Apolipoprotein epsilon4 and neuropsychological performance in Alzheimer's disease and vascular dementia (original) (raw)
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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...
Proceedings of the …, 2010
The epsilon4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer's disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the epsilon4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of epsilon4 carriers (n = 67) vs. noncarriers (n = 24) with mild AD from the Alzheimer's Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.
Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society, 2014
The ε4 alelle of the apolipoprotein E gene is known to be a key genetic risk factor for Alzheimer's disease and possibly for other neurological disorders. Some evidence in the literature indicates that the ε4 allele interferes with human cognition independently of chronological age and diagnosis of Alzheimer's disease. The present study investigated the correlation of allelic variants of apolipoprotein E with the cognitive performance of elderly individuals without apparent cognitive impairment. This was a cross-sectional analysis that included 213 non-demented elderly individuals (age ≥60 years) from the Brazilian Federal District. The analysis assessed the subjects for cognitive domains including short- and long-term episodic memory, processing speed, and attention and executive functions. Sociodemographic and other clinical characteristics were gathered and analyzed as covariates. Being sufficiently powered, the present study did not identify differential performance acro...
Journal of Neurology, Neurosurgery & Psychiatry, 1996
Background and objectives-Apolipoprotein E (apoE) has been implicated in regenerative processes in the brain after trauma, as well as in the pathogenesis of Alzheimer's disease. Inheritance of a specific apoe allele (apoe4) determines in part the risk and the mean age at onset of Alzheimer's disease. ApoE has been found to bind isoform specifically to ,-amyloid protein, the major component of senile plaques, and to the microtubule associated protein tau, which forms paired helical filaments and neurofibrillary tangles. The aim was to further examine the relation between apoe alleles, especially apoe4, and the development of neuropathological changes associated with Alzheimer's disease. Methods-Brains of patients with Alzheimer's disease (n = 44) and vascular dementia (n = 11) and of age matched controls (n = 29) were studied. Senile plaques and neurofibrillary tangles in the hippocampus and frontal cortex were quantified. Results-No correlation was found between the number of apoe4 alleles and the number of senile plaques and neurofibrillary tangles in the hippocampus or the frontal cortex of patients with Alzheimer's disease, or vascular dementia, or control groups. No significant differences in duration or severity of dementia were found between patients with or without the apoe4 allele. No increased frequency of apoe4 was found in vascular dementia. Conclusion and comment-Although the apoe genotype clearly affects whether Alzheimer's disease will develop or not, the present study suggests that it has no influence on pathology or clinical intellectual status, once the dementia has manifested itself. No increased apoe4 allele frequency was found in neuropathologically diagnosed patients with vascular dementia in whom concomitant Alzheimer's disease can be excluded.
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.
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:
1998
SUMMARY To better de®ne the in¯uence of apolipoprotein E (ApoE) e4 genotype on the cognitive and biochemical features of Alzheimer's disease (AD), cross-sectional analysis of global cognitive measures and cerebrospinal ¯uid studies gathered on AD subjects at a tertiary care facility between 1986 and 1997 was carried out. The 112 AD patients examined included 62 women and 50 men with a mean (SD) age of 64.2 (9.2) years. Patient demographics, illness onset age and duration, education level and global cognitive measures were recorded systematically. Genetic analysis for ApoE allele type and biochemical characterization of CSF, including total tau concentration, was performed. Descriptive statistics of demographics, cognitive and CSF measures were performed by chi-square, ANOVA and Tukey's tests. Overrepresentation of the e4 allele was found, with 45.5% of AD patients heterozygous and 20.5% homozygous for ApoE e4. Overall, ApoE e4 status had no eect on mean onset age of AD (F 1.56; p 0.214), but an earlier mean onset age of AD (F 4.10; p 0.02) was seen in the late-onset subjects. No dierences were found with regard to ApoE e4 status and measures of disease, duration of illness or global cognitive performance. Although CSF tau was elevated in our sample (575.4+290.3 pg/ml), ApoE e4 status did not in¯uence total CSF tau or neurotransmitter metabolite levels. ApoE e4 genotype had no impact on a variety of illness severity, cognitive and CSF examinations in the largest cross-sectional analysis of AD subjects yet reported. # 1998 US Government.