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Interleukin-1 plays a role in normal homeostasis and in the inflammatory response which is deemed to be responsible for the development of major chronic diseases that are highly prevalent in the elderly. Aim of this study is to evaluate the factors influencing the serum levels of Interleukin-1 β, in a large and representative population.Data were from the InCHIANTI project, a study of factors contributing to the decline of mobility in late life, which sampled people living in two sites in the surroundings of Florence. Blood samples were obtained from 1292 participants and frozen aliquots were stored at −80 °C. The serum levels of several cytokines were measured by enzyme linked immunosorbent assay using an ultrasensitive commercial kit. Interleukin-1 β serum levels were associated with congestive heart failure (p>0.001) and angina (p=0.02), with Ca2+ serum levels (p=0.02), and with a history of dyslipidemia (p=0.05). We found no association between serum IL-1β level and age, sex, consumption of cardioactive drugs and serum levels of IL-1Ra, IL-6, sIL-6R, IL-10 and TNF-α.Our data could lend support to the hypothesis that IL-1β is mainly involved in the functional alterations of cardiomyocytes under conditions marked by mononuclear cell infiltration and by downregulation of calcium. [Copyright &y& Elsevier]

Iron overload is observed in neurodegenerative diseases, especially Alzheimer's disease (AD) and Parkinson's disease (PD). Homozygotes for the iron-overload (haemochromatosis) causing HFE p.C282Y variant have increased risk of dementia and PD. Whether brain iron deposition is causal or secondary to the neurodegenerative processes in the general population is unclear. We analysed 39,533 UK Biobank participants of European genetic ancestry with brain MRI data. We studied brain iron estimated by R2* and quantitative susceptibility mapping (QSM) in 8 subcortical regions: accumbens, amygdala, caudate, hippocampus, pallidum, putamen, substantia nigra, and thalamus. We performed genome-wide associations studies (GWAS) and used Mendelian Randomization (MR) methods to estimate the causal effect of brain iron on grey matter volume, and risk of AD, non-AD and PD. We also used MR to test whether genetic liability to AD or PD causally increased brain iron (R2* and QSM). In GWAS of R2* and QSM we replicated 83% of previously reported genetic loci and identified 174 further loci across all eight brain regions. Higher genetically predicted brain iron, using both R2* and QSM, was associated with lower grey matter volumes in the caudate, putamen and thalamus (e.g., Beta-putamenQSM: −0.37, p = 2*10–46). Higher genetically predicted thalamus R2* was associated with increased risk of non-AD dementia (OR 1.36(1.16;1.60), p = 2*10–4) but not AD (p > 0.05). In males, genetically predicted putamen R2* increased non-AD dementia risk, but not in females. Higher genetically predicted iron in the caudate, putamen, and substantia nigra was associated with an increased risk of PD (Odds Ratio QSM ∼ substantia-nigra 1.21(1.07;1.37), p = 0.003). Genetic liability to AD or PD was not associated with R2* or QSM in the dementia or PD-associated regions. Our genetic analysis supports a causal effect of higher iron deposition in specific subcortical brain regions for Parkinson's disease, grey matter volume, and non-Alzheimer's dementia. • Genetic evidence supports a causal relationship between higher brain iron with lower grey matter volumes in specific areas. • Higher genetically predicted thalamus R2* increased risk of non-Alzheimer's dementia only. • Higher genetically predicted iron in the caudate, putamen, and substantia nigra increased risk of Parkinson's disease. • Higher iron deposition in specific subcortical brain regions caused non-Alzheimer's dementia and Parkinson's disease. [ABSTRACT FROM AUTHOR]

Abstract: This study examines the association between personality traits and bruxism, the repetitive grinding or clenching of teeth. Community-dwelling participants (N =470) had a comprehensive oral examination by a dentist and completed a dental history and personality questionnaires. Consistent with the literature on state anxiety and depression as antecedents of bruxism, Neuroticism-related traits were associated with self-reported teeth grinding. These traits were also associated with other oral complaints often associated with anxiety (jaw clicks, difficulty chewing food, and dry mouth), but not with more general oral health complaints (unhealthy gums, bleeding gums, and canker sores) or with dentist-assessed occlusal wear or tongue indentations. This study provides evidence for the association between Neuroticism and bruxism and other stress-related oral health symptoms. [Copyright &y& Elsevier]

Abstract: This study examined the association between personality traits (as measured by the NEO-PI-R) and subjective ratings of mental and physical health (as measured by the SF-36) in two samples of older adults differing in health status (Baltimore Longitudinal Study of Aging, BLSA, n =393, vs. Medicare Primary and Consumer-Directed Care Demonstration, Medicare PCC, n =648). The association between personality traits and subjective mental health did not differ significantly across samples. The association between personality and subjective physical health, however, was significantly stronger in the healthy BLSA sample than in the medically challenged Medicare PCC sample. Differences in health conditions and recent hospitalizations partially accounted for this effect. Lifespan developmental considerations and implications for the use of subjective health ratings as outcome measures in clinical studies are discussed. [Copyright &y& Elsevier]

Abstract: Sarcopenia, or loss of muscle mass and strength, plays a major role in the disablement process in older adults and increases the risk of impaired physical performance, falls, physical disability, frailty, and death. Oxidative stress is a major mechanism implicated in the pathogenesis of sarcopenia; aging muscle shows increased oxidative damage to DNA, protein, and lipids. Carotenoids quench free radicals, reduce damage from reactive oxygen species, and appear to modulate redox-sensitive transcription factors such as NF-κB that are involved in the upregulation of IL-6 and other proinflammatory cytokines. Recent epidemiological studies in community-dwelling older adults show that low serum/plasma carotenoids are independently associated with low skeletal muscle strength and the development of walking disability. These observations are consistent with a growing number of studies showing that a diet with high intake of fruits and vegetables is associated with a reduced risk of inflammation, hypertension, diabetes, cardiovascular disease, and mortality. [Copyright &y& Elsevier]

• High resolution 3D segmentation of human skeletal muscle mitochondria. • High-throughput, easy-to-use and versatile segmentation pipeline. • Orders of magnitude increase in acquisition and segmentation of large volumes. • Large scale statistical analysis of sub-cellular organelles. Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) is an imaging approach that enables analysis of the 3D architecture of cells and tissues at resolutions that are 1–2 orders of magnitude higher than that possible with light microscopy. The slow speeds of data collection and manual segmentation are two critical problems that limit the more extensive use of FIB-SEM technology. Here, we present an easily accessible robust method that enables rapid, large-scale acquisition of data from tissue specimens, combined with an approach for semi-automated data segmentation using the open-source machine learning Weka segmentation software, which dramatically increases the speed of image analysis. We demonstrate the feasibility of these methods through the 3D analysis of human muscle tissue by showing that our process results in an improvement in speed of up to three orders of magnitude as compared to manual approaches for data segmentation. All programs and scripts we use are open source and are immediately available for use by others. [ABSTRACT FROM AUTHOR]

Abstract The reduction-oxidation state of NAD+/NADH is critical for cellular health with NAD+ and its metabolites playing critical roles in aging and pathologies. Given the inherent autooxidation of reduced dinucleotides (i.e. NADH/NADPH), and the well-established differential stability, the accurate measurement of NAD+ and its metabolites is technically challenging. Moreover, sample processing, normalization and measurement strategies can profoundly alter results. Here we developed a rapid and sensitive liquid chromatography mass spectrometry-based method to quantify the NAD+ metabolome with careful consideration of these intrinsic chemical instabilities. Utilizing this method we assess NAD+ metabolite stabilities and determine the presence and concentrations of NAD+ metabolites in clinically relevant human samples including cerebrospinal fluid, erythrocytes, and primate skeletal muscle. Highlights • A rapid and sensitive LC-MS/MS-based method to quantify the NAD+ metabolome was developed. • NAD+ metabolite stabilities were assessed in different matrices. • Sample processing results in significant changes in NAD+ and its metabolites levels. • Multiple NAD + metabolites identified in cerebrospinal fluid for the first time. [ABSTRACT FROM AUTHOR]

Abstract White matter microstructure can be measured with diffusion tensor imaging (DTI). While increasing age is a predictor of white matter (WM) microstructure changes, roles of other possible modifiers, such as cardiovascular risk factors, APOE ε4 allele status and biological sex have not been clarified. We investigated 665 cognitively normal participants from the Baltimore Longitudinal Study of Aging (age 50–95, 56.7% female) with a total of 1384 DTI scans. WM microstructure was assessed by fractional anisotropy (FA) and mean diffusivity (MD). A vascular burden score was defined as the sum of five risk factors (hypertension, obesity, elevated cholesterol, diabetes and smoking status). Linear mixed effects models assessed the association of baseline vascular burden on baseline and on rates of change of FA and MD over a mean follow-up of 3.6 years, while controlling for age, race, and scanner type. We also compared DTI trajectories in APOE ε4 carriers vs. non-carriers and men vs. women. At baseline, higher vascular burden was associated with lower FA and higher MD in many WM structures including association, commissural, and projection fibers. Higher baseline vascular burden was also associated with greater longitudinal decline in FA in the hippocampal part of the cingulum and the fornix (crus)/stria terminalis and splenium of the corpus callosum, and with greater increases in MD in the splenium of the corpus callosum. APOE ε4 carriers did not differ from non-carriers in baseline DTI metrics but had greater decline in FA in the genu and splenium of the corpus callosum. Men had higher FA and lower MD in multiple WM regions at baseline but showed greater increase in MD in the genu of the corpus callosum. Women showed greater decreases over time in FA in the gyrus part of the cingulum, compared to men. Our findings show that modifiable vascular risk factors (1) have a negative impact on white matter microstructure and (2) are associated with faster microstructural deterioration of temporal WM regions and the splenium of the corpus callosum in cognitively normal adults. Reducing vascular burden in aging could modify the rate of WM deterioration and could decrease age-related cognitive decline and impairment. [ABSTRACT FROM AUTHOR]

• Cross-sectional and longitudinal cerebellar volume and verbal memory were examined. • Identified age-dependent cross-sectional associations with baseline volumes. • Baseline cerebellum volumes were not associated with longitudinal verbal memory. • Vermis lobule VI-VII and cerebellum WM change was associated with change in memory. • Association between cerebellar WM volume and memory remained after HC adjustment. The cerebellum is involved in higher-order cognitive functions, e.g., learning and memory, and is susceptible to age-related atrophy. Yet, the cerebellum's role in age-related cognitive decline remains largely unknown. We investigated cross-sectional and longitudinal associations between cerebellar volume and verbal learning and memory. Linear mixed effects models and partial correlations were used to examine the relationship between changes in cerebellum volumes (total cerebellum, cerebellum white matter [WM], cerebellum hemisphere gray matter [GM], and cerebellum vermis subregions) and changes in verbal learning and memory performance among 549 Baltimore Longitudinal Study of Aging participants (2,292 visits). All models were adjusted by baseline demographic characteristics (age, sex, race, education), and APOE e4 carrier status. In examining associations between change with change, we tested an additional model that included either hippocampal (HC), cuneus, or postcentral gyrus (PoCG) volumes to assess whether cerebellar volumes were uniquely associated with verbal learning and memory. Cross-sectionally, the association of baseline cerebellum GM and WM with baseline verbal learning and memory was age-dependent, with the oldest individuals showing the strongest association between volume and performance. Baseline volume was not significantly associated with change in learning and memory. However, analysis of associations between change in volumes and changes in verbal learning and memory showed that greater declines in verbal memory were associated with greater volume loss in cerebellum white matter, and preserved GM volume in cerebellum vermis lobules VI-VII. The association between decline in verbal memory and decline in cerebellar WM volume remained after adjustment for HC, cuneus, and PoCG volume. Our findings highlight that associations between cerebellum volume and verbal learning and memory are age-dependent and regionally specific. [ABSTRACT FROM AUTHOR]

Background Older adults are more susceptible to higher inflammatory levels and depression. Moreover, diet may influence inflammation as well as depression but no previous study examined whether inflammatory dietary patterns are related to depression in an older population. To investigate the longitudinal association between inflammatory dietary patterns (using reduced rank regression (RRR)) and depressive symptoms in a population sample of Italian older adults. Methods We included 827 participants (aged ≥ 65 years) at baseline in 1998. Follow-up measurements were collected after 3, 6 and 9 years. We used RRR to identify inflammatory dietary patterns at baseline. The Centre for Epidemiologic Studies Depression (CES-D) scale was used to assess depressive symptoms by using continuous scores and depression by using a cut-off point (CES-D ≥ 20). Results We identified two inflammatory dietary patterns using different sets of response variables. Dietary pattern I was related to inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor α and was characterized by high intakes of refined grains, sweet snacks, pasta and rice. After full adjustment for confounders, no longitudinal association was found when comparing extreme quartiles of this dietary pattern and depressive symptoms (Q1 vs Q4, model 4: B = 0.04, 95% CI: −0.06, 0.13) or depression (Q1 vs Q4, model 4: OR = 0.90, 95% CI: 0.55, 1.45). Dietary pattern II was related to inflammatory markers CRP, IL-18, IL-1β, IL-1 receptor antagonist and was characterized by high intakes of pasta, sugar-sweetened beverages, processed meat and chocolate and sweets. When comparing extreme quartiles, this dietary pattern was not longitudinally associated with depressive symptoms (Q1 vs Q4, model 4: B = −0.04, 95% CI: −0.13, 0.05) but an inverse association was found for depression (Q1 vs Q4, model 4: OR = 0.56, 95% CI: 0.40, 0.94). Conclusion Our study does not support the hypothesis that dietary patterns linked to inflammatory markers are associated with higher depressive symptoms and higher depression incidence. However, dietary intake in our population of older adults was quite homogeneous which makes it difficult to show clear associations. [ABSTRACT FROM AUTHOR]

Mounting evidence indicates that myelin breakdown may represent an early phenomenon in neurodegeneration, including Alzheimer's disease (AD). Understanding the factors influencing myelin synthesis and breakdown will be essential for the development and evaluation of therapeutic interventions. In this work, we assessed associations between genetic variance in apolipoprotein E (APOE) and cerebral myelin content. Quantitative magnetic resonance imaging (qMRI) was performed on a cohort of 92 cognitively unimpaired adults ranging in age from 24 to 94 years. We measured whole-brain myelin water fraction (MWF), a direct measure of myelin content, as well as longitudinal and transverse relaxation rates (R 1 and R 2), sensitive measures of myelin content, in carriers of the APOE ε4 or APOE ε2 alleles and individuals with the ε33 genotype. Automated brain mapping algorithms and statistical models were used to evaluate the relationships between MWF or relaxation rates and APOE isoforms, accounting for confounding variables including age, sex, and race, in several cerebral structures. Our results indicate that carriers of APOE ε2 exhibited significantly higher myelin content, that is, higher MWF, R 1 or R 2 values, in most brain regions investigated as compared to noncarriers, while ε4 carriers exhibited trends toward lower myelin content compared to noncarriers. Finally, all qMRI metrics exhibited quadratic, inverted U-shape, associations with age; attributed to the development of myelination from young to middle age followed by progressive loss of myelin afterwards. Sex and race effects on myelination were, overall, nonsignificant. These findings suggest that individual genetic background may influence cerebral myelin maintenance. Although preliminary, this work lays the foundation for further investigations to clarify the relationship between APOE genotype and myelination, which may suggest potential targets in treatment or prevention of AD. [ABSTRACT FROM AUTHOR]

Background Circulating interleukin-6 levels increase with advancing age and are a risk factor for various diseases and mortality. The characterization of gene expression profiles associated with interleukin-6 levels might suggest important molecular events underlying its regulation. Methods and results We studied the association of transcriptional profiles with interleukin-6 levels in 2422 participants from the Framingham Heart Study Offspring Cohort using Affymetrix Human Exon 1.0 ST Array. We identified 4139 genes that were significantly associated with interleukin-6 levels (FDR < 0.05) after adjusting for age, sex and blood cell components. We then replicated 807 genes in the InCHIANTI study with 694 participants. Many of the top genes are involved in inflammation-related pathways or erythrocyte function, including JAK/Stat signaling pathway and interleukin-10 signaling pathway. Conclusion We identified and replicated 807 genes that were associated with circulating interleukin-6 levels. Future characterization of interleukin-6 regulation networks may facilitate the identification of additional potential targets for treating inflammation-related diseases. [ABSTRACT FROM AUTHOR]

Abstract: Associations among personality as measured by the Five Factor Model, physical activity, and muscle strength were assessed using data from the Baltimore Longitudinal Study of Aging (N =1220, age: mean =58, SD =16). General linear modeling with adjustment for age, sex, race, and body mass index, and bootstrapping for mediation were used. We found neuroticism and most of its facets to negatively correlate with strength. The extraversion domain and its facets of warmth, activity, and positive-emotions were positively correlated with strength, independent of covariates. Mediation analysis results suggest that these associations are partly explained by physical activity level. Findings extend the evidence of an association between personality and physical function to its strength component and indicate health behavior as an important pathway. [Copyright &y& Elsevier]

Abstract: Recent genetic and proteomic studies demonstrate that clusterin/apolipoprotein-J is associated with risk, pathology, and progression of Alzheimer''s disease (AD). Our main aim was to examine associations between plasma clusterin concentration and longitudinal changes in brain volume in normal aging and mild cognitive impairment (MCI). A secondary objective was to examine associations between peripheral concentration of clusterin and its concentration in the brain within regions that undergo neuropathological changes in AD. Non-demented individuals (N=139; mean baseline age 70.5years) received annual volumetric MRI (912 MRI scans in total) over a mean six-year interval. Sixteen participants (92 MRI scans in total) were diagnosed during the course of the study with amnestic MCI. Clusterin concentration was assayed by ELISA in plasma samples collected within a year of the baseline MRI. Mixed effects regression models investigated whether plasma clusterin concentration was associated with rates of brain atrophy for control and MCI groups and whether these associations differed between groups. In a separate autopsy sample of individuals with AD (N=17) and healthy controls (N=4), we examined the association between antemortem clusterin concentration in plasma and postmortem levels in the superior temporal gyrus, hippocampus and cerebellum. The associations of plasma clusterin concentration with rates of change in brain volume were significantly different between MCI and control groups in several volumes including whole brain, ventricular CSF, temporal gray matter as well as parahippocampal, superior temporal and cingulate gyri. Within the MCI but not control group, higher baseline concentration of plasma clusterin was associated with slower rates of brain atrophy in these regions. In the combined autopsy sample of AD and control cases, representing a range of severity in AD pathology, we observed a significant association between clusterin concentration in the plasma and that in the superior temporal gyrus. Our findings suggest that clusterin, a plasma protein with roles in amyloid clearance, complement inhibition and apoptosis, is associated with rate of brain atrophy in MCI. Furthermore, peripheral concentration of clusterin also appears to reflect its concentration within brain regions vulnerable to AD pathology. These findings in combination suggest an influence of this multi-functional protein on early stages of progression in AD pathology. [Copyright &y& Elsevier]

Abstract: Major sources of flavonoids were identified, and mean intakes over several decades were reported, among 1638 participants (mean age 62.1±16.0y), of the Baltimore Longitudinal Study of Aging (BLSA). Dietary data were collected using 7-d diet records during three time periods (1980s, 1990s and 2000-present), and the USDA flavonoid, proanthocyanidin and isoflavone databases were used to estimate dietary flavonoid intakes. Dietary intake data were divided according to decade of visit. Foods were matched with appropriate foods in the USDA databases. Mixed dishes were disaggregated to individual foods and a similar procedure was followed. Total flavonoids and five sub-classes of flavonoids, including flavonols, flavones, flavanones, flavan-3-ols and anthocyanidins, were computed by summing appropriate compounds. The median intakes of flavonoids and the contributions of various foods to intakes were calculated by decade. Age and sex adjusted mean (SE) daily intakes of flavonoids increased from 250 (7.4) in the 1980s to 280 (9.9)mg in the 2000s. Top contributors of flavonoids were tea, apple/pear (and juices), citrus fruits (and juices), peaches, plums, grapes, nectarines (and juices) and chocolate. The data show an increase in the consumption of flavonoids over the three decades, which appears to be related to intake of fruit. [Copyright &y& Elsevier]

Abstract: Lenalidomide, an analog of thalidomide, modified responses of stimulated T cells from healthy young (ages 21–40years) and old (≥age 65years) subjects. At 0.03μM to 1μM, lenalidomide enhanced generation of IL-2 and IFN-γ by T cell receptor-stimulated T cells of young subjects up to respective maximum increases of 17-fold and three-fold, but at 0.3μM and 1μM suppressed IL-17 generation. The same concentrations of lenalidomide enhanced IL-2 and IFN-γ generation by stimulated T cells of old subjects more, with greater respective maximal increases of up to 120-fold and six-fold, without suppressing IL-17 generation. Lenalidomide enhanced proliferation and suppressed apoptosis of stimulated T cells from old subjects, by IL-2-dependent mechanisms, and restored diminished T cell chemotactic responses to CCL21 and sphingosine 1-phosphate. The reversal of T cell abnormalities of immunosenescence by low concentrations of lenalidomide suggest a potential for improvement of immunity in the elderly. [Copyright &y& Elsevier]

Abstract: Our objective was to identify major dietary sources of whole grains and to describe the construction of a database of whole grain content of foods. Dietary information was collected with 7-d food records from men and women in the Baltimore Longitudinal Study of Aging, mean age 62.1±16.0 years, who participated in the dietary assessment portion of the study (n =1516), and estimates of whole grain intake were obtained from a newly developed database. The Pyramid Servings database and 1994–1996 Continuing Survey of Food Intakes by Individuals (CSFII) recipe ingredients database were then used to calculate both servings and gram weights of whole grain intakes. Mean intakes of whole grains, refined grains, and total grains, as well as frequency of intake for major whole grain food groups and whole grain content for each group, were calculated. Top contributors of whole grains were ready-to-eat breakfast cereals (made with whole grain as well as bran), hot breakfast cereals (made with whole grain), multi-grain bread, and whole wheat bread. While more research is needed to better understand the benefits of whole grains, the development of research tools, including databases to accurately assess whole grain intake, is a critical step in completing such research. [Copyright &y& Elsevier]

Myelin loss and iron accumulation are cardinal features of aging and various neurodegenerative diseases. Oligodendrocytes incorporate iron as a metabolic substrate for myelin synthesis and maintenance. An emerging hypothesis in Alzheimer's disease research suggests that myelin breakdown releases substantial stores of iron that may accumulate, leading to further myelin breakdown and neurodegeneration. We assessed associations between iron content and myelin content in critical brain regions using quantitative magnetic resonance imaging (MRI) on a cohort of cognitively unimpaired adults ranging in age from 21 to 94 years. We measured whole-brain myelin water fraction (MWF), a surrogate of myelin content, using multicomponent relaxometry, and whole-brain iron content using susceptibility weighted imaging in all individuals. MWF was negatively associated with iron content in most brain regions evaluated indicating that lower myelin content corresponds to higher iron content. Moreover, iron content was significantly higher with advanced age in most structures, with men exhibiting a trend towards higher iron content as compared to women. Finally, relationship between MWF and age, in all brain regions investigated, suggests that brain myelination continues until middle age, followed by degeneration at older ages. This work establishes a foundation for further investigations of the etiology and sequelae of myelin breakdown and iron accumulation in neurodegeneration and may lead to new imaging markers for disease progression and treatment. [ABSTRACT FROM AUTHOR]

• Greater annual rates of memory decline were associated with greater volume loss in multiple temporal and occipital regions. • Decline in verbal fluency was associated with greater ventricular size and decline in frontal, temporal, and parietal regions. • Decline in visuospatial ability was associated with volume loss in 3 temporal and parietal regions. • Declines in Trail-Making Test-A were associated with volume loss in 4 temporal and parietal regions. • Declines in Trail-Making Test-B were associated with ventricular size and volume loss in 10 regions. Investigation of relationships between age-related changes in regional brain volumes and changes in domain-specific cognition could provide insights into the neural underpinnings of individual differences in cognitive aging. Domain-specific cognition (memory, verbal fluency, visuospatial ability) and tests of executive function and attention (Trail-Making Test Part A and B) and 47 brain volumes of interest (VOIs) were assessed in 836 Baltimore Longitudinal Study of Aging participants with mean follow-up of 4.1 years (maximum 23.1 years). To examine the correlation between changes in domain-specific cognition and changes in brain volumes, we used bivariate linear mixed effects models with unstructured variance-covariance structure to estimate longitudinal trajectories for each variable of interest and correlations among the random effects of these measures. Higher annual rates of memory decline were associated with greater volume loss in 14 VOIs primarily within the temporal and occipital lobes. Verbal fluency decline was associated with greater ventricular enlargement and volume loss in 24 VOIs within the frontal, temporal, and parietal lobes. Decline in visuospatial ability was associated with volume loss in 3 temporal and parietal VOIs. Declines on the attentional test were associated with volume loss in 4 VOIs located within temporal and parietal lobes. Greater declines on the executive function test were associated with greater ventricular enlargement and volume loss in 10 frontal, parietal, and temporal VOIs. Our findings highlight domain-specific patterns of regional brain atrophy that may contribute to individual differences in cognitive aging. [ABSTRACT FROM AUTHOR]