Cognitive Resilience to Apolipoprotein E ε4

Background Several studies have shown higher Alzheimer’s disease (AD) incidence rates are in African-Americans (AAs) than Caucasians (CCs). If this finding is consistent across studies, it raises important etiologic questions regarding factors responsible for this discrepancy. It also affects the likely public health burden of AD in the US in the future, as the non-Caucasian population becomes the majority. Objective Estimate the AA/CC rate ratio for AD incidence across all available studies. Methods We conducted a meta-analysis of population-based studies for the rate ratio (RR) of AD incidence for AAs versus CCs, after identifying six relevant studies from the literature. We calculated an AA/CC rate ratio across all studies using inverse-variance weighting, and assessed inter-study heterogeneity. Using these incidence data, as well as data on survival after diagnosis, and on all-cause mortality, we also estimated the US prevalence of AD among AAs and CCs. Results There were six population-based studies with data comparing AD incidence between AAs and CCs, with an estimated 370 AA and 640 CC incident cases. The meta-analysis RR showed that the AD rate for AAs was 64% higher than for CCs (RR = 1.64 (95% CI 1.35–2.00)), with no evidence of heterogeneity. We estimated the current US AD prevalence for ages 65–90 to be 5.5% for CCs, and 8.6% for AAs (prevalence ratio 1.56). Conclusion AAs have an increased risk of incident and prevalent AD compared to CCs for reasons which are unknown, but are hypothesized to reflect biological, psychological, and socioeconomic factors.

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“…Existing data do not indicate neuropathological differences between racial groups in AD upon autopsy [33, 34], although data remain sparse.…”

Section: Discussionmentioning

confidence: 99%

A Meta-Analysis of Alzheimer’s Disease Incidence and Prevalence Comparing African-Americans and Caucasians

Steenland

Goldstein

Levey

et al. 2016

JAD

185

157

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“…The reason for this is unclear, and may be related to a variety of factors. The ε 4 allele is more common in individuals of African‐American/African descent compared with Caucasians (Farrer et al.,1997; Kern et al., 2015), and evidence suggests that ε 4 allele effects are weaker in the former (Kaup et al., 2015). Caucasian patients are more likely to have better access to healthcare and rehabilitation following TBI (Gasquoine, 2009; ).…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E epsilon 4 (APOE‐ε4) genotype is associated with decreased 6‐month verbal memory performance after mild traumatic brain injury

et al. 2017

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IntroductionThe apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear.Methods mTBI patients (Glasgow Coma Scale score 13–15, no neurosurgical intervention, extracranial Abbreviated Injury Scale score ≤1) aged ≥18 years with APOE genotyping results were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK‐TBI Pilot) study. Cohorts determined by APOE‐ε4(+/−) were assessed for associations with 6‐month verbal memory, measured by California Verbal Learning Test, Second Edition (CVLT‐II) subscales: Immediate Recall Trials 1–5 (IRT), Short‐Delay Free Recall (SDFR), Short‐Delay Cued Recall (SDCR), Long‐Delay Free Recall (LDFR), and Long‐Delay Cued Recall (LDCR). Multivariable regression controlled for demographic factors, seizure history, loss of consciousness, posttraumatic amnesia, and acute intracranial pathology on computed tomography (CT).ResultsIn 114 mTBI patients (APOE‐ε4(−)=79; APOE‐ε4(+)=35), ApoE‐ε4(+) was associated with long‐delay verbal memory deficits (LDFR: B = −1.17 points, 95% CI [−2.33, −0.01], p = .049; LDCR: B = −1.58 [−2.63, −0.52], p = .004), and a marginal decrease on SDCR (B = −1.02 [−2.05, 0.00], p = .050). CT pathology was the strongest predictor of decreased verbal memory (IRT: B = −8.49, SDFR: B = −2.50, SDCR: B = −1.85, LDFR: B = −2.61, LDCR: B = −2.60; p < .001). Seizure history was associated with decreased short‐term memory (SDFR: B = −1.32, p = .037; SDCR: B = −1.44, p = .038).ConclusionThe APOE‐ε4 allele may confer an increased risk of impairment of 6‐month verbal memory for patients suffering mTBI, with implications for heightened surveillance and targeted therapies. Acute intracranial pathology remains the driver of decreased verbal memory performance at 6 months after mTBI.

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“…There is heritability of high cognitive function into old age (143, 144). The roles of specific genes or gene polymorphisms, and epigenetic programs have been reported (114, 115, 119, 145–150). But the apparent “default” trajectory of age-related cognitive decline may be altered by physical activity, inclusive of regimented exercise, strength training, or usual activity such as walking.…”

Section: Age-dependent Accumulation Of Cd28null Nk-like T Cells With mentioning

confidence: 99%

Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging

2016

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The fundamental challenge of aging and long-term survivorship is maintenance of functional independence and compression of morbidity despite a life history of disease. Inasmuch as immunity is a determinant of individual health and fitness, unraveling novel mechanisms of immune homeostasis in late life is of paramount interest. Comparative studies of young and old persons have documented age-related atrophy of the thymus, the contraction of diversity of the T cell receptor (TCR) repertoire, and the intrinsic inefficiency of classical TCR signaling in aged T cells. However, the elderly have highly heterogeneous health phenotypes. Studies of defined populations of persons aged 75 and older have led to the recognition of successful aging, a distinct physiologic construct characterized by high physical and cognitive functioning without measurable disability. Significantly, successful agers have a unique T cell repertoire; namely, the dominance of highly oligoclonal αβT cells expressing a diverse array of receptors normally expressed by NK cells. Despite their properties of cell senescence, these unusual NK-like T cells are functionally active effectors that do not require engagement of their clonotypic TCR. Thus, NK-like T cells represent a beneficial remodeling of the immune repertoire with advancing age, consistent with the concept of immune plasticity. Significantly, certain subsets are predictors of physical/cognitive performance among older adults. Further understanding of the roles of these NK-like T cells to host defense, and how they integrate with other physiologic domains of function are new frontiers for investigation in Aging Biology. Such pursuits will require a research paradigm shift from the usual young-versus-old comparison to the analysis of defined elderly populations. These endeavors may also pave way to age-appropriate, group-targeted immune interventions for the growing elderly population.

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Cognitive Resilience to Apolipoprotein E ε4

Cited by 71 publications

References 35 publications

A Meta-Analysis of Alzheimer’s Disease Incidence and Prevalence Comparing African-Americans and Caucasians

A Meta-Analysis of Alzheimer’s Disease Incidence and Prevalence Comparing African-Americans and Caucasians

Apolipoprotein E epsilon 4 (APOE‐ε4) genotype is associated with decreased 6‐month verbal memory performance after mild traumatic brain injury

Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging

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