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Background: An inflammatory diet is related to poorer cognition, but the underlying brain pathways are unknown., Objective: The aim of this study was to examine associations between the Energy-Adjusted Dietary Inflammatory Index (E-DII) and brain volume, small vessel disease, and cognition in people with and without type 2 diabetes mellitus (T2DM)., Design: This is a secondary cross-sectional analysis of data from the Cognition and Diabetes in Older Tasmanians study., Participants/settings: This study included 641 participants (n = 326 with T2DM) enrolled between 2005 and 2011 from Tasmania, Australia., Main Outcome Measures: The E-DII was computed from the 80-item Dietary Questionnaire for Epidemiological Studies, version 2. Brain volumes (gray matter, white matter, and white matter hyperintensities), infarcts, and microbleeds were obtained from magnetic resonance imaging. Global cognition was derived from a comprehensive battery of neuropsychological tests., Statistical Analysis: Logistic and linear regressions were performed to examine associations between E-DII and brain measures and a global cognitive score, adjusting for demographics, energy, T2DM, mood, ambulatory activity, and cardiovascular risk factors. An E-DII × T2DM interaction term was tested in each model., Results: The mean (standard deviation) age of participants was 69.8 (7.4) years. There were no associations between the E-DII and any of the brain structural measures or global cognitive function in fully adjusted models. There was a modification effect for T2DM on the association between E-DII and gray matter volume (T2DM: β = 1.38, 95% CI -3.03 to 5.79; without T2DM: β = -4.34, 95% CI, -8.52 to -0.16), but not with any of the other outcome measures., Conclusions: In this cross-sectional study, E-DII was not associated with brain structure or global cognition. In 1 of the 7 outcomes, a significant modification effect for T2DM was found for the associations between E-DII and gray matter. Future prospective studies are needed to clarify the associations between diet-related inflammation and brain health., (Copyright © 2021 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive dysfunction is common in older adults, particularly in those with type 2 diabetes (T2D). Higher adherence to the Dietary Guidelines for Americans is associated with better brain health. However, it is unclear if adherence to the Australian Dietary Guidelines (ADG) is associated with cognition or brain structure in older adults., Objective: The aims of this study were to 1) examine the relation between adherence to the ADG, cognition, and brain MRI and 2) determine whether T2D modifies any associations., Methods: The Cognition and Diabetes in Older Tasmanians Study is a cross-sectional study in 688 people (n = 343 with T2D) aged 55-90 y. A validated 80-item food-frequency questionnaire was used to assess dietary intake. Adherence to the 2013 ADG was estimated using the Dietary Guidelines Index (DGI). Cognitive function in multiple domains was assessed with a comprehensive battery of neuropsychological tests and brain structure with MRI. Multivariable linear models were used to assess the associations between DGI, cognitive z scores, and brain structure. Effect modification for T2D was examined with a DGI × T2D product term., Results: The mean age of the sample was 69.9 y (SD: 7.4 y), with 57.1% men. The mean DGI was 54.8 (SD: 10.7; range: 24.1-84.6). No associations were observed between the Australian DGI and cognition or brain MRI measures. T2D did not modify any associations (P > 0.05)., Conclusions: This is the first study to investigate associations between adherence to the ADG and brain health in the older adults with and without T2D. Future prospective studies are required to clarify if there are long-term associations., (Copyright © The Author(s) 2020.)

Aims/hypothesis: The aims of the study were to examine whether type 2 diabetes mellitus is associated with greater brain atrophy and cognitive decline, and whether brain atrophy mediates associations between type 2 diabetes and cognitive decline., Methods: Participants without dementia aged 55-90 years from the Cognition and Diabetes in Older Tasmanians (CDOT) study underwent brain MRI (ventricular and total brain volume) and neuropsychological measures (global function and seven cognitive domains) at three time points over 4.6 years. Mixed models were used to examine longitudinal associations of type 2 diabetes with cognitive and MRI measures, adjusting for covariates. A test of mediation was used to determine whether brain atrophy explained associations between type 2 diabetes and cognitive decline., Results: A total of 705 participants (diabetes: n = 348, mean age 68.2 years [SD 7.0]; no diabetes: n = 357, mean age 72.5 years [SD 7.1]) were available at baseline. Adjusting for age, sex, education and vascular risk factors, there were significant diabetes × time interactions for verbal memory (β -0.06; 95% CI -0.09, -0.02) and verbal fluency (β -0.03; 95% CI -0.06, -0.00). Although people with diabetes had lower brain (β -14.273; 95% CI -21.197, -6.580) and greater ventricular (β 2.672; 95% CI 0.152, 5.193) volumes at baseline, there were no significant diabetes × time interactions (p > 0.05) or evidence of mediation of the diabetes-cognition relationship by brain atrophy., Conclusions/interpretation: In older community-dwelling people, type 2 diabetes is associated with decline in verbal memory and fluency over ~5 years. The effect of diabetes on brain atrophy may begin earlier (midlife).

Background: Type 2 diabetes (T2D) is associated with an increased risk of cognitive impairment and dementia with poorly understood underlying mechanisms., Objective: We examined the role of blood pressure (BP), aortic stiffness, and hemodynamics in this association., Methods: Cross-sectional sample of late middle-aged twins discordant for T2D from the Australian Twin Registry. Measurements included neuropsychological battery and brain MRI including arterial spin labelling (ASL) to measure cerebral perfusion. Mobil-o-Graph devices were used to non-invasively obtain 24-hour BP, aortic stiffness, and hemodynamic measures. Using mixed modelling, we studied associations of T2D with cognition, MRI measures, BP, aortic stiffness, and hemodynamics., Results: There were 23 twin pairs with mean age 63.7 (SD = 6.1) years. T2D (β=-0.45, p < 0.001) and age (β=-0.05, p = 0.022) were independently associated with poorer attention but not with memory or perceptual speed. T2D was associated with reduced nocturnal central systolic BP dipping (β=-3.79, p = 0.027), but not with BP, aortic stiffness, cerebral perfusion, or other hemodynamic measures. There was a statistically significant interaction between T2D and central systolic BP dipping in predicting attention scores (both p < 0.05 for the interaction term) whereby there was a positive association between BP dipping and attention scores in those with T2D, but not in those without T2D., Conclusion: We found an association between T2D and reduced nocturnal central systolic dipping, but not with any other measures of BP, stiffness or hemodynamic measures. Further study of the role of nocturnal central BP dipping in the association between T2D and cognitive impairment may help identify potential mechanisms.

Background: Frailty is a prevalent geriatric condition associated with poor health outcomes. The pathogenesis of frailty is incompletely understood. We aimed to evaluate the relationship between cerebral small vessel disease (SVD) and frailty., Methods: People aged between 60 and 85 years were randomly selected from the electoral roll into the Tasmanian Study of Cognition and Gait. Participants completed standardized questionnaires regarding medical history and underwent objective sensorimotor, gait, and cognitive testing. These data were used to calculate a frailty index score. Magnetic resonance imaging was performed on all participants to measure SVD. Automated quantification was used to measure white matter hyperintensities (WMH), with manual consensus for subcortical infarction (SI) and cerebral microbleeds (CMB). Multivariable linear regression was used to determine the association between SVD and frailty., Results: The mean age of the sample (n = 388) was 72.0 years (SD 7.0), 44% (172/388) were female and the median Frailty Index was 0.20 (interquartile range 0.12, 0.27). WMH, SI, and CMB in unadjusted models were positively associated with higher frailty scores (p < .05). In final models including all brain variables, higher burden of WMH (β = 2.16; 95% confidence interval [CI] 0.75, 3.57; p = .003), but not SI (β = 2.96; 95% CI -0.44, 6.35; p = .09) or CMB (β = -0.46; 95% CI -4.88, 3.96; p = .84), was independently associated with a higher frailty score., Conclusions: We provide cross-sectional evidence for a positive association between larger burden of WMH and frailty. Longitudinal design is required to determine the temporality of this relationship., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function., Research Design and Methods: This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures., Results: T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P ≤ 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume., Conclusions: Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.

IntroductionThe incidence of both type 1 diabetes (T1D) and type 2 diabetes (T2D) is increasing. Life expectancy is improving in T1D, resulting in a growing population of elderly adults with diabetes. While it is well established that older adults with T2D are at increased risk of cognitive impairment, little is known regarding cognitive aging in T1D and how their cognitive profiles may differ from T2D.Research design and methodsWe compared baseline cognitive function and low cognitive function by diabetes status (n=734 T1D, n=232 T2D, n=247 without diabetes) among individuals from the Study of Longevity in Diabetes (mean age=68). We used factor analysis to group cognition into five domains and a composite measure of total cognition. Using linear and logistic regression models, we examined the associations between diabetes type and cognitive function, adjusting for demographics, comorbidities, depression, and sleep quality.ResultsT1D was associated with lower scores on total cognition, language, executive function/psychomotor processing speed, and verbal episodic memory, and greater odds of low executive function/psychomotor processing speed (OR=2.99, 95% CI 1.66 to 5.37) and verbal episodic memory (OR=1.92, 95% CI 1.07 to 3.46), compared with those without diabetes. T2D was associated with lower scores on visual episodic memory. Compared with T2D, T1D was associated with lower scores on verbal episodic memory and executive function/psychomotor processing speed and greater odds of low executive function/psychomotor processing speed (OR=1.74, 95% CI 1.03 to 2.92).ConclusionsOlder adults with T1D had significantly poorer cognition compared with those with T2D and those without diabetes even after accounting for a range of comorbidities. Future studies should delineate how to reduce risk in this vulnerable population who are newly surviving to old age.

IntroductionWomen comprise two-thirds of people with dementia, making female sex a significant dementia risk factor. Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are known dementia risk factors with an increasing global incidence. Understanding whether subtle sex differences persist in cognitive function prior to dementia in the context of diabetes may help elucidate the magnitude of sex effects on dementia risk.Research design and methodsWe examined cross-sectional data from the Study of Longevity in Diabetes (SOLID), a prospective cohort study of members of Kaiser Permanente Northern California aged 60 years and older with T1D (n=758), T2D (n=232) and without either T1D or T2D (n=247). We used factor analysis to generate summary scores of cognitive domains and used regression analyses to examine the associations between sex and cognition adjusting for sociodemographic and cardiovascular confounders.ResultsWe included 1237 participants (630 women and 607 men) with mean age 68 years. By design, the distribution of men and women in T1D, T2D and no diabetes was similar. Women had better cognitive performance than men in global cognition (β=0.21, 95% CI 0.16 to 0.26), language (β=0.08, 95% CI 0.004 to 0.15), executive function (β=0.13, 95% CI 0.05 to 0.20), episodic verbal memory (β=0.68, 95% CI 0.59 to 0.77) and attention (β=0.20, 95% CI 0.11 to 0.28) but not in episodic visual memory (β=0.006, 95% CI -0.07 to 0.09) adjusting for age and education independent of diabetes status. We did not find an interaction between sex and diabetes status for any of the cognitive outcomes.ConclusionsWomen in late mid-life have better cognitive performance than men in many cognitive domains independent of the presence of T1D or T2D. Further work is required to understand whether these differences change over time or in older cohorts and to understand their relationship to subsequent dementia.

Low fitness and obesity at midlife are individually associated with later‐life decline in cognition and health. However, the relationship between profiles of midlife fitness and obesity with midlife cognition is unclear and was examined by this study. Participants from the third follow‐up of the Childhood Determinants of Adult Health study (2014–2019; aged 36–49 years) were assessed for obesity (body mass index [BMI]), cardiorespiratory (physical work capacity) and muscular fitness (isometric grip and leg strength), and these factors were entered into a latent profile analysis. Psychomotor‐attention, learning–working memory and global cognition composites were derived from z‐scores of individual CogState battery tests. Linear regression analyses examined associations between profiles of fitness and obesity with cognition, adjusting for age, sex, education, alcohol and smoking. Using data from 617 participants [44.4 ± 2.6 (mean ± SD) years, 52% female], we identified 5 mutually exclusive profiles of obesity and fitness. Relative to those with the lowest fitness and highest BMI (5% of sample), those with a profile of (1) highest muscular fitness and average BMI (9%), (2) average muscular fitness and BMI (61%) and (3) highest cardiorespiratory fitness (CRF) and below average BMI (7%) all exhibited better global cognition [at least 0.44 (0.12, 0.77) SD, 95% CI] and psychomotor‐attention performance [at least 0.59 (0.27, 0.91) SD, 95% CI]. Compared with low fitness and unhealthy BMI levels, possessing average or high muscular and CRF and a healthy BMI in midlife was associated with better cognitive performance. Enhancing fitness and reducing obesity in midlife could contribute to improved cognitive performance in middle age. Highlights: Profiles containing adults with a combination of low levels of cardiorespiratory and muscular fitness and higher levels of obesity were associated with lower psychomotor‐attention and global cognition at midlife.Possessing average or higher levels of fitness, and lower obesity at midlife, was associated with better cognitive performance at midlife compared to those with lower fitness and unhealthy BMIs.Maintaining fitness and reducing obesity at midlife may contribute to greater cognitive performance at midlife and beyond and reduce the risk of cognitive decline. [ABSTRACT FROM AUTHOR]

Background: To examine the effect of frailty on cognitive decline independent of cerebral small vessel disease (cSVD) and brain atrophy, and whether associations between neuropathology and cognition differed depending on frailty status.Methods: The Tasmanian Study of Cognition and Gait was a population-based longitudinal cohort study with data collected at 3 phases from 2005 to 2012. Participants aged 60-85 were randomly selected from the electoral roll. Various data were used to operationalize a 36-item frailty index (FI) at baseline. Brain MRI was undertaken to obtain baseline measures of neuropathology. A neuropsychological battery was used to assess cognition at each time point. Generalized linear mixed models were used to examine the effect of frailty and MRI measures on cognition over time. The associations between MRI measures and cognition were explored after stratifying the sample by baseline frailty status. All analyses were adjusted for age, sex, and education.Results: A total of 385 participants were included at baseline. The mean age was 72.5 years (standard deviation [SD] 7.0), 44% were female (n = 171). In fully adjusted linear mixed models, frailty (FI × time β -0.001, 95% confidence interval [CI] -0.003, -0.001, p = .03) was associated with decline in global cognition, independent of brain atrophy, and cSVD. The association between cSVD and global cognition was significant only in those with low levels of frailty (p = .03).Conclusion: These findings suggest that frailty is an important factor in early cognitive dysfunction, and measuring frailty may prove useful to help identify future risk of cognitive decline. [ABSTRACT FROM AUTHOR]

Sharing in embryology and function between the eye and brain has led to interest in whether assessments of the eye reflect brain changes seen in neurodegeneration. We aimed to examine the associations between measures of retinal layer thickness using optical coherence tomography (OCT) and multimodal measures of brain structure and function. Using a convenient sample of twins discordant for type 2 diabetes, we performed cognitive testing, structural brain MRI (tissue volumetry), diffusion tensor imaging (white matter microstructure), and arterial spin labelling (cerebral blood flow). OCT images were recorded and retinal thickness maps generated. We used mixed level modelling to examine the relationship between retinal layer thicknesses and brain measures. We enrolled 35 people (18 pairs, mean age 63.8 years, 63% female). Ganglion cell layer thickness was positively associated with memory, speed, gray matter volume, and altered mean diffusivity. Ganglion cell layer thickness was strongly positively associated with regional cerebral blood flow. We found only a limited number of associations between other retinal layer thickness and measures of brain structure or function. Ganglion cell layer thickness showed consistent associations with a range of brain measures suggesting it may have utility as a marker for future dementia risk. [ABSTRACT FROM AUTHOR]

Background: The contribution of cerebral small vessel disease (cSVD) to the pathogenesis of frailty remains uncertain. We aimed to examine the associations between cSVD with progression of frailty in a population-based study of older people.Methods: People aged between 60 and 85 years were randomly selected form the electoral roll to participate in the Tasmanian Study of Cognition and Gait. Participants underwent self-reported questionnaires, objective gait, cognitive and sensorimotor testing over three phases ranging between 2005 and 2012. These data were used to calculate a 41-item frailty index (FI) at three time points. Baseline brain magnetic resonance imaging was performed on all participants to measure cSVD. Generalized mixed models were used to examine associations between baseline cSVD and progression of frailty, adjusted for confounders of age, sex, level of education, and total intracranial volume.Results: At baseline (n = 388) mean age was 72 years (SD = 7.0), 44% were female, and the median FI score was 0.20 (interquartile range [IQR] 0.12, 0.27). In fully adjusted models higher burden of baseline white matter hyperintensity (WMH) was associated with frailty progression over 4.4 years (β = 0.03, 95% CI: 0.01, 0.05; p = .004) independent of other SVD markers. Neither baseline infarcts (p = .23), nor microbleeds at baseline (p = .65) were associated with progression of frailty.Conclusions: We provide evidence for an association between baseline WMHs and progression of frailty. Our findings add to a growing body of literature suggesting WMH is a marker for frailty. [ABSTRACT FROM AUTHOR]

Background: Unhealthy dietary patterns (DPs) are associated with poorer cognition, but few studies have investigated the underlying brain structural mechanisms.Objective: We aimed to examine the relations between DPs, brain structure, and cognition in older people with and without type 2 diabetes.Methods: This cross-sectional study consisted of a sample of people with (n = 343) and without type 2 diabetes (n = 346) aged 55-90 y. The 80-item Cancer Council of Victoria FFQ was used to assess dietary intake. Two DPs (prudent and traditional) for people with type 2 diabetes and 3 DPs (prudent, traditional, and Western) for those without type 2 diabetes were derived using principal component analysis. Neuropsychological tests assessed 6 cognitive domains. Brain MRI was performed to obtain gray, white matter, and hippocampal volumes and markers of small vessel disease (microbleeds, infarcts, and white matter hyperintensities). Multivariable linear regression was used to assess the cross-sectional associations between DPs, brain MRI, and cognitive variables.Results: For those without type 2 diabetes, higher adherence to the Western DP was associated with lower gray matter volume (β = -3.03 95% CI: -5.67, -0.38; P = 0.03). The addition of a cardiovascular risk score, mood, and physical activity weakened associations such that they were no longer significant (β = -1.97 (95% CI: -4.68, 0.74) P = 0.15) for the Western DP. There were no significant associations for the other DPs in people with and without type 2 diabetes.Conclusions: In this cross-sectional study, DPs were not independently associated with brain structure in people with or without type 2 diabetes. Future prospective studies are needed to clarify the role of vascular risk factors on associations between DPs and brain health. [ABSTRACT FROM AUTHOR]

Background: Hypertension is an established risk factor for dementia. However, it is unclear whether there are differential effects of angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blockers (ARB) on brain health. In human observational studies, the evidence for superiority of either agent remains unclear.Objective: To compare brain atrophy and cognitive decline between people treated with ACEi or ARB.Methods: Participants aged 55-90 years without dementia had brain magnetic resonance imaging and neuropsychological assessments performed at 3 time points. The sample was enriched with people with type 2 diabetes (T2D). Multivariable mixed models were used to examine longitudinal associations of antihypertensive medication class with change in cognition and total brain volume.Results: Of 565 people with longitudinal data, there were 163 on ACEi (mean age 69.9 years, T2D:64% with) and 125 on ARB (mean age 69.6 years, T2D:62%) at baseline. The baseline characteristics of those taking either an ACEi or ARB were similar with regards to age, sex, blood pressure control, and vascular risk factors. The mean duration of follow up was 3.2 years. The baseline association of ACEi and ARB use with total brain volume was similar in both groups. However, those taking an ARB had a slower rate of brain atrophy than those taking an ACEi (p = 0.031). Neither ACEi nor ARB use was associated with baseline cognitive function or cognitive decline.Conclusions: These results support the theory that ARB may be preferable to ACEi to reduce brain atrophy. The mechanisms underlying this differential association warrant further investigation. [ABSTRACT FROM AUTHOR]

Chris Moran was supported by a NHMRC-ARC (Australian Research Council) Dementia Research Fellowship (application ID 1109482)." now reads: "NHMRC (National Health and Medical Research Council) project grant (application ID 1063608). This project received seed funding from a Pfizer Neuroscience Research Grant (2011) (application ID WS1931543). This project received seed funding from a Pfizer Neuroscience Research Grant (2011) (application ID WS1931543). [Extracted from the article]