Memory performance in healthy elderly without Alzheimer's disease: effectsof time and apolipoprotein-E

Transgenic mice expressing human APOE-epsilon4 develop an age-dependent dec line in memory without pathological features of Alzheimer's disease (AD). T his implicates APOE in the maintenance of memory during normal senescence, but parallel human studies are limited because longitudinal investigations of memory usually do not exclude patients with AD or "questionable" AD (QD) . The current study examined the effect of APOE on cognitive function over rime in elderly without dementia. We hypothesised that, compared to other A POE alleles memory decline even in healthy elderly would be greater among t hose with an APOE-epsilon4. The results of neuropsychological tests. grouped into domains of memory, la nguage and visuospatial/cognitive function by factor analysis, were examine d at three intervals over a seven-year period in 563 healthy elderly withou t AD or QD using generalized estimating equations. Memory performance decli ned over time. while scores on the visuospatial/cognitive and language fact ors did not change. Increased age was associated with lower scores, and hig her education with higher scores on all factors at each interval, No APOE a llele was associated with performance on a specific cognitive factor at any interval, but the presence of an APOE-epsilon4 allele was associated with a more rapid decline in the memory factor over the follow-up period. The ef fect was most pronounced among individuals with less than 10 years of forma l education. There was no similar time-dependent relationship between APOE- epsilon4 and the language or visuospatial/cognitive factors. Transgenic mice and elderly humans without AD or QD expressing APOE-epsilon 4 show a decline in memory performance over time. These observations provid e evidence for an APOE-specific effect on memory during senescence. (C) 200 1 Elsevier Science Inc. All rights reserved.