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Introduction: Older Black adults are at risk of cerebral small vessel disease (CSVD), which contributes to dementia risk. Two subtypes of CSVD, arteriolosclerosis and ischemic lacunar infarcts, have been independently linked to lower cognition and higher dementia risk, but their combined effects on cognition in older Black adults are unclear., Methods: Mixed models were used to examine the associations of in vivo measures of arteriolosclerosis (ARTS) and ischemic lacunar infarcts to cognitive level and change in 370 older Black adults without dementia.  RESULTS: Modeled together, higher ARTS load accounted for lower levels of global cognition, episodic memory, semantic memory, and perceptual speed, whereas higher infarct load accounted for lower levels of working memory. There were no associations with rate of cognitive change., Discussion: Both arteriolosclerosis and ischemic infarcts impact the cognitive health of older Black adults, but arteriolosclerosis affects cognition more broadly and offers promise as an in vivo biomarker of dementia risk., Highlights: Older Black adults are at risk of cerebral small vessel disease (CSVD) and dementia. Examined magnetic resonance imaging-derived measure of arteriolosclerosis (ARTS), infarcts, and cognition. ARTS load was widely associated with lower cognition after adjusting for infarct load. Infarct load was specifically associated with lower complex attention. More within-Black in vivo studies of CSVD subtypes and cognition are needed., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Acculturation-related characteristics, that is, factors directly connected to culture and familial relationships, are associated with engaged research participation within Latino communities. Despite this, little empirical data exists on whether acculturation changes over time in older Latinos, which has potential implications for Alzheimer's disease and related dementias (ADRD) research study design including longer duration clinical trial implementation., Methods: Self-identified Latinos ( n = 222; mean age = 71, 76% female) participating in one of three ongoing longitudinal community-based cohort studies of aging who reported their nativity outside of the United States/District of Columbia (US/DC) contributed, on average, 4.0 ± 1.2 years of annually collected data. This included acculturation-related characteristics of total, language-, and social-based scores from the Short Acculturation Scale for Hispanics (SASH) and total and domain-specific scores from an abbreviated Sabogal Familism questionnaire. We used ordinal mixed effects models and linear mixed effects models (as appropriate) to assess change in acculturation metrics after adjusting for age, sex, education, income, and duration of time in the US/DC., Results: Although none of the SASH metrics changed over time ( P -values ≥ 0.25), all Familism metrics declined over time ( P -values ≤ 0.044). Additionally, select participant-based characteristics including years of education were significantly (and differentially) associated with level of, but not change in, acculturation-related outcomes., Discussion: Results suggest that specific acculturation-related factors (i.e., familism) change over time in older Latinos, and participant-based characteristics associated with baseline levels of (but not change in) acculturation more generally. Thus, acculturation-related characteristics are not all static, trait-like qualities but rather a multi-faceted, and at times evolving, construct. Considering this dynamic phenotyping is important when contextualizing older Latinos' lived experience, and when designing, adapting, and conducting ADRD clinical trials and other health-related interventions., Competing Interests: The co‐authors of this manuscript have no conflicts of interest related to the contents of the work presented herein. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background We previously outlined the importance of considering acculturation within the context of older Latino adults' lived experience (ie, acculturation in context) to better capture contributors to cognitive aging. We now examine this conceptual framework as related to level of and change in cardiovascular health, and whether cardiovascular health modifies previously documented associations of acculturation in context with cognition. Methods and Results Acculturation in context data from 192 Latino participants without dementia at baseline (age ~70 years) were compiled into 3 separate composite scores: acculturation-related (nativity, language-, and social-based preferences), contextually related socioenvironmental (experiences of discrimination, social isolation, social networks), and familism-related (Latino-centric family ethos). A modified American Heart Association's Life's Simple 7 (mLS7; ie, smoking, physical activity, body mass index, blood pressure, total cholesterol, blood glucose) was used to measure cardiovascular health. Mixed effects regressions simultaneously tested the association of all 3 composite scores with total mLS7 adjusting for confounders. Separate models tested whether mLS7 modified associations of the 3 composite scores and cognition. The contextually related socioenvironmental composite score reflecting higher discrimination, higher social isolation, and smaller social networks (estimate=0.22, SE=0.10, P =0.02) and the familism score (estimate=0.16, SE=0.07, P =0.02) both significantly associated with change in total mLS7. The acculturation-related composite was not significantly associated with change in mLS7. No composite was significantly associated with level of mLS7. Total mLS7, however, significantly modified associations between the acculturation-related composite and change in working memory (estimate=-0.02, SE=0.01, P =0.043). Conclusions Acculturation within the context of older Latino adults' lived experience is important for maintaining cardiovascular health, relationships that also affect domain-specific cognitive decline.

Background: Latinos are at higher risk of developing mild cognitive impairment (MCI) and Alzheimer's disease than non-Latino Whites. Acculturation factors may influence this risk, yet there are few studies that have examined associations of acculturation, particularly in the context of socioenvironmental and familial factors, and brain health in older Latinos., Objective: To examine potential associations between acculturation in context and brain health in older Latinos., Methods: Using three previously established composites of acculturation-in-context, (acculturation-related: nativity status, language preference, acculturation scores; contextually-related socioenvironmental: perceived discrimination, loneliness/social isolation, social network size; and familism), and diffusion-tensor imaging (DTI), associations with white matter structural integrity were examined in 92 Latino adults without dementia participating in one of three epidemiological studies of aging. Linear regression models were used to test associations with DTI-derived metrics (fractional anisotropy, FA; trace) as separate outcomes and acculturation composite scores as individual predictors, while adjusting for age, sex, education, scanner, and white matter hyperintensities (voxelwise and total volumes normalized by intracranial volume)., Results: Higher scores on the socioenvironmental composite were associated with lower FA in two clusters of left-hemisphere connections. Cluster 1 was dominated by both short association pathways connecting frontal regions and projection pathways connecting frontal regions with the thalamus. Cluster 2 was dominated by long association pathways connecting parietal, frontal, and temporal regions., Conclusions: This study of older Latino adults demonstrated an association between reduced brain white matter integrity and contextually related socioenvironmental experiences known to increase risk of MCI and Alzheimer's disease.

While there has been a proliferation of neuroimaging studies on cognitive decline in older non-Hispanic White adults, there is a dearth of knowledge regarding neuroimaging correlates of cognitive decline in Black adults. Resting-state functional neuroimaging approaches may be particularly sensitive to early cognitive decline, but there are no studies that we know of that apply this approach to examining associations of brain function to cognition in older Black adults. We investigated the association of cognitive decline with whole-brain voxel-wise functional connectivity to the hippocampus, a key brain region functionally implicated in early Alzheimer's dementia, in 132 older Black adults without dementia participating in the Minority Aging Research Study and Rush Memory and Aging Project, two longitudinal studies of aging that include harmonized annual cognitive assessments and magnetic resonance imaging brain imaging. In models adjusted for demographic factors (age, education, sex), global cognitive decline was associated with functional connectivity of the hippocampus to three clusters in the right and left frontal regions of the dorsolateral prefrontal cortex. In domain-specific analyses, decline in semantic memory was associated with functional connectivity of the hippocampus to bilateral clusters in the precentral gyrus, and decline in perceptual speed was inversely associated with connectivity of the hippocampus to the bilateral intracalcarine cortex and the right fusiform gyrus. These findings elucidate neurobiological mechanisms underlying cognitive decline in older Black adults and may point to specific targets of intervention for Alzheimer's disease., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Peripheral inflammation is elevated in older Black adults, an elevation which prior work has suggested may be due to chronic stress associated with systemic racism and related adverse cardiovascular health conditions. Inflammation is also involved in the pathogenic processes of dementia; however, limited (and mixed) results exist concerning inflammation and cognitive decline in Black adults. We characterized patterns of inflammation and their role in cognitive decline in 280 older Black adults (age = 72.99 ± 6.00 years; 69.6% female) from the Minority Aging Research Study (MARS) who were without dementia at baseline and followed between 2 and 15 years (mean = 9 years). Participants completed a blood draw at baseline and annual cognitive evaluations. Serum was assayed for 9 peripheral inflammatory markers; 19 neuropsychological test scores were used to create indices of global cognition and five cognitive domains. Principal component analysis with varimax rotation characterized patterns of inflammation with factor loadings > 0.6 per component contributing to two composite scores representing acute/upstream and chronic/downstream inflammation. These composites were used as separate predictors in linear mixed regression models to determine associations with level and change in cognition adjusting for relevant covariates. Higher baseline upstream/acute inflammation associated with lower baseline semantic memory (p = .040) and perceptual speed (p = .046); it was not related to cognitive decline. By contrast, higher baseline downstream/chronic inflammation associated with faster declines in global cognition (p = .010), episodic (p = .027) and working memory (p = .006); it was not related to baseline cognition. For older Black adults, chronic, but not acute, inflammation may be a risk factor for changes in cognition., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Elevations in blood pressure (BP) and associated white matter hyperintensities (WMHs) are chronic comorbid conditions among older Black adults. We investigated whether WMHs modify the association between late-life BP and cognition within older Black adults., Methods: A total of 167 Black adults (age, ~75 years; without dementia at baseline) participating in neuroimaging studies at the Rush Alzheimer's Disease Center were evaluated for BP markers of cardiovascular health, including systolic BP, diastolic BP, pulse pressure, mean arterial pressure (MAP), and hypertension, and were assessed for global and domain-specific cognition at baseline and annually for up to 8 years. WMHs adjusted for intracranial volume were quantified at baseline., Results: Models adjusted for relevant confounders and the interaction of these variables with time revealed differential associations between BP markers and baseline cognition; however, only elevated diastolic BP predicted faster cognitive, that is, episodic memory, decline (estimate = -0.002, standard error = 0.0009, p = .002). Although WMH burden did not modify the association between diastolic BP and episodic memory decline, it did interact with diastolic BP to lower episodic memory at baseline (estimate = -0.051, standard error = 0.012, p = .0001); that is, greater WMHs combined with higher diastolic BP resulted in the lowest baseline episodic memory scores. A similar profile was noted for WMHs, MAP, and baseline episodic memory. Hypertension was neither associated with cognition nor modified by WMH burden after multiple comparisons correction., Conclusion: Late-life diastolic BP was associated with faster rates of episodic memory decline in older Black adults; together with higher WMH burden, it (and MAP) lowered the point at which individuals begin their course of decline toward pathological aging., (Copyright © 2022 by the American Psychosomatic Society.)

Blacks are at higher risk of developing cognitive impairment with age than non-Hispanic Whites, yet most brain morphometry and cognition research is performed with White samples or with mixed samples that control for race or compare across racial groups. A deeper understanding of the within-group variability in associations between brain structure and cognitive decline in Blacks is critically important for designing appropriate outcomes for clinical trials, predicting adverse outcomes, and developing interventions to preserve cognitive function, but no studies have examined these associations longitudinally within Blacks. We performed deformation-based morphometry in 376 older Black participants without dementia and examined associations of deformation-based morphometry with cognitive level and decline for global cognition and five cognitive domains. After correcting for widespread age-associated effects, there remained regions with less tissue and more cerebrospinal fluid associated with level and rate of decline in global cognition, memory, and perceptual speed. Further study is needed to examine the moderators of these associations, identify adverse outcomes predicted by brain morphometry, and deepen knowledge of underlying biological mechanisms., (Copyright © 2021. Published by Elsevier Inc.)

Background: COVID-19 has placed an extraordinary and disproportionate level of responsibility and risk on certified nursing assistants (CNAs) caring for persons with dementia (PWD) relative to their training, resources, and compensation levels. Nearly one-quarter of COVID-19 deaths in the United States have been nursing home residents and staff. Despite providing the majority of direct care, CNAs are amongst the most under-resourced and under-trained frontline workers. Given their essentiality, it is critical to support CNAs during the COVID-19 pandemic. The purpose of this work is to provide CNAs with a space to strengthen their knowledge and confidence in caring for PWD. This pilot study applies a virtual reality (VR) curriculum to train CNAs regarding the lived experiences of PWD and their loved ones. The VR vignette portrays a Latinx woman, Beatriz, through progressive stages of Alzheimer's disease., Method: Chicago Methodist Senior Services (CMSS) CNAs were recruited (N=7; 86% female, 86% Black) for a seven-week online training program consisting of 1.5 hours per week. Each class included a didactic lecture and an Embodied Labs VR module depicting a first-person experience of dementia through a distributive model approach. The program concluded with two recorded focus groups. Participants completed the UCLA Geriatric Attitudes Scale, a dementia knowledge assessment, the Interpersonal Reactivity Index surveys, and a COVID-19 Impact questionnaire. Current analyses include qualitative content analysis for focus group data and descriptive, quantitative statistics for pre-and post-VR intervention surveys., Result: Preliminary results demonstrate that CNAs endorsed a positive change in attitudes toward older adults (p=0.069), a deepened understanding of dementia, and increased confidence in caregiving skills. Focus groups allowed CNAs to discuss changes in resident behavior and support one another through a virtual platform during a global pandemic., Conclusion: Combining traditional didactic lectures with VR-based curricula provided CNAs with foundational knowledge and first-hand experience of dementia pathology. Participants reported greater levels of insight and empathy for PWD. Future aims include expansion of training content to include end-of-life conversations, LGBTQIA aging, and Lewy body dementia., (© 2021 the Alzheimer's Association.)

Background: Neuroimaging data from large epidemiologic cohort studies often come from multiple scanners. The variations of MRI measurements due to differences in magnetic field strength, image acquisition protocols, and scanner vendors can influence the interpretation of aggregated data. The purpose of the present study was to compare methods that meta-analyze findings from a small number of different MRI scanners., Methods: We proposed a bootstrap resampling method using individual participant data and compared it with two common random effects meta-analysis methods, DerSimonian-Laird and Hartung-Knapp, and a conventional pooling method that combines MRI data from different scanners. We first performed simulations to compare the power and coverage probabilities of the four methods in the absence and presence of scanner effects on measurements. We then examined the association of age with white matter hyperintensity (WMH) volumes from 787 participants., Results: In simulations, the bootstrap approach performed better than the other three methods in terms of coverage probability and power when scanner differences were present. However, the bootstrap approach was consistent with pooling, the optimal approach, when scanner differences were absent. In the association of age with WMH volume, we observed that age was significantly associated with WMH volumes using the bootstrap approach, pooling, and the DerSimonian-Laird method, but not using the Hartung-Knapp method (p < 0.0001 for the bootstrap approach, DerSimonian-Laird, and pooling but p = 0.1439 for the Hartung-Knapp approach)., Conclusion: The bootstrap approach using individual participant data is suitable for integrating outcomes from multiple MRI scanners regardless of absence or presence of scanner effects on measurements., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Scam susceptibility places older adults - even those with intact cognition - at great risk. Lower grey matter volumes, particularly within right medial temporal regions, are associated with higher scam susceptibility; however, very little is known about white matter associates. We investigated associations between white matter integrity measured using diffusion tensor imaging (DTI) and scam susceptibility in 302 non-demented older adults (75% female; mean years: age = 81.3 + 7.5, education = 15.7 + 2.9). Participants completed comprehensive neuroimaging (including DTI, T1- and T2-weighted imaging), a self-report measure of scam susceptibility, and neuropsychological testing. Tract-Based Spatial Statistics (TBSS) investigated associations of DTI-derived measures of fractional anisotropy (FA), trace of the diffusion tensor, axial and radial diffusivity (separately) with scam susceptibility adjusting for age, sex, education, and white matter hyperintensities (WMH; total volume and voxelwise separately). Statistical significance was determined at p < 0.05, Family Wise Error corrected. TBSS revealed significant negative associations between FA in tracts connecting a number of right hemisphere white matter regions and scam susceptibility, particularly after additional adjustment for global cognitive functioning. The pathways implicated were mainly in right temporal-parietal and temporal-occipital regions. Association of trace, axial, and radial diffusivity with scam susceptibility were not significant in fully-adjusted models. Lower white matter integrity within right hemisphere tracts was associated with higher scam susceptibility independent of relevant confounds including global cognition. Thus, a right hemisphere brain network that includes key structures implicated in multi-sensory processing of immediate and future consequences may serve as a neurobiologic substrate of scam susceptibility in vulnerable older adults.

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Temporal discounting, the tendency to select a smaller reward offered sooner over a larger reward offered at a later time, has been associated with a number of real-world decision-making outcomes important for health and wellbeing. Neurobiological mechanisms supporting temporal discounting have been explored among younger participants, and these have considered white matter integrity. However, the white matter correlates of temporal discounting in older adults are unclear. We hypothesized that greater temporal discounting would be associated with poorer white matter integrity measures, more specifically lower fractional anisotropy and higher trace, in older adults. Participants were 302 older persons without dementia (mean age = 81.38, mean years of education = 15.75, 75.5% female, mean MMSE = 28.29) from the Rush Memory and Aging Project, a community-based longitudinal study of aging. Temporal discounting was assessed using standard elicitation questions. White matter integrity was assessed with diffusion tensor imaging (DTI). Regression models were adjusted for the effects of age, sex, education, and white matter lesions. Secondary models further adjusted for global cognition. Results revealed significant associations between temporal discounting and white matter integrity measures (FA and trace) in bilateral frontal, frontostriatal, and temporal-parietal lobe white matter tracts, and results remained significant after further accounting for global cognition. These results suggest that temporal discounting is inversely associated with white matter integrity in old age and that this association is independent of global cognition.

The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρ genetic  = -0.59, p-value = 3.14 × 10 -6 ), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.

Objective: HIV infection sets off an immediate immune response and inflammatory cascade that can lead to neuronal injury and cognitive impairment, but the relationship between immune markers, regional brain volumes, and cognition remains understudied in HIV-infected adults., Methods: Cross-sectional associations were examined between serum immune markers of activation (neopterin) and inflammation (interleukin [IL]-1β, IL-6, tumor necrosis factor alpha, and C-reactive protein) with regional brain volumes (cortical, subcortical, total gray matter, hippocampus, and subfields) and cognition in 66 HIV-infected, virally suppressed, adults who underwent 3.0-T MRI as part of the Research Core of the Rush Center of Excellence on Disparities in HIV and Aging. Immune markers were assayed from frozen plasma, values were entered into linear regression models as predictors of regional brain volumes, and interactive effects of immune response and regional brain volumes on cognition were examined., Results: No inflammatory marker was associated with any regional brain volume. Higher neopterin level was associated with lower total hippocampal, presubiculum, and cornu ammonis (CA) subfield volumes. Higher neopterin level and lower total hippocampal volume were independently associated with lower episodic memory, and neopterin level fully mediated the effect of hippocampal atrophy on episodic memory. Higher neopterin levels were associated with lower presubiculum, CA1, and CA4/dentate volumes and lower semantic memory, working memory, and global cognition., Conclusion: Immune activation in response to HIV infection, measured by neopterin, has a deleterious and targeted effect on regional brain structure, which can be visualized with clinically available MRI measures of hippocampus and its subfields, and this effect is associated with lower cognitive function.

The objective of this work was to test the hypotheses that a) more frequent cognitive activity in late life is associated with higher brain diffusion anisotropy and lower trace of the diffusion tensor, and b) brain diffusion characteristics partially mediate the association of late life cognitive activity with cognition. As part of a longitudinal cohort study, 379 older people without dementia rated their frequency of participation in cognitive activities, completed a battery of cognitive function tests, and underwent diffusion tensor imaging. We used tract-based spatial statistics to test the association between late life cognitive activity and brain diffusion characteristics. Clusters with statistically significant findings defined regions of interest in which we tested the hypothesis that diffusion characteristics partially mediate the association of late life cognitive activity with cognition. More frequent cognitive activity in late life was associated with higher level of global cognition after adjustment for age, sex, education, and indicators of early life cognitive enrichment (p = 0.001). More frequent cognitive activity was also related to higher fractional anisotropy in the left superior and inferior longitudinal fasciculi, left fornix, and corpus callosum, and lower trace in the thalamus (p < 0.05, FWE-corrected). After controlling for fractional anisotropy or trace from these regions, the regression coefficient for the association of late life cognitive activity with cognition was reduced by as much as 26 %. These findings suggest that the association of late life cognitive activity with cognition may be partially mediated by brain diffusion characteristics.

Susceptibility to scams is a significant issue among older adults, even among those with intact cognition. Age-related changes in brain macrostructure may be associated with susceptibility to scams; however, this has yet to be explored. Based on previous work implicating frontal and temporal lobe functioning as important in decision making, we tested the hypothesis that susceptibility to scams is associated with smaller grey matter volume in frontal and temporal lobe regions in a large community-dwelling cohort of non-demented older adults. Participants (N = 327, mean age = 81.55, mean education = 15.30, 78.9 % female) completed a self-report measure used to assess susceptibility to scams and an MRI brain scan. Results indicated an inverse association between overall grey matter and susceptibility to scams in models adjusted for age, education, and sex; and in models further adjusted for cognitive function. No significant associations were observed for white matter, cerebrospinal fluid, or total brain volume. Models adjusted for age, education, and sex revealed seven clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, left middle temporal, left orbitofrontal, right ventromedial prefrontal, right middle temporal, right precuneus, and right dorsolateral prefrontal regions. In models further adjusted for cognitive function, results revealed three significant clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, right hippocampal, and right middle temporal regions. Lower grey matter concentration in specific brain regions may be associated with susceptibility to scams, even after adjusting for cognitive ability. Future research is needed to determine whether grey matter reductions in these regions may be a biomarker for susceptibility to scams in old age.

Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive impairment (MCI). We used data from participants of the Rush Memory and Aging Project. Brain MRI was available in 209 subjects without dementia or MCI (mean age 80; education = 15 years; 74 % women). WMH and gray matter were automatically segmented, and the total WMH and gray matter volumes were measured. Both MRI-derived measures were normalized by the intracranial volume. Cognitive data included composite measures of five different cognitive domains, based on 19 individual tests. Linear regression analyses, adjusted for age, sex, and education, were used to examine the relationship of logarithmically-transformed total WMH volume and of total gray matter volume to cognition. Larger total WMH volumes were associated with lower levels of perceptual speed (p < 0.001), but not with episodic memory, semantic memory, working memory, or visuospatial abilities (all p > 0.10). Smaller total gray matter volumes were associated with lower levels of perceptual speed (p = 0.013) and episodic memory (p = 0.001), but not with the other three cognitive domains (all p > 0.14). Larger total WMH volume was correlated with smaller total gray matter volume (p < 0.001). In a model with both MRI-derived measures included, the relation of WMH to perceptual speed remained significant (p < 0.001), while gray matter volumes were no longer related (p = 0.14). This study of older community-dwelling individuals without overt cognitive impairment suggests that the association of larger total WMH volume with lower perceptual speed is independent of total gray matter volume. These results help elucidate the pathological processes leading to lower cognitive function in aging.

The translocator protein, a microglial-expressed marker of neuroinflammation, has been implicated in Alzheimer's disease, which is characterized by alterations in vascular and inflammatory states. ATSPOvariant, rs6971, determines binding affinity of exogenous radioligandsin vivo; however, the effect of these altered binding characteristics on inflammatory and cerebrovascular biomarkers has not been assessed. In 2345 living subjects (Alzheimer's Disease Neuroimaging Initiative, n = 1330) and postmortem brain samples (Religious Orders Study and Memory and Aging Project, n = 1015), we analyzed effects of rs6971 on white matter hyperintensisites, cerebral infarcts, circulating inflammatory biomarkers, amyloid angiopathy, and microglial activation. We found that rs6971 does not alter translocator protein in a way that impacts cerebrovascular and inflammatory states known to be affected in dementia., (© The Author(s) 2016.)

A deeper understanding of brain macrostructure and its associations with cognition in persons who are considered cognitively healthy is critical to the early detection of persons at risk of developing dementia. Few studies have examined the associations of all three gray-matter macrostructural brain indices (volume, thickness, surface area) with age and cognition, in the same persons who are over the age of 65 and do not have cognitive impairment. We performed automated morphometric reconstruction of total gray matter, cortical gray matter, subcortical gray matter and 84 individual regions in 186 persons (60 % over the age of 80) without cognitive impairment. Morphometric measures were scaled and expressed as difference per decade of age and an adjusted score was created to identify those regions in which there was greater atrophy per decade of age compared to cortical or subcortical brain averages. The results showed that there is substantial total volume loss and cortical thinning in cognitively healthy older persons. Thinning was more widespread than volume loss, but volume loss, particularly in temporoparietal and hippocampal regions, was more strongly associated with cognition.

Alzheimer's disease (AD) is associated with insulin resistance and specific regional declines in cerebral metabolism. The effects of a novel mTOT modulating insulin sensitizer (MSDC-0160) were explored in non-diabetic patients with mild AD to determine whether treatment would impact glucose metabolism measured by FDG-PET in regions that decline in AD. MSDC-0160 (150 mg once daily; N=16) compared to placebo (N=13) for 12 weeks did not result in a significant difference in glucose metabolism in pre-defined regions when referenced to the pons or whole brain. However, glucose metabolism referenced to cerebellum was maintained in MSDC-0160 treated participants while it significantly declined for placebo patients in anterior and posterior cingulate, and parietal, lateral temporal, medial temporal cortices. Voxel-based analyses showed additional differences in FDG-PET related to MSDC-0160 treatment. These exploratory results suggest central effects of MSDC-0160 and provide a basis for further investigation of mTOT modulating insulin sensitizers in AD patients.

Temporal discounting occurs when a greater delayed reward is forsaken for a smaller immediate reward, and has been associated with a number of financial and health care outcomes important for older adults. Using resting-state fMRI and seed regions of interest in the left and right fronto-insular (FI) cortices, we explored the neurobiological substrate of temporal discounting in 123 non-demented older adults from the Rush Memory and Aging Project. For the left FI cortex, temporal discounting was positively associated with functional connectivity to the right ventromedial prefrontal cortex and middle temporal regions, and negatively associated with parahippocampal and right cerebellar regions. For the right FI cortex, temporal discounting was negatively associated with functional connectivity to a right cerebellar region. Connectivity maps of both left and right seed regions of interest overlapped in the right cerebellum. Results support the notion of different brain functional connectivity patterns associated with the dynamic range of temporal discounting in old age., (© 2013.)

Risk aversion is associated with several important real world outcomes. Although the neurobiological correlates of risk aversion have been studied in young persons, little is known of the neurobiological correlates of risk aversion among older persons. Resting-state functional MRI data were collected on 134 non-demented participants of the Rush Memory and Aging Project, a community-based cohort study of aging. Risk aversion was measured using a series of standard questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing, with potential gains varied across questions. Participants determined to be "high" (n=27) and "low" (n=27) in risk aversion were grouped accordingly. Using a spherical seed region of interest in the anterior cingulate cortex, voxel-wise functional connectivity network similarities were observed in bilateral frontal, anterior and posterior cingulate, insula, basal ganglia, temporal, parietal, and thalamic regions. Differences in functional connectivity were observed such that those low in risk aversion had greater connectivity to clusters in the superior, middle, and medial frontal regions, as well as cerebellar, parietal, occipital, and inferior temporal regions. Those high in risk aversion had greater connectivity to clusters in the inferior and orbital frontal, parahippocampal, and insula regions, as well as thalamic, parietal, precentral gyrus, postcentral gyrus, and middle temporal regions. Similarities and differences in functional connectivity patterns may reflect the historical recruitment of specific brain regions as a network in the active processing of risk in older adults., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Parkinsonian signs in older persons are associated with numerous adverse health outcomes, however there is limited information about factors which predict progression of these signs. Using generalized linear models, we examined the association between efficiency in visuoperceptual and conceptual processing, measured by repetition priming, and rate of change in parkinsonian signs in a large sample of older persons without cognitive impairment or Parkinson's disease. Subjects with better visuoperceptual priming, measured by threshold word-identification and word-stem completion, at study baseline, progressed more slowly during follow-up of up to 11 years. Conceptual priming was not associated with change in parkinsonian signs. The findings demonstrate that individual differences in visuoperceptual processing efficiency, measured by repetition priming, occur in older persons without cognitive impairment and predict important changes in motor function. Reduced visuoperceptual priming in aging may be an early signal of vulnerability in a corticostrial circuit that contributes to sensorimotor integration.

Two decades of research examining repetition priming in aging and Alzheimer's disease (AD) has yielded a large body of contradictory findings due to differences between studies in participant and task characteristics. Recent research that has employed methodological advances indicates that this form of implicit memory is preserved in healthy aging. When a priming deficit does occur in studies of aging, it is likely a very early signal of neurological disease. Future directions for research in this area include linking priming ability to known risk factors for development of AD, integrating priming measures into clinical neuropsychological assessment batteries, and implementing programs of cognitive retraining that enhance memory using stimulus repetition techniques.

Decline in explicit memory with advancing age is a common finding, but it is unclear whether implicit memory (repetition priming) declines or remains stable. Meta-analyses of studies that examined differences between extreme groups (young-old), typically at a single point in time and on a single test, suggest that a mild reduction in priming occurs with advancing age. The authors examined explicit memory and priming, on multiple tests over 4 annual data-collection waves, in a large group of older persons without dementia at baseline. Explicit memory declined significantly, but priming remained stable. Findings indicate that explicit memory and priming are dissociable on the basis of age-related change and that mildly reduced priming is not an inevitable consequence of growing older., (copyright (c) 2004 APA, all rights reserved.)