Effect of apolipoprotein E4 on clinical, neuroimaging, and biomarker measures in noncarrier participants in the Dominantly Inherited Alzheimer Network

Bussy, Aurélie; Snider, B. Joy; Coble, Dean W.; Xiong, Chengjie; Fagan, Anne M.; Cruchaga, Carlos; Benzinger, Tammie L.S.; Gordon, Brian A.; Hassenstab, Jason; Bateman, Randall J.; Morris, John C.

doi:10.1016/j.neurobiolaging.2018.10.011

Cited by 41 publications

(28 citation statements)

References 64 publications

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“…Higher prevalence of dementia was found among the younger elderly, aged 65-69 years, in Latin American countries compared with developed nations, whereas the older elderly presented a higher rate of dementia in developed countries (3) . These findings corroborate those of studies associating differences in functional or cognitive performance with social, ethnic, economic, cultural or demographic diversity (4,5,6,7) , as well as with genetic factors (8) . Cognitive-behavioral and functional-structural changes may occur as a result of education, a multidimensional variable that encompasses quality of life, socioeconomic level, and activities of daily living (9) .…”

Section: Introductionsupporting

confidence: 88%

Narrative discourse of young and older brazilian adults associated with demographic factors

Luchesi

Silva

2020

CoDAS

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Purpose: 1) Compare the discourse performance between young and older adults from the Brazilian Federal District (DF); 2) Compare the mean discourse performance of participants from the DF with the normative discourse of a population from a different region of the country; 3) Verify whether the variables age, educational level and socioeconomic status and scores on the cognitive, behavioral and functional screening tests were associated with discourse performance. Method: A total of 60 healthy volunteers from the DF, 30 older adults and 30 young adults, were selected. Participants were divided into two subgroups according to educational level: low education and high education. The four narrative discourse subtests of the Montreal Communication Evaluation Battery, Brazilian Portuguese version (MAC-BR) were applied to the study sample. Results: Discourse scores of the older adults were statistically higher than those of the young adults. The discourse scores in the high education group were also better than those in the low education group, with statistically significant difference observed in only one of the MAC-BR subtests. Discourse performance was associated with the sociodemographic variable and the scores on the cognitive and functional screening tests. The discourse performance of the DF sample differed from the national normative discourse with statistically significant difference. Conclusion: The discourse performance of older adults from the Brazilian Federal District differed from that of young adults from the same region, as well as from that of older adults from southern Brazil. Discourse performance was associated with several different variables.

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Section: Introductionsupporting

confidence: 88%

Narrative discourse of young and older brazilian adults associated with demographic factors

Luchesi

Silva

2020

CoDAS

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“…Interestingly, the APOE gene has three common alleles encoding three protein isoforms: ApoE2, ApoE3, and ApoE4. During the preclinical phase of AD, carriers of the ApoE4 allele increase cerebral amyloid deposition at an earlier age and do so faster than non-carriers (Grimmer et al, 2010;Morris et al, 2010;Risacher et al, 2013;Bussy et al, 2019). Apolipoprotein E seems to exert its effects on neurodegeneration independently from Aβ plaques by modulating tau pathology.…”

Section: Apolipoprotein E and The Inflammatory Hypothesismentioning

confidence: 99%

Alzheimer’s Disease: What Can We Learn From the Peripheral Olfactory System?

et al. 2020

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The sense of smell has been shown to deteriorate in patients with some neurodegenerative disorders. In Parkinson's disease (PD) and Alzheimer's disease (AD), decreased ability to smell is associated with early disease stages. Thus, olfactory neurons in the nose and olfactory bulb (OB) may provide a window into brain physiology and pathophysiology to address the pathogenesis of neurodegenerative diseases. Because nasal olfactory receptor neurons regenerate throughout life, the olfactory system offers a broad variety of cellular mechanisms that could be altered in AD, including odorant receptor expression, neurogenesis and neurodegeneration in the olfactory epithelium, axonal targeting to the OB, and synaptogenesis and neurogenesis in the OB. This review focuses on pathophysiological changes in the periphery of the olfactory system during the progression of AD in mice, highlighting how the olfactory epithelium and the OB are particularly sensitive to changes in proteins and enzymes involved in AD pathogenesis. Evidence reviewed here in the context of the emergence of other typical pathological changes in AD suggests that olfactory impairments could be used to understand the molecular mechanisms involved in the early phases of the pathology.

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“…Some studies show accelerated cognitive decline in APOE ε4 homozygotes but not heterozygotes [13][14][15]. Furthermore, the association between APOE ε4 and cognition is thought to be modified by age; some [16][17][18] but not all studies [19,20] report better cognitive performance among ε4 carriers at younger ages. The antagonistic pleiotropy hypothesis [21,22], whereby a gene is thought to have different effects on health during different life stages, is a possible explanation for the age-varying association of APOE ε4 with cognitive performance over the life course [18,22,23].…”

Section: Introductionmentioning

confidence: 99%

The association of APOE ε4 with cognitive function over the adult life course and incidence of dementia: 20 years follow-up of the Whitehall II study

et al. 2021

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Background Approximately 25% of the general population carries at least one ε4 allele of the Apolipoprotein E (APOE ε4), the strongest genetic risk factor for late onset Alzheimer’s disease. Beyond its association with late-onset dementia, the association between APOE ε4 and change in cognition over the adult life course remains uncertain. This study aims to examine whether the association between Apolipoprotein E (APOE) ε4 zygosity and cognition function is modified between midlife and old age. Methods A cohort study of 5561 participants (mean age 55.5 (SD = 5.9) years, 27.1% women) with APOE genotyping and repeated cognitive tests for reasoning, memory, and semantic and phonemic fluency, during a mean (SD) follow-up of 20.2 (2.8) years (the Whitehall II study). We used joint models to examine the association of APOE genotype with cognitive function trajectories between 45 and 85 years taking drop-out, dementia, and death into account and Fine and Gray models to examine associations with dementia. Results Compared to non-carriers, heterozygote (prevalence 25%) and homozygote (prevalence 2%) APOE ε4 carriers had increased risk of dementia, sub-distribution hazard ratios 2.19 (95% CI 1.73, 2.77) and 5.97 (95% CI 3.85, 9.28) respectively. Using data spanning 45–85 years with non-ε4 carriers as the reference, ε4 homozygotes had poorer global cognitive score starting from 65 years; ε4 heterozygotes had better scores between 45 and 55 years, then no difference until poorer cognitive scores from 75 years onwards. In analysis of individual cognitive tests, better cognitive performance in the younger ε4 heterozygotes was primarily attributable to executive function. Conclusions Both heterozygous and homozygous ε4 carriers had poorer cognition and greater risk of dementia at older ages. Our findings show some support for a complex antagonist pleiotropic effect of APOE ε4 heterozygosity over the adult life course, characterized by cognitive advantage in midlife.

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Effect of apolipoprotein E4 on clinical, neuroimaging, and biomarker measures in noncarrier participants in the Dominantly Inherited Alzheimer Network

Cited by 41 publications

References 64 publications

Narrative discourse of young and older brazilian adults associated with demographic factors

Narrative discourse of young and older brazilian adults associated with demographic factors

Alzheimer’s Disease: What Can We Learn From the Peripheral Olfactory System?

The association of APOE ε4 with cognitive function over the adult life course and incidence of dementia: 20 years follow-up of the Whitehall II study

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