Michele G. Sullivan

Up to 61% of children getting intramuscular injections in the shoulder are probably receiving overpenetration injuries, because the recommended needles are longer than the average fat and muscle layer of the deltoid, according to results of an imaging study of 250 children.

“Our data suggest that the [national] recommendations for needle length for intramuscular injection in the shoulder will overpenetrate the muscle layer and strike bone or periosteum in 11%, 55%, and 61% of patients who receive 5/8-, 7/8-, or 1-inch needles,” wrote William C. Lippert and his colleague, Dr. Eric J. Wall. “This could cause severe pain and also impair delivery to the intramuscular level.”

Their imaging study of a subset of 250 children aged 2 months to 18 years concluded that weight and gender should guide needle selection for shoulder injections. Since girls have less muscle in the deltoid, they should generally receive shorter needles than boys (Pediatrics 2008 Aug. 11 [Epub doi:10.1542/peds.2008-0374]).

Mr. Lippert, of Tulane University, New Orleans, and Dr. Wall, of Cincinnati Children's Hospital Medical Center, used MRI and CT scans of the shoulders and thighs of the study population to determine the optimal needle lengths for boys and girls receiving intramuscular injections. All the children had normal shoulder and thigh anatomy; scans were collected as part of care they received at a large children's hospital.

The researchers used fat and muscle thickness, correlated to weight, age, and gender, to determine the safest needle lengths; they then compared their findings with the current recommendations by the Centers for Disease Control and Prevention. For thigh injections, the CDC recommends a 1-inch needle for infants aged 1–12 months and a 1- to 11/4-inch needle for toddlers aged 12–24 months. For shoulder injections, the CDC recommends a 5/8- to 1-inch needle in children aged 1–18 years.

Thigh scans were obtained for 100 patients aged 2 months to 6 years. Using the CDC recommendations, the researchers said, overpenetration would occur in 11% of those injected with a 1-inch needle and 39% of those injected with a 11/4-inch needle.

A total of 150 patients aged 12 months-18 years had scans of the shoulder. The risk for overpenetration with CDC-recommended needles was much greater for deltoid injections. Overpenetration would occur in 11% of children injected with a 5/8-inch needle, 55% of those injected with a 7/8-inch needle, and 61% of those injected with a 1-inch needle.

The investigators also compared muscle and fat thickness between boys and girls of different ages. On average, girls had more fat and muscle in the thighs than did boys of a similar age, and more fat but less muscle in the deltoid.

The researchers suggested that revisions of the CDC needle-length recommendations are in order. For thigh injections of children up to age 6 years, a 7/8- or 1-inch needle is the best option; it would underpenetrate only 2% and overpenetrate only 4% of these pediatric patients. “With these recommendations, 90% of all children who receive a vaccination in the thigh will be vaccinated into the intramuscular level, in comparison with the 64% intramuscular delivery rate if using the current CDC recommendations,” the researchers said.

Their recommendations for the male and female shoulder are more complicated, because of the variance in tissue thickness between the genders. The investigators recommended a 1/2-inch needle for girls weighing 70 kg or less and boys weighing 75 kg or less. A 5/8-inch needle should be used for girls weighing 70–115 kg and boys weighing 75–140 kg. A 7/8-inch or longer needle should be used for girls weighing more than 115 kg and boys weighing more than 140 kg.

“With these recommendations, 90% of both female and male patients would be vaccinated safely at the intramuscular level. Also, these recommendations ensure a 0% overpenetration rate for all patients,” they said.

Nonetheless, the researchers admitted their study had limitations: “Because of wide geographic variation in infant and child weight, it is difficult to make universal needle-length recommendations.”

Neither of the investigators reported any financial disclosures with regard to the study.

Up to 61% of children getting intramuscular injections in the shoulder are probably receiving overpenetration injuries, because the recommended needles are longer than the average fat and muscle layer of the deltoid, according to results of an imaging study of 250 children.

“Our data suggest that the [national] recommendations for needle length for intramuscular injection in the shoulder will overpenetrate the muscle layer and strike bone or periosteum in 11%, 55%, and 61% of patients who receive 5/8-, 7/8-, or 1-inch needles,” wrote William C. Lippert and his colleague, Dr. Eric J. Wall. “This could cause severe pain and also impair delivery to the intramuscular level.”

Their imaging study of a subset of 250 children aged 2 months to 18 years concluded that weight and gender should guide needle selection for shoulder injections. Since girls have less muscle in the deltoid, they should generally receive shorter needles than boys (Pediatrics 2008 Aug. 11 [Epub doi:10.1542/peds.2008-0374]).

Mr. Lippert, of Tulane University, New Orleans, and Dr. Wall, of Cincinnati Children's Hospital Medical Center, used MRI and CT scans of the shoulders and thighs of the study population to determine the optimal needle lengths for boys and girls receiving intramuscular injections. All the children had normal shoulder and thigh anatomy; scans were collected as part of care they received at a large children's hospital.

The researchers used fat and muscle thickness, correlated to weight, age, and gender, to determine the safest needle lengths; they then compared their findings with the current recommendations by the Centers for Disease Control and Prevention. For thigh injections, the CDC recommends a 1-inch needle for infants aged 1–12 months and a 1- to 11/4-inch needle for toddlers aged 12–24 months. For shoulder injections, the CDC recommends a 5/8- to 1-inch needle in children aged 1–18 years.

Thigh scans were obtained for 100 patients aged 2 months to 6 years. Using the CDC recommendations, the researchers said, overpenetration would occur in 11% of those injected with a 1-inch needle and 39% of those injected with a 11/4-inch needle.

A total of 150 patients aged 12 months-18 years had scans of the shoulder. The risk for overpenetration with CDC-recommended needles was much greater for deltoid injections. Overpenetration would occur in 11% of children injected with a 5/8-inch needle, 55% of those injected with a 7/8-inch needle, and 61% of those injected with a 1-inch needle.

The investigators also compared muscle and fat thickness between boys and girls of different ages. On average, girls had more fat and muscle in the thighs than did boys of a similar age, and more fat but less muscle in the deltoid.

The researchers suggested that revisions of the CDC needle-length recommendations are in order. For thigh injections of children up to age 6 years, a 7/8- or 1-inch needle is the best option; it would underpenetrate only 2% and overpenetrate only 4% of these pediatric patients. “With these recommendations, 90% of all children who receive a vaccination in the thigh will be vaccinated into the intramuscular level, in comparison with the 64% intramuscular delivery rate if using the current CDC recommendations,” the researchers said.

Their recommendations for the male and female shoulder are more complicated, because of the variance in tissue thickness between the genders. The investigators recommended a 1/2-inch needle for girls weighing 70 kg or less and boys weighing 75 kg or less. A 5/8-inch needle should be used for girls weighing 70–115 kg and boys weighing 75–140 kg. A 7/8-inch or longer needle should be used for girls weighing more than 115 kg and boys weighing more than 140 kg.

“With these recommendations, 90% of both female and male patients would be vaccinated safely at the intramuscular level. Also, these recommendations ensure a 0% overpenetration rate for all patients,” they said.

Nonetheless, the researchers admitted their study had limitations: “Because of wide geographic variation in infant and child weight, it is difficult to make universal needle-length recommendations.”

Neither of the investigators reported any financial disclosures with regard to the study.

Up to 61% of children getting intramuscular injections in the shoulder are probably receiving overpenetration injuries, because the recommended needles are longer than the average fat and muscle layer of the deltoid, according to results of an imaging study of 250 children.

“Our data suggest that the [national] recommendations for needle length for intramuscular injection in the shoulder will overpenetrate the muscle layer and strike bone or periosteum in 11%, 55%, and 61% of patients who receive 5/8-, 7/8-, or 1-inch needles,” wrote William C. Lippert and his colleague, Dr. Eric J. Wall. “This could cause severe pain and also impair delivery to the intramuscular level.”

Their imaging study of a subset of 250 children aged 2 months to 18 years concluded that weight and gender should guide needle selection for shoulder injections. Since girls have less muscle in the deltoid, they should generally receive shorter needles than boys (Pediatrics 2008 Aug. 11 [Epub doi:10.1542/peds.2008-0374]).

Mr. Lippert, of Tulane University, New Orleans, and Dr. Wall, of Cincinnati Children's Hospital Medical Center, used MRI and CT scans of the shoulders and thighs of the study population to determine the optimal needle lengths for boys and girls receiving intramuscular injections. All the children had normal shoulder and thigh anatomy; scans were collected as part of care they received at a large children's hospital.

The researchers used fat and muscle thickness, correlated to weight, age, and gender, to determine the safest needle lengths; they then compared their findings with the current recommendations by the Centers for Disease Control and Prevention. For thigh injections, the CDC recommends a 1-inch needle for infants aged 1–12 months and a 1- to 11/4-inch needle for toddlers aged 12–24 months. For shoulder injections, the CDC recommends a 5/8- to 1-inch needle in children aged 1–18 years.

Thigh scans were obtained for 100 patients aged 2 months to 6 years. Using the CDC recommendations, the researchers said, overpenetration would occur in 11% of those injected with a 1-inch needle and 39% of those injected with a 11/4-inch needle.

A total of 150 patients aged 12 months-18 years had scans of the shoulder. The risk for overpenetration with CDC-recommended needles was much greater for deltoid injections. Overpenetration would occur in 11% of children injected with a 5/8-inch needle, 55% of those injected with a 7/8-inch needle, and 61% of those injected with a 1-inch needle.

The investigators also compared muscle and fat thickness between boys and girls of different ages. On average, girls had more fat and muscle in the thighs than did boys of a similar age, and more fat but less muscle in the deltoid.

The researchers suggested that revisions of the CDC needle-length recommendations are in order. For thigh injections of children up to age 6 years, a 7/8- or 1-inch needle is the best option; it would underpenetrate only 2% and overpenetrate only 4% of these pediatric patients. “With these recommendations, 90% of all children who receive a vaccination in the thigh will be vaccinated into the intramuscular level, in comparison with the 64% intramuscular delivery rate if using the current CDC recommendations,” the researchers said.

Their recommendations for the male and female shoulder are more complicated, because of the variance in tissue thickness between the genders. The investigators recommended a 1/2-inch needle for girls weighing 70 kg or less and boys weighing 75 kg or less. A 5/8-inch needle should be used for girls weighing 70–115 kg and boys weighing 75–140 kg. A 7/8-inch or longer needle should be used for girls weighing more than 115 kg and boys weighing more than 140 kg.

“With these recommendations, 90% of both female and male patients would be vaccinated safely at the intramuscular level. Also, these recommendations ensure a 0% overpenetration rate for all patients,” they said.

Nonetheless, the researchers admitted their study had limitations: “Because of wide geographic variation in infant and child weight, it is difficult to make universal needle-length recommendations.”

Neither of the investigators reported any financial disclosures with regard to the study.

MADRID – Rasagiline may have a disease-modifying effect for patients with Parkinson's, delaying the progression of symptoms early in the disease at least in the short term, a new placebo-controlled trial has found.

The study was designed to assess the drug's neuroprotective potential with a delayed-start design. Patients initially randomized to rasagiline showed an immediate symptomatic benefit, while those on placebo declined. After 9 months, the placebo patients also began taking rasagiline. By the end of the second 9 months, they too had improved, although their symptoms remained significantly worse than those of the early-start group.

“We can say with certainty that early treatment provided benefits that couldn't be achieved with later introduction of the exact same drug,” Dr. C. Warren Olanow said at the annual meeting of the European Federation of Neurological Societies. “The question now is, why did this occur? Even though we have to speculate, and we don't have long-term data, we believe it must be related somehow to neuroprotection. It can't be completely explained by symptomatic improvement.”

Dr. Olanow, chairman of neurology at Mount Sinai School of Medicine, New York, was the principal investigator for the trial's North American arm. He and his colleague, Dr. Olivier Rascol of Toulouse (France) University Hospital, who supervised the European arm, jointly presented the newly released results.

The 18-month study included 1,176 patients with newly diagnosed Parkinson's disease (mean time since diagnosis, 4.5 months). Their mean age was 62 years; they all had very mild symptoms at the time of enrollment, with a mean total score of just 20 on the Unified Parkinson's Disease Rating Scale (UPDRS). Their mean modified Hoehn and Yahr score was 1.5.

Patients were randomized to placebo or to 1 or 2 mg rasagiline daily for the first 36 weeks. At 36 weeks, patients taking the drug continued receiving it, while patients taking placebo were randomized to either 1 or 2 mg of rasagiline. Everyone was followed for another 36 weeks. The investigators only presented the results of the 1-mg dose, saying that by the end of the trial, the 2-mg dose did not provide significant benefit over placebo.

Within 12 weeks of starting rasagiline, patients showed a mean 2-point decrease (improvement) on the UPDRS. Placebo patients showed a slight improvement as well, but it was not statistically significant. At 12 weeks both groups began to experience increases (worsening) of the UPDRS; however, the placebo group's score increased significantly more quickly and to a higher level. By 36 weeks, the mean score in placebo patients had increased by 3 points from baseline, while the active patients had lost their initial improvement and returned to their baseline score.

At this time point, all placebo patients were randomized to 1 or 2 mg rasagiline, while the early-start patients continued with their original regimen. By 45 weeks (9 weeks after initiating rasagiline) the delayed-start group showed a significant 1-point improvement in the UPDRS.

There was a very small improvement in the early-start group as well, which Dr. Rascol attributed to a placebo effect.

At week 45, both groups started to worsen. Although the UPDRS scores remained separated by about 2 points, the trajectory of worsening was virtually identical. By week 72–the end of the trial–the mean UPDRS in the early-start group was 2, while the mean score in the delayed-start group was 3.5–a significant difference.

If both groups had eventually reached the same level of clinical improvement, the trial would have shown that rasagiline works by improving symptoms, Dr. Rascol said. The fact that the delayed-start group improved, but never as much as the early-start group, indicates that something about early dosing slowed disease progression. “It showed that starting the treatment early improves the outcome of the patients in a way that cannot be simply explained by symptomatic benefit,” he said.

He acknowledged that the 2-point separation in scores, on a scale that reaches almost 200, was quite small. “However, some of these patients were only exposed to the drug for 9 months, and it can't be expected that the separation between the scores will be very large, especially since these patients have very early disease which progresses slowly.”

The follow-up period is enough to show that rasagiline provides very early benefit, Dr. Olanow said. Whether that benefit will remain constant, improve, or decline over time is still an unknown. “If I want to know what happens to these patients after 15 years on this drug, I'd have to follow them for 15 years, and these people don't have 15 years to sit around and wait. If we can conclude the benefit of this drug is real and can't be attributed to symptomatic effect then we can impute that it has a real disease-modifying effect. If you had Parkinson's, would you rather take a drug that shows initial disease slowing–without knowing what it does in 10 years–or not? That is the choice we face.”

Adverse events were mild and similar to those already documented. The most frequent were nausea and vomiting and orthostatic hypotension (4% each).

Rasagiline, which is already approved at the 1-mg dose for symptomatic treatment of Parkinson's, is a potent monoamine oxidase-B inhibitor. Its putative neuroprotective effects are not fully understood, Dr. Rascol said. “It may enhance the survival of the dopamine cell, or it may enhance the endogenous compensatory mechanisms the brain uses to cope with the loss of dopamine. Alternatively, rasagiline could reduce or avoid some undesirable adaptation of the brain involved in loss of dopamine.”

The trial was cosponsored by the drug's developer and manufacturer Teva Pharmaceutical Industries, headquartered in Israel, and Lundbeck A/S of Copenhagen. Both Dr. Olanow and Dr. Rascol are paid consultants for the companies.

MADRID – Rasagiline may have a disease-modifying effect for patients with Parkinson's, delaying the progression of symptoms early in the disease at least in the short term, a new placebo-controlled trial has found.

The study was designed to assess the drug's neuroprotective potential with a delayed-start design. Patients initially randomized to rasagiline showed an immediate symptomatic benefit, while those on placebo declined. After 9 months, the placebo patients also began taking rasagiline. By the end of the second 9 months, they too had improved, although their symptoms remained significantly worse than those of the early-start group.

“We can say with certainty that early treatment provided benefits that couldn't be achieved with later introduction of the exact same drug,” Dr. C. Warren Olanow said at the annual meeting of the European Federation of Neurological Societies. “The question now is, why did this occur? Even though we have to speculate, and we don't have long-term data, we believe it must be related somehow to neuroprotection. It can't be completely explained by symptomatic improvement.”

Dr. Olanow, chairman of neurology at Mount Sinai School of Medicine, New York, was the principal investigator for the trial's North American arm. He and his colleague, Dr. Olivier Rascol of Toulouse (France) University Hospital, who supervised the European arm, jointly presented the newly released results.

The 18-month study included 1,176 patients with newly diagnosed Parkinson's disease (mean time since diagnosis, 4.5 months). Their mean age was 62 years; they all had very mild symptoms at the time of enrollment, with a mean total score of just 20 on the Unified Parkinson's Disease Rating Scale (UPDRS). Their mean modified Hoehn and Yahr score was 1.5.

Patients were randomized to placebo or to 1 or 2 mg rasagiline daily for the first 36 weeks. At 36 weeks, patients taking the drug continued receiving it, while patients taking placebo were randomized to either 1 or 2 mg of rasagiline. Everyone was followed for another 36 weeks. The investigators only presented the results of the 1-mg dose, saying that by the end of the trial, the 2-mg dose did not provide significant benefit over placebo.

Within 12 weeks of starting rasagiline, patients showed a mean 2-point decrease (improvement) on the UPDRS. Placebo patients showed a slight improvement as well, but it was not statistically significant. At 12 weeks both groups began to experience increases (worsening) of the UPDRS; however, the placebo group's score increased significantly more quickly and to a higher level. By 36 weeks, the mean score in placebo patients had increased by 3 points from baseline, while the active patients had lost their initial improvement and returned to their baseline score.

At this time point, all placebo patients were randomized to 1 or 2 mg rasagiline, while the early-start patients continued with their original regimen. By 45 weeks (9 weeks after initiating rasagiline) the delayed-start group showed a significant 1-point improvement in the UPDRS.

There was a very small improvement in the early-start group as well, which Dr. Rascol attributed to a placebo effect.

At week 45, both groups started to worsen. Although the UPDRS scores remained separated by about 2 points, the trajectory of worsening was virtually identical. By week 72–the end of the trial–the mean UPDRS in the early-start group was 2, while the mean score in the delayed-start group was 3.5–a significant difference.

If both groups had eventually reached the same level of clinical improvement, the trial would have shown that rasagiline works by improving symptoms, Dr. Rascol said. The fact that the delayed-start group improved, but never as much as the early-start group, indicates that something about early dosing slowed disease progression. “It showed that starting the treatment early improves the outcome of the patients in a way that cannot be simply explained by symptomatic benefit,” he said.

He acknowledged that the 2-point separation in scores, on a scale that reaches almost 200, was quite small. “However, some of these patients were only exposed to the drug for 9 months, and it can't be expected that the separation between the scores will be very large, especially since these patients have very early disease which progresses slowly.”

The follow-up period is enough to show that rasagiline provides very early benefit, Dr. Olanow said. Whether that benefit will remain constant, improve, or decline over time is still an unknown. “If I want to know what happens to these patients after 15 years on this drug, I'd have to follow them for 15 years, and these people don't have 15 years to sit around and wait. If we can conclude the benefit of this drug is real and can't be attributed to symptomatic effect then we can impute that it has a real disease-modifying effect. If you had Parkinson's, would you rather take a drug that shows initial disease slowing–without knowing what it does in 10 years–or not? That is the choice we face.”

Adverse events were mild and similar to those already documented. The most frequent were nausea and vomiting and orthostatic hypotension (4% each).

Rasagiline, which is already approved at the 1-mg dose for symptomatic treatment of Parkinson's, is a potent monoamine oxidase-B inhibitor. Its putative neuroprotective effects are not fully understood, Dr. Rascol said. “It may enhance the survival of the dopamine cell, or it may enhance the endogenous compensatory mechanisms the brain uses to cope with the loss of dopamine. Alternatively, rasagiline could reduce or avoid some undesirable adaptation of the brain involved in loss of dopamine.”

The trial was cosponsored by the drug's developer and manufacturer Teva Pharmaceutical Industries, headquartered in Israel, and Lundbeck A/S of Copenhagen. Both Dr. Olanow and Dr. Rascol are paid consultants for the companies.

MADRID – Rasagiline may have a disease-modifying effect for patients with Parkinson's, delaying the progression of symptoms early in the disease at least in the short term, a new placebo-controlled trial has found.

The study was designed to assess the drug's neuroprotective potential with a delayed-start design. Patients initially randomized to rasagiline showed an immediate symptomatic benefit, while those on placebo declined. After 9 months, the placebo patients also began taking rasagiline. By the end of the second 9 months, they too had improved, although their symptoms remained significantly worse than those of the early-start group.

“We can say with certainty that early treatment provided benefits that couldn't be achieved with later introduction of the exact same drug,” Dr. C. Warren Olanow said at the annual meeting of the European Federation of Neurological Societies. “The question now is, why did this occur? Even though we have to speculate, and we don't have long-term data, we believe it must be related somehow to neuroprotection. It can't be completely explained by symptomatic improvement.”

Dr. Olanow, chairman of neurology at Mount Sinai School of Medicine, New York, was the principal investigator for the trial's North American arm. He and his colleague, Dr. Olivier Rascol of Toulouse (France) University Hospital, who supervised the European arm, jointly presented the newly released results.

The 18-month study included 1,176 patients with newly diagnosed Parkinson's disease (mean time since diagnosis, 4.5 months). Their mean age was 62 years; they all had very mild symptoms at the time of enrollment, with a mean total score of just 20 on the Unified Parkinson's Disease Rating Scale (UPDRS). Their mean modified Hoehn and Yahr score was 1.5.

Patients were randomized to placebo or to 1 or 2 mg rasagiline daily for the first 36 weeks. At 36 weeks, patients taking the drug continued receiving it, while patients taking placebo were randomized to either 1 or 2 mg of rasagiline. Everyone was followed for another 36 weeks. The investigators only presented the results of the 1-mg dose, saying that by the end of the trial, the 2-mg dose did not provide significant benefit over placebo.

Within 12 weeks of starting rasagiline, patients showed a mean 2-point decrease (improvement) on the UPDRS. Placebo patients showed a slight improvement as well, but it was not statistically significant. At 12 weeks both groups began to experience increases (worsening) of the UPDRS; however, the placebo group's score increased significantly more quickly and to a higher level. By 36 weeks, the mean score in placebo patients had increased by 3 points from baseline, while the active patients had lost their initial improvement and returned to their baseline score.

At this time point, all placebo patients were randomized to 1 or 2 mg rasagiline, while the early-start patients continued with their original regimen. By 45 weeks (9 weeks after initiating rasagiline) the delayed-start group showed a significant 1-point improvement in the UPDRS.

There was a very small improvement in the early-start group as well, which Dr. Rascol attributed to a placebo effect.

At week 45, both groups started to worsen. Although the UPDRS scores remained separated by about 2 points, the trajectory of worsening was virtually identical. By week 72–the end of the trial–the mean UPDRS in the early-start group was 2, while the mean score in the delayed-start group was 3.5–a significant difference.

If both groups had eventually reached the same level of clinical improvement, the trial would have shown that rasagiline works by improving symptoms, Dr. Rascol said. The fact that the delayed-start group improved, but never as much as the early-start group, indicates that something about early dosing slowed disease progression. “It showed that starting the treatment early improves the outcome of the patients in a way that cannot be simply explained by symptomatic benefit,” he said.

He acknowledged that the 2-point separation in scores, on a scale that reaches almost 200, was quite small. “However, some of these patients were only exposed to the drug for 9 months, and it can't be expected that the separation between the scores will be very large, especially since these patients have very early disease which progresses slowly.”

The follow-up period is enough to show that rasagiline provides very early benefit, Dr. Olanow said. Whether that benefit will remain constant, improve, or decline over time is still an unknown. “If I want to know what happens to these patients after 15 years on this drug, I'd have to follow them for 15 years, and these people don't have 15 years to sit around and wait. If we can conclude the benefit of this drug is real and can't be attributed to symptomatic effect then we can impute that it has a real disease-modifying effect. If you had Parkinson's, would you rather take a drug that shows initial disease slowing–without knowing what it does in 10 years–or not? That is the choice we face.”

Adverse events were mild and similar to those already documented. The most frequent were nausea and vomiting and orthostatic hypotension (4% each).

Rasagiline, which is already approved at the 1-mg dose for symptomatic treatment of Parkinson's, is a potent monoamine oxidase-B inhibitor. Its putative neuroprotective effects are not fully understood, Dr. Rascol said. “It may enhance the survival of the dopamine cell, or it may enhance the endogenous compensatory mechanisms the brain uses to cope with the loss of dopamine. Alternatively, rasagiline could reduce or avoid some undesirable adaptation of the brain involved in loss of dopamine.”

The trial was cosponsored by the drug's developer and manufacturer Teva Pharmaceutical Industries, headquartered in Israel, and Lundbeck A/S of Copenhagen. Both Dr. Olanow and Dr. Rascol are paid consultants for the companies.

BARCELONA – Pregabalin reduced alcohol craving scores just as effectively as did naltrexone and was associated with a longer period of alcohol abstinence, especially in patients with a comorbid psychiatric disorder, according to the first randomized comparison trial of the two drugs.

Pregabalin also positively affected anxiety, hostility, and psychoticism–additional benefits for patients with a combination of alcohol and psychiatric problems, Dr. Giovanni Martinotti reported in a poster at the annual congress of the European College of Neuropsychopharmacology.

“The mechanisms involved in the efficacy of pregabalin could be less related to craving for alcohol and more connected to the treatment of these comorbid psychiatric disorders,” wrote Dr. Martinotti of Catholic University's treatment unit for alcoholism and multiple drug abuse, Rome.

His 16-week study included 59 alcohol-dependent patients, with a mean of 15 years' alcohol addiction; their mean daily alcohol consumption was 8 drinks. These patients (mean age 40 years) were detoxified over 5-10 days, and then randomized to either naltrexone 50 mg daily (28) or pregabalin at an average dose of 275 mg daily (31).

No significant differences in craving scores were found over the treatment period. More patients taking pregabalin remained alcohol free for the entire study (15 vs. 11) and, although this was not statistically significant, a survival curve showed that those taking pregabalin remained abstinent for a significantly longer period. There were no significant differences in posttreatment relapses.

Patients taking pregabalin showed significantly lower withdrawal scores than did those taking naltrexone, with the difference apparent in as little as 2 weeks.

Psychiatric symptoms were assessed with the Symptom Checklist 90-Revised. By this measure, those taking pregabalin showed significant decreases in the general “positive symptoms total” index, as well as in the subscales for phobic anxiety, hostility, and psychoticism, he wrote.

Among those patients with a dual diagnosis of alcohol-use disorder and a psychiatric disorder, pregabalin was associated with a significantly higher total abstinence score than was naltrexone (50% vs. 15%).

“If it could be confirmed in placebo-controlled trials that pregabalin is efficacious in decreasing alcohol use, lessening craving, and attenuating psychopathological symptom severity, we will have gained a valuable agent for the treatment of alcohol-dependent subjects,” Dr. Martinotti wrote.

Dr. Martinotti said he had no disclosures to make regarding the study.

BARCELONA – Pregabalin reduced alcohol craving scores just as effectively as did naltrexone and was associated with a longer period of alcohol abstinence, especially in patients with a comorbid psychiatric disorder, according to the first randomized comparison trial of the two drugs.

Pregabalin also positively affected anxiety, hostility, and psychoticism–additional benefits for patients with a combination of alcohol and psychiatric problems, Dr. Giovanni Martinotti reported in a poster at the annual congress of the European College of Neuropsychopharmacology.

“The mechanisms involved in the efficacy of pregabalin could be less related to craving for alcohol and more connected to the treatment of these comorbid psychiatric disorders,” wrote Dr. Martinotti of Catholic University's treatment unit for alcoholism and multiple drug abuse, Rome.

His 16-week study included 59 alcohol-dependent patients, with a mean of 15 years' alcohol addiction; their mean daily alcohol consumption was 8 drinks. These patients (mean age 40 years) were detoxified over 5-10 days, and then randomized to either naltrexone 50 mg daily (28) or pregabalin at an average dose of 275 mg daily (31).

No significant differences in craving scores were found over the treatment period. More patients taking pregabalin remained alcohol free for the entire study (15 vs. 11) and, although this was not statistically significant, a survival curve showed that those taking pregabalin remained abstinent for a significantly longer period. There were no significant differences in posttreatment relapses.

Patients taking pregabalin showed significantly lower withdrawal scores than did those taking naltrexone, with the difference apparent in as little as 2 weeks.

Psychiatric symptoms were assessed with the Symptom Checklist 90-Revised. By this measure, those taking pregabalin showed significant decreases in the general “positive symptoms total” index, as well as in the subscales for phobic anxiety, hostility, and psychoticism, he wrote.

Among those patients with a dual diagnosis of alcohol-use disorder and a psychiatric disorder, pregabalin was associated with a significantly higher total abstinence score than was naltrexone (50% vs. 15%).

“If it could be confirmed in placebo-controlled trials that pregabalin is efficacious in decreasing alcohol use, lessening craving, and attenuating psychopathological symptom severity, we will have gained a valuable agent for the treatment of alcohol-dependent subjects,” Dr. Martinotti wrote.

Dr. Martinotti said he had no disclosures to make regarding the study.

BARCELONA – Pregabalin reduced alcohol craving scores just as effectively as did naltrexone and was associated with a longer period of alcohol abstinence, especially in patients with a comorbid psychiatric disorder, according to the first randomized comparison trial of the two drugs.

Pregabalin also positively affected anxiety, hostility, and psychoticism–additional benefits for patients with a combination of alcohol and psychiatric problems, Dr. Giovanni Martinotti reported in a poster at the annual congress of the European College of Neuropsychopharmacology.

“The mechanisms involved in the efficacy of pregabalin could be less related to craving for alcohol and more connected to the treatment of these comorbid psychiatric disorders,” wrote Dr. Martinotti of Catholic University's treatment unit for alcoholism and multiple drug abuse, Rome.

His 16-week study included 59 alcohol-dependent patients, with a mean of 15 years' alcohol addiction; their mean daily alcohol consumption was 8 drinks. These patients (mean age 40 years) were detoxified over 5-10 days, and then randomized to either naltrexone 50 mg daily (28) or pregabalin at an average dose of 275 mg daily (31).

No significant differences in craving scores were found over the treatment period. More patients taking pregabalin remained alcohol free for the entire study (15 vs. 11) and, although this was not statistically significant, a survival curve showed that those taking pregabalin remained abstinent for a significantly longer period. There were no significant differences in posttreatment relapses.

Patients taking pregabalin showed significantly lower withdrawal scores than did those taking naltrexone, with the difference apparent in as little as 2 weeks.

Psychiatric symptoms were assessed with the Symptom Checklist 90-Revised. By this measure, those taking pregabalin showed significant decreases in the general “positive symptoms total” index, as well as in the subscales for phobic anxiety, hostility, and psychoticism, he wrote.

Among those patients with a dual diagnosis of alcohol-use disorder and a psychiatric disorder, pregabalin was associated with a significantly higher total abstinence score than was naltrexone (50% vs. 15%).

“If it could be confirmed in placebo-controlled trials that pregabalin is efficacious in decreasing alcohol use, lessening craving, and attenuating psychopathological symptom severity, we will have gained a valuable agent for the treatment of alcohol-dependent subjects,” Dr. Martinotti wrote.

Dr. Martinotti said he had no disclosures to make regarding the study.

CHICAGO – A postmortem analysis of subjects with both Alzheimer's disease and diabetes found up to 80% fewer amyloid beta plaques in the brains of those who took both insulin and oral diabetic medication while alive.

The finding might shed some light on a discrepancy that has puzzled Alzheimer's researchers: Epidemiologic studies confirm a significantly increased risk of Alzheimer's and other dementias among subjects with diabetes, but their brains generally appear less physically ravaged by the disease, Michal Schnaider Beeri, Ph.D., said at the International Conference on Alzheimer's Disease.

“It appears that medication might be one explanation for this apparent discrepancy between epidemiologic and neuropathology studies,” said Dr. Beeri of the Mount Sinai School of Medicine, New York. “It also suggests that diabetes medications may beneficially influence neurologic pathways involving Aβ [amyloid beta] processing and Aβ-related brain lesions.”

The study involved 148 brains from the Mount Sinai School of Medicine Brain Bank. All were from subjects with Alzheimer's disease, half of whom also had diabetes. The subjects were matched for age (mean age 81 years), sex (57% female), and dementia severity (mean clinical dementia rating score 2.4).

Dr. Beeri and her colleagues divided the subjects into categories according to the use of diabetic medications. Of the 124 subjects with diabetes, 49 were taking insulin only, 28 were taking oral diabetes medications only, 18 were taking a combination of agents, and 29 were on no medications. All of these groups were compared against one another, and against the subjects without diabetes.

No significant associations were seen between medication and the presence of tau neurofibrillary tangles. But they found a very strong interaction between medication and Aβ42 plaques in the entorhinal cortex, hippocampus, and amygdala.

Plaque presence was rated from 0 (none) to 2 (severe). Subjects without diabetes had a rating of about 1.5, as did those with diabetes who were taking only oral medications. Subjects with diabetes who took no diabetes medications had a rating of about 1.25. Subjects taking insulin had a lower, but not significantly lower, plaque rating (1, considered sparse), compared with those without diabetes, those with diabetes who were not taking medications, and those who took only oral agents, Dr. Beeri said.

The largest differences were found between subjects on combination therapy (insulin and oral medications) and those who took only oral agents and subjects without diabetes. Combination therapy subjects had a plaque rating of about 0.25, or 80% lower than in the subjects in the other two groups. Those who had taken combination therapy also had far fewer plaques than did those who took no medications, as well as those who took only insulin, she said.

“The results of this study suggest that combination of insulin with other diabetes medication is associated with a substantial reduction in brain neuritic plaque density consistent with the effects of both on the neurobiology of insulin,” Dr. Beeri said at the meeting, presented by the Alzheimer's Association. “Insulin and insulin sensitizers (oral hypoglycemics) are designed to target organs at the periphery, but they also seem to have also an effect on the brain. This suggests the possibility of therapeutic targeting of insulin signaling pathways of the brain for the reduction of Aβ-associated neuropathology of Alzheimer's.”

Brains exposed to both insulin and oral hypoglycemic drugs showed fewer amyloid plaques (white arrows) than those of without diabetes, but no fewer neurofibrillary tangles (black arrows). COURTESY DR. VAHRAM HAROUTUNIAN

CHICAGO – A postmortem analysis of subjects with both Alzheimer's disease and diabetes found up to 80% fewer amyloid beta plaques in the brains of those who took both insulin and oral diabetic medication while alive.

The finding might shed some light on a discrepancy that has puzzled Alzheimer's researchers: Epidemiologic studies confirm a significantly increased risk of Alzheimer's and other dementias among subjects with diabetes, but their brains generally appear less physically ravaged by the disease, Michal Schnaider Beeri, Ph.D., said at the International Conference on Alzheimer's Disease.

“It appears that medication might be one explanation for this apparent discrepancy between epidemiologic and neuropathology studies,” said Dr. Beeri of the Mount Sinai School of Medicine, New York. “It also suggests that diabetes medications may beneficially influence neurologic pathways involving Aβ [amyloid beta] processing and Aβ-related brain lesions.”

The study involved 148 brains from the Mount Sinai School of Medicine Brain Bank. All were from subjects with Alzheimer's disease, half of whom also had diabetes. The subjects were matched for age (mean age 81 years), sex (57% female), and dementia severity (mean clinical dementia rating score 2.4).

Dr. Beeri and her colleagues divided the subjects into categories according to the use of diabetic medications. Of the 124 subjects with diabetes, 49 were taking insulin only, 28 were taking oral diabetes medications only, 18 were taking a combination of agents, and 29 were on no medications. All of these groups were compared against one another, and against the subjects without diabetes.

No significant associations were seen between medication and the presence of tau neurofibrillary tangles. But they found a very strong interaction between medication and Aβ42 plaques in the entorhinal cortex, hippocampus, and amygdala.

Plaque presence was rated from 0 (none) to 2 (severe). Subjects without diabetes had a rating of about 1.5, as did those with diabetes who were taking only oral medications. Subjects with diabetes who took no diabetes medications had a rating of about 1.25. Subjects taking insulin had a lower, but not significantly lower, plaque rating (1, considered sparse), compared with those without diabetes, those with diabetes who were not taking medications, and those who took only oral agents, Dr. Beeri said.

The largest differences were found between subjects on combination therapy (insulin and oral medications) and those who took only oral agents and subjects without diabetes. Combination therapy subjects had a plaque rating of about 0.25, or 80% lower than in the subjects in the other two groups. Those who had taken combination therapy also had far fewer plaques than did those who took no medications, as well as those who took only insulin, she said.

“The results of this study suggest that combination of insulin with other diabetes medication is associated with a substantial reduction in brain neuritic plaque density consistent with the effects of both on the neurobiology of insulin,” Dr. Beeri said at the meeting, presented by the Alzheimer's Association. “Insulin and insulin sensitizers (oral hypoglycemics) are designed to target organs at the periphery, but they also seem to have also an effect on the brain. This suggests the possibility of therapeutic targeting of insulin signaling pathways of the brain for the reduction of Aβ-associated neuropathology of Alzheimer's.”

Brains exposed to both insulin and oral hypoglycemic drugs showed fewer amyloid plaques (white arrows) than those of without diabetes, but no fewer neurofibrillary tangles (black arrows). COURTESY DR. VAHRAM HAROUTUNIAN

CHICAGO – A postmortem analysis of subjects with both Alzheimer's disease and diabetes found up to 80% fewer amyloid beta plaques in the brains of those who took both insulin and oral diabetic medication while alive.

The finding might shed some light on a discrepancy that has puzzled Alzheimer's researchers: Epidemiologic studies confirm a significantly increased risk of Alzheimer's and other dementias among subjects with diabetes, but their brains generally appear less physically ravaged by the disease, Michal Schnaider Beeri, Ph.D., said at the International Conference on Alzheimer's Disease.

“It appears that medication might be one explanation for this apparent discrepancy between epidemiologic and neuropathology studies,” said Dr. Beeri of the Mount Sinai School of Medicine, New York. “It also suggests that diabetes medications may beneficially influence neurologic pathways involving Aβ [amyloid beta] processing and Aβ-related brain lesions.”

The study involved 148 brains from the Mount Sinai School of Medicine Brain Bank. All were from subjects with Alzheimer's disease, half of whom also had diabetes. The subjects were matched for age (mean age 81 years), sex (57% female), and dementia severity (mean clinical dementia rating score 2.4).

Dr. Beeri and her colleagues divided the subjects into categories according to the use of diabetic medications. Of the 124 subjects with diabetes, 49 were taking insulin only, 28 were taking oral diabetes medications only, 18 were taking a combination of agents, and 29 were on no medications. All of these groups were compared against one another, and against the subjects without diabetes.

No significant associations were seen between medication and the presence of tau neurofibrillary tangles. But they found a very strong interaction between medication and Aβ42 plaques in the entorhinal cortex, hippocampus, and amygdala.

Plaque presence was rated from 0 (none) to 2 (severe). Subjects without diabetes had a rating of about 1.5, as did those with diabetes who were taking only oral medications. Subjects with diabetes who took no diabetes medications had a rating of about 1.25. Subjects taking insulin had a lower, but not significantly lower, plaque rating (1, considered sparse), compared with those without diabetes, those with diabetes who were not taking medications, and those who took only oral agents, Dr. Beeri said.

The largest differences were found between subjects on combination therapy (insulin and oral medications) and those who took only oral agents and subjects without diabetes. Combination therapy subjects had a plaque rating of about 0.25, or 80% lower than in the subjects in the other two groups. Those who had taken combination therapy also had far fewer plaques than did those who took no medications, as well as those who took only insulin, she said.

“The results of this study suggest that combination of insulin with other diabetes medication is associated with a substantial reduction in brain neuritic plaque density consistent with the effects of both on the neurobiology of insulin,” Dr. Beeri said at the meeting, presented by the Alzheimer's Association. “Insulin and insulin sensitizers (oral hypoglycemics) are designed to target organs at the periphery, but they also seem to have also an effect on the brain. This suggests the possibility of therapeutic targeting of insulin signaling pathways of the brain for the reduction of Aβ-associated neuropathology of Alzheimer's.”

Brains exposed to both insulin and oral hypoglycemic drugs showed fewer amyloid plaques (white arrows) than those of without diabetes, but no fewer neurofibrillary tangles (black arrows). COURTESY DR. VAHRAM HAROUTUNIAN

BARCELONA – Patients with childhood-onset depression who have a variant in the gene that codes for brain-derived neurotrophic factor also show unique variations in their electroencephalograms, opening the door to a possible screening tool for children deemed at risk for these psychiatric disorders.

Although the evidence is preliminary, “We're getting pretty good data showing that people who are at risk of early-onset depression can be identified by a combination of EEG and genetic information,” Dr. James Kennedy said at the annual congress of the European College of Neuropsychopharmacology.

“The gene that codes for brain-derived neurotrophic factor (BDNF) has been studied for about 15 years,” Dr. Kennedy said. “Emerging evidence indicates that this protein, which is reduced in depression, rises in the bloodstream after treatment with antidepressants or electroconvulsive therapy.” Postmortem studies of suicide completers have shown that the protein is significantly decreased, compared with controls, he said.

As head of psychiatric neurogenetics at the Centre for Addiction and Mental Health, Toronto, Dr. Kennedy has been one of the key players in proving a link between the genetic variant and early-onset depression. Working with Maria Kovacs, Ph.D., of the University of Pittsburgh, Dr. Kennedy has confirmed this link in two large data sets–a group of 191 patients (children and adults) in the United States, with up to 25 years of follow-up, and a cohort of 258 child patients in Hungary.

Three variants are possible, Dr. Kennedy said: The gene can be homozygous for valine, homozygous for methionine, or contain both proteins. In both the Pittsburgh and Hungarian cohorts, the valine/methionine combination was significantly more common among cases than controls.

“In the Hungarian sample, we also looked at how the variants were transmitted from parents to children,” Dr. Kennedy said. “The valine version was transmitted 100 times in the families of depressed children, while the methionine version as transmitted only 59 times. This is a highly significant indication that the valine version is creating a higher risk for childhood-onset depression.”

His most recent study looked at EEG patterns in 187 adults with a history of childhood-onset depression and 93 healthy controls. Dr. Kennedy expected to find changes in the leads recording hippocampal activity, because BDNF is highly expressed in that area. Instead, he found changes in the theta waves. The changes were not seen in controls and occurred significantly more often in cases with the valine/methionine polymorphism.

“This suggests that that the functional BDNF variant affects EEG symmetry in the parietal brain regions in individuals with childhood-onset major depression,” Dr. Kennedy and his colleagues wrote in the study (Neuromuscular Medicine 2008; doi:10.1007/s12017-008-8038-x).

BARCELONA – Patients with childhood-onset depression who have a variant in the gene that codes for brain-derived neurotrophic factor also show unique variations in their electroencephalograms, opening the door to a possible screening tool for children deemed at risk for these psychiatric disorders.

Although the evidence is preliminary, “We're getting pretty good data showing that people who are at risk of early-onset depression can be identified by a combination of EEG and genetic information,” Dr. James Kennedy said at the annual congress of the European College of Neuropsychopharmacology.

“The gene that codes for brain-derived neurotrophic factor (BDNF) has been studied for about 15 years,” Dr. Kennedy said. “Emerging evidence indicates that this protein, which is reduced in depression, rises in the bloodstream after treatment with antidepressants or electroconvulsive therapy.” Postmortem studies of suicide completers have shown that the protein is significantly decreased, compared with controls, he said.

As head of psychiatric neurogenetics at the Centre for Addiction and Mental Health, Toronto, Dr. Kennedy has been one of the key players in proving a link between the genetic variant and early-onset depression. Working with Maria Kovacs, Ph.D., of the University of Pittsburgh, Dr. Kennedy has confirmed this link in two large data sets–a group of 191 patients (children and adults) in the United States, with up to 25 years of follow-up, and a cohort of 258 child patients in Hungary.

Three variants are possible, Dr. Kennedy said: The gene can be homozygous for valine, homozygous for methionine, or contain both proteins. In both the Pittsburgh and Hungarian cohorts, the valine/methionine combination was significantly more common among cases than controls.

“In the Hungarian sample, we also looked at how the variants were transmitted from parents to children,” Dr. Kennedy said. “The valine version was transmitted 100 times in the families of depressed children, while the methionine version as transmitted only 59 times. This is a highly significant indication that the valine version is creating a higher risk for childhood-onset depression.”

His most recent study looked at EEG patterns in 187 adults with a history of childhood-onset depression and 93 healthy controls. Dr. Kennedy expected to find changes in the leads recording hippocampal activity, because BDNF is highly expressed in that area. Instead, he found changes in the theta waves. The changes were not seen in controls and occurred significantly more often in cases with the valine/methionine polymorphism.

“This suggests that that the functional BDNF variant affects EEG symmetry in the parietal brain regions in individuals with childhood-onset major depression,” Dr. Kennedy and his colleagues wrote in the study (Neuromuscular Medicine 2008; doi:10.1007/s12017-008-8038-x).

BARCELONA – Patients with childhood-onset depression who have a variant in the gene that codes for brain-derived neurotrophic factor also show unique variations in their electroencephalograms, opening the door to a possible screening tool for children deemed at risk for these psychiatric disorders.

Although the evidence is preliminary, “We're getting pretty good data showing that people who are at risk of early-onset depression can be identified by a combination of EEG and genetic information,” Dr. James Kennedy said at the annual congress of the European College of Neuropsychopharmacology.

“The gene that codes for brain-derived neurotrophic factor (BDNF) has been studied for about 15 years,” Dr. Kennedy said. “Emerging evidence indicates that this protein, which is reduced in depression, rises in the bloodstream after treatment with antidepressants or electroconvulsive therapy.” Postmortem studies of suicide completers have shown that the protein is significantly decreased, compared with controls, he said.

As head of psychiatric neurogenetics at the Centre for Addiction and Mental Health, Toronto, Dr. Kennedy has been one of the key players in proving a link between the genetic variant and early-onset depression. Working with Maria Kovacs, Ph.D., of the University of Pittsburgh, Dr. Kennedy has confirmed this link in two large data sets–a group of 191 patients (children and adults) in the United States, with up to 25 years of follow-up, and a cohort of 258 child patients in Hungary.

Three variants are possible, Dr. Kennedy said: The gene can be homozygous for valine, homozygous for methionine, or contain both proteins. In both the Pittsburgh and Hungarian cohorts, the valine/methionine combination was significantly more common among cases than controls.

“In the Hungarian sample, we also looked at how the variants were transmitted from parents to children,” Dr. Kennedy said. “The valine version was transmitted 100 times in the families of depressed children, while the methionine version as transmitted only 59 times. This is a highly significant indication that the valine version is creating a higher risk for childhood-onset depression.”

His most recent study looked at EEG patterns in 187 adults with a history of childhood-onset depression and 93 healthy controls. Dr. Kennedy expected to find changes in the leads recording hippocampal activity, because BDNF is highly expressed in that area. Instead, he found changes in the theta waves. The changes were not seen in controls and occurred significantly more often in cases with the valine/methionine polymorphism.

“This suggests that that the functional BDNF variant affects EEG symmetry in the parietal brain regions in individuals with childhood-onset major depression,” Dr. Kennedy and his colleagues wrote in the study (Neuromuscular Medicine 2008; doi:10.1007/s12017-008-8038-x).

SAN FRANCISCO — The increased use of β-blockers may be contributing to a proportionate increase in pulseless electrical activity in cardiac arrest, Dr. Scott Youngquist reported in a poster presented at the 12th International Conference on Emergency Medicine.

His retrospective study concluded that patients whose presenting rhythm was pulseless electrical activity (PEA) were five times as likely to be taking a β-blocker as those presenting with ventricular fibrillation—a finding that raises questions about the presumed causes and treatment of PEA arrest.

“We know that β-blockers prevent patients from going into ventricular fibrillation,” Dr. Youngquist said in an interview. “But patients who have [ventricular fibrillation] as a presenting rhythm in cardiac arrest can often be shocked back into a normal rhythm. Unfortunately, there's often not much you can do for someone in PEA. The outcome is usually very poor. Furthermore, β-blockade may thwart the one medication we have: epinephrine.”

Both β-blocker use and presenting PEA in cardiac arrest have increased over the past 20 years, said Dr. Youngquist, now at the University of Utah, Salt Lake City. β-Blockers are now the fourth most-commonly prescribed medication for hypertension, and about 60% of post-MI patients at all hospitals are discharged on β-blockers.

At the same time, however, PEA has gone up as well. In the 1980s and 1990s, ventricular fibrillation (VF) accounted for up to 60% of all out-of-hospital cardiac arrests in the United States. Now, VF accounts for only about 25% of arrests, Dr. Youngquist said, and the reason is unclear.

Dr. Youngquist and his colleagues theorized that the temporal association between the two trends might be more than coincidental. They performed a chart review of 478 out-of-hospital cardiac arrests that presented to Harbor-UCLA Medical Center, Los Angeles, from 2001 to 2006. Most of the patients (59%) were male; the median age was 70 years.

The researchers excluded the records of patients for whom β-blocker status was unknown and for those who arrived in asystole, leaving them with a final cohort of 179; 100 (56%) of these presented with PEA and 79 (44%) with VF. Overall, 65 (36%) were taking β-blockers and 114 (64%) were not.

Significantly more patients presenting with PEA than VF were on β-blockers at the time of their arrest (49% vs. 20%). In a univariate analysis, patients taking a β-blocker were almost four times as likely to present with PEA as they were to present with ventricular fibrillation. After adjustment for misclassification of β-blocker use, confounding, and random error, the odds ratio rose to five.

Although the results are interesting, they raise as many questions as they answer. However, “if larger studies confirm this, they may suggest that we need to change the way we treat the patient in PEA,” Dr. Youngquist said.

For example, glucagon is typically used to reverse a β-blocker overdose, he added, and there are some animal studies that suggest glucagon also may be useful in treating PEA.

SAN FRANCISCO — The increased use of β-blockers may be contributing to a proportionate increase in pulseless electrical activity in cardiac arrest, Dr. Scott Youngquist reported in a poster presented at the 12th International Conference on Emergency Medicine.

His retrospective study concluded that patients whose presenting rhythm was pulseless electrical activity (PEA) were five times as likely to be taking a β-blocker as those presenting with ventricular fibrillation—a finding that raises questions about the presumed causes and treatment of PEA arrest.

“We know that β-blockers prevent patients from going into ventricular fibrillation,” Dr. Youngquist said in an interview. “But patients who have [ventricular fibrillation] as a presenting rhythm in cardiac arrest can often be shocked back into a normal rhythm. Unfortunately, there's often not much you can do for someone in PEA. The outcome is usually very poor. Furthermore, β-blockade may thwart the one medication we have: epinephrine.”

Both β-blocker use and presenting PEA in cardiac arrest have increased over the past 20 years, said Dr. Youngquist, now at the University of Utah, Salt Lake City. β-Blockers are now the fourth most-commonly prescribed medication for hypertension, and about 60% of post-MI patients at all hospitals are discharged on β-blockers.

At the same time, however, PEA has gone up as well. In the 1980s and 1990s, ventricular fibrillation (VF) accounted for up to 60% of all out-of-hospital cardiac arrests in the United States. Now, VF accounts for only about 25% of arrests, Dr. Youngquist said, and the reason is unclear.

Dr. Youngquist and his colleagues theorized that the temporal association between the two trends might be more than coincidental. They performed a chart review of 478 out-of-hospital cardiac arrests that presented to Harbor-UCLA Medical Center, Los Angeles, from 2001 to 2006. Most of the patients (59%) were male; the median age was 70 years.

The researchers excluded the records of patients for whom β-blocker status was unknown and for those who arrived in asystole, leaving them with a final cohort of 179; 100 (56%) of these presented with PEA and 79 (44%) with VF. Overall, 65 (36%) were taking β-blockers and 114 (64%) were not.

Significantly more patients presenting with PEA than VF were on β-blockers at the time of their arrest (49% vs. 20%). In a univariate analysis, patients taking a β-blocker were almost four times as likely to present with PEA as they were to present with ventricular fibrillation. After adjustment for misclassification of β-blocker use, confounding, and random error, the odds ratio rose to five.

Although the results are interesting, they raise as many questions as they answer. However, “if larger studies confirm this, they may suggest that we need to change the way we treat the patient in PEA,” Dr. Youngquist said.

For example, glucagon is typically used to reverse a β-blocker overdose, he added, and there are some animal studies that suggest glucagon also may be useful in treating PEA.

SAN FRANCISCO — The increased use of β-blockers may be contributing to a proportionate increase in pulseless electrical activity in cardiac arrest, Dr. Scott Youngquist reported in a poster presented at the 12th International Conference on Emergency Medicine.

His retrospective study concluded that patients whose presenting rhythm was pulseless electrical activity (PEA) were five times as likely to be taking a β-blocker as those presenting with ventricular fibrillation—a finding that raises questions about the presumed causes and treatment of PEA arrest.

“We know that β-blockers prevent patients from going into ventricular fibrillation,” Dr. Youngquist said in an interview. “But patients who have [ventricular fibrillation] as a presenting rhythm in cardiac arrest can often be shocked back into a normal rhythm. Unfortunately, there's often not much you can do for someone in PEA. The outcome is usually very poor. Furthermore, β-blockade may thwart the one medication we have: epinephrine.”

Both β-blocker use and presenting PEA in cardiac arrest have increased over the past 20 years, said Dr. Youngquist, now at the University of Utah, Salt Lake City. β-Blockers are now the fourth most-commonly prescribed medication for hypertension, and about 60% of post-MI patients at all hospitals are discharged on β-blockers.

At the same time, however, PEA has gone up as well. In the 1980s and 1990s, ventricular fibrillation (VF) accounted for up to 60% of all out-of-hospital cardiac arrests in the United States. Now, VF accounts for only about 25% of arrests, Dr. Youngquist said, and the reason is unclear.

Dr. Youngquist and his colleagues theorized that the temporal association between the two trends might be more than coincidental. They performed a chart review of 478 out-of-hospital cardiac arrests that presented to Harbor-UCLA Medical Center, Los Angeles, from 2001 to 2006. Most of the patients (59%) were male; the median age was 70 years.

The researchers excluded the records of patients for whom β-blocker status was unknown and for those who arrived in asystole, leaving them with a final cohort of 179; 100 (56%) of these presented with PEA and 79 (44%) with VF. Overall, 65 (36%) were taking β-blockers and 114 (64%) were not.

Significantly more patients presenting with PEA than VF were on β-blockers at the time of their arrest (49% vs. 20%). In a univariate analysis, patients taking a β-blocker were almost four times as likely to present with PEA as they were to present with ventricular fibrillation. After adjustment for misclassification of β-blocker use, confounding, and random error, the odds ratio rose to five.

Although the results are interesting, they raise as many questions as they answer. However, “if larger studies confirm this, they may suggest that we need to change the way we treat the patient in PEA,” Dr. Youngquist said.

For example, glucagon is typically used to reverse a β-blocker overdose, he added, and there are some animal studies that suggest glucagon also may be useful in treating PEA.

Topiramate is associated with a significantly increased risk of major congenital malformations, whether given as monotherapy or as part of a polytherapy antiepileptic regimen, Dr. Stephen Hunt and his colleagues have reported.

Although the associations were strong—an 11-fold increase in the risk of oral clefts and a 14-fold increase in the risk of hypospadias, compared with background rates in the United Kingdom—the confidence intervals surrounding them were wide, noted Dr. Hunt of the Royal Group of Hospitals, Belfast, Northern Ireland. Therefore, the data “should be interpreted with caution,” he and his colleagues wrote (Neurology 2008;71:272–6).

The U.K. registry is one of three national registries that track pregnancy outcomes in women taking antiepileptic drugs. Neither of the others—a North American and an Australian registry—has reported an association between topiramate and birth defects, said Dr. Kimford Meador, the Melvin Greer Professor of Neurology at the University of Florida, Gainesville.

“The U.K. data are the first data on topiramate risks during pregnancy,” Dr. Meador said in an interview. “The data suggest an association of increased malformations with topiramate exposure during pregnancy. However, the sample is small and the confidence intervals are large, so no definitive conclusion can be drawn.”

Because the results are preliminary, clinicians and their patients should be cautious when they consider medication changes, said Dr. Martha Morrell, director of the Columbia Comprehensive Epilepsy Center, New York.

“The first objective of treatment is to control seizures,” she said in an interview. “Seizures during pregnancy place the mother at risk for injury and may also pose risk for the fetus. These results will be compared to data coming from other pregnancy registries as they become available. In the meantime, women taking topiramate should not make any adjustment in medications without consulting a physician.”

The analysis was drawn from the U.K. Epilepsy and Pregnancy Register, a prospective observational registry and follow-up study that tracks pregnancy outcomes among women in the United Kingdom who are taking antiepileptic medications. The present study included outcomes for 203 pregnancies with exposure to topiramate during the first trimester. Most of the women (133) were taking the drug as part of a polytherapy regimen (mean topiramate dose, 299 mg/day); the rest were on topiramate monotherapy (mean dose 245 mg/day). Of all these pregnancies, 178 (88%) resulted in a live birth; there were a total of 31 congenital anomalies among these infants (16 major and 15 minor).

Among women on monotherapy, there were eight infants born with anomalies, three of which were considered major. Two infants had a cleft lip/palate, and one had hypospadias. The average daily dose of topiramate for the mothers of these infants was 400 mg/day, compared with the average 238-mg dose among women on monotherapy who had normal pregnancy outcomes. Dosage had no significant effect on gestational age or birth weight.

The five minor anomalies in the monotherapy group were sacral dimple, “clicky” hips, plagiocephaly, webbed toes, and immature hip joints.

In the polytherapy group, there were 23 malformations, 13 of which were considered major. The major anomalies included pyloric stenosis, anal atresia, hypospadias, cleft palate, talipes, and dislocated hips. The average daily dosage for mothers of infants with a major anomaly was 342 mg, which was not significantly higher than the average dose of 294 mg/day for mothers on polytherapy who had normal infants. As in the monotherapy group, there were no significant dosage associations with gestational age or birth weight.

The combination of valproate with topiramate as duotherapy was associated with the highest rate of major congenital malformations (36%; 12 cases), followed by a regimen of three or more antiepileptic drugs (24%; 23 cases). Conversely, only 8% of polytherapy regimens that did not include valproate resulted in a major anomaly.

“It is not clear if this is a consequence of an interaction between the drugs, a reflection of unidentified patient characteristics, or due to valproate, which has increasingly been shown to be associated with a high risk of major congenital malformations,” Dr. Hunt and his colleagues wrote.

The results are particularly compelling in light of the rapid expansion of indications for topiramate, which in 2004 was approved for prophylaxis of migraine—a condition that is much more common than epilepsy among women of childbearing years, the authors noted.

Janssen-Cilag, U.K. manufacturer of topiramate (Topamax), and other pharmaceutical firms provided unrestricted educational grants to help support the study. Several of the study authors have received honoraria from Janssen-Cilag and other pharmaceutical firms.

Topiramate is associated with a significantly increased risk of major congenital malformations, whether given as monotherapy or as part of a polytherapy antiepileptic regimen, Dr. Stephen Hunt and his colleagues have reported.

Although the associations were strong—an 11-fold increase in the risk of oral clefts and a 14-fold increase in the risk of hypospadias, compared with background rates in the United Kingdom—the confidence intervals surrounding them were wide, noted Dr. Hunt of the Royal Group of Hospitals, Belfast, Northern Ireland. Therefore, the data “should be interpreted with caution,” he and his colleagues wrote (Neurology 2008;71:272–6).

The U.K. registry is one of three national registries that track pregnancy outcomes in women taking antiepileptic drugs. Neither of the others—a North American and an Australian registry—has reported an association between topiramate and birth defects, said Dr. Kimford Meador, the Melvin Greer Professor of Neurology at the University of Florida, Gainesville.

“The U.K. data are the first data on topiramate risks during pregnancy,” Dr. Meador said in an interview. “The data suggest an association of increased malformations with topiramate exposure during pregnancy. However, the sample is small and the confidence intervals are large, so no definitive conclusion can be drawn.”

Because the results are preliminary, clinicians and their patients should be cautious when they consider medication changes, said Dr. Martha Morrell, director of the Columbia Comprehensive Epilepsy Center, New York.

“The first objective of treatment is to control seizures,” she said in an interview. “Seizures during pregnancy place the mother at risk for injury and may also pose risk for the fetus. These results will be compared to data coming from other pregnancy registries as they become available. In the meantime, women taking topiramate should not make any adjustment in medications without consulting a physician.”

The analysis was drawn from the U.K. Epilepsy and Pregnancy Register, a prospective observational registry and follow-up study that tracks pregnancy outcomes among women in the United Kingdom who are taking antiepileptic medications. The present study included outcomes for 203 pregnancies with exposure to topiramate during the first trimester. Most of the women (133) were taking the drug as part of a polytherapy regimen (mean topiramate dose, 299 mg/day); the rest were on topiramate monotherapy (mean dose 245 mg/day). Of all these pregnancies, 178 (88%) resulted in a live birth; there were a total of 31 congenital anomalies among these infants (16 major and 15 minor).

Among women on monotherapy, there were eight infants born with anomalies, three of which were considered major. Two infants had a cleft lip/palate, and one had hypospadias. The average daily dose of topiramate for the mothers of these infants was 400 mg/day, compared with the average 238-mg dose among women on monotherapy who had normal pregnancy outcomes. Dosage had no significant effect on gestational age or birth weight.

The five minor anomalies in the monotherapy group were sacral dimple, “clicky” hips, plagiocephaly, webbed toes, and immature hip joints.

In the polytherapy group, there were 23 malformations, 13 of which were considered major. The major anomalies included pyloric stenosis, anal atresia, hypospadias, cleft palate, talipes, and dislocated hips. The average daily dosage for mothers of infants with a major anomaly was 342 mg, which was not significantly higher than the average dose of 294 mg/day for mothers on polytherapy who had normal infants. As in the monotherapy group, there were no significant dosage associations with gestational age or birth weight.

The combination of valproate with topiramate as duotherapy was associated with the highest rate of major congenital malformations (36%; 12 cases), followed by a regimen of three or more antiepileptic drugs (24%; 23 cases). Conversely, only 8% of polytherapy regimens that did not include valproate resulted in a major anomaly.

“It is not clear if this is a consequence of an interaction between the drugs, a reflection of unidentified patient characteristics, or due to valproate, which has increasingly been shown to be associated with a high risk of major congenital malformations,” Dr. Hunt and his colleagues wrote.

The results are particularly compelling in light of the rapid expansion of indications for topiramate, which in 2004 was approved for prophylaxis of migraine—a condition that is much more common than epilepsy among women of childbearing years, the authors noted.

Janssen-Cilag, U.K. manufacturer of topiramate (Topamax), and other pharmaceutical firms provided unrestricted educational grants to help support the study. Several of the study authors have received honoraria from Janssen-Cilag and other pharmaceutical firms.

Topiramate is associated with a significantly increased risk of major congenital malformations, whether given as monotherapy or as part of a polytherapy antiepileptic regimen, Dr. Stephen Hunt and his colleagues have reported.

Although the associations were strong—an 11-fold increase in the risk of oral clefts and a 14-fold increase in the risk of hypospadias, compared with background rates in the United Kingdom—the confidence intervals surrounding them were wide, noted Dr. Hunt of the Royal Group of Hospitals, Belfast, Northern Ireland. Therefore, the data “should be interpreted with caution,” he and his colleagues wrote (Neurology 2008;71:272–6).

The U.K. registry is one of three national registries that track pregnancy outcomes in women taking antiepileptic drugs. Neither of the others—a North American and an Australian registry—has reported an association between topiramate and birth defects, said Dr. Kimford Meador, the Melvin Greer Professor of Neurology at the University of Florida, Gainesville.

“The U.K. data are the first data on topiramate risks during pregnancy,” Dr. Meador said in an interview. “The data suggest an association of increased malformations with topiramate exposure during pregnancy. However, the sample is small and the confidence intervals are large, so no definitive conclusion can be drawn.”

Because the results are preliminary, clinicians and their patients should be cautious when they consider medication changes, said Dr. Martha Morrell, director of the Columbia Comprehensive Epilepsy Center, New York.

“The first objective of treatment is to control seizures,” she said in an interview. “Seizures during pregnancy place the mother at risk for injury and may also pose risk for the fetus. These results will be compared to data coming from other pregnancy registries as they become available. In the meantime, women taking topiramate should not make any adjustment in medications without consulting a physician.”

The analysis was drawn from the U.K. Epilepsy and Pregnancy Register, a prospective observational registry and follow-up study that tracks pregnancy outcomes among women in the United Kingdom who are taking antiepileptic medications. The present study included outcomes for 203 pregnancies with exposure to topiramate during the first trimester. Most of the women (133) were taking the drug as part of a polytherapy regimen (mean topiramate dose, 299 mg/day); the rest were on topiramate monotherapy (mean dose 245 mg/day). Of all these pregnancies, 178 (88%) resulted in a live birth; there were a total of 31 congenital anomalies among these infants (16 major and 15 minor).

Among women on monotherapy, there were eight infants born with anomalies, three of which were considered major. Two infants had a cleft lip/palate, and one had hypospadias. The average daily dose of topiramate for the mothers of these infants was 400 mg/day, compared with the average 238-mg dose among women on monotherapy who had normal pregnancy outcomes. Dosage had no significant effect on gestational age or birth weight.

The five minor anomalies in the monotherapy group were sacral dimple, “clicky” hips, plagiocephaly, webbed toes, and immature hip joints.

In the polytherapy group, there were 23 malformations, 13 of which were considered major. The major anomalies included pyloric stenosis, anal atresia, hypospadias, cleft palate, talipes, and dislocated hips. The average daily dosage for mothers of infants with a major anomaly was 342 mg, which was not significantly higher than the average dose of 294 mg/day for mothers on polytherapy who had normal infants. As in the monotherapy group, there were no significant dosage associations with gestational age or birth weight.

The combination of valproate with topiramate as duotherapy was associated with the highest rate of major congenital malformations (36%; 12 cases), followed by a regimen of three or more antiepileptic drugs (24%; 23 cases). Conversely, only 8% of polytherapy regimens that did not include valproate resulted in a major anomaly.

“It is not clear if this is a consequence of an interaction between the drugs, a reflection of unidentified patient characteristics, or due to valproate, which has increasingly been shown to be associated with a high risk of major congenital malformations,” Dr. Hunt and his colleagues wrote.

The results are particularly compelling in light of the rapid expansion of indications for topiramate, which in 2004 was approved for prophylaxis of migraine—a condition that is much more common than epilepsy among women of childbearing years, the authors noted.

Janssen-Cilag, U.K. manufacturer of topiramate (Topamax), and other pharmaceutical firms provided unrestricted educational grants to help support the study. Several of the study authors have received honoraria from Janssen-Cilag and other pharmaceutical firms.

SAN FRANCISCO — Visual disturbances—including blurred vision, floaters, central scotoma, and even complete loss of vision—can be a symptom of hypoglycemia in some patients with diabetes, according to Dr. Mukhtar Khan.

Although not all those with diabetes experience visual disturbances during a hypoglycemic event, those who are susceptible might experience two or more, which resolve soon after blood glucose stabilizes, Dr. Khan wrote in a poster presented at the annual meeting of the Endocrine Society.

“Most clinicians are usually concerned about hyperglycemia and its effects,” he said in an interview. “It is also important to keep the effects of hypoglycemia in mind, especially the visual effects, as these can have devastating consequences in diabetic patients in situations such as operating a motor vehicle.”

His observational study enrolled 40 patients with diabetes (mean age 46 years) who had a history of visual symptoms during hypoglycemic episodes. Most of the patients (26) had type 1 diabetes; the rest had type 2 diabetes. Nineteen were on insulin pumps, while 21 were on various insulin regimens, including glargine, lispro, aspart, and mixed regimens.

For most of the patients (57%), visual symptoms occurred when blood glucose dropped to 30–50 mg/dL. For 25%, symptoms occurred at a glucose level of 51–65 mg/dL, while a minority (10%) experienced them at a level of 66–80 mg/dL. The remaining patients were unable to document their blood glucose level at the onset of visual symptoms.

Blurred vision was the most commonly reported symptom (77%). About half of the group (47%) reported seeing floaters. Dimming of vision occurred in 37%; central scotoma (a black spot or “hole” in the central visual field) in 32%; and double vision in 22%. A few patients (5%) reported a complete loss of vision during hypoglycemia. Most (67%) reported more than one symptom during the episode.

The visual disturbances resolved after blood glucose stabilized, Dr. Khan said. “After hypoglycemia correction, the symptoms resolved within 5–15 minutes in 16 subjects; 20–30 minutes in 17 subjects; and 35–90 minutes in three subjects. Two subjects, who experienced a complete loss of vision at a blood glucose level in the 30- to 40-mg/dL range, reported gradual resolution of visual symptoms in 180 minutes and 300 minutes after improvement in the glucose level.”

Two patients did not report the time to resolution of their symptoms, noted Dr. Khan of the State University of New York, Syracuse.

“Patients with diabetes should be counseled about recognition and early management of visual effects of hypoglycemia,” Dr. Khan said. “Prevention of hypoglycemia should be given as much importance as hyperglycemia during management of diabetes.”

SAN FRANCISCO — Visual disturbances—including blurred vision, floaters, central scotoma, and even complete loss of vision—can be a symptom of hypoglycemia in some patients with diabetes, according to Dr. Mukhtar Khan.

Although not all those with diabetes experience visual disturbances during a hypoglycemic event, those who are susceptible might experience two or more, which resolve soon after blood glucose stabilizes, Dr. Khan wrote in a poster presented at the annual meeting of the Endocrine Society.

“Most clinicians are usually concerned about hyperglycemia and its effects,” he said in an interview. “It is also important to keep the effects of hypoglycemia in mind, especially the visual effects, as these can have devastating consequences in diabetic patients in situations such as operating a motor vehicle.”

His observational study enrolled 40 patients with diabetes (mean age 46 years) who had a history of visual symptoms during hypoglycemic episodes. Most of the patients (26) had type 1 diabetes; the rest had type 2 diabetes. Nineteen were on insulin pumps, while 21 were on various insulin regimens, including glargine, lispro, aspart, and mixed regimens.

For most of the patients (57%), visual symptoms occurred when blood glucose dropped to 30–50 mg/dL. For 25%, symptoms occurred at a glucose level of 51–65 mg/dL, while a minority (10%) experienced them at a level of 66–80 mg/dL. The remaining patients were unable to document their blood glucose level at the onset of visual symptoms.

Blurred vision was the most commonly reported symptom (77%). About half of the group (47%) reported seeing floaters. Dimming of vision occurred in 37%; central scotoma (a black spot or “hole” in the central visual field) in 32%; and double vision in 22%. A few patients (5%) reported a complete loss of vision during hypoglycemia. Most (67%) reported more than one symptom during the episode.

The visual disturbances resolved after blood glucose stabilized, Dr. Khan said. “After hypoglycemia correction, the symptoms resolved within 5–15 minutes in 16 subjects; 20–30 minutes in 17 subjects; and 35–90 minutes in three subjects. Two subjects, who experienced a complete loss of vision at a blood glucose level in the 30- to 40-mg/dL range, reported gradual resolution of visual symptoms in 180 minutes and 300 minutes after improvement in the glucose level.”

Two patients did not report the time to resolution of their symptoms, noted Dr. Khan of the State University of New York, Syracuse.

“Patients with diabetes should be counseled about recognition and early management of visual effects of hypoglycemia,” Dr. Khan said. “Prevention of hypoglycemia should be given as much importance as hyperglycemia during management of diabetes.”

SAN FRANCISCO — Visual disturbances—including blurred vision, floaters, central scotoma, and even complete loss of vision—can be a symptom of hypoglycemia in some patients with diabetes, according to Dr. Mukhtar Khan.

Although not all those with diabetes experience visual disturbances during a hypoglycemic event, those who are susceptible might experience two or more, which resolve soon after blood glucose stabilizes, Dr. Khan wrote in a poster presented at the annual meeting of the Endocrine Society.

“Most clinicians are usually concerned about hyperglycemia and its effects,” he said in an interview. “It is also important to keep the effects of hypoglycemia in mind, especially the visual effects, as these can have devastating consequences in diabetic patients in situations such as operating a motor vehicle.”

His observational study enrolled 40 patients with diabetes (mean age 46 years) who had a history of visual symptoms during hypoglycemic episodes. Most of the patients (26) had type 1 diabetes; the rest had type 2 diabetes. Nineteen were on insulin pumps, while 21 were on various insulin regimens, including glargine, lispro, aspart, and mixed regimens.

For most of the patients (57%), visual symptoms occurred when blood glucose dropped to 30–50 mg/dL. For 25%, symptoms occurred at a glucose level of 51–65 mg/dL, while a minority (10%) experienced them at a level of 66–80 mg/dL. The remaining patients were unable to document their blood glucose level at the onset of visual symptoms.

Blurred vision was the most commonly reported symptom (77%). About half of the group (47%) reported seeing floaters. Dimming of vision occurred in 37%; central scotoma (a black spot or “hole” in the central visual field) in 32%; and double vision in 22%. A few patients (5%) reported a complete loss of vision during hypoglycemia. Most (67%) reported more than one symptom during the episode.

The visual disturbances resolved after blood glucose stabilized, Dr. Khan said. “After hypoglycemia correction, the symptoms resolved within 5–15 minutes in 16 subjects; 20–30 minutes in 17 subjects; and 35–90 minutes in three subjects. Two subjects, who experienced a complete loss of vision at a blood glucose level in the 30- to 40-mg/dL range, reported gradual resolution of visual symptoms in 180 minutes and 300 minutes after improvement in the glucose level.”

Two patients did not report the time to resolution of their symptoms, noted Dr. Khan of the State University of New York, Syracuse.

“Patients with diabetes should be counseled about recognition and early management of visual effects of hypoglycemia,” Dr. Khan said. “Prevention of hypoglycemia should be given as much importance as hyperglycemia during management of diabetes.”

CHICAGO — Hormone therapy might preserve cognition and memory in postmenopausal women, and even attenuate some of the cognitive deficits that occur in Alzheimer's disease, new research suggests.

Controversy exists over the possible cognitive benefits of hormone therapy in older women, Mary Tierney, Ph.D., said at the International Conference on Alzheimer's Disease. “While preclinical and observational studies have shown a positive effect of estradiol on the brain and cognitive function, randomized controlled trials using conjugated equine estrogens have shown no treatment effects in women at risk for Alzheimer's disease, or in women who have the illness.”

In fact, the most widely quoted study, the Women's Health Initiative Memory Study (WHIMS), suggested that hormone therapy (HT) might even hurt, rather than help, said Dr. Tierney of the Sunnybrook Health Sciences Centre, Toronto. The 4-year substudy of the Women's Health Initiative examined the effect of hormone therapy on mild cognitive impairment and dementia in more than 7,000 women aged 65–79 years.

“Forty women in the estrogen plus progesterone group developed dementia of any type, but only 21 in the placebo group did,” Dr. Tierney said. “However, there were no significant differences in the estrogen-only arm compared to placebo.”

Additionally, she noted, a breakdown of the dementias by etiology showed that many of them were vascular in nature—which contributed to the criticism of the Women's Health Initiative for including women who had experienced a stroke.

These concerns, plus her own hypothesis that the “minidoses” of hormones used in many randomized trials might be too low to offer protective benefit, prompted Dr. Tierney and her colleagues to undertake a new study. The 2-year trial randomized 142 women aged 61–87 years to either placebo or to 1 mg estradiol daily plus 0.35 mg progestin 3 days per week.

The primary outcome was the annual change in scores on the short-delay verbal recall portion of the California Verbal Learning Test (CVLT); the test's other memory components were used as secondary outcomes.

None of the women selected for the trial had dementia, but all had normal or below normal baseline memory scores, Dr. Tierney noted. The subjects' mean age was 74 years; their mean age at menopause was 49 years. The multivariate analysis controlled for age, years of education, apo E4 status, and prior hormone therapy use.

There was no significant difference between groups on the primary end point of delayed recall, Dr. Tierney said. But when she split the group according to baseline CVLT scores, significant differences did emerge. Compared with women who scored below the 50th percentile on their baseline test, those on HT who scored above the 50th percentile showed significantly less decline in delayed verbal recall than did those in the placebo group. Similar, but nonsignificant, differences occurred on immediate recall, interference recall, cued recall, and recognition memory.

The findings suggest that hormone therapy might exert a protective influence on memory among women who have not begun to experience significant cognitive decline, Dr. Tierney said. “Our findings suggest that the critical period for estrogen exposure to benefit cognition may not be limited to the menopause transition, since these women were more than 20 years postmenopausal,” but might also be related to the state of brain function when therapy is initiated.

Two studies by another group of researchers suggest that hormone therapy positively influences postmenopausal memory and hippocampal activity, and might offer some protective effect against the cognitive decline seen in Alzheimer's.

Kara Bottiggi Dassel, Ph.D., of the Barrow Neurological Institute, Phoenix, examined the effect of past hormone use on the cognitive deficits of Alzheimer's patients. Dr. Dassel extracted her data from the Arizona Alzheimer's Disease Consortium.

The study included 49 women (average age 75 years) who were categorized as current hormone therapy users (20), past users (18), or never-users (11). All of these women had a diagnosis of Alzheimer's disease; there were no differences in functional levels or Clinical Dementia Rating scores, suggesting that they were of a similar disease stage. The women were evaluated for global cognition, memory, and executive functioning.

While there were no significant differences on measures of memory, past users scored significantly better than never-users on the dementia rating scale, with a mean score difference of 31 points—considered clinically meaningful.

Past users also scored significantly better than never-users on the Controlled Oral Word Association Test and the clock drawing test, both measures of executive function. On the word association test, the mean score difference was 18 words; on the clock drawing test, the mean difference was 3.4. Again, Dr. Dassel said, both differences were considered clinically meaningful.

She then examined hormone use by baseline dementia ratings. Women were split into “higher functioning” (mean dementia rating score 68) or “lower functioning” (mean dementia rating score 120).

Among the higher-functioning group, 45% were past hormone therapy users, 45% were current users, and 10% were never-users. Among the lower-functioning group, 25% were past users, 35% were current users, and 40% were never-users.

“The length of illness was similar among women in the higher group, suggesting that there is less of a decline in cognitive functioning in the hormone therapy users.”

Dr. Dassel's colleague, Leslie Baxter, Ph.D., presented a study suggesting that hormone therapy also boosts hippocampal activity and might contribute to the persistent differences in memory between men and women as they age.

Dr. Baxter's study comprised 66 postmenopausal women and 37 men aged 50–87 years, all of whom underwent memory testing and functional magnetic resonance imaging of the brain. Again, the women were divided into groups according to their hormone therapy use: never-users (16), discontinuous users (34), and continuous users (16).

There were no between-group differences in age or education. All of these subjects underwent memory testing with the Rey Auditory Verbal Learning Test's total learning and delayed recall tests, and functional magnetic resonance imaging of the brain.

Discontinuous hormone therapy users scored significantly better than men did on all the memory tests. A nonsignificant performance trend also emerged, with discontinuous hormone therapy users performing better than continuous users, continuous users performing better than nonusers, and nonusers performing better than men.

Functional MRI showed that during a memory test (a novelty vs. familiar paradigm), the discontinuous hormone therapy users and men had significantly greater hippocampal activity than the never-users. Continuous users also had higher hippocampal activity than never-users, although not significantly so.

The researchers couldn't draw any conclusions about a definitive time frame during which hormone therapy use was associated with better memory, either in terms of duration of use or in the time of initiation. But, they said, “Both cognitive and … hippocampal integrity measures suggest that women benefited from hormone therapy at any point during menopause—not necessarily continuously—and that it helped preserve the sex difference in memory.”

None of the researchers identified any potential conflicts of interest.

A graphic representation shows increased hippocampal activity in discontinuous HT users during a memory task. Images courtesy Dr. Kara Bottiggi Dassel

CHICAGO — Hormone therapy might preserve cognition and memory in postmenopausal women, and even attenuate some of the cognitive deficits that occur in Alzheimer's disease, new research suggests.

Controversy exists over the possible cognitive benefits of hormone therapy in older women, Mary Tierney, Ph.D., said at the International Conference on Alzheimer's Disease. “While preclinical and observational studies have shown a positive effect of estradiol on the brain and cognitive function, randomized controlled trials using conjugated equine estrogens have shown no treatment effects in women at risk for Alzheimer's disease, or in women who have the illness.”

In fact, the most widely quoted study, the Women's Health Initiative Memory Study (WHIMS), suggested that hormone therapy (HT) might even hurt, rather than help, said Dr. Tierney of the Sunnybrook Health Sciences Centre, Toronto. The 4-year substudy of the Women's Health Initiative examined the effect of hormone therapy on mild cognitive impairment and dementia in more than 7,000 women aged 65–79 years.

“Forty women in the estrogen plus progesterone group developed dementia of any type, but only 21 in the placebo group did,” Dr. Tierney said. “However, there were no significant differences in the estrogen-only arm compared to placebo.”

Additionally, she noted, a breakdown of the dementias by etiology showed that many of them were vascular in nature—which contributed to the criticism of the Women's Health Initiative for including women who had experienced a stroke.

These concerns, plus her own hypothesis that the “minidoses” of hormones used in many randomized trials might be too low to offer protective benefit, prompted Dr. Tierney and her colleagues to undertake a new study. The 2-year trial randomized 142 women aged 61–87 years to either placebo or to 1 mg estradiol daily plus 0.35 mg progestin 3 days per week.

The primary outcome was the annual change in scores on the short-delay verbal recall portion of the California Verbal Learning Test (CVLT); the test's other memory components were used as secondary outcomes.

None of the women selected for the trial had dementia, but all had normal or below normal baseline memory scores, Dr. Tierney noted. The subjects' mean age was 74 years; their mean age at menopause was 49 years. The multivariate analysis controlled for age, years of education, apo E4 status, and prior hormone therapy use.

There was no significant difference between groups on the primary end point of delayed recall, Dr. Tierney said. But when she split the group according to baseline CVLT scores, significant differences did emerge. Compared with women who scored below the 50th percentile on their baseline test, those on HT who scored above the 50th percentile showed significantly less decline in delayed verbal recall than did those in the placebo group. Similar, but nonsignificant, differences occurred on immediate recall, interference recall, cued recall, and recognition memory.

The findings suggest that hormone therapy might exert a protective influence on memory among women who have not begun to experience significant cognitive decline, Dr. Tierney said. “Our findings suggest that the critical period for estrogen exposure to benefit cognition may not be limited to the menopause transition, since these women were more than 20 years postmenopausal,” but might also be related to the state of brain function when therapy is initiated.

Two studies by another group of researchers suggest that hormone therapy positively influences postmenopausal memory and hippocampal activity, and might offer some protective effect against the cognitive decline seen in Alzheimer's.

Kara Bottiggi Dassel, Ph.D., of the Barrow Neurological Institute, Phoenix, examined the effect of past hormone use on the cognitive deficits of Alzheimer's patients. Dr. Dassel extracted her data from the Arizona Alzheimer's Disease Consortium.

The study included 49 women (average age 75 years) who were categorized as current hormone therapy users (20), past users (18), or never-users (11). All of these women had a diagnosis of Alzheimer's disease; there were no differences in functional levels or Clinical Dementia Rating scores, suggesting that they were of a similar disease stage. The women were evaluated for global cognition, memory, and executive functioning.

While there were no significant differences on measures of memory, past users scored significantly better than never-users on the dementia rating scale, with a mean score difference of 31 points—considered clinically meaningful.

Past users also scored significantly better than never-users on the Controlled Oral Word Association Test and the clock drawing test, both measures of executive function. On the word association test, the mean score difference was 18 words; on the clock drawing test, the mean difference was 3.4. Again, Dr. Dassel said, both differences were considered clinically meaningful.

She then examined hormone use by baseline dementia ratings. Women were split into “higher functioning” (mean dementia rating score 68) or “lower functioning” (mean dementia rating score 120).

Among the higher-functioning group, 45% were past hormone therapy users, 45% were current users, and 10% were never-users. Among the lower-functioning group, 25% were past users, 35% were current users, and 40% were never-users.

“The length of illness was similar among women in the higher group, suggesting that there is less of a decline in cognitive functioning in the hormone therapy users.”

Dr. Dassel's colleague, Leslie Baxter, Ph.D., presented a study suggesting that hormone therapy also boosts hippocampal activity and might contribute to the persistent differences in memory between men and women as they age.

Dr. Baxter's study comprised 66 postmenopausal women and 37 men aged 50–87 years, all of whom underwent memory testing and functional magnetic resonance imaging of the brain. Again, the women were divided into groups according to their hormone therapy use: never-users (16), discontinuous users (34), and continuous users (16).

There were no between-group differences in age or education. All of these subjects underwent memory testing with the Rey Auditory Verbal Learning Test's total learning and delayed recall tests, and functional magnetic resonance imaging of the brain.

Discontinuous hormone therapy users scored significantly better than men did on all the memory tests. A nonsignificant performance trend also emerged, with discontinuous hormone therapy users performing better than continuous users, continuous users performing better than nonusers, and nonusers performing better than men.

Functional MRI showed that during a memory test (a novelty vs. familiar paradigm), the discontinuous hormone therapy users and men had significantly greater hippocampal activity than the never-users. Continuous users also had higher hippocampal activity than never-users, although not significantly so.

The researchers couldn't draw any conclusions about a definitive time frame during which hormone therapy use was associated with better memory, either in terms of duration of use or in the time of initiation. But, they said, “Both cognitive and … hippocampal integrity measures suggest that women benefited from hormone therapy at any point during menopause—not necessarily continuously—and that it helped preserve the sex difference in memory.”

None of the researchers identified any potential conflicts of interest.

A graphic representation shows increased hippocampal activity in discontinuous HT users during a memory task. Images courtesy Dr. Kara Bottiggi Dassel

CHICAGO — Hormone therapy might preserve cognition and memory in postmenopausal women, and even attenuate some of the cognitive deficits that occur in Alzheimer's disease, new research suggests.

Controversy exists over the possible cognitive benefits of hormone therapy in older women, Mary Tierney, Ph.D., said at the International Conference on Alzheimer's Disease. “While preclinical and observational studies have shown a positive effect of estradiol on the brain and cognitive function, randomized controlled trials using conjugated equine estrogens have shown no treatment effects in women at risk for Alzheimer's disease, or in women who have the illness.”

In fact, the most widely quoted study, the Women's Health Initiative Memory Study (WHIMS), suggested that hormone therapy (HT) might even hurt, rather than help, said Dr. Tierney of the Sunnybrook Health Sciences Centre, Toronto. The 4-year substudy of the Women's Health Initiative examined the effect of hormone therapy on mild cognitive impairment and dementia in more than 7,000 women aged 65–79 years.

“Forty women in the estrogen plus progesterone group developed dementia of any type, but only 21 in the placebo group did,” Dr. Tierney said. “However, there were no significant differences in the estrogen-only arm compared to placebo.”

Additionally, she noted, a breakdown of the dementias by etiology showed that many of them were vascular in nature—which contributed to the criticism of the Women's Health Initiative for including women who had experienced a stroke.

These concerns, plus her own hypothesis that the “minidoses” of hormones used in many randomized trials might be too low to offer protective benefit, prompted Dr. Tierney and her colleagues to undertake a new study. The 2-year trial randomized 142 women aged 61–87 years to either placebo or to 1 mg estradiol daily plus 0.35 mg progestin 3 days per week.

The primary outcome was the annual change in scores on the short-delay verbal recall portion of the California Verbal Learning Test (CVLT); the test's other memory components were used as secondary outcomes.

None of the women selected for the trial had dementia, but all had normal or below normal baseline memory scores, Dr. Tierney noted. The subjects' mean age was 74 years; their mean age at menopause was 49 years. The multivariate analysis controlled for age, years of education, apo E4 status, and prior hormone therapy use.

There was no significant difference between groups on the primary end point of delayed recall, Dr. Tierney said. But when she split the group according to baseline CVLT scores, significant differences did emerge. Compared with women who scored below the 50th percentile on their baseline test, those on HT who scored above the 50th percentile showed significantly less decline in delayed verbal recall than did those in the placebo group. Similar, but nonsignificant, differences occurred on immediate recall, interference recall, cued recall, and recognition memory.

The findings suggest that hormone therapy might exert a protective influence on memory among women who have not begun to experience significant cognitive decline, Dr. Tierney said. “Our findings suggest that the critical period for estrogen exposure to benefit cognition may not be limited to the menopause transition, since these women were more than 20 years postmenopausal,” but might also be related to the state of brain function when therapy is initiated.

Two studies by another group of researchers suggest that hormone therapy positively influences postmenopausal memory and hippocampal activity, and might offer some protective effect against the cognitive decline seen in Alzheimer's.

Kara Bottiggi Dassel, Ph.D., of the Barrow Neurological Institute, Phoenix, examined the effect of past hormone use on the cognitive deficits of Alzheimer's patients. Dr. Dassel extracted her data from the Arizona Alzheimer's Disease Consortium.

The study included 49 women (average age 75 years) who were categorized as current hormone therapy users (20), past users (18), or never-users (11). All of these women had a diagnosis of Alzheimer's disease; there were no differences in functional levels or Clinical Dementia Rating scores, suggesting that they were of a similar disease stage. The women were evaluated for global cognition, memory, and executive functioning.

While there were no significant differences on measures of memory, past users scored significantly better than never-users on the dementia rating scale, with a mean score difference of 31 points—considered clinically meaningful.

Past users also scored significantly better than never-users on the Controlled Oral Word Association Test and the clock drawing test, both measures of executive function. On the word association test, the mean score difference was 18 words; on the clock drawing test, the mean difference was 3.4. Again, Dr. Dassel said, both differences were considered clinically meaningful.

She then examined hormone use by baseline dementia ratings. Women were split into “higher functioning” (mean dementia rating score 68) or “lower functioning” (mean dementia rating score 120).

Among the higher-functioning group, 45% were past hormone therapy users, 45% were current users, and 10% were never-users. Among the lower-functioning group, 25% were past users, 35% were current users, and 40% were never-users.

“The length of illness was similar among women in the higher group, suggesting that there is less of a decline in cognitive functioning in the hormone therapy users.”

Dr. Dassel's colleague, Leslie Baxter, Ph.D., presented a study suggesting that hormone therapy also boosts hippocampal activity and might contribute to the persistent differences in memory between men and women as they age.

Dr. Baxter's study comprised 66 postmenopausal women and 37 men aged 50–87 years, all of whom underwent memory testing and functional magnetic resonance imaging of the brain. Again, the women were divided into groups according to their hormone therapy use: never-users (16), discontinuous users (34), and continuous users (16).

There were no between-group differences in age or education. All of these subjects underwent memory testing with the Rey Auditory Verbal Learning Test's total learning and delayed recall tests, and functional magnetic resonance imaging of the brain.

Discontinuous hormone therapy users scored significantly better than men did on all the memory tests. A nonsignificant performance trend also emerged, with discontinuous hormone therapy users performing better than continuous users, continuous users performing better than nonusers, and nonusers performing better than men.

Functional MRI showed that during a memory test (a novelty vs. familiar paradigm), the discontinuous hormone therapy users and men had significantly greater hippocampal activity than the never-users. Continuous users also had higher hippocampal activity than never-users, although not significantly so.

The researchers couldn't draw any conclusions about a definitive time frame during which hormone therapy use was associated with better memory, either in terms of duration of use or in the time of initiation. But, they said, “Both cognitive and … hippocampal integrity measures suggest that women benefited from hormone therapy at any point during menopause—not necessarily continuously—and that it helped preserve the sex difference in memory.”

None of the researchers identified any potential conflicts of interest.

A graphic representation shows increased hippocampal activity in discontinuous HT users during a memory task. Images courtesy Dr. Kara Bottiggi Dassel

CHICAGO — A simple blood test could soon allow clinicians to diagnose Alzheimer's disease accurately.

In an initial study of 88 patients, the test findings agreed with expert clinical diagnosis more than 90% of the time and had an overall accuracy of 97%. If the validation study confirms this, the test could be on the market by mid-fall, Dr. Louis Kirby said at the International Conference on Alzheimer's Disease.

An easy blood test that would diagnose early Alzheimer's could have enormous impact, said Dr. Kirby, whose company, Provista Life Sciences, owns the patent.

The test, to be marketed as LymPro, assumes that lymphocytes mirror a unique neuronal cell-cycle dysregulation seen in Alzheimer's patients, Dr. Kirby said at the meeting presented by the Alzheimer's Association. “Normally, neurons divide and mature, and then remain active for decades without dividing again. A great deal of relatively new research suggests that in Alzheimer's disease, neurons prepare to reenter the cell division process in an abnormal fashion.”

Neurons that undergo this change proceed almost to mitosis but are then unable to redifferentiate. Researchers have concluded that the neurons then either die or produce Alzheimer's pathology (research summary—Biochim. Biophys. Acta 2007;1772:413-21).

Research also suggests that peripheral lymphocytes in Alzheimer's patients display a similar cell-cycle defect when exposed to a mitogenic stimulus, Dr. Kirby said. A 2001 study found that these lymphocytes were less able to express CD-69, a marker of white cell growth and proliferation, than lymphocytes from control patients. In fact, this study found that the expression of CD-69 inversely correlated with the level of dementia as measured by the Mini-Mental State Examination score (Neuroreport 2001;12:3969-72).

Dr. Thomas Arendt, of the University of Leipzig (Germany), was the lead investigator on many of these studies. He developed the LymPro test and has licensed the technology to Dr. Kirby's Arizona-based company.

Dr. Kirby's initial study included 88 patients: 32 with probable Alzheimer's disease, 26 with Parkinson's dementia, and 30 cognitively intact controls. All diagnoses were based on clinical testing and observation by dementia experts.

After applying a mitogenic stimulus to the peripheral lymphocytes in each blood sample, researchers could reliably differentiate between controls, Alzheimer's, and Parkinson's patients based on variations in the CD-69 levels, Dr. Kirby said. The test had 91% sensitivity and a 92% specificity, with an overall accuracy of nearly 97%.

And, Dr. Kirby said, since the blood test score correlated with the level of dementia on the Mini-Mental State Examination, “We have confidence that we should be able to dial back the diagnosis into the mild cognitive impairment stage, and—hopefully—even into the preclinical state.”

CHICAGO — A simple blood test could soon allow clinicians to diagnose Alzheimer's disease accurately.

In an initial study of 88 patients, the test findings agreed with expert clinical diagnosis more than 90% of the time and had an overall accuracy of 97%. If the validation study confirms this, the test could be on the market by mid-fall, Dr. Louis Kirby said at the International Conference on Alzheimer's Disease.

An easy blood test that would diagnose early Alzheimer's could have enormous impact, said Dr. Kirby, whose company, Provista Life Sciences, owns the patent.

The test, to be marketed as LymPro, assumes that lymphocytes mirror a unique neuronal cell-cycle dysregulation seen in Alzheimer's patients, Dr. Kirby said at the meeting presented by the Alzheimer's Association. “Normally, neurons divide and mature, and then remain active for decades without dividing again. A great deal of relatively new research suggests that in Alzheimer's disease, neurons prepare to reenter the cell division process in an abnormal fashion.”

Neurons that undergo this change proceed almost to mitosis but are then unable to redifferentiate. Researchers have concluded that the neurons then either die or produce Alzheimer's pathology (research summary—Biochim. Biophys. Acta 2007;1772:413-21).

Research also suggests that peripheral lymphocytes in Alzheimer's patients display a similar cell-cycle defect when exposed to a mitogenic stimulus, Dr. Kirby said. A 2001 study found that these lymphocytes were less able to express CD-69, a marker of white cell growth and proliferation, than lymphocytes from control patients. In fact, this study found that the expression of CD-69 inversely correlated with the level of dementia as measured by the Mini-Mental State Examination score (Neuroreport 2001;12:3969-72).

Dr. Thomas Arendt, of the University of Leipzig (Germany), was the lead investigator on many of these studies. He developed the LymPro test and has licensed the technology to Dr. Kirby's Arizona-based company.

Dr. Kirby's initial study included 88 patients: 32 with probable Alzheimer's disease, 26 with Parkinson's dementia, and 30 cognitively intact controls. All diagnoses were based on clinical testing and observation by dementia experts.

After applying a mitogenic stimulus to the peripheral lymphocytes in each blood sample, researchers could reliably differentiate between controls, Alzheimer's, and Parkinson's patients based on variations in the CD-69 levels, Dr. Kirby said. The test had 91% sensitivity and a 92% specificity, with an overall accuracy of nearly 97%.

And, Dr. Kirby said, since the blood test score correlated with the level of dementia on the Mini-Mental State Examination, “We have confidence that we should be able to dial back the diagnosis into the mild cognitive impairment stage, and—hopefully—even into the preclinical state.”

CHICAGO — A simple blood test could soon allow clinicians to diagnose Alzheimer's disease accurately.

In an initial study of 88 patients, the test findings agreed with expert clinical diagnosis more than 90% of the time and had an overall accuracy of 97%. If the validation study confirms this, the test could be on the market by mid-fall, Dr. Louis Kirby said at the International Conference on Alzheimer's Disease.

An easy blood test that would diagnose early Alzheimer's could have enormous impact, said Dr. Kirby, whose company, Provista Life Sciences, owns the patent.

The test, to be marketed as LymPro, assumes that lymphocytes mirror a unique neuronal cell-cycle dysregulation seen in Alzheimer's patients, Dr. Kirby said at the meeting presented by the Alzheimer's Association. “Normally, neurons divide and mature, and then remain active for decades without dividing again. A great deal of relatively new research suggests that in Alzheimer's disease, neurons prepare to reenter the cell division process in an abnormal fashion.”

Neurons that undergo this change proceed almost to mitosis but are then unable to redifferentiate. Researchers have concluded that the neurons then either die or produce Alzheimer's pathology (research summary—Biochim. Biophys. Acta 2007;1772:413-21).

Research also suggests that peripheral lymphocytes in Alzheimer's patients display a similar cell-cycle defect when exposed to a mitogenic stimulus, Dr. Kirby said. A 2001 study found that these lymphocytes were less able to express CD-69, a marker of white cell growth and proliferation, than lymphocytes from control patients. In fact, this study found that the expression of CD-69 inversely correlated with the level of dementia as measured by the Mini-Mental State Examination score (Neuroreport 2001;12:3969-72).

Dr. Thomas Arendt, of the University of Leipzig (Germany), was the lead investigator on many of these studies. He developed the LymPro test and has licensed the technology to Dr. Kirby's Arizona-based company.

Dr. Kirby's initial study included 88 patients: 32 with probable Alzheimer's disease, 26 with Parkinson's dementia, and 30 cognitively intact controls. All diagnoses were based on clinical testing and observation by dementia experts.

After applying a mitogenic stimulus to the peripheral lymphocytes in each blood sample, researchers could reliably differentiate between controls, Alzheimer's, and Parkinson's patients based on variations in the CD-69 levels, Dr. Kirby said. The test had 91% sensitivity and a 92% specificity, with an overall accuracy of nearly 97%.

And, Dr. Kirby said, since the blood test score correlated with the level of dementia on the Mini-Mental State Examination, “We have confidence that we should be able to dial back the diagnosis into the mild cognitive impairment stage, and—hopefully—even into the preclinical state.”