Increased Mental Slowing Associated With the APOE ɛ4 Allele After Trihexyphenidyl Oral Anticholinergic Challenge in Healthy Elderly

Pomara, Nunzio; Belzer, Ken; Sidtis, John J.; Hernando, Raymundo; Pena, Corazon De La

doi:10.1097/jgp.0b013e31815aff75

Cited by 10 publications

(10 citation statements)

References 31 publications

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“…The evidence that anticholinergic drugs such as scopolamine reduce information-processing speed, is strong and consistent (7, 10, 11, 12). However, while it has been claimed that scopolamine reduces working-memory capacity (9), tasks that require simultaneous manipulation and storage of information (often viewed as the defining characteristic of working memory) have not shown an effect of acute scopolamine administration, including variants of the N back task administered here (10, 28).…”

Section: Discussionmentioning

confidence: 96%

“…The extensive literature demonstrating cognitive decrements in the elderly following acute administration of potent anticholinergics (7, 9, 11), could suggest that anticholinergic medications (both prescription and OTC) contribute to the cognitive decrements found in studies of normal aging because of the high likelihood that participants in such studies will be taking anticholinergic drugs. While the present results do show the anticholinergic burden present in participants’ serum to be significantly related to their cognitive performance, the magnitude and breadth of this relationship was smaller than that seen with experimental administration of scopolamine.…”

Section: Discussionmentioning

confidence: 99%

“…The source of these deficits has been attributed to a drug-induced reduction in information-processing capacity (9), similar to that postulated to underlie the cognitive decline found with normal aging. Anticholinergic medications have been shown to slow the speed of cognitive operations (7, 10, 11, 12) as well as possibly reducing working-memory capacity (9). While the decrements associated with acute scopolamine administration are well established, there is limited evidence that similar effects occur with the lower anticholinergic burden associated with chronic anticholinergic drug use by the elderly.…”

Section: Objectivementioning

confidence: 99%

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Cognitive Slowing Associated With Elevated Serum Anticholinergic Activity in Older Individuals is Decreased by Caffeine Use

Nebes

Pollock

Halligan

et al. 2011

The American Journal of Geriatric Psychiatry

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Objectives The present study examined whether some of the age-associated decrements in basic cognitive resources (information-processing speed and working memory) result from anticholinergic medication use (as measured by serum anticholinergic activity) and whether such decrements are lessened by caffeine. Design Cross-sectional observational study Setting University medical center Participants 152 normal-elderly community volunteers Measurements Two tests each of information-processing speed and of working memory were administered and blood samples were drawn before and after cognitive testing to determine serum levels of anticholinergic activity and of paraxanthine - a caffeine metabolite. Results Elevated serum anticholinergic activity was associated with a significant but modest slowing in information-processing time, but only in those individuals who had low levels of serum paraxanthine. Serum anticholinergic activity did not correlate with performance on tests of working-memory. Conclusions These results suggest that anticholinergic medications are a relatively minor contributor to the decrements in basic processing resources commonly found in studies of normal aging.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Objectivementioning

confidence: 99%

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Cognitive Slowing Associated With Elevated Serum Anticholinergic Activity in Older Individuals is Decreased by Caffeine Use

Nebes

Pollock

Halligan

et al. 2011

The American Journal of Geriatric Psychiatry

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“…However, use of such medications was a specific exclusion criterion for this study. Pomara et al 7 examined the effect that acute administration of an anticholinergic medication had on the Mood Rating Scale, but analyzed only questions related to sedation and confusion. Of these, only self-rated mental slowing showed a greater anticholinergic effect in ε4 carriers.…”

Section: Discussionmentioning

confidence: 99%

“…In a large community-based study, Carriere et al 4 found an interactive effect of anticholinergic drugs and APOE genotype such that anticholinergic drug users had a 2-fold higher risk of a longitudinal cognitive decline if they carried the ε4 genotype. A recent study 7 using a measure of subjective mental symptoms showed a significant interaction between drug condition (anticholinergic medication vs. placebo) and APOE genotype ( P < 0.03), with ε4 carriers showing a greater drug effect. Also, the magnitude of this anticholinergic drug effect correlated with memory recall performance only in the ε4 carriers ( P < 0.01).…”

Section: Introductionmentioning

confidence: 95%

The Greater Sensitivity of Elderly APOE ε4 Carriers to Anticholinergic Medications is Independent of Cerebrovascular Disease Risk

Nebes

Pollock

Perera

et al. 2012

The American Journal of Geriatric Pharmacotherapy

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Background Recent studies found use of anticholinergic medications to be associated with greater performance decrements in older persons who carry an ε4 allele of the apolipoprotein E (APOE) gene than in those carrying only ε2 or ε3 alleles. Objectives The present study examined whether the apparently greater behavioral toxicity of anticholinergic drugs in ε4 carriers may result from an increased risk of cerebrovascular disease, which is more common in ε4 carriers. Methods Cross-sectional data were available from 240 normal elderly [pe1]community volunteers who had participated in 2 different studies of the cognitive and motor effects of normal aging. As part of these studies, information was gathered on subjects' use of anticholinergic medications (based on an inventory of medications taken within 24 hours of testing), risk of cerebrovascular disease (Framingham Stroke Risk Profile), and APOE genotype. Performance data were also available from measures of general cognitive status (Mini-Mental State Examination), executive function (Trail Making Test), mood (Geriatric Depression Scale), sleep (Pittsburgh Sleep Quality Index), and walking speed. Logistic and linear regression models were used to examine how outcomes differed between genotypes and drug use, independent of the risk of cerebrovascular disease. Results In persons with a non-ε4 genotype, anticholinergic medication use did not significantly affect any of the behavioral measures. By contrast, among ε4 carriers, those taking anticholinergic drugs performed significantly worse than did those not taking such drugs on tests of general cognitive status, executive function, mood, and sleep. Adjusting for participants' stroke risk had a minimal effect on these results. Conclusions Anticholinergic medication use was associated with poorer performance on measures of cognition, sleep, and mood only in older persons who carried 1 or more ε4 alleles of the APOE gene; this effect did not appear to be the result of an increased risk of cerebrovascular disease.

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Drugs With Anticholinergic Properties, Cognitive Decline, and Dementia in an Elderly General Population

Carrière¹,

Fourrier‐Réglat²,

Dartigues³

et al. 2009

Arch Intern Med

332

243

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Increased Mental Slowing Associated With the APOE ɛ4 Allele After Trihexyphenidyl Oral Anticholinergic Challenge in Healthy Elderly

Cited by 10 publications

References 31 publications

Cognitive Slowing Associated With Elevated Serum Anticholinergic Activity in Older Individuals is Decreased by Caffeine Use

Cognitive Slowing Associated With Elevated Serum Anticholinergic Activity in Older Individuals is Decreased by Caffeine Use

The Greater Sensitivity of Elderly APOE ε4 Carriers to Anticholinergic Medications is Independent of Cerebrovascular Disease Risk

Drugs With Anticholinergic Properties, Cognitive Decline, and Dementia in an Elderly General Population

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