Apolipoprotein E epsilon4 allele and lorazepam effects on memory in high-functioning older adults

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• The apolipoprotein E (APOE) epsilon4 allele is a known risk factor for late-onset Alzheimer disease.
• Evidence linking APOE epsilon4 to cognitive changes in healthy individuals is inconsistent.

Purpose of the Study:

• To investigate if the APOE epsilon4 allele increases vulnerability to lorazepam-induced verbal learning impairment in non-demented older adults.

Main Methods:

• A placebo-controlled crossover study involving 64 cognitively intact, highly educated older adults.
• Participants included 24 APOE epsilon4 carriers and 40 non-carriers.
• Verbal learning was assessed using the Buschke Selective Reminding Test after placebo and lorazepam (0.5 and 1.0 mg) administration.

Main Results:

• Lorazepam caused a dose-dependent decrease in long-term recall up to 2.5 hours post-administration.
• At 5 hours, APOE epsilon4 non-carriers showed memory improvement, while carriers exhibited a persistent deficit.
• The memory deficit at 5 hours was primarily observed in APOE epsilon4 carriers with lower baseline cognitive performance.

Conclusions:

• The APOE epsilon4 allele may impair recovery from cognitive challenges rather than immediate drug response in older adults.
• While APOE epsilon4 increases risk for cognitive effects, it is not the sole predictor.
• Studying recovery from cognitive challenges may illuminate the role of APOE epsilon4 in Alzheimer disease and age-related cognitive decline.