Selective familiarity deficits in otherwise cognitively intact aging individuals with genetic risk for Alzheimer's disease (original) (raw)
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Archives of Neurology, 2009
To evaluate the influences of a family history of Alzheimer dementia (FHxAD) and the apolipoprotein E ε4 genotype (APOE ε4) on cognitive decline. Design, Setting, and Participants: Residents of Cache County, Utah, aged 65 years or older, were invited to participate. At baseline, 2957 participants provided DNA for genotyping of APOE and a detailed FHxAD. They also completed the Modified Mini-Mental State Examination. Cognitive status was reexamined after 3 and 7 years. We used mixed-effects models to examine the association among FHxAD, APOE ε4, and cognitive trajectories. Main Outcome Measure: Modified Mini-Mental State Examination score trajectories over time. Results: Compared with participants who did not have APOE ε4 or an FHxAD, those with APOE ε4 scored lower on the Modified Mini-Mental State Examination at base-line (−0.70 points; 95% confidence interval [CI], −1.15 to −0.24). Participants with an FHxAD and APOE ε4 differed less, if at all, in baseline score (−0.46 points; 95% CI, −1.09 to 0.16) but declined faster during the 7-year study (−9.75 points [95% CI, −10.82 to −8.67] vs −2.91 points [95% CI, −3.37 to −2.44]). After exclusion of participants who developed prodromal AD or incident dementia, the group with an FHxAD and APOE ε4 declined much less during the 7-year study (−1.54; 95% CI, −2.59 to −0.50). Conclusions: Much of the association among FHxAD, APOE ε4, and cognitive decline may be attributed to undetected incipient (latent) disease. In the absence of latent disease, the 2 factors do not appear individually to be associated with cognitive decline, although they may be additive.
High apolipoprotein E ε4 allele frequency in Age-related memory decline
Annals of Neurology, 1996
Many studies have demonstrated a strong association between the presence of one or two ~4 alleles and Alzheimer's disease (AD), although few data are available on the apolipoprotein E (APOE) ~4 frequencies at the preclinical stages of AD. Thus, with a view to determining whether APOE genotyping could be useful in the early detection of AD, we determined the APOE allele frequencies in patients with memory complaints without dementia (age-related memory decline, ARMD). We found an APOE ~4 allele frequency of 0.315 in the ARMD group, similar to 0.293 in the AD group, in contrast to 0.057 in the control group. Significant differences ( t = -2.91, df = 25, p = 0.008) were found between the Alzheimer's Disease Assessment Scale (ADAS) total scores in the ARMD patients with at least one ~4 allele (mean = 24.2) compared with the ARMD patients without the ~4 allele (mean = 14.7). Our results suggest that the patients with memory complaints, a high ADAS score, and the presence of one or two APOE-4 alleles could be at high risk for developing AD. Thus, we propose that genotyping in conjunction with the ADAS scale may prove useful as diagnostic markers of AD in the presymptomatic stages.
Prospective memory and apolipoprotein e in healthy aging and early stage Alzheimer's disease
Neuropsychology, 2006
The present study examined whether prospective memory performance discriminates healthy aging from very mild dementia of the Alzheimer type (DAT) and individuals at risk for DAT due to the presence of the ApoE ε4 allele. Four groups of subjects (young adults, young-old controls, old-old controls, very mild DAT) engaged in an event-based prospective memory task wherein they responded to a specific word embedded in a general knowledge test. Results indicated that prospective memory performance was clearly impaired in the very mild DAT group relative to the healthy older control groups. Moreover, prospective memory performance appears to capture unique variance in discriminating these two groups above and beyond standard retrospective memory tests. However, prospective memory was not affected by ApoE status in the young-old control group and contrary to predictions, the ε4 + old-old controls showed better performance than the ε4 -subjects. In contrast to the healthy individuals, in the very mild DAT group, ε4 + subjects showed deficits in performance relative to the ε4 -subjects. Discussion focuses on prospective memory as a cognitive indicator of early stage DAT.
The apolipoprotein E gene and its age-specific effects on cognitive function
2010
The E4 allele of the apolipoprotein E gene (APOE) is a well-established determinant of Alzheimer's disease but its relation to cognitive function is much less understood. We studied the age-specific effects of the APOE* E4 allele on cognitive function and cardiovascular risk factors in 2208 related individuals. APOE* E4 allele was significantly associated with reduced test scores for Adult Verbal Learning Test, particularly on the memory and learning sub domains, in persons older than 50 years of age.
Apolipoprotein E ɛ4–related effects on cognition are limited to the Alzheimer’s disease spectrum
GeroScience
Whether the deleterious effects of APOE4 are restricted to the Alzheimer’s disease (AD) spectrum or cause cognitive impairment irrespectively of the development of AD is still a matter of debate, and the focus of this study. Our analyses included APOE4 genotype, neuropsychological variables, amyloid-βeta (Aβ) and Tau markers, FDG-PET values, and hippocampal volumetry data derived from the healthy controls sample of the ADNI database. We formed 4 groups of equal size (n = 30) based on APOE4 carriage and amyloid-PET status. Baseline and follow-up (i.e., 48 months post-baseline) results indicated that Aβ-positivity was the most important factor to explain poorer cognitive performance, while APOE4 only exerted a significant effect in Aβ-positive subjects. Additionally, multiple regression analyses evidenced that, within the Aβ-positive sample, hippocampal volumetry explained most of the variability in cognitive performance for APOE4 carriers. These findings represent a strong support fo...
Dementia and Geriatric Cognitive Disorders, 2004
The presence of the apolipoprotein E (APOE) Â4 allele is a definite risk factor for the onset of Alzheimer's disease (AD). Its presence seems to affect especially the memory in the early stage of the disease, but the effect on the progression of the disease and survival is still controversial. Some longitudinal studies could be influenced by variables other than APOE, such as the response to medical treatment, rehabilitation therapy and inclusion of patients at different stages of progression at baseline. Moreover, the inclusion in the same study sample of patients of different ages at onset of the disease (below 65 or above 80 years) appears arbitrary. In our study, we evaluated a population of newly diagnosed untreated AD patients at their first neuropsychological examination and with the onset of their first symptoms not longer than 3 years ago. In order to analyse the different effects of the APOE Â4 allele on the different ages at the onset of the disease, we split the study sample into two groups:
Psychology and Aging, 1998
This study examined whether baseline cognitive performance and 3-year longitudinal changes were influenced by apolipoprotein E e4 (APOE-c4) allele. Participants consisted of 20 APOE-e4 (2 e2/e4; 17 £3/«4; 1 e4/e4) and 54 non-e4 (12 e2/t3; 42 e3/e3) very old adults without dementia (M = 81.82 ± 5.06 years) participating in a population-based longitudinal study. Cognitive performance was indexed by the Mini-Mental State Examination and multiple indexes of memory, visuospatial, and verbal performance. The results indicated no significant baseline differences between the 2 APOE groups in any cognitive performance measure. However, analyses revealed that the APOE-e4 group experienced greater negative change in recognition memory for faces and words. Changes in tasks assessing other abilities did not vary as a function of APOE status. The authors concluded that APOE-e4 status may not influence cognitive performance in adults without dementia and speculated that when such effects do occur (e.g., decline in recognition memory), these may be related to impending dementia, rather than to the influence of the specific genotype on cognition in normal aging.
Journal of the International Neuropsychological Society, 2004
The aim of the study was to determine whether the «4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the «4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale-Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of «4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an «4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative «4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies.