reduced AD risk. Advanced education is believed to represent a cognitive reserve that delays presentation of AD’s effects on memory and cognitive function, rather than providing a protective effect against accumulation of AD pathology. Higher-educated individuals appear to experience a somewhat more rapid rate of cognitive decline when AD does become apparent, perhaps because they have accumulated a greater degree of AD pathology at that point compared with less-educated persons.

Among 117 persons with dementia in the Bronx Aging Study, each additional year of formal education delayed the time of accelerated decline by 0.21 years. After accelerated decline began, each year of additional formal education was associated with a slightly faster rate of memory decline.²⁵

The longitudinal, population-based Kungsholmen Project in Stockholm, Sweden, found an association between daily mentally stimulating activities and decreased risk of all-cause dementia.²⁶ Similarly, higher levels of leisure activity were linked to reduced risk of all-cause dementia in a longitudinal study of 1,772 persons age ≥65 living in Manhattan, NY.²⁷ In a randomized, single-controlled study of the long-term effects of cognitive training, elderly individuals from 6 U.S. cities showed sustained improvement in specific cognitive performance up to 5 years after training sessions began, including memory, reasoning, and speed of processing.²⁸

It seems reasonable to encourage older patients to maintain or increase physical, cognitive, and leisure activities as well as social interaction. These interventions can improve the quality of life and lower the risk of depression, which may be a response to cognitive decline or an independent risk factor for dementia (Box 3). The Table lists “brain exercises” you can suggest to patients to increase their mental and social activity.

Head trauma. The Multi-Institutional Research in Alzheimer’s Genetic Epidemiology (MIRAGE) project found an association between AD risk and a history of head trauma, especially in persons with APOE e4 alleles.²⁹ Conversely, the Rotterdam Study showed no change in dementia risk for persons with a history of head trauma.³⁰

Even in the absence of conclusive evidence supporting AD prevention, protecting the head by buckling seat belts while driving, wearing helmets when participating in sports, and “fall-proofing” the home is recommended.

Box 3

Table

Brain exercises to suggest to patients

Related resource

• For an extensive bibliography of literature on Alzheimer’s disease risk factors and prevention, see this article at CurrentPsychiatry.com.

Drug brand names

• Atorvastatin • Lipitor
• Celecoxib • Celebrex
• Donepezil • Aricept
• Medroxyprogesterone • Provera
• Pravastatin • Pravachol
• Rofecoxib • Vioxx
• Simvastatin • Zocor

Disclosures

Dr. Bassil reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Dr. Grossberg receives research/grant support from and is a consultant to Bristol-Myers Squibb, Forest Pharmaceuticals, Novartis, Pfizer Inc., and Wyeth Pharmaceuticals. He also receives research/grant support from Baxter.

Discuss this article

Pharmacologic treatments for Alzheimer’s disease (AD) may improve symptoms but have not been shown to prevent AD onset. Primary prevention therefore remains the goal. Although preventing AD by managing risk factors such as age or genetics is beyond our control (Box 1), we can do something about other factors.

This article summarizes the findings of many studies that address AD prevention and includes an online-only bibliography for readers seeking an in-depth review. The evidence does not support a firm recommendation for any specific form of primary prevention and has revealed hazards associated with estrogen therapy and nonsteroidal anti-inflammatory drugs (Box 2). Most important, it suggests that you could reduce your patients’ risk of developing AD by routinely supporting their mental, physical, and social health.

The potential benefits of modifying an individual’s AD risk factors likely will depend on his or her genetic makeup, environment, and lifestyle. Even so, counseling patients to exercise more and improve their diets—such as by eating more fish, fruits, and vegetables and less saturated fat—might help protect the brain. Your ongoing efforts to manage hypertension, hypercholesterolemia, and diabetes also may reduce their AD risk.

Box 1

Box 2

Cardiovascular risk factors

The risk of developing AD or vascular dementia appears to be increased by conditions that damage the heart or blood vessels. Recent evidence suggests that successfully managing cardiovascular risk factors may decrease the likelihood of dementia in later life.

Hypertension is associated with a higher risk of AD and all-cause dementia. Curiously, some studies have shown that low blood pressure also increases dementia risk, suggesting a U-shaped relationship between blood pressure and cognitive decline. Systolic hypertension in midlife may be associated with dementia 20 years later.

One might assume that antihypertensive therapy would help prevent dementia, but the data are conflicting. The Systolic Hypertension in Europe (SYST-EUR) study¹ showed a 53% reduction in vascular dementia or mixed dementia among patients receiving antihypertensive medication and a 60% reduction in AD. Similarly, the PROGRESS² clinical trial of prevention of recurrent stroke by antihypertensive treatment reported a 34% reduction in a composite measure of cognitive impairment and dementia. On the other hand, cognitive function neither improved nor worsened in the Hypertension in the Very Elderly Trial (HYVET-COG),³ whether patients received blood pressure treatment or placebo.

Hyperlipidemia. Lipid metabolism likely is an important pathway in amyloid beta-protein deposition, tau phosphorylation, and disruption of synaptic plasticity and neurodegenerative endpoints. Cognitive decline and incident dementia have been associated with higher dietary intake of saturated fats, partially hydrogenated unsaturated fatty acids (trans fats), and cholesterol. Not all studies have found this association, however. This could be because serum cholesterol levels may decrease in early dementia, limiting the ability to detect an effect of hypercholesterolemia on dementia risk when measurements are made later in life.

Using statins (3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors) to treat hypercholesterolemia has been hypothesized to impede large vessel atherosclerosis and its consequences and to trigger metabolic effects in the brain related to AD pathogenesis. Mechanisms by which statins might help prevent dementia include:

• a direct association between amyloid processing and cholesterol in the brain
• an indirect effect by decreasing the risk of stroke, as even small cerebral infarcts worsen AD severity.

Nonrandomized epidemiologic studies such as the Cardiovascular Health Study⁴ and MRC/BHF Heart Protection Study⁵ suggested that statin treatment might reduce the incidence of dementia, the degree of age-related cognitive decline, and AD’s neuropathologic burden. Large, randomized, controlled trials have not supported these observations, however. Statins failed to reduce the incidence of dementia in:

• the Heart Protection Study, testing simvastatin for 5 years in 20,536 subjects age 40 to 80⁵
• the 3-year Preventive Study of Pravastatin in the Elderly at Risk (PROSPER) of 5,800 subjects.⁶

Similarly, patients receiving adjunctive atorvastatin or placebo showed no significant differences in cognition assessments after 72 weeks in the Lipitor’s Effect in Alzheimer’s Dementia (LEADe) study. This trial enrolled 640 subjects age 50 to 90 with mild-to-moderate dementia who were treated with donepezil.⁷ A recent Cochrane review concluded that high serum cholesterol may contribute to the development of AD and vascular dementia, but lowering cholesterol levels with statins does not prevent these problems.⁸

Diabetes mellitus. Diabetes and cognitive decline are closely associated. Diabetes is associated with a 50% to 100% increase in risk of AD and dementia overall and a 100% to 150% increased risk of vascular dementia. The mechanism by which diabetes increases dementia risk is uncertain but does not appear to be mediated entirely through vascular disease. High and low insulin levels may increase the risk of dementia, independent of diabetes and blood glucose. Increased peripheral insulin levels are associated with reduced brain atrophy and cognitive impairment in patients with early AD, suggesting a role for insulin signaling in AD pathophysiology. A possible relationship between insulin and beta amyloid metabolism is being studied.

Elevated postprandial plasma glucose has been associated with accelerated declines in cognitive performance.⁹ An inverse correlation has been noted between some cognitive measures and hemoglobin A1C levels.¹⁰ It is not clear that treating diabetes reduces the risk of dementia. In addition, in the prospective, population-based Rotterdam study, elderly patients with type 2 diabetes treated with insulin had the highest incidence of dementia.¹¹

Tobacco smoke directly affects neuronal function, integrity, and survival. Chronic smoking has been linked to decreased global cerebral blood flow, accelerated cerebral atrophy, and ventricular enlargement.

Some studies suggest an increased risk of dementia in middle-aged and elderly smokers, possibly through a cerebrovascular mechanism such as stroke. Other studies found no association between smoking and dementia risk, and 1 suggested that nicotine may protect against AD by reducing senile plaque formation. Any protective effect of smoking would be offset by increased risks of lung cancer, chronic obstructive pulmonary disease, and vascular dementia.

The apolipoprotein E epsilon 4 (APOE e4) gene may explain, at least in part, the conflicting results of these studies. In 2 population-based cohorts,^12,13 smoking was associated with memory decline in patients without, but not with, the APOE e4 genotype.

Dietary factors

Antioxidants. The brains of patients with AD contain elevated levels of endogenous antioxidants. In vitro studies show exogenous antioxidants can reduce the toxicity of beta-amyloid in brain tissue of persons with AD. These findings have led to interest in assessing the role of dietary antioxidants such as vitamins E and C for AD prevention.

High-dose alpha-tocopherol (vitamin E, 2,000 IU/d) may slow disease progression in patients with AD, but this association is not consistently found. Furthermore, a meta-analysis of 19 randomized controlled trials (RCTs) totaling >135,000 patients found an association between vitamin E doses >400 IU/d and increased all-cause mortality.¹⁴ High-dose vitamin E supplementation for primary or secondary prevention of AD may be dangerous and is not recommended.

The lack of consistent efficacy data for vitamin C in preventing or treating AD may discourage its routine use for this purpose.¹⁵

Homocysteine is a risk factor for stroke and heart disease. It also could play a role in vascular dementia through its association with large- and small-vessel disease.

Low folate and hyperhomocysteinemia have been associated with dementia or cognitive impairment, although a cause-effect relationship is not clear. In non-demented elderly populations, plasma homocysteine is inversely associated with poor performance in tests of global cognitive function, particularly in measures of psychomotor speed.

In a recent double-blind RCT, folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age, especially information processing and sensorimotor speed.¹⁶ No other good evidence, however, has shown that homocysteine-lowering therapy using folic acid or other vitamin B supplements improves cognitive function or prevents cognitive decline.

Fish and omega-3 fatty acids. High total fat, saturated fat, and total cholesterol intake increases the risk for incident dementia. In epidemiologic studies, low omega-3 fatty acid serum levels have been linked to increased dementia risk.

Fish consumption may be beneficial in reducing the risk of dementia or cognitive decline. A prospective study of 815 elderly persons found 60% less risk of developing AD in those who ate ≥1 fish meal per week, compared with those who rarely or never ate fish.¹⁷ In the Framingham study, individuals who at baseline were in the top quartile of docosahexaenoic acid consumption had lower dementia rates over 9 years of follow-up.¹⁸ Results from cross-sectional and longitudinal studies have been inconsistent; some have shown that high intake of n-3 polyunsaturated fatty acids is associated with less cognitive decline,¹⁹ whereas others have not.²⁰

Although we cannot offer unequivocal advice regarding seafood or omega-3 fatty acid intake for primary prevention of dementia without evidence from RCTs, these uncontrolled studies show promise.

Mediterranean diet (MeDi) components include abundant fruits and vegetables, fish or shellfish at least twice weekly, very limited red meat, olive oil or canola oil instead of butter or margarine, tree nuts such as walnuts or pecans, red wine in moderation, and using herbs and spices instead of salt to season food. High adherence to the MeDi has been associated with a significantly lower risk for incident AD. The MeDi may affect the risk of developing AD²¹ as well as subsequent disease course, with a possible dose-response relationship in lower mortality.²²

Eating fruits and vegetables has been associated with improved cognitive performance²² and decreased incident dementia in elderly subjects.¹⁸

Alcohol. A U-shaped relationship exists between alcohol consumption and dementia risk. High alcohol intake is associated with clinical problem drinking and alcoholism and can lead to cognitive decline. Conversely, moderate wine consumption (250 to 500 mL/d) may be protective—compared with more or less than this amount—and is associated with approximately 50% less risk of dementia.

Alcohol use may increase the risk of dementia in persons carrying the APOE e4 allele, according to the population-based Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study from Sweden.²³ After an average 21 years of follow-up of 1,449 individuals, researchers found that environmental factors—such as physical inactivity, dietary fat intake, alcohol consumption, and smoking at midlife—were associated with an increased risk of dementia at age 65 to 79 in APOE e4 carriers compared with noncarriers. The study also found that physical inactivity, dietary fat intake, and smoking at midlife increase AD risk, especially among APOE e4 carriers.

In the absence of evidence from RCTs, we cannot recommend alcohol to reduce the risk of AD.

Lifestyle and activity

Three components of lifestyle—social, mental, and physical activity—are inversely associated with the risk for dementia, AD, and cognitive impairment.

Physical exercise has been thought to enhance brain neurotrophic factor and modify apoptosis. Exercise can deter stroke and microvascular disease and improve regional cerebral blood flow. In the Cardiovascular Health Study, participants who expended the highest quartile of energy had a lower risk of all-cause dementia and AD compared with participants who expended the lowest quartile of energy.²⁴

Mental and social activity. Epidemiologic studies have shown associations between higher educational achievement and other socioeconomic factors and reduced AD risk. Advanced education is believed to represent a cognitive reserve that delays presentation of AD’s effects on memory and cognitive function, rather than providing a protective effect against accumulation of AD pathology. Higher-educated individuals appear to experience a somewhat more rapid rate of cognitive decline when AD does become apparent, perhaps because they have accumulated a greater degree of AD pathology at that point compared with less-educated persons.

Among 117 persons with dementia in the Bronx Aging Study, each additional year of formal education delayed the time of accelerated decline by 0.21 years. After accelerated decline began, each year of additional formal education was associated with a slightly faster rate of memory decline.²⁵

The longitudinal, population-based Kungsholmen Project in Stockholm, Sweden, found an association between daily mentally stimulating activities and decreased risk of all-cause dementia.²⁶ Similarly, higher levels of leisure activity were linked to reduced risk of all-cause dementia in a longitudinal study of 1,772 persons age ≥65 living in Manhattan, NY.²⁷ In a randomized, single-controlled study of the long-term effects of cognitive training, elderly individuals from 6 U.S. cities showed sustained improvement in specific cognitive performance up to 5 years after training sessions began, including memory, reasoning, and speed of processing.²⁸

It seems reasonable to encourage older patients to maintain or increase physical, cognitive, and leisure activities as well as social interaction. These interventions can improve the quality of life and lower the risk of depression, which may be a response to cognitive decline or an independent risk factor for dementia (Box 3). The Table lists “brain exercises” you can suggest to patients to increase their mental and social activity.

Head trauma. The Multi-Institutional Research in Alzheimer’s Genetic Epidemiology (MIRAGE) project found an association between AD risk and a history of head trauma, especially in persons with APOE e4 alleles.²⁹ Conversely, the Rotterdam Study showed no change in dementia risk for persons with a history of head trauma.³⁰

Even in the absence of conclusive evidence supporting AD prevention, protecting the head by buckling seat belts while driving, wearing helmets when participating in sports, and “fall-proofing” the home is recommended.

Box 3

Table

Brain exercises to suggest to patients

Related resource

• For an extensive bibliography of literature on Alzheimer’s disease risk factors and prevention, see this article at CurrentPsychiatry.com.

Drug brand names

• Atorvastatin • Lipitor
• Celecoxib • Celebrex
• Donepezil • Aricept
• Medroxyprogesterone • Provera
• Pravastatin • Pravachol
• Rofecoxib • Vioxx
• Simvastatin • Zocor

Disclosures

Dr. Bassil reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Dr. Grossberg receives research/grant support from and is a consultant to Bristol-Myers Squibb, Forest Pharmaceuticals, Novartis, Pfizer Inc., and Wyeth Pharmaceuticals. He also receives research/grant support from Baxter.

Discuss this article

Pharmacologic treatments for Alzheimer’s disease (AD) may improve symptoms but have not been shown to prevent AD onset. Primary prevention therefore remains the goal. Although preventing AD by managing risk factors such as age or genetics is beyond our control (Box 1), we can do something about other factors.

This article summarizes the findings of many studies that address AD prevention and includes an online-only bibliography for readers seeking an in-depth review. The evidence does not support a firm recommendation for any specific form of primary prevention and has revealed hazards associated with estrogen therapy and nonsteroidal anti-inflammatory drugs (Box 2). Most important, it suggests that you could reduce your patients’ risk of developing AD by routinely supporting their mental, physical, and social health.

The potential benefits of modifying an individual’s AD risk factors likely will depend on his or her genetic makeup, environment, and lifestyle. Even so, counseling patients to exercise more and improve their diets—such as by eating more fish, fruits, and vegetables and less saturated fat—might help protect the brain. Your ongoing efforts to manage hypertension, hypercholesterolemia, and diabetes also may reduce their AD risk.

Box 1

Box 2

Cardiovascular risk factors

The risk of developing AD or vascular dementia appears to be increased by conditions that damage the heart or blood vessels. Recent evidence suggests that successfully managing cardiovascular risk factors may decrease the likelihood of dementia in later life.

Hypertension is associated with a higher risk of AD and all-cause dementia. Curiously, some studies have shown that low blood pressure also increases dementia risk, suggesting a U-shaped relationship between blood pressure and cognitive decline. Systolic hypertension in midlife may be associated with dementia 20 years later.

One might assume that antihypertensive therapy would help prevent dementia, but the data are conflicting. The Systolic Hypertension in Europe (SYST-EUR) study¹ showed a 53% reduction in vascular dementia or mixed dementia among patients receiving antihypertensive medication and a 60% reduction in AD. Similarly, the PROGRESS² clinical trial of prevention of recurrent stroke by antihypertensive treatment reported a 34% reduction in a composite measure of cognitive impairment and dementia. On the other hand, cognitive function neither improved nor worsened in the Hypertension in the Very Elderly Trial (HYVET-COG),³ whether patients received blood pressure treatment or placebo.

Hyperlipidemia. Lipid metabolism likely is an important pathway in amyloid beta-protein deposition, tau phosphorylation, and disruption of synaptic plasticity and neurodegenerative endpoints. Cognitive decline and incident dementia have been associated with higher dietary intake of saturated fats, partially hydrogenated unsaturated fatty acids (trans fats), and cholesterol. Not all studies have found this association, however. This could be because serum cholesterol levels may decrease in early dementia, limiting the ability to detect an effect of hypercholesterolemia on dementia risk when measurements are made later in life.

Using statins (3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors) to treat hypercholesterolemia has been hypothesized to impede large vessel atherosclerosis and its consequences and to trigger metabolic effects in the brain related to AD pathogenesis. Mechanisms by which statins might help prevent dementia include:

• a direct association between amyloid processing and cholesterol in the brain
• an indirect effect by decreasing the risk of stroke, as even small cerebral infarcts worsen AD severity.

Nonrandomized epidemiologic studies such as the Cardiovascular Health Study⁴ and MRC/BHF Heart Protection Study⁵ suggested that statin treatment might reduce the incidence of dementia, the degree of age-related cognitive decline, and AD’s neuropathologic burden. Large, randomized, controlled trials have not supported these observations, however. Statins failed to reduce the incidence of dementia in:

• the Heart Protection Study, testing simvastatin for 5 years in 20,536 subjects age 40 to 80⁵
• the 3-year Preventive Study of Pravastatin in the Elderly at Risk (PROSPER) of 5,800 subjects.⁶

Similarly, patients receiving adjunctive atorvastatin or placebo showed no significant differences in cognition assessments after 72 weeks in the Lipitor’s Effect in Alzheimer’s Dementia (LEADe) study. This trial enrolled 640 subjects age 50 to 90 with mild-to-moderate dementia who were treated with donepezil.⁷ A recent Cochrane review concluded that high serum cholesterol may contribute to the development of AD and vascular dementia, but lowering cholesterol levels with statins does not prevent these problems.⁸

Diabetes mellitus. Diabetes and cognitive decline are closely associated. Diabetes is associated with a 50% to 100% increase in risk of AD and dementia overall and a 100% to 150% increased risk of vascular dementia. The mechanism by which diabetes increases dementia risk is uncertain but does not appear to be mediated entirely through vascular disease. High and low insulin levels may increase the risk of dementia, independent of diabetes and blood glucose. Increased peripheral insulin levels are associated with reduced brain atrophy and cognitive impairment in patients with early AD, suggesting a role for insulin signaling in AD pathophysiology. A possible relationship between insulin and beta amyloid metabolism is being studied.

Elevated postprandial plasma glucose has been associated with accelerated declines in cognitive performance.⁹ An inverse correlation has been noted between some cognitive measures and hemoglobin A1C levels.¹⁰ It is not clear that treating diabetes reduces the risk of dementia. In addition, in the prospective, population-based Rotterdam study, elderly patients with type 2 diabetes treated with insulin had the highest incidence of dementia.¹¹

Tobacco smoke directly affects neuronal function, integrity, and survival. Chronic smoking has been linked to decreased global cerebral blood flow, accelerated cerebral atrophy, and ventricular enlargement.

Some studies suggest an increased risk of dementia in middle-aged and elderly smokers, possibly through a cerebrovascular mechanism such as stroke. Other studies found no association between smoking and dementia risk, and 1 suggested that nicotine may protect against AD by reducing senile plaque formation. Any protective effect of smoking would be offset by increased risks of lung cancer, chronic obstructive pulmonary disease, and vascular dementia.

The apolipoprotein E epsilon 4 (APOE e4) gene may explain, at least in part, the conflicting results of these studies. In 2 population-based cohorts,^12,13 smoking was associated with memory decline in patients without, but not with, the APOE e4 genotype.

Dietary factors

Antioxidants. The brains of patients with AD contain elevated levels of endogenous antioxidants. In vitro studies show exogenous antioxidants can reduce the toxicity of beta-amyloid in brain tissue of persons with AD. These findings have led to interest in assessing the role of dietary antioxidants such as vitamins E and C for AD prevention.

High-dose alpha-tocopherol (vitamin E, 2,000 IU/d) may slow disease progression in patients with AD, but this association is not consistently found. Furthermore, a meta-analysis of 19 randomized controlled trials (RCTs) totaling >135,000 patients found an association between vitamin E doses >400 IU/d and increased all-cause mortality.¹⁴ High-dose vitamin E supplementation for primary or secondary prevention of AD may be dangerous and is not recommended.

The lack of consistent efficacy data for vitamin C in preventing or treating AD may discourage its routine use for this purpose.¹⁵

Homocysteine is a risk factor for stroke and heart disease. It also could play a role in vascular dementia through its association with large- and small-vessel disease.

Low folate and hyperhomocysteinemia have been associated with dementia or cognitive impairment, although a cause-effect relationship is not clear. In non-demented elderly populations, plasma homocysteine is inversely associated with poor performance in tests of global cognitive function, particularly in measures of psychomotor speed.

In a recent double-blind RCT, folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age, especially information processing and sensorimotor speed.¹⁶ No other good evidence, however, has shown that homocysteine-lowering therapy using folic acid or other vitamin B supplements improves cognitive function or prevents cognitive decline.

Fish and omega-3 fatty acids. High total fat, saturated fat, and total cholesterol intake increases the risk for incident dementia. In epidemiologic studies, low omega-3 fatty acid serum levels have been linked to increased dementia risk.

Fish consumption may be beneficial in reducing the risk of dementia or cognitive decline. A prospective study of 815 elderly persons found 60% less risk of developing AD in those who ate ≥1 fish meal per week, compared with those who rarely or never ate fish.¹⁷ In the Framingham study, individuals who at baseline were in the top quartile of docosahexaenoic acid consumption had lower dementia rates over 9 years of follow-up.¹⁸ Results from cross-sectional and longitudinal studies have been inconsistent; some have shown that high intake of n-3 polyunsaturated fatty acids is associated with less cognitive decline,¹⁹ whereas others have not.²⁰

Although we cannot offer unequivocal advice regarding seafood or omega-3 fatty acid intake for primary prevention of dementia without evidence from RCTs, these uncontrolled studies show promise.

Mediterranean diet (MeDi) components include abundant fruits and vegetables, fish or shellfish at least twice weekly, very limited red meat, olive oil or canola oil instead of butter or margarine, tree nuts such as walnuts or pecans, red wine in moderation, and using herbs and spices instead of salt to season food. High adherence to the MeDi has been associated with a significantly lower risk for incident AD. The MeDi may affect the risk of developing AD²¹ as well as subsequent disease course, with a possible dose-response relationship in lower mortality.²²

Eating fruits and vegetables has been associated with improved cognitive performance²² and decreased incident dementia in elderly subjects.¹⁸

Alcohol. A U-shaped relationship exists between alcohol consumption and dementia risk. High alcohol intake is associated with clinical problem drinking and alcoholism and can lead to cognitive decline. Conversely, moderate wine consumption (250 to 500 mL/d) may be protective—compared with more or less than this amount—and is associated with approximately 50% less risk of dementia.

Alcohol use may increase the risk of dementia in persons carrying the APOE e4 allele, according to the population-based Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study from Sweden.²³ After an average 21 years of follow-up of 1,449 individuals, researchers found that environmental factors—such as physical inactivity, dietary fat intake, alcohol consumption, and smoking at midlife—were associated with an increased risk of dementia at age 65 to 79 in APOE e4 carriers compared with noncarriers. The study also found that physical inactivity, dietary fat intake, and smoking at midlife increase AD risk, especially among APOE e4 carriers.

In the absence of evidence from RCTs, we cannot recommend alcohol to reduce the risk of AD.

Lifestyle and activity

Three components of lifestyle—social, mental, and physical activity—are inversely associated with the risk for dementia, AD, and cognitive impairment.

Physical exercise has been thought to enhance brain neurotrophic factor and modify apoptosis. Exercise can deter stroke and microvascular disease and improve regional cerebral blood flow. In the Cardiovascular Health Study, participants who expended the highest quartile of energy had a lower risk of all-cause dementia and AD compared with participants who expended the lowest quartile of energy.²⁴

Mental and social activity. Epidemiologic studies have shown associations between higher educational achievement and other socioeconomic factors and reduced AD risk. Advanced education is believed to represent a cognitive reserve that delays presentation of AD’s effects on memory and cognitive function, rather than providing a protective effect against accumulation of AD pathology. Higher-educated individuals appear to experience a somewhat more rapid rate of cognitive decline when AD does become apparent, perhaps because they have accumulated a greater degree of AD pathology at that point compared with less-educated persons.

Among 117 persons with dementia in the Bronx Aging Study, each additional year of formal education delayed the time of accelerated decline by 0.21 years. After accelerated decline began, each year of additional formal education was associated with a slightly faster rate of memory decline.²⁵

The longitudinal, population-based Kungsholmen Project in Stockholm, Sweden, found an association between daily mentally stimulating activities and decreased risk of all-cause dementia.²⁶ Similarly, higher levels of leisure activity were linked to reduced risk of all-cause dementia in a longitudinal study of 1,772 persons age ≥65 living in Manhattan, NY.²⁷ In a randomized, single-controlled study of the long-term effects of cognitive training, elderly individuals from 6 U.S. cities showed sustained improvement in specific cognitive performance up to 5 years after training sessions began, including memory, reasoning, and speed of processing.²⁸

It seems reasonable to encourage older patients to maintain or increase physical, cognitive, and leisure activities as well as social interaction. These interventions can improve the quality of life and lower the risk of depression, which may be a response to cognitive decline or an independent risk factor for dementia (Box 3). The Table lists “brain exercises” you can suggest to patients to increase their mental and social activity.

Head trauma. The Multi-Institutional Research in Alzheimer’s Genetic Epidemiology (MIRAGE) project found an association between AD risk and a history of head trauma, especially in persons with APOE e4 alleles.²⁹ Conversely, the Rotterdam Study showed no change in dementia risk for persons with a history of head trauma.³⁰

Even in the absence of conclusive evidence supporting AD prevention, protecting the head by buckling seat belts while driving, wearing helmets when participating in sports, and “fall-proofing” the home is recommended.

Box 3

Table

Brain exercises to suggest to patients

Related resource

• For an extensive bibliography of literature on Alzheimer’s disease risk factors and prevention, see this article at CurrentPsychiatry.com.

Drug brand names

• Atorvastatin • Lipitor
• Celecoxib • Celebrex
• Donepezil • Aricept
• Medroxyprogesterone • Provera
• Pravastatin • Pravachol
• Rofecoxib • Vioxx
• Simvastatin • Zocor

Disclosures

Dr. Bassil reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Dr. Grossberg receives research/grant support from and is a consultant to Bristol-Myers Squibb, Forest Pharmaceuticals, Novartis, Pfizer Inc., and Wyeth Pharmaceuticals. He also receives research/grant support from Baxter.