Age, Sex, and<i>APOE</i>ε4 Effects on Memory, Brain Structure, and β-Amyloid Across the Adult Life Span

Jack, Clifford R.; Wiste, Heather J.; Weigand, Stephen D.; Knopman, David S.; Vemuri, Prashanthi; Mielke, Michelle M.; Lowe, Val J.; Senjem, Matthew L.; Gunter, Jeffrey L.; Machulda, Mary M.; Gregg, Brian E.; Pankratz, V. Shane; Rocca, Walter A.; Petersen, Ronald C.

doi:10.1001/jamaneurol.2014.4821

Cited by 321 publications

(311 citation statements)

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“…We also found sex differences in florbetapir uptake, in contrast to prior studies, 3 with more amyloid positivity in women. Some epidemiologic data have suggested that age-adjusted incidence of AD is higher in women, 32 and our data suggest that this may be through more amyloid deposition.…”

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confidence: 79%

“…Use of PET ligands that bind to Ab allows for the evaluation of Ab in persons with or without clinical symptoms. Although a recent meta-analysis reported positive amyloid scans in 10% of healthy 50-to 90-year-old participants, and in 27% of similarly aged adults with mild cognitive impairment (MCI), 1 few studies in persons of European extraction 2,3 have evaluated patterns of Ab deposition using PET, and none in black participants, to our knowledge. Using Ab imaging in a biracial cohort would allow further exploration of racial disparities in dementia etiology.…”

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confidence: 97%

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The ARIC-PET amyloid imaging study

et al. 2016

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Objective: To evaluate differences in amyloid deposition in a community-based cohort without dementia by age, sex, race, education, and APOE e4 allele status. Methods:Recruited from the longitudinal Atherosclerosis Risk in Communities study, 329 participants without dementia, ages 67-88 years, were imaged using florbetapir PET at 3 US community sites (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi). Standardized uptake value ratios (SUVRs) were calculated; global cortical SUVR .1.2 was evaluated as the primary outcome. Age, race, sex, education level, and number of APOE e4 alleles were evaluated in multivariable models including vascular risk factors, brain white matter hyperintensity and total intracranial volume, and cognitive status.Results: A total of 141 of the participants (43%) were black. In multivariable models, odds of elevated SUVR was increased in participants with increasing age (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.01-2.65 per 10 years of age) and black race (OR 2.08, 95% CI 1.23-3.51) but did not differ by educational level. Each e4 allele was associated with increased odds of elevated SUVR (OR 2.65, 95% CI 1.61-4.39).Conclusions: In this community-based cohort without dementia, florbetapir uptake is associated with older age and APOE genotype. Black race was associated with higher SUVR, after adjusting for demographics, vascular risk factors, cognitive status, white matter hyperintensity volume, and APOE genotype, with effect sizes nearing those seen for APOE e4. Replication of these findings is needed in other cohorts, and reasons for and consequences of these observed differences by race warrant further study. The prevailing hypothesis behind the pathophysiology of Alzheimer disease (AD) focuses on the accumulation of brain amyloid in b-amyloid (Ab) plaques as a critical mechanism. Use of PET ligands that bind to Ab allows for the evaluation of Ab in persons with or without clinical symptoms. Although a recent meta-analysis reported positive amyloid scans in 10% of healthy 50-to 90-year-old participants, and in 27% of similarly aged adults with mild cognitive impairment (MCI), 1 few studies in persons of European extraction 2,3 have evaluated patterns of Ab deposition using PET, and none in black participants, to our knowledge. Using Ab imaging in a biracial cohort would allow further exploration of racial disparities in dementia etiology.Dementia is more prevalent in blacks than in whites, 4-6 although AD-type neuropathologic findings are found on autopsy with equal prevalence in both groups. 7,8 Thus, a larger component

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confidence: 97%

The ARIC-PET amyloid imaging study

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“…However, when examining the sample split by gender, the negative association only remained for the women. Although the propensity of the literature supports similar age‐related hippocampal volume loss for men and women (Jack et al., 2015; Mu, Xie, Wen, Weng, & Shuyun, 1999; Raz et al., 2004, 2005), there are reports of both women‐ and men‐specific age–hippocampal volume relationships (Murphy et al.,1996; Pruessner et al., 2001). For the current sample, the lack of significant association in the men may be explained by this gender not experiencing a similar age‐related trajectory in hippocampal volume, and therefore not experiencing the benefits of CRF on hippocampal volume.…”

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Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease

et al. 2017

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IntroductionCardiorespiratory fitness (CRF) has been shown to be related to brain health in older adults. In individuals at risk for developing Alzheimer's disease (AD), CRF may be a modifiable risk factor that could attenuate anticipated declines in brain volume and episodic memory. The objective of this study was to determine the association between CRF and both hippocampal volume and episodic memory in a cohort of cognitively healthy older adults with familial and/or genetic risk for Alzheimer's disease (AD).MethodsEighty‐six enrollees from the Wisconsin Registry for Alzheimer's Prevention participated in this study. Participants performed a graded maximal exercise test, underwent a T‐1 anatomical magnetic resonance imaging scan, and completed the Rey Auditory Verbal Learning Test (RAVLT).ResultsThere were no significant relationships between CRF and HV or RAVLT memory scores for the entire sample. When the sample was explored on the basis of gender, CRF was significantly associated with hippocampal volume for women. For men, significant positive associations were observed between CRF and RAVLT memory scores.SummaryThese results suggest that CRF may be protective against both hippocampal volume and episodic memory decline in older adults at risk for AD, but that the relationships may be gender specific.

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“…We performed MRI studies at 3T (Signa; GE Healthcare, Waukesha, WI) with an 8-channel phased-array head coil, acquiring both a 3D magnetizationprepared rapid-acquisition gradient echo (MPRAGE) sequence and a fluid-attenuated inversion recovery sequence. 19 From each participant's MPRAGE, we measured hippocampal volume (HV) using FreeSurfer software (version 5.3), which was then adjusted for total intracranial volume. 20 Cortical (0.10 mm) and subcortical infarctions (white matter [WM], central gray matter [GM], cerebellum, brainstem) were ascertained by experienced image analysts and confirmed by a radiologist.…”

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Multimorbidity and neuroimaging biomarkers among cognitively normal persons

et al. 2016

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Objective: To assess the cross-sectional association between multimorbidity and imaging biomarkers of brain pathology in the population-based Mayo Clinic Study of Aging (MCSA). Methods:The study consisted of 1,449 MCSA participants who were cognitively normal at the time of MRI. A subset of the participants also had 11 C-Pittsburgh compound B (n 5 689) and 18 fluorodeoxyglucose (n 5 688) PET scans available. Information on multimorbidity (defined as $2 chronic conditions) in the 5 years prior to the first imaging study was captured from the medical record using ICD-9 codes for chronic conditions and the Rochester Epidemiology Project medical records linkage system. The cross-sectional association of multimorbidity and imaging biomarkers was examined using logistic and linear regression models.Results: Among 1,449 cognitively normal participants (mean age 79 years; 50.9% men), 85.4% had multimorbidity ($2 chronic conditions). Multimorbidity and severe multimorbidity ($4 chronic conditions) were associated with abnormal Alzheimer disease (AD) signature meta-region of interest (meta-ROI) 18 Conclusions: Multimorbidity was associated with brain pathology through mechanisms independent of amyloid deposition and such neuronal injury and pathology was present before any symptomatic evidence of cognitive impairment. Longitudinal follow-up will provide insights into potential causal associations of multimorbidity with changes in brain pathology. Multimorbidity has a prevalence of 20%-30% in the general population, 1 and increases with age from 55% to 98% among persons older than 60 years.1 Multimorbidity is becoming the norm among adults in primary care settings, 2 mandating the need to investigate not only the causes, but also the association with future health outcomes. Multimorbidity is associated with an increased risk for hospitalizations and increased length of stay, worsening quality of life and physical functioning, polypharmacy, mild cognitive impairment, 3 and depression, resulting in significant economic costs for the health care system.2 Several of the common chronic conditions that contribute to multimorbidity are established risk factors for mild cognitive impairment (MCI) or dementia (e.g., vascular diseases, cerebrovascular disease, depression, or chronic obstructive pulmonary disease).3-8 We hypothesized, therefore, that multimorbidity may also be associated with abnormal brain imaging findings that are characteristically present in persons with Alzheimer disease (AD) dementia, but this association has not been studied. Thus, the objective of this study was to determine the cross-sectional associations between multimorbidity From the Departments of Health Sciences Research

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Age, Sex, andAPOEε4 Effects on Memory, Brain Structure, and β-Amyloid Across the Adult Life Span

Cited by 321 publications

References 60 publications

The ARIC-PET amyloid imaging study

The ARIC-PET amyloid imaging study

Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease

Multimorbidity and neuroimaging biomarkers among cognitively normal persons

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