The wake and sleep-modulating neurons of the lateral hypothalamic area demonstrate a differential pattern of degeneration in Alzheimer's disease.

Background: Sleep-wake dysfunction is an early and common event in Alzheimer's disease (AD). The lateral hypothalamic area (LHA) regulates the sleep and wake cycle through wake-promoting orexinergic and sleep-promoting melanin-concentrating hormone (MCH) neurons. These neurons share close anatomical proximity with functional reciprocity. This study investigated the pattern of neuronal loss (ORX and MCH) in the LHA in AD. Understanding the degeneration pattern of these neurons will be instrumental in designing potential therapeutics to slow down the disease progression and remediate the sleep-wake dysfunction in AD. Methods: Postmortem human brain tissue of subjects with AD (across progressive stages) and controls were examined using unbiased stereology. Neuronal counting was done using double immunohistochemistry with ORX, pTau (CP13), and MCH, pTau (CP13) labeled neurons on formalin-fixed, celloidin-embedded tissue. Results: We observed a progressive decline in orexinergic (ORX) neurons and a relative preservation of the melanin-concentrating hormone (MCH) neurons. The decline in ORX neurons was seen from BB 2 (56%, p=0.0634). By the late stage of the disease (BB 5-6), the decline in ORX neurons was 76% (p=0.0043). In contrast, the MCH neurons demonstrated an insignificant decline by BB 6 (25%, p=0.1313). Conclusions: Our data demonstrated very early substantial ORX neuronal loss in the LHA, while MCH neurons were resilient to AD pTau accumulation. Interventions capable of preventing ORX neuronal loss and inhibiting pTau accumulation in the LHA can reinstate sleep-wake dysfunction in AD and possibly prevent the progression of the disease.

Sex and Socioeconomic Disparities in Dementia Risk: A Population Attributable Fractions Analysis in Argentina.

INTRODUCTION, twelve modifiable risk factors (RF) account for 40% of dementia cases worldwide. However, limited data exists on such factors in middle- and low-income countries. We aimed to estimate the population-attributable fractions (PAFs) for the 12 RF in Argentina, assessing changes over a decade, and exploring socioeconomic and sex influences. METHODS, we conducted cross-sectional analyses of the 12 RF from Argentinian surveys conducted in 2009, 2015, and 2018, including 96,321 people. We calculated PAFs, and stratified estimates based on sex and income. RESULTS, we estimated an overall PAF of 59.6%(95%CI=58.9%-60.3%). The largest PAFs were hypertension=9.3%(8.7%-9.9%), physical inactivity=7.4%(6.8%-8.2%), and obesity=7.4%(6.8%-7.9%). Men were more impacted by excessive alcohol, while women by isolation and smoking. Lower income linked to higher PAFs in education, hypertension, and obesity. DISCUSSION, Argentina has a higher PAF for dementia than the world population, with distinct RF distribution. PAF varied by sex and economic status, advocating tailored prevention strategies.

Synaptic proteasome is inhibited in Alzheimer's disease models and associates with memory impairment in mice.

The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, and elimination of oxidized/misfolded proteins. Here, we investigate proteasome function and localization at synapses in Alzheimer's disease (AD) post-mortem brain tissue and in experimental models. We found a marked increase in ubiquitinylated proteins in post-mortem AD hippocampi compared to controls. Using several experimental models, we show that amyloid-ß oligomers (AßOs) inhibit synaptic proteasome activity and trigger a reduction in synaptic proteasome content. We further show proteasome inhibition specifically in hippocampal synaptic fractions derived from APPswePS1ΔE9 mice. Reduced synaptic proteasome activity instigated by AßOs is corrected by treatment with rolipram, a phosphodiesterase-4 inhibitor, in mice. Results further show that dynein inhibition blocks AßO-induced reduction in dendritic proteasome content in hippocampal neurons. Finally, proteasome inhibition induces AD-like pathological features, including reactive oxygen species and dendritic spine loss in hippocampal neurons, inhibition of hippocampal mRNA translation, and memory impairment in mice. Results suggest that proteasome inhibition may contribute to synaptic and memory deficits in AD.

Social Isolation, Loneliness, and Cognitive Performance in Older Adults: Evidence From the ELSI-Brazil Study.

BACKGROUND: The association between social isolation and cognitive performance has been less investigated in low-to-middle-income countries (LMIC) and the presence of depression as a moderator on this association has not been examined. The authors examined the associations of social isolation and perceived loneliness with cognitive performance in the Brazilian Longitudinal Study of Aging. METHODS: In this cross-sectional analysis, social isolation was evaluated by a composite score including marital status, social contact, and social support. The dependent variable was global cognitive performance, which considered memory, verbal fluency, and temporal orientation tests. Linear and logistic regressions were adjusted for sociodemographic and clinical variables. The authors added interaction terms of depressive symptoms with social isolation and loneliness to examine whether depression, measured through the Center for Epidemiologic Studies-Depression Scale, modified these associations. RESULTS: Among 6,986 participants (mean age = 62.1 ± 9.2 years), higher levels of social connections were associated with better global cognitive performance (B = 0.02, 95%CI: 0.02; 0.04). Perceived loneliness was associated with worse cognition (B = -0.26, 95%CI = -0.34; -0.18). Interactions of depressive symptoms with social connections scores were found on memory z-score and with loneliness on global and memory z-scores, suggesting a weaker association between social isolation or loneliness and cognition among those with depressive symptoms. CONCLUSION: In a large sample from an LMIC, social isolation and loneliness were associated with worse cognitive performance. Surprisingly, depressive symptoms decrease the strength of these associations. Future longitudinal studies are important to assess the direction of the association between social isolation and cognitive performance.

The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex.

The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has ~10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.

Age-Associated Upregulation of Glutamate Transporters and Glutamine Synthetase in Senescent Astrocytes In Vitro and in the Mouse and Human Hippocampus.

Aging is marked by complex and progressive physiological changes, including in the glutamatergic system, that lead to a decline of brain function. Increased content of senescent cells in the brain, such as glial cells, has been reported to impact cognition both in animal models and human tissue during normal aging and in the context of neurodegenerative disease. Changes in the glutamatergic synaptic activity rely on the glutamate-glutamine cycle, in which astrocytes handle glutamate taken up from synapses and provide glutamine for neurons, thus maintaining excitatory neurotransmission. However, the mechanisms of glutamate homeostasis in brain aging are still poorly understood. Herein, we showed that mouse senescent astrocytes in vitro undergo upregulation of GLT-1, GLAST, and glutamine synthetase (GS), along with the increased enzymatic activity of GS and [3H]-D-aspartate uptake. Furthermore, we observed higher levels of GS and increased [3H]-D-aspartate uptake in the hippocampus of aged mice, although the activity of GS was similar between young and old mice. Analysis of a previously available RNAseq dataset of mice at different ages revealed upregulation of GLAST and GS mRNA levels in hippocampal astrocytes during aging. Corroborating these rodent data, we showed an increased number of GS + cells, and GS and GLT-1 levels/intensity in the hippocampus of elderly humans. Our data suggest that aged astrocytes undergo molecular and functional changes that control glutamate-glutamine homeostasis upon brain aging.

Hyperphosphorylated Tau in Mesial Temporal Lobe Epilepsy: a Neuropathological and Cognitive Study.

Temporal lobe epilepsy (TLE) often courses with cognitive deficits, but its underlying neuronal basis remains unclear. Confluent data suggest that epilepsy share pathophysiological mechanisms with neurodegenerative diseases. However, as most studies analyze subjects 60 years old and older, it is challenging to rule out that neurodegenerative changes arise from age-related mechanisms rather than epilepsy in these individuals. To fill this gap, we conducted a neuropathological investigation of the hippocampal formation of 22 adults with mesial TLE and 20 age- and sex-matched controls (both younger than 60 years). Moreover, we interrogated the relationship between these neuropathological metrics and cognitive performance. Hippocampal formation extracted from patients with drug-resistant mesial TLE undergoing surgery and postmortem non-sclerotic hippocampal formation of clinically and neuropathologically controls underwent immunohistochemistry against amyloid ß (Aß), hyperphosphorylated tau (p-tau), and TAR DNA-binding protein-43 (TDP-43) proteins, followed by quantitative analysis. Patients underwent a comprehensive neuropsychological evaluation prior to surgery. TLE hippocampi showed a significantly higher burden of p-tau than controls, whereas Aß deposits and abnormal inclusions of TDP-43 were absent in both groups. Patients with hippocampal sclerosis (HS) type 2 had higher immunostaining for p-tau than patients with HS type 1. In addition, p-tau burden was associated with impairment in attention tasks and seizures frequency. In this series of adults younger than 60 years-old, the increase of p-tau burden associated with higher frequency of seizures and attention impairment suggests the involvement of tau pathology as a potential contributor to cognitive deficits in mesial TLE.

Association between objective sleep measures and cognitive performance: a cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study.

Sleep disturbances often co-exist, which challenges our understanding of their potential impact on cognition. We explored the cross-sectional associations of insomnia and objective measures of sleep with cognitive performance in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) study stratified by middle-aged and older adults. Participants aged ≥55 years underwent cognitive evaluations, polygraphy for 1 night, and actigraphy for 7 days. Insomnia was evaluated using the Clinical Interview Scheduled Revised. Obstructive sleep apnea (OSA) and short sleep duration (SSD) were defined by an apnea-hypopnea index (AHI) of ≥15 events/h and <6 h/ night, respectively. In 703 participants (mean [SD] age 62 [6] years, 44% men), cognition was evaluated using a 10-word list, verbal fluency, and trail-making tests. The frequencies of insomnia, SSD, and OSA were 11%, 24%, and 33%, respectively. In all, 4% had comorbid OSA and insomnia, and 11% had both OSA and SSD. Higher wake after sleep onset (ß = -0.004, 95% confidence interval [CI] -0.008, -0.001) and the number of awakenings (ß = -0.006, 95% CI -0.012, -0.001) were associated with worse verbal fluency performance. Compared to those without insomnia, older participants with insomnia had worse global performance (ß = -0.354, 95% CI -0.671, -0.038). Insomnia was an effect modifier in the associations between AHI and executive function performance (p for the interaction between insomnia and AHI = 0.004) and between oxygen saturation <90% and memory performance (p for the interaction between insomnia and oxygen saturation = 0.02). Although some associations between sleep measures and cognition were significant, they should be considered with caution due to the large sample size and multiple testing performed in this study.

Risk factors for dementia in Brazil: Differences by region and race.

INTRODUCTION: Twelve risk factors (RFs) account for 40% of dementia cases worldwide. However, most data for population attributable fractions (PAFs) are from high-income countries (HIC). We estimated how much these RFs account for dementia cases in Brazil, stratifying estimates by race and socioeconomic level. METHODS: We calculated the prevalence and communalities of 12 RFs using 9412 Brazilian Longitudinal Study of Aging participants, then stratified according to self-reported race and country macro-regions. RESULTS: The overall weighted PAF was 48.2%. Less education had the largest PAF (7.7%), followed by hypertension (7.6%), and hearing loss (6.8%). PAF was 49.0% and 54.0% in the richest and poorest regions, respectively. PAFs were similar among White and Black individuals (47.8% and 47.2%, respectively) but the importance of the main RF varied by race. DISCUSSION: Brazil's potential for dementia prevention is higher than in HIC. Education, hypertension, and hearing loss should be priority targets.

Neuropathological correlates of neuropsychiatric symptoms in dementia.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood. METHODS: In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angiopathy (CAA), and hyaline atherosclerosis. Post mortem interviews collected systematic information regarding NPS and cognitive status. A total of 1038 cases were included: no pathology (NP; n = 761), Alzheimer's disease (AD; n = 189), LBD (n = 60), and AD+LBD (n = 28). RESULTS: Hallucinations were associated with higher LB Braak stages, while higher NFT Braak staging was associated with depression, agitation, and greater number of symptoms in the Neuropsychiatric Inventory. Cases with dual AD+LBD pathology had the highest risk of hallucinations, agitation, apathy, and total symptoms but a multiplicative interaction between these pathologies was not significant. DISCUSSION: LB and AD pathology contribute differentially to NPS likely with an additive process contributing to the increased burden of NPS.

Global and local ancestry modulate APOE association with Alzheimer's neuropathology and cognitive outcomes in an admixed sample.

Dementia is more prevalent in Blacks than in Whites, likely due to a combination of environmental and biological factors. Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE ε4 risk and Alzheimer's disease (AD) pathology, the most frequent cause of dementia. We investigated the interaction between African ancestry, AD-related neuropathology, APOE genotype, and functional cognition in a postmortem sample of 400 individuals with a range of AD pathology severity and lack of comorbid neuropathology from a cohort of community-dwelling, admixed Brazilians. Increasing proportions of African ancestry (AFR) correlated with a lower burden of neuritic plaques (NP). However, for individuals with a severe burden of NP and neurofibrillary tangles (NFT), AFR proportion was associated with worse Clinical Dementia Rating sum of boxes (CDR-SOB). Among APOE ε4 carriers, the association between AFR proportion and CDR-SOB disappeared. APOE local ancestry inference of a subset of 309 individuals revealed that, in APOE ε4 noncarriers, non-European APOE background correlated with lower NP burden and, also, worse cognitive outcomes than European APOE when adjusting by NP burden. Finally, APOE ε4 was associated with worse AD neuropathological burden only in a European APOE background. APOE genotype and its association with AD neuropathology and clinical pattern are highly influenced by ancestry, with AFR associated with lower NP burden and attenuated APOE ε4 risk compared to European ancestry.

Factors Associated with Behavioral and Psychological Symptoms of Dementia during COVID-19.

(1) Background: Preventive measures to control the spread of COVID-19 are essential, but they often cause social isolation and diminish the physical and mental health of older adults. In cognitively impaired individuals, the pandemic has worsened behavioral and psychological symptoms of dementia (BPSD). Here, we explored the factors contributing to the worsening of BPSD during the COVID-19 pandemic. (2) Methods: Potential patients were identified at a memory clinic in Japan between June 2017 and June 2021. Eligible patients had a diagnosis of mild cognitive impairment (MCI) or dementia during the study period. The outcome was BPSD, as assessed by using the Dementia Behavioral Disorders Scale. Information on patients' lifestyle habits and use of care services was obtained for use as primary explanatory variables; multiple regression analysis was performed to examine the relationship between BPSD and care services use or lifestyle habits. The model was adjusted for sociodemographic factors, and the interaction terms of the pandemic period with lifestyle and service use were included to evaluate the effects of COVID-19. (3) Results: We identified 977 participants with MCI and 1380 with dementia (MCI group: 69.8% age 75 years or older, 54.2% female; dementia group: 79.8% age 75 years or older, 64.8% female). After adjustment for possible confounders, significantly worse BPSD was demonstrated in those who used daycare services during COVID-19 (both MCI and dementia patients; p = 0.007 and p = 0.025 respectively) and in those with poor nutritional function (dementia patients; p = 0.040). (4) Conclusions and Implications: During COVID-19, poor nutritional status and use of daycare services were associated with BPSD in those with cognitive decline. These findings indicate the need to fully examine the quantity and quality of care services for people with cognitive decline during emergencies and to continue to provide effective services.

Frequency of LATE neuropathologic change across the spectrum of Alzheimer's disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese-American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia-broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with "frequent" neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aß phase = 0 (lacking detectable Aß plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer's disease neuropathology.

Increased Prevalence of Depression and Anxiety Among Subjects With Metabolic Syndrome in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Metabolic syndrome (MetS) and common mental disorders are prevalent conditions. However, the relationship of MetS and its components with depression, anxiety, and common mental disorders has not been sufficiently addressed in low-/middle-income countries. OBJECTIVE: To investigate whether depression, anxiety, and common mental disorders are associated with MetS and its components in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: A cross-sectional analysis of the ELSA-Brasil baseline visit (2008-2010) was performed. Adults without cardiovascular diseases had their MetS status defined by the National Cholesterol Education Program's Adult Treatment Panel III criteria. We assessed mental disorders using the Clinical Interview Schedule-Revised. We employed multiple logistic regression models adjusted for sociodemographic and behavioral factors. The dependent variables were mental disorders, and the independent variables were MetS and its components. We also performed analyses stratified by age and gender. RESULTS: Our sample included 12,725 participants (54.9% women, mean age of 51.8 ± 8.9 y). MetS and depressive disorders were significantly associated (odds ratio [OR] = 1.55, 95% confidence interval [CI] 1.30-1.85). Increased abdominal circumference (OR = 1.54, 95% CI 1.29-1.84), diabetes mellitus (OR = 1.24, 95% CI 1.02-1.50), hypertriglyceridemia (OR = 1.33, 95% CI 1.11-1.60), and low high-density lipoprotein cholesterol (only when adjusted for sociodemographic factors) (OR = 1.25, 95% CI 1.02-1.52) were also associated with depression. This association remained significant for all stratified analyses. Finally, MetS was also significantly associated with anxiety disorders (OR = 1.19, 95% CI 1.07-1.32) and common mental disorders (OR = 1.27, 95% CI 1.17-1.39). CONCLUSIONS: Our cross-sectional findings suggested that depression, anxiety, and common mental disorder are associated with MetS. Depression was also associated with abdominal obesity, elevated blood glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol, but not with hypertension.

Hearing Loss and Cognitive Function: Baseline Findings From the Brazilian Longitudinal Study of Adult Health: ELSA-Brasil.

OBJECTIVE: Hearing loss (HL) has been associated with cognitive impairment in high-income countries. However, no study has investigated this association in low- and middle-income countries. Therefore, our aim was to investigate the association between cognitive function and HL in the Brazilian Longitudinal Study of Adult Health. DESIGN: Cross-sectional analysis of Longitudinal Study of Adult Health (ELSA-Brasil) with 802 individuals (35-74 years old). Hearing was measured using pure-tone audiometry. A pure-tone average (s) of thresholds at 500, 1000, 2000, and 4000 Hz was calculated. HL was defined as a PTA above 25 dB in the better ear or either ear, as a categorical variable. Cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer's Disease word list memory test, the semantic and phonemic verbal fluency (VF) tests, and the Trail Making test version B. To investigate the association between cognitive performance and HL, we used linear regression models adjusted for sociodemographic and clinical variables. RESULTS: Of the total of participants, 7.6% had HL. After adjustment for sociodemographic and health confounding variables, only VF was associated with HL; a 10 dB increase in the PTA in the better ear was associated with worse performance in the phonemic VF test (ß = -0.115 [95% CI, -0.203 to -0.027], p = 0.01). We found a significant interaction between HL and age in the VF domain ( p = 0.01). HL was related to poor VF performance among older adults only. CONCLUSION: In a community-dwelling sample of most middle-aged adults, objectively measured HL was associated with lower VF. These results should be evaluated with caution, given the likelihood of residual confounding and the fact that only VF showed an association with HL.

Cross-national harmonization of cognitive measures across HRS HCAP (USA) and LASI-DAD (India).

BACKGROUND: As global populations age, cross-national comparisons of cognitive health and dementia risk are increasingly valuable. It remains unclear, however, whether country-level differences in cognitive function are attributable to population differences or bias due to incommensurate measurement. To demonstrate an effective method for cross-national comparison studies, we aimed to statistically harmonize measures of episodic memory and language function across two population-based cohorts of older adults in the United States (HRS HCAP) and India (LASI-DAD). METHODS: Data for 3,496 HRS HCAP (≥65 years) and 3,152 LASI-DAD (≥60 years) participants were statistically harmonized for episodic memory and language performance using confirmatory factor analysis (CFA) methods. Episodic memory and language factor variables were investigated for differential item functioning (DIF) and precision. RESULTS: CFA models estimating episodic memory and language domains based on a priori adjudication of comparable items fit the data well. DIF analyses revealed that four out of ten episodic memory items and five out of twelve language items measured the underlying construct comparably across samples. DIF-modified episodic memory and language factor scores showed comparable patterns of precision across the range of the latent trait for each sample. CONCLUSIONS: Harmonization of cognitive measures will facilitate future investigation of cross-national differences in cognitive performance and differential effects of risk factors, policies, and treatments, reducing study-level measurement and administrative influences. As international aging studies become more widely available, advanced statistical methods such as those described in this study will become increasingly central to making universal generalizations and drawing valid conclusions about cognitive aging of the global population.

Education, but not occupation, is associated with cognitive impairment: The role of cognitive reserve in a sample from a low-to-middle-income country.

INTRODUCTION: Education, and less frequently occupation, has been associated with lower dementia risk in studies from high-income countries. We aimed to investigate the association of cognitive impairment with education and occupation in a low-middle-income country sample. METHODS: In this cross-sectional study, cognitive function was assessed by the Clinical Dementia Rating sum of boxes (CDR-SOB). We investigated the association of occupation complexity and education with CDR-SOB using adjusted linear regression models for age, sex, and neuropathological lesions. RESULTS: In 1023 participants, 77% had < 5 years of education, and 56% unskilled occupations. Compared to the group without education, those with formal education had lower CDR-SOB (1-4 years: ß $\beta \;$ = -0.99, 95% confidence interval [CI] = -1.85; -0.14, P = .02; ≥5 years: ß $\beta \;$ = -1.42, 95% CI = -2.47; -0.38, P = .008). Occupation complexity and demands were unrelated to cognition. DISCUSSION: Education, but not occupation, was related to better cognitive abilities independent of the presence of neuropathological insults.

Association Between Adherence to the MIND Diet and Cognitive Performance is Affected by Income: The ELSA-Brasil Study.

BACKGROUND: The relationship between the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet and cognition has not been widely investigated in low- to middle-income countries. We investigated the relationship between MIND diet and cognition in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline data. METHODS: We included 11,788 participants. MIND diet adherence was based on the intake of 15 components according to a food frequency questionnaire. We analyzed the association between MIND diet adherence and global cognition, memory, and executive function using adjusted linear regression. We examined the interaction between income and MIND diet adherence on cognition and presented income stratified analyses. RESULTS: MIND diet adherence was not associated with cognition in the whole sample. Income was an effect modifier of MIND adherence on global cognition (P=0.03) and executive function (P<0.001). For participants with high income, greater adherence was associated with better executive function [ß=0.015, 95% confidence interval (CI)=0.002; 0.028, P=0.025]; while for participants with low income, greater adherence was associated with lower global cognition (ß=-0.020, 95% CI=-0.036; -0.005, P=0.010) and executive function (ß=-0.023, 95% CI=-0.039; -0.007, P=0.004). Adherence to the MIND diet was higher among participants with high income (P<0.001). CONCLUSION: For high-income participants, greater adherence was associated with better cognitive performance; for low-income participants, greater adherence was associated with lower cognitive performance.