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P3‐183: The impact of lorazepam on cognition on APOE–ϵ4 carriers versus noncarriers
Author(s) -
Stonnington Cynthia M.,
Snyder Peter J.,
Hentz Joseph G.,
Reiman Eric M.,
Caselli Richard J.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1749
Subject(s) - lorazepam , psychology , audiology , somnolence , verbal learning , neuropsychology , verbal memory , memory impairment , placebo , psychiatry , cognition , medicine , clinical psychology , adverse effect , alternative medicine , pathology
Background: The apolipoprotein E (APOE) 4 allele is a common Alzheimer’s disease (AD) susceptibility gene. Previously, sleepiness was negatively correlated with memory in an exploratory cross-sectional study of cognitively normal APOE4 homozygotes. If the induction of acute somnolence by lorazepam were to expose neuropsychological deficits in at-risk individuals, then it could be applied to a pharmacologic challenge for prediction of subsequent cognitive decline. Methods: Eighteen 3/4 heterozygotes (HTZ) and 18 4 noncarriers (NC), 50 to 65 years of age, all healthy and cognitively normal, participated in the study. In a double blind, crossover design, we performed neuropsychological testing before, 2.5 hours, and 5 hours after participants received a single 2 mg dose of lorazepam or placebo. Main outcome measures were the Groton Maze Learning Test (GMLT), Rey Auditory Verbal Learning Test (AVLT), and 1-Back test. NC were matched to HTZ by age and years of education. Results: At 2.5 hours after the dose of lorazepam, the GMLT total errors score (P .04) and the AVLT long-term memory ( P .01) and percent recall (P .005) measures of verbal memory were more impaired in HTZ than NC. A MANOVA comparing the vector of all six GMLT and AVLT measures for HTZ versus the vector of all six measures for NC yielded P .003 for 2.5 hours and P .58 for 5 hours. No differences between HTZ and NC were observed for measures of somnolence, speed, attention, or performance on the 1-Back test at any of the time points. At 5 hours, HTZ continued to make substantially more errors than NC ( P .17) only on the GMLT. Conclusions: Our study suggests that somnolence induced by lorazepam impairs verbal and visuospatial memory more in healthy middle-aged APOE 4 carriers than noncarriers. The results warrant further research with a larger sample to determine if lorazepam induces an even greater effect in 4 homozygotes, whether substantial lorazepam-induced memory impairment predicts subsequent onset of cognitive decline and conversion to mild cognitive impairment or AD, and whether adverse effects of clinical lorazepam administration are greater in 4 carriers.