Minority Aging Research Study Research Articles

The Effects of APOE Alleles, Cognitive Activities, and Social Activities on Cognitive Decline in African Americans.

Older African Americans are among the fastest growing populations, yet are underrepresented in studies examining risk factors related to decline. The present study examines whether biological factors (APOE alleles) interact with behavioral factors including cognitive activities (e.g., reading, playing games) and social activities (e.g., participating in social groups) to predict cognitive decline in African Americans. 734 African American adults from the Minority Aging Research Study (MARS), aged 65 and older (with no known dementia at the time of enrollment) underwent annual cognitive testing for up to 10 years. At baseline, APOE status was determined and participants reported their frequency of participation in social and cognitive activities. Structural equation modelling was used to examine the effects of APOE, cognitive activities, and social activities on cognitive decline, and their interaction effects over a ten-year period. The number of APOE alleles had an effect on cognitive decline, such that a greater number of APOE4 alleles was associated with greater cognitive decline, whereas a greater number of APOE2 alleles was associated with less cognitive decline. Cognitive and social activities did not interact with APOE count to predict cognitive decline, however, APOE4 and social activities had additive, independent effects on cognitive decline. Results replicate prior findings linking APOE4 to cognitive decline and highlight the importance of APOE2 and social activities in delaying cognitive decline in African Americans.

Depression, loneliness, and lower social activity as partial mediators of the association between visual impairment and cognitive decline.

Sensory impairment is a hypothesized risk factor for cognitive decline; however, the psychosocial pathways are not well understood. We evaluated whether the association between visual impairment (VI) and cognitive decline was partially mediated via depressive symptoms, loneliness, or social activity. We used data from 2601 older adults enrolled in the Memory and Aging Project in 1997 and the Minority Aging Research Study in 2004 with neuropsychological tests across five domains measured annually for up to 16years. VI was assessed with the Rosenbaum Pocket Vision Screener. Depressive symptoms, loneliness, and social activity were self-reported using validated scales. We used structural equation models to estimate the associations of VI with baseline and change in cognitive function, directly and indirectly through each mediator (depressive symptoms, loneliness, and social activity). We evaluated mediation via "psychological distress" using a latent variable combining depressive symptoms and loneliness. The association between VI and global cognitive decline was mediated via lower social activity (indirect effect) [95% confidence interval (CI)] of linear slope: -0.025 (-0.048, -0.011), via loneliness (-0.011 [95% CI: -0.028, -0.002]), and via psychological distress (-0.017 [95% CI: -0.042, -0.003]). We did not find sufficient evidence for mediation via depressive symptoms alone. The harmful effect of VI on cognitive decline may be partially mediated through loneliness and lower social activity.

The time course of motor and cognitive decline in older adults and their associations with brain pathologies: a multicohort study

Many studies have reported that impaired gait precedes cognitive impairment in older people. We aimed to characterise the time course of cognitive and motor decline in older individuals and the association of these declines with the pathologies of Alzheimer's disease and related dementias. This multicohort study used data from three community-based cohort studies (Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study, all in the USA). The inclusion criteria for all three cohorts were no clinical dementia at the time of enrolment and consent to annual clinical assessments. Eligible participants consented to post-mortem brain donation and had post-mortem pathological assessments and three or more repeated annual measures of cognition and motor functions. Clinical and post-mortem data were analysed using functional mixed-effects models. Global cognition was based on 19 neuropsychological tests, a hand strength score was based on grip and pinch strength, and a gait score was based on the number of steps and time to walk 8 feet and turn 360°. Brain pathologies of Alzheimer's disease and related dementias were assessed at autopsy. From 1994 to 2022, there were 1570 eligible cohort participants aged 65 years or older, 1303 of whom had cognitive and motor measurements and were included in the analysis. Mean age at death was 90·3 years (SD 6·3), 905 (69%) participants were female, and 398 (31%) were male. Median follow-up time was 9 years (IQR 5-11). On average, cognition was stable from 25 to 15 years before death, when cognition began to decline. By contrast, gait function and hand strength declined during the entire study. The combinations of pathologies of Alzheimer's disease and related dementias associated with cognitive and motor decline and their onsets of associations varied; only tau tangles, Parkinson's disease pathology, and macroinfarcts were associated with decline of all three phenotypes. Tau tangles were significantly associated with cognitive decline, gait function decline, and hand function decline (p<0·0001 for each); however, the association with cognitive decline persisted for more than 11 years before death, but the association with hand strength only began 3·57 years before death and the association with gait began 3·49 years before death. By contrast, the association of macroinfarcts with declining gait function began 9·25 years before death (p<0·0001) compared with 6·65 years before death (p=0·0005) for cognitive decline and 2·66 years before death (p=0·024) for decline in hand strength. Our findings suggest that average motor decline in older adults precedes cognitive decline. Macroinfarcts but not tau tangles are associated with declining gait function that precedes cognitive decline. This suggests the need for further studies to test if gait impairment is a clinical proxy for preclinical vascular cognitive impairment. National Institutes of Health.

Purpose in Life and Its Association to Parkinsonism.

Purpose in life has been associated with diverse health outcomes; however, few studies have examined its associations with progressive motor decline in older adults. We tested if higher purpose would be associated with lower likelihood of incident parkinsonism as well as with lower levels and slower rates of increase in parkinsonian signs. Participants were 2,626 older adults from the Rush Memory and Aging Project and Minority Aging Research Study followed for an average of 7.2 years (standard deviation [SD] = 4.6). Purpose was measured using the purpose in life subscale of the modified Ryff's and Keyes's measure of psychological well-being. Four parkinsonian signs (i.e., parkinsonian gait, rigidity, bradykinesia, and tremor) were assessed using the United Parkinson's Disease Rating Scale. We examined purpose with risk of developing incident parkinsonism using Cox proportional hazards models. We also used linear mixed-effect models to assess the association between purpose and parkinsonian sign trajectories. After including demographics, health conditions, and health behaviors in the model, for a 1-SD increase in purpose, the hazards ratio for incident parkinsonism was 0.88 (95% confidence interval [CI] 0.80, 0.97). A 1-SD increase in purpose was associated with a -0.19 (95% CI -0.24, -0.15) point lower score in the global parkinsonian summary score at baseline but no differences in rate of change were evident. Higher purpose was associated with lower hazards of incident parkinsonism and lower levels of parkinsonian signs at baseline. Associations were seen even after adjustment for a wide range of covariates. Findings suggest higher purpose may contribute to maintenance of healthy physical function among older adults.

Estimating dementia risk in an African American population using the DCTclock.

The prevalence of Alzheimer's disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptation of the well-established clock drawing test. The DCTclock can estimate dementia risk for both general cognitive impairment and the presence of AD pathology. Here we performed a retrospective analysis to assess the performance of the DCTclock to estimate future conversion to ADRD in African American participants from the Rush Alzheimer's Disease Research Center Minority Aging Research Study (MARS) and African American Clinical Core (AACORE). We assessed baseline DCTclock scores in 646 participants (baseline median age = 78.0 ± 6.4, median years of education = 14.0 ± 3.2, 78% female) and found significantly lower baseline DCTclock scores in those who received a dementia diagnosis within 3 years. We also found that 16.4% of participants with a baseline DCTclock score less than 60 were significantly more likely to develop dementia in 5 years vs. those with the highest DCTclock scores (75-100). This research demonstrates the DCTclock's ability to estimate the 5-year risk of developing dementia in an African American population. Early detection of elevated dementia risk using the DCTclock could provide patients, caregivers, and clinicians opportunities to plan and intervene early to improve cognitive health trajectories. Early detection of dementia risk can also enhance participant selection in clinical trials while reducing screening costs.

DISCRIMINATION IS ASSOCIATED WITH HIGHER ODDS OF HOSPITALIZATIONS AMONG OLDER AFRICAN AMERICANS

Abstract Everyday discrimination—experiences of being treated unfairly based on background characteristics like race—is linked to poor physical and mental health throughout the lifespan. Whether more experiences of discrimination are associated with higher likelihood of being hospitalized in older African Americans has not been explored. Hospitalization can represent both poor health and healthcare access. Participants were community-dwelling African Americans from the Rush Memory and Aging Project or Minority Aging Research Study, longitudinal studies of aging (N=301 with at least 12 months linked Medicare fee-for-service claims; mean age 72.5 years (standard deviation [SD]: 5.7), 79% female). Discrimination was assessed using the Detroit Area Study Everyday Discrimination Scale. Hospitalizations (sub-categorized as elective/non-elective, surgical) were quantified using Medicare claims. Mixed-effects ordinal logistic regression models tested associations between baseline discrimination and subsequent odds of hospitalizations per year (0, 1, 2+). The mean baseline discrimination score was 1.7 (SD: 2.2). Over an average 6.5 years (SD: 4.1), 160 participants had at least 1 hospitalization (respectively, 118, 87, and 127 participants had at least 1 nonelective, elective, or surgical hospitalization). Adjusting for age, sex, education, income, depressive symptoms, and medical comorbidity, more experiences of discrimination were associated with higher odds of hospitalization (odds ratio [OR] per point higher on discrimination score=1.12, 95% CI: 1.03-1.22), and higher odds of nonelective (OR=1.12, 95% CI: 1.01-1.24), but not surgical or elective hospitalizations. Drivers of these associations, which may include preventive healthcare avoidance due to discrimination or poor health due to the chronic stress response to discrimination, should be explored.

RECIPROCAL RELATIONSHIP BETWEEN SENSE OF PURPOSE AND COGNITIVE CHANGE IN OLDER ADULTHOOD: A COORDINATED ANALYSIS

Abstract Sense of purpose (i.e., the extent to which one has personally meaningful goals and directions guiding them through life) is a consistent promoter of healthy aging for older adults. Unfortunately, while individuals benefit from having a high sense of purpose as they age, many people’s sense of purpose declines during older adulthood. Some evidence suggests that these declines may in part be explained by health declines experienced later in life. With sense of purpose being a powerful predictor of cognitive functioning in older adulthood, the current project evaluates whether this relationship may be more reciprocal in nature. Using a coordinated data analytic approach, this work investigates how sense of purpose and cognitive functioning promote each other and change together as older adults age. Longitudinal data comes from the Health and Retirement Study (N=15,497; 4 waves over 12 years), Memory and Aging Project (N=1,700; up to 15 waves over 15 years), Minority Aging Research Study (N=950; up to 12 waves over 12 years), and Wisconsin Longitudinal Study (N=22,334; 3 waves over 18 years). Based on a series of random intercept cross-lagged panel models, initial results indicate that sense of purpose change precedes cognitive functioning change and vice versa, when accounting for between-person and concurrent within-person associations. Moreover, bivariate latent growth models show that longer-term change in sense of purpose co-occurs alongside changes in cognitive functioning. In this talk, we will discuss how promoting sense of purpose can support successful cognitive aging, and the repercussions of cognitive decline for sense of purpose.

RECRUITMENT SUCCESSES AND CHALLENGES OF EMPLOYING IN-HOME SENSOR TECHNOLOGY WITH OLDER AFRICAN AMERICAN ADULTS

Abstract Older African Americans are under-represented in clinical research studies of aging. Many previous studies have shown results of in-home monitoring technologies to collect objective data for aging in place but few studies include minoritized populations. The CART platform uses home-based sensor technology to unobtrusively assess activity in the home and was embedded in homes of participants from the Minority Aging Research Study (MARS), an ongoing longitudinal study of cognitive decline in older African Americans. This presentation will highlight efforts to engage, recruit, and retain older African American participants in Chicago, with a particular focus on challenges and lessons learned. Recruitment consisted of presentations and mailings to potentially eligible MARS participants based on pre-specified inclusion criteria. Of 153 participants who met initial eligibility criteria, 36 refused before consent, 34 were ineligible after screening, and we enrolled 76 non-Hispanic African Americans participants (80% women; mean age = 80.4 (6.3) years); mean education = 16 (2.8) years; 78% without cognitive impairment). Enrolled participants were slightly younger, more likely to be female, and had higher education. There was no difference in cognitive impairment between those who enrolled compared to those who were ineligible after screening. Since enrollment, 11 have withdrawn and 7 are no longer active. The most common challenges include privacy concerns, broadband internet issues, emerging medical conditions, or changes in residency or resident occupancy. These results demonstrate that older African Americans participating in an ongoing longitudinal study can be recruited and retained in an ancillary study that involves home-based sensor technology.

The association between menopause and dementia risk

AbstractBackgroundWomen have a higher prevalence of Alzheimer’s disease compared to men. Studies are conflicting as to whether an earlier age of menopause or hysterectomy prior to natural menopause, are associated with an increased risk of cognitive impairment. The goal of this study was to determine whether age of menopause and hysterectomy are associated with incident dementia in a group of older, community‐dwelling women.MethodFemale participants from three ongoing Rush cohorts, the Rush Memory and Aging Project, the Religious Orders Study, and the Minority Aging Research Study were included (total n = 3122, mean age = 77 years at baseline, SD = 7.8). Annual clinical assessments allowed for dementia status categorization, based on detailed neuropsychological testing and clinical judgment, using the NINDS‐ADRDA criteria. Age at menopause and hysterectomy status was based on self‐report at baseline. Data on ovarian preservation or removal at time of surgery was not available. Age of menopause was categorized into tertiles (&lt;45, 45‐50, &gt;50). Risk of dementia, with age at dementia diagnosis as the outcome, was evaluated using Cox proportional regression models adjusting for race, early‐life socioeconomic status, education, diabetes, and smoking status.ResultAt the time of these analyses, women were followed for an average of 8.3 years (SD = 5.6). Women in the earliest tertile of menopause age were less likely to be white, more likely to report having diabetes, and have longer hormone therapy use (p&lt;0.01). In fully adjusted models, women with menopause at age 45‐50 (HR 0.80, 95% CI 0.67‐0.96) and age &gt;50 (HR 0.74, 95% CI 0.62‐0.90) had a lower risk of dementia compared to women with menopause at age &lt;45. Hysterectomy prior to natural menopause was not associated with an elevated risk of dementia (HR = 1.01, 95% CI 0.87‐1.19).ConclusionIn a group of older women, earlier age at menopause but not hysterectomy was associated with an elevated risk of dementia. Future research will determine whether these associations differ by race or ethnicity and the factors that may contribute to such differences.Funding: P30‐AG072975, R01‐AG17917, R01‐AG22081

Cerebral amyloid angiopathy is associated with higher gray matter regional R2 relaxation rate: An ex‐vivo MRI and pathology study

AbstractBackgroundCerebral amyloid angiopathy (CAA) is characterized by accumulation of amyloid‐ß (Aß) protein in the walls of cortical and meningeal small vessels. CAA is common in older adults. It has been linked to intracerebral hemorrhage and cognitive decline. In this study, the association of CAA with the transverse relaxation rate R2 values was investigated in gray matter regions from a large number of community‐based older adults.MethodCerebral hemispheres from 802 older adults participating in four cohort studies of aging, the Rush Memory and Aging Project, the Minority Aging Research Study, the Religious Orders Study, and the Clinical Core of the Rush Alzheimer’s Disease Research Center (Fig. 1a) were included in this work. All hemispheres were imaged ex‐vivo using 3T MRI scanners. R2 maps were generated from multi‐echo spin‐echo images. Gray matter was segmented into 34 cortical and 8 subcortical regions. Median R2 values were obtained from each region. Following ex‐vivo MRI, all hemispheres underwent detailed neuropathologic assessment (Fig. 1b). Evaluated neuropathologies included: CAA, Aß plaques, neurofibrillary tangles, gross infarcts, microinfarcts, TDP‐43 pathology, hippocampal sclerosis, Lewy bodies, atherosclerosis, and arteriolosclerosis. Multiple linear regression was conducted in each segmented gray matter region separately to test the association of the corresponding median R2 value with the global CAA score, controlling for all other neuropathologies, age at death, sex, education, postmortem interval to fixation and to imaging, and scanners. False discovery rate (FDR) was used to correct for multiple comparisons. Statistical significance was set at p&lt;0.05.ResultA significant positive association of median R2 with CAA pathology was found in several cortical regions of the temporal and frontal lobes as well as in subcortical structures (Fig. 2,3). No gray matter region showed lower median R2 for higher CAA score. Furthermore, we obtained similar findings when also controlling in the linear regression models for normalized regional volume and for clinical variables such as history of hypertension, diabetes, smoking, blood pressure levels, and the presence of the APOE‐e4 allele.ConclusionThis investigation showed that CAA is independently associated with elongated R2 in cortical regions of the temporal and frontal lobes as well as in subcortical structures.

Brain MRI diffusion abnormalities associated with arteriolosclerosis pathology

AbstractBackgroundBrain arteriolosclerosis is one of the main pathologies of cerebral small vessel disease. It involves the thickening of the vessel wall and stenosis of arterioles causing lower cognitive and motor function, and higher odds of dementia. This work intends to explore the independent association of brain arteriolosclerosis with diffusion abnormalities in the white matter (WM) of community‐based older adults.MethodParticipants comprised community‐dwelling older adults (N = 175) from four studies of aging (Rush Memory and Aging Project, Religious Orders Study, Minority Aging Research Study, and Clinical Core of the Rush Alzheimer’s Disease Research Center) (Fig.1A). Whole brain 3D T1w MPRAGE, T2w FLAIR, and diffusion‐weighted MRI (2×2×2mm3, b = 1,000s/mm2 for 40 diffusion gradient directions, and 6 b = 0s/mm2 volumes) data were acquired in‐vivo using 3T MRI scanners. The fractional anisotropy (FA) and trace maps were transformed to the space of the IIT Human Brain Atlas v.5.0 and projected onto the WM skeleton of the IIT atlas. Following a participant’s death, the extracted brain underwent a detailed evaluation by a neuropathologist. Assessed neuropathologies included arteriolosclerosis, Alzheimer’s pathology, LATE‐NC, gross and microscopic infarcts, atherosclerosis, and cerebral amyloid angiopathy (Fig.1B). Linear regression was used in voxels of the WM skeleton to test the association of FA or trace with the severity of arteriolosclerosis controlling for all other neuropathologies, white matter hyperintensities (WMH), demographic variables (age at scan, sex, years of education), antemortem interval to imaging, and scanner. The statistical analyses were carried out using FSL’s PALM tool with 5,000 permutations and threshold‐free cluster enhancement. The significance level was set at p&lt;0.05, after family‐wise error rate (FWER) correction for multiple testing.ResultArteriolosclerosis score was associated with lower FA (Fig.2) and higher trace (Fig.3) of the diffusion tensor throughout the brain in multiple WM regions, even in areas typically free of WMH. Other neuropathologies or the effects of WMH on diffusion characteristics had no impact on these relationships.ConclusionThe current study showed that, regardless of the impact of other neuropathologies or visible WMH, brain arteriolosclerosis in older persons is associated with diffusion abnormalities that extend throughout the WM.

Brain MRI diffusion abnormalities associated with arteriolosclerosis pathology

AbstractBackgroundBrain arteriolosclerosis is one of the main pathologies of cerebral small vessel disease. It involves the thickening of the vessel wall and stenosis of arterioles causing lower cognitive and motor function, and higher odds of dementia. This work intends to explore the independent association of brain arteriolosclerosis with diffusion abnormalities in the white matter (WM) of community‐based older adults.MethodParticipants comprised community‐dwelling older adults (N = 175) from four studies of aging (Rush Memory and Aging Project, Religious Orders Study, Minority Aging Research Study, and Clinical Core of the Rush Alzheimer’s Disease Research Center) (Fig.1A). Whole brain 3D T1w MPRAGE, T2w FLAIR, and diffusion‐weighted MRI (2×2×2mm3, b = 1,000s/mm2 for 40 diffusion gradient directions, and 6 b = 0s/mm2 volumes) data were acquired in‐vivo using 3T MRI scanners. The fractional anisotropy (FA) and trace maps were transformed to the space of the IIT Human Brain Atlas v.5.0 and projected onto the WM skeleton of the IIT atlas. Following a participant’s death, the extracted brain underwent a detailed evaluation by a neuropathologist. Assessed neuropathologies included arteriolosclerosis, Alzheimer’s pathology, LATE‐NC, gross and microscopic infarcts, atherosclerosis, and cerebral amyloid angiopathy (Fig.1B).Linear regression was used in voxels of the WM skeleton to test the association of FA or trace with the severity of arteriolosclerosis controlling for all other neuropathologies, white matter hyperintensities (WMH), demographic variables (age at scan, sex, years of education), antemortem interval to imaging, and scanner. The statistical analyses were carried out using FSL’s PALM tool with 5,000 permutations and threshold‐free cluster enhancement. The significance level was set at p&lt;0.05, after family‐wise error rate (FWER) correction for multiple testing.ResultArteriolosclerosis score was associated with lower FA (Fig.2) and higher trace (Fig.3) of the diffusion tensor throughout the brain in multiple WM regions, even in areas typically free of WMH. Other neuropathologies or the effects of WMH on diffusion characteristics had no impact on these relationships.ConclusionThe current study showed that, regardless of the impact of other neuropathologies or visible WMH, brain arteriolosclerosis in older persons is associated with diffusion abnormalities that extend throughout the WM.

Associations of subcortical shapes with age‐related neuropathologies in community‐based older adults

AbstractBackgroundAge‐related neuropathologies lead to substantial atrophy of subcortical brain regions. However, the effects of age‐related neuropathologies on the shape of subcortical brain structures are not well understood because a) definitive diagnosis of most neuropathologies is only possible at autopsy and b) multiple neuropathologies often coexist in the brain of older adults. The purpose of this work was to integrate ex‐vivo MRI and detailed neuropathologic examination in a large number of community‐based older adults.Method Participants and Data Cerebral hemispheres from 842 older adults participating in four longitudinal, clinical‐pathologic cohort studies of aging: the Rush Memory and Aging Project (MAP), the Religious Orders Study (ROS), the Minority Aging Research Study (MARS) and the Clinical Core (CC) of the Rush Alzheimer’s Disease Research Center (ADRC)1,2 (Fig.1) were included in this work. All hemispheres were imaged at room temperature while immersed in 4% formaldehyde solution using clinical 3T MRI scanners approximately 30 days postmortem. After ex‐vivo MRI, each hemisphere underwent detailed neuropathologic examination by a board‐certified neuropathologist (Fig.1). Ex‐vivo MRI and Shape Estimation The subcortical structures were segmented in ex‐vivo T2‐weighted MR images from all participants. Shape analysis was performed using SPHARM‐PDM3. For each subcortical structure, signed shape differences were computed from the average mesh for all vertices and all participants. Statistical Analysis Vertex‐wise linear regression was performed for each subcortical structure, modeling the signed shape difference at each vertex (dependent variable) as a function of neuropathologies (specifically amyloid‐β plaques, neurofibrillary tangles, limbic‐predominant age‐related TDP‐43 encephalopathy neuropathological change (LATE‐NC), Lewy bodies, arteriolosclerosis, atherosclerosis, gross and microscopic infarcts, and cerebral amyloid angiopathy), and controlling for age at death, sex, years of education, postmortem interval to fixation, postmortem interval to imaging, and scanner. The statistical analysis was conducted using PALM4 with family‐wise error rate correction.ResultThe results are shown in Figure 2. These findings for tangles and LATE‐NC were in good agreement with our previous work5,6. Finally, although MRI was conducted ex‐vivo, we expect the results to translate well to in‐vivo7.ConclusionThe differences in spatial patterns of the effects of various neuropathologies may contribute towards the development of tools for in‐vivo prediction of these neuropathologies.

Associations of subcortical shapes with age‐related neuropathologies in community‐based older adults

AbstractBackgroundAge‐related neuropathologies lead to substantial atrophy of subcortical brain regions. However, the effects of age‐related neuropathologies on the shape of subcortical brain structures are not well understood because a) definitive diagnosis of most neuropathologies is only possible at autopsy and b) multiple neuropathologies often coexist in the brain of older adults. The purpose of this work was to integrate ex‐vivo MRI and detailed neuropathologic examination in a large number of community‐based older adults.MethodParticipants and Data Cerebral hemispheres from 842 older adults participating in four longitudinal, clinical‐pathologic cohort studies of aging: the Rush Memory and Aging Project (MAP), the Religious Orders Study (ROS), the Minority Aging Research Study (MARS) and the Clinical Core (CC) of the Rush Alzheimer’s Disease Research Center (ADRC)1,2 (Fig.1) were included in this work. All hemispheres were imaged at room temperature while immersed in 4% formaldehyde solution using clinical 3T MRI scanners approximately 30 days postmortem. After ex‐vivo MRI, each hemisphere underwent detailed neuropathologic examination by a board‐certified neuropathologist (Fig.1). Ex‐vivo MRI and Shape Estimation The subcortical structures were segmented in ex‐vivo T2‐weighted MR images from all participants. Shape analysis was performed using SPHARM‐PDM3. For each subcortical structure, signed shape differences were computed from the average mesh for all vertices and all participants. Statistical Analysis Vertex‐wise linear regression was performed for each subcortical structure, modeling the signed shape difference at each vertex (dependent variable) as a function of neuropathologies (specifically amyloid‐ß plaques, neurofibrillary tangles, limbic‐predominant age‐related TDP‐43 encephalopathy neuropathological change (LATE‐NC), Lewy bodies, arteriolosclerosis, atherosclerosis, gross and microscopic infarcts, and cerebral amyloid angiopathy), and controlling for age at death, sex, years of education, postmortem interval to fixation, postmortem interval to imaging, and scanner. The statistical analysis was conducted using PALM4 with family‐wise error rate correction.ResultThe results are shown in Figure 2. These findings for tangles and LATE‐NC were in good agreement with our previous work5,6. Finally, although MRI was conducted ex‐vivo, we expect the results to translate well to in‐vivo7.ConclusionThe differences in spatial patterns of the effects of various neuropathologies may contribute towards the development of tools for in‐vivo prediction of these neuropathologies.

Effect of early‐ and mid‐life cognitive enrichment on Alzheimer’s disease pathology and late‐life cognition

AbstractBackgroundCognitive reserve and brain maintenance may explain individual differences in trajectories of cognitive and brain aging due to various life exposures (e.g., education, cognitive enrichment). Cognitive reserve refers to the advantages that life exposures exert on cognitive abilities despite brain aging or disease; brain maintenance refers to the protective effects of life exposures on the brain itself (e.g., reduced rate of neuropathology accumulation). Previous findings showed that early‐life cognitive enrichment (ELCE) was associated with slower cognitive decline, which was partially mediated through global Alzheimer’s disease pathology. Building on this work, this study investigated mediation by β‐amyloid and tau pathology (reflecting brain maintenance) as well as moderation by early‐ and mid‐life cognitive enrichment (ELCE, MLCE; reflecting cognitive reserve) on cognitive functioning at last visit proximate to death.MethodThere were 1015 community‐based participants (M baseline age = 82.57±6.35) from the Rush Memory and Aging Project (MAP) and Minority Aging Research Study (MARS) cohorts, who completed annual cognitive and clinical assessments. ELCE and MLCE composite measures were derived from z‐scored self‐reported indicators obtained at baseline (Table 1). Summary measures of β‐amyloid and tau burden were derived from immunohistochemistry at autopsy. Late‐life cognition was measured using a global composite of 19 z‐scored neuropsychological tests obtained at last visit. To test for cognitive reserve, separate linear regression models examined whether ELCE and MLCE moderated relations between β‐amyloid or tau and cognition, adjusted for age at death and sex. To test for brain maintenance, a series of mediation analyses examined whether β‐amyloid and/or tau burden mediated the relationship of ELCE and MLCE with cognition.ResultELCE (p = .005) and MLCE (p = .005) moderated the relationship between tau—but not β‐amyloid—and late‐life cognition proximate to death (Figure 1). Mediation analyses revealed an indirect effect of β‐amyloid—but not tau—on the relation between ELCE (B = 0.058, p = .004) and MLCE (B = 0.040, p = .03) and late‐life cognition (Figure 2).ConclusionELCE and MLCE improve late‐life cognition partially through reducing β‐amyloid, but not tau, accumulation (i.e., brain maintenance). In contrast, ELCE and MLCE are protective against late‐life cognitive impairment in the presence of tau pathology (i.e., cognitive reserve), but not β‐amyloid.

Afternoons can be a critical time of the day that reflects associations between life‐space mobility and loneliness among living alone older adults: longitudinal analyses with motion sensor data

AbstractBackgroundDaily activity patterns of life‐space mobility can serve as indicators for loneliness and subsequent cognitive change. Assessment of life‐space mobility often uses self‐reported data, and the measurement intervals are often less frequent than needed to capture change over time. This study examined whether the life‐space mobility changed when loneliness was reported weekly.MethodsParticipants were 139 older adults who lived alone (age = 78.1±8.6, 103 (74%) were female, 32 (23%) were African Americans, 19 (14%) had MCI diagnosis) and were enrolled in ORCATECH (ORegon Center for Aging &amp; TECHnology) longitudinal aging studies and Minority Aging Research Study. Passive infrared motion sensors were placed in common rooms of each participant’s home (bathroom; bedroom; kitchen; living room). Time spent in each room across the day (morning; afternoon; evening; night) and out‐of‐home were used as indicators of life‐space mobility and were derived from home sensor data. Participants reported whether they felt lonely on a weekly basis using an online survey sent via email. Generalized estimating equations were used to correlate the time spent in each room and out‐of‐home and the likelihood of feeling lonely. Age, gender, education, race, cognitive status (MCI/ non‐MCI), and average daily time out‐of‐home were controlled in the model.ResultsWe analyzed 4994 weeks of data; 232 weeks had an incidence of loneliness (5%). Spending an additional hour in the bedroom in the afternoon (noon‐6 pm) was associated with a 21% increase in the likelihood of experiencing loneliness (p = .03). Spending an additional hour out‐of‐home in the afternoon was associated with a 13% decrease in the likelihood of experiencing loneliness (p = .02). Time spent in the kitchen, bathroom, and living room in a day was unrelated to weekly loneliness.ConclusionTime spent outside the home may suggest an expansion of life‐space, while spending time in one’s bedroom may indicate contraction of life space. Our findings suggest carefully monitoring a person’s location in the afternoon might help detect loneliness in this population. Frequent and objective measurements of life‐space mobility can produce renewed insights into the experience of loneliness among older adults who live alone, and thus, inform timely interventions for loneliness and prevent cognitive decline.

Financial Risk Aversion Among Older Black and White Adults.

Risk aversion has a substantial impact on decision making and is associated with key demographic characteristics. However, few studies have investigated whether risk aversion varies by race. We investigated racial differences in financial risk aversion in 684 older Black and White adults without dementia in the Minority Aging Research Study and Rush Memory and Aging Project matched for age, education, sex, and cognition using Mahalanobis distance. We also investigated whether select contextual factors (self-reported discrimination, socioeconomic status, and literacy) mediated or affective factors (trust, loneliness, and neuroticism) moderated any observed racial differences. In regression models adjusted for age, education, sex, and cognitive function, older Black adults were more risk averse than older White adults (Beta = 0.1264, standard error = 0.0227, p value ≤ .00001). None of the contextual or affective factors mediated or moderated this association. Older Black adults are more financially risk averse than older White adults. Because risk aversion may be associated with important financial and health outcomes in older age, more research is needed to investigate the reasons for this difference.

Changes in Body Mass Index and Incident Mild Cognitive Impairment Among African American Older Adults.

Previous research suggests a decline in body mass index (BMI) among older adults is associated with negative health outcomes, including mild cognitive impairment (MCI) and incident dementia. However, no studies have examined the effects of education or developing MCI on BMI trajectories over time. The purpose of this investigation was to characterize trajectories of change in BMI among older adults who develop MCI. Participants were from the Minority Aging Research Study (MARS), a longitudinal cohort study of cognitive decline and Alzheimer's disease in older African Americans living in the greater Chicago, Illinois, area. The study included annual clinical evaluations of cognitive status, as well as measurements of height and weight for BMI calculation. Older African American participants without cognitive impairment at baseline were included in the present analysis (N = 436, 78% women, mean baseline age = 72 [SD = 5.7], mean education = 15 [SD = 3.5]). In piecewise linear mixed-effects models that included a random intercept and 2 random slopes, BMI declined over time (B = -0.20, SE = 0.02, p < .001), with a faster decline after MCI diagnosis (additional decline, B = -0.15, SE = 0.06, p = .019). Older age was associated with lower baseline BMI (B = -0.19, SE = 0.05, p < .001), as was higher education (B = -0.34, SE = 0.09, p < .001). Further, higher education was associated with a slower decline in BMI before MCI (B = 0.02, SE = 0.006, p = .001), but a faster decline after MCI (B = -0.06, SE = 0.022, p = .003). These results suggest an accelerated decline in BMI following an MCI diagnosis, with higher education related to an even faster BMI decline.

High-throughput digital quantification of Alzheimer disease pathology and associated infrastructure in large autopsy studies.

High-throughput digital pathology offers considerable advantages over traditional semiquantitative and manual methods of counting pathology. We used brain tissue from 5 clinical-pathologic cohort studies of aging; the Religious Orders Study, the Rush Memory and Aging Project, the Minority Aging Research Study, the African American Clinical Core, and the Latino Core to (1) develop a workflow management system for digital pathology processes, (2) optimize digital algorithms to quantify Alzheimer disease (AD) pathology, and (3) harmonize data statistically. Data from digital algorithms for the quantification of β-amyloid (Aβ, n = 413) whole slide images and tau-tangles (n = 639) were highly correlated with manual pathology data (r = 0.83 to 0.94). Measures were robust and reproducible across different magnifications and repeated scans. Digital measures for Aβ and tau-tangles across multiple brain regions reproduced established patterns of correlations, even when samples were stratified by clinical diagnosis. Finally, we harmonized newly generated digital measures with historical measures across multiple large autopsy-based studies. We describe a multidisciplinary approach to develop a digital pathology pipeline that reproducibly identifies AD neuropathologies, Aβ load, and tau-tangles. Digital pathology is a powerful tool that can overcome critical challenges associated with traditional microscopy methods.

21 Socioeconomic Influences on Instrumental Activities of Daily Living in Older Black Adults

Objective:Socioeconomic factors, spanning from childhood to mid-adulthood, were examined in an older adult Black cohort to better understand their influence on the ability to complete instrumental activities of daily living. Previous research with socioeconomic factors has primarily focused on cognitive changes rather than everyday functioning. Additionally, research that has been conducted examining functioning has been with predominantly White samples.Participants and Methods:Data on Black participants were obtained from Rush University’s Memory and Aging Project (MAP), Minority Aging Research Study (MARS), and the Latino CORE study (CORE). Participants (n = 1,273) were predominately female (79.9%) and ranged in age from 54 - 97 years (M = 73 years old). Participants were stratified into two groups based on their consensus diagnosis: no cognitive impairment (NCI; 76.1%) and mild cognitive impairment (MCI). Linear regression analyses were utilized on each group to examine predictors of decreased functioning in instrumental activities of daily living. Predictors included income levels during childhood, at age 40, and current income level. Additionally, sex, education level, and parental education levels were included in the models.Results:Impairment of functioning in instrumental activities of daily living was predicted by the age of the participants at the time of their visit in both NCI and MCI groups (p &lt; 0.001). Current income levels for the NCI participants significantly predicted functioning in IADLs (p &lt; 0.001). This relationship was not present for the MCI group, rather, total family income at age 40 better predicted functioning (p = 0.043).Conclusions:Previous research has found that early and mid-life socioeconomic circumstances have cascading and complex effects on late life cognition. These same associations may be applicable to functioning with instrumental activities of daily living as they are with cognition. In the present study, current income levels were influential on the functioning of participants without cognitive impairment. Although, when examining those with mild cognitive impairment, mid-life economic circumstances were more impactful on everyday functioning. While the economic status of both groups were predictors of functioning, these findings highlight the importance of better understanding socioeconomic factors across the lifespan and all levels of cognition.