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OBJECTIVES: To test the hypothesis that higher level of purpose in life is associated with lower likelihood of dementia and mild cognitive impairment (MCI) in older Brazilians. METHODS: As part of the Pathology, Alzheimer's and Related Dementias Study (PARDoS), informants of 1,514 older deceased Brazilians underwent a uniform structured interview. The informant interview included demographic data, the Clinical Dementia Rating scale to diagnose dementia and MCI, the National Institute of Mental Health Diagnostic Interview Schedule for depression, and a 6-item measure of purpose in life, a component of well-being. RESULTS: Purpose scores ranged from 1.5 to 5.0 with higher values indicating higher levels of purpose. On the Clinical Dementia Rating Scale, 940 persons (62.1%) had no cognitive impairment, 121 (8.0%) had MCI, and 453 (29.9%) had dementia. In logistic regression models adjusted for age at death, sex, education, and race, higher purpose was associated with lower likelihood of MCI (odds ratio = .58; 95% confidence interval [CI]: .43, .79) and dementia (odds ratio = .49, 95% CI: .41, .59). Results were comparable after adjusting for depression (identified in 161 [10.6%]). Neither race nor education modified the association of purpose with cognitive diagnoses. CONCLUSIONS: Higher purpose in life is associated with lower likelihood of MCI and dementia in older black and white Brazilians.

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BACKGROUND: While dementia has been associated with specific causes of death, previous studies were relatively small autopsy series or population-based studies lacking autopsy confirmation and were restricted to Non-Latinx Whites. Here, we examine the association of dementia with autopsy-verified causes of death in racially-diverse older Brazilians. METHODS: As part of the Pathology, Alzheimer´s and Related Dementias Study (PARDoS), a community-based study in Brazil, we included 1941 racially-diverse deceased, 65 years or older at death. We conducted a structured interview with legal informants including the Clinical Dementia Rating (CDR) Scale for dementia proximate to death. Causes of death were assessed after full-body autopsy and macroscopic examination of the brain, thoracic and abdominal/pelvic organs. Up to four causes of death were reported for each decedent. Causes of death were classified as circulatory, infectious, cancer and other. Logistic regression was used to determine associations of dementia with cause of death, controlling for age, sex, race, and education. RESULTS: Dementia was associated with a higher odds of an infectious cause of death (OR = 1.81, 95%CI:1.45-2.25), and with a lower odds of a circulatory disease as cause of death (OR = 0.69, 95%CI:0.54-0.86) and cancer as cause of death (OR = 0.41, 95%CI:0.24-0.71). Dementia was associated with a higher odds of pneumonia (OR = 1.92, 95%CI:1.53-2.40) and pulmonary embolism (OR = 2.31, 95%CI:1.75-3.05) as causes of death and with a lower odds of acute myocardial infarction (OR = 0.42, 95%CI:0.31-0.56) and arterial disease (OR = 0.76, 95%CI:0.61-0.94) as causes of death. CONCLUSION: Racially-diverse older Brazilians with dementia had a higher odds of an infectious cause of death and a lower odds of cancer and circulatory disease as causes of death than those without dementia.

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INTRODUCTION: Knowledge is limited about behavioral and psychological symptoms of mild cognitive impairment (MCI) and dementia in racial and ethnic minorities. METHODS: As part of the Pathology, Alzheimer's and Related Dementias Study (PARDoS), we interviewed knowledgeable informants of 2319 older Brazilian decedents (67% white, 11% black, 22% mixed) using the informant portion of the Clinical Dementia Rating Scale to classify MCI and dementia and the Neuropsychiatric Inventory to assess behavioral and psychological symptoms. RESULTS: We identified four clusters of neuropsychiatric symptoms: agitation, affect/apathy, psychosis, and behavioral problems. On the Clinical Dementia Rating Scale, 1407 had no cognitive impairment, 180 had MCI, and 732 had dementia. Both MCI and dementia were associated with symptoms in each behavioral/psychological cluster (all P's < .001). There was little evidence of racial differences in the association of MCI and dementia with these neuropsychiatric symptoms. CONCLUSION: MCI and dementia are associated with elevated behavioral and psychological symptoms in older black and white Brazilians.

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BACKGROUND: Literacy is more consistently reported than education as protective against dementia in developing regions. OBJECTIVE: To study the association of verbal literacy, numeracy, and music literacy with dementia in older Black and White Brazilians with a broad spectrum of education. METHODS: We studied 1,818 Black, Mixed-race, and White deceased Brazilians 65 years or older at death (mean = 79.64). Data were retrospectively obtained within 36 hours after death in a face-to-face interview with an informant, usually a family member. Dementia was classified using the Clinical Dementia Rating (CDR) scale. Three forms of literacy were ascertained: verbal literacy (10 questions: reading and writing), numeracy (3 questions: multiplication, percentages, and use of a calculator), and music literacy (1 question: reading music). Black (11%) and Mixed-race (23%) older adults were combined in analyses. Models adjusted for age and sex. RESULTS: Dementia was identified in 531 people. Participants had 0 to 25 years of education (median = 4). More literacy was associated with lower odds of dementia (all p≤0.039). Participants that read music had about half the odds of having dementia. Participants in the highest quartile of numeracy and verbal literacy had respectively 27%and 15%lower odds of having dementia compared to the lowest quartile. Literacy was lower in Blacks (p < 0.001, except music p = 0.894) but the effect of literacy on dementia was similar (interaction p > 0.237). In secondary analyses, playing instruments without reading music was not associated with dementia (p = 0.887). CONCLUSION: In a large sample of Brazilians, verbal literacy, numeracy, and music literacy were associated with lower odds of dementia. The effect was similar across races.

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OBJECTIVE: To examine the link between social and emotional isolation and likelihood of dementia among older black and white Brazilians. DESIGN: Cross-sectional clinical-pathological cohort study. SETTING: Medical center in Sao Paulo, Brazil. PARTICIPANTS: As part of the Pathology, Alzheimer's and Related Dementias Study, we conducted uniform structured interviews with knowledgeable informants (72% children) of 1,493 older (age > 65) Brazilian decedents. MEASUREMENTS: The interview included measures of social isolation (number of family and friends in at least monthly contact with decedent), emotional isolation (short form of UCLA Loneliness Scale), and major depression plus the informant portion of the Clinical Dementia Rating Scale to diagnose dementia and its precursor, mild cognitive impairment (MCI). RESULTS: Decedents had a median social network size of 8.0 (interquartile range = 9.0) and a median loneliness score of 0.0 (interquartile range = 1.0). On the Clinical Dementia Rating Scale, 947 persons had no cognitive impairment, 122 had MCI, and 424 had dementia. In a logistic regression model adjusted for age, education, sex, and race, both smaller network size (odds ratio [OR] = 0.975; 95% confidence interval [CI]: 0.962, 0.989) and higher loneliness (OR = 1.145; 95% CI: 1.060, 1.237) were associated with higher likelihood of dementia. These associations persisted after controlling for depression (present in 10.4%) and did not vary by race. After controlling for depression, neither network size nor loneliness was related to MCI. CONCLUSION: Social and emotional isolation are associated with higher likelihood of dementia in older black and white Brazilians.

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BACKGROUND: Self-reported discrimination is a source of psychosocial stress that has been previously associated with poor cognitive function in older African Americans without dementia. OBJECTIVE: Here, we examine the association of discrimination with dementia and cognitive impairment in racially diverse older Brazilians. METHODS: We included 899 participants 65 years or older (34.3% Black) from the Pathology, Alzheimer's and Related Dementias Study (PARDoS), a community-based study of aging and dementia. A structured interview with informants of the deceased was conducted. The interview included the Clinical Dementia Rating (CDR) Scale for the diagnosis of dementia and cognitive impairment proximate to death and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a second measure of cognitive impairment. Informant-reported discrimination was assessed using modified items from the Major and Everyday Discrimination Scales. RESULTS: Discrimination was reported by informants of 182 (20.2%) decedents and was more likely reported by informants of Blacks than Whites (25.3% versus 17.6%, p = 0.006). Using the CDR, a higher level of informant-reported discrimination was associated with higher odds of dementia (OR: 1.24, 95% CI 1.08 -1.42, p = 0.002) and cognitive impairment (OR: 1.21, 95% CI: 1.06 -1.39, p = 0.004). Similar results were observed using the IQCODE (estimate: 0.07, SE: 0.02, p = 0.003). The effects were independent of race, sex, education, socioeconomic status, major depression, neuroticism, or comorbidities. CONCLUSION: Higher level of informant-reported discrimination was associated with higher odds of dementia and cognitive impairment in racially diverse older Brazilians.

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OBJECTIVE: Exposure to negative life events (NLEs) and neuroticism are associated with dementia. It is unknown whether neuroticism explains or modifies the association of NLEs with dementia in older Black and White Brazilians. METHODS: A total of 1747 decedents 65 years and older White and Black (11% Black and 23% Mixed) Brazilians, 53% women, were included in the analyses. Data were obtained in a face-to-face interview with an informant (71% their children) who knew the decedents for 47 years on average. Dementia was classified using the Clinical Dementia Rating. NLEs were assessed with a 10-item scale involving common problems (e.g., death, illness, alcoholism, and financial). Neuroticism was assessed with a 6-item neuroticism scale adapted from the NEO Five-Factor Inventory. Models adjusted for age, sex, and education. Black and mixed-race were combined in the analyses. RESULTS: NLEs (median of 2) were more common in Blacks than Whites (2.04 vs. 1.82, p = 0.007). More NLEs increased the odds of dementia (OR = 1.112, ß = 0.106, p = 0.002), similarly in Blacks and Whites (ß interaction  = 0.046, p = 0.526). More NLEs were also associated with higher neuroticism (ß = 0.071, p < 0.0001), in Whites but not in Blacks (ß interaction  = -0.048, p = 0.006). Neuroticism was associated with higher odds of dementia (OR = 1.658, ß = 0.506, p=<0.001), in Whites but not in Blacks (ß interaction  = -0.420, p = 0.040). Overall, 34% of the effect of NLEs on dementia was associated with the underlying neuroticism trait in Whites (65%, Indirect OR = 1.060, p < 0.001) but no association was evident in Blacks (6%, Indirect OR = 1.008, p = 0.326). Neuroticism did not moderate the association of NLEs with dementia (OR = 0.979, ß = -0.021, p = 0.717). CONCLUSION: The association of NLEs and dementia is partially explained by neuroticism in older White but not in Blacks Brazilians.

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Accumulation of oxidative mitochondrial DNA (mtDNA) damage and impaired base excision repair (BER) in brains have been associated with Alzheimer's disease (AD). However, it is still not clear how these affect mtDNA stability, as reported levels of mtDNA mutations in AD are conflicting. Thus, we investigated whether alterations in BER correlate with mtDNA instability in AD using postmortem brain samples from cognitively normal AD subjects and individuals who show neuropathological features of AD, but remained cognitively normal (high-pathology control). To date, no data on DNA repair and mtDNA stability are available for these individuals. BER activities, mtDNA mutations, and mtDNA copy number were measured in the nuclear and mitochondrial extracts. Significantly lower uracil DNA glycosylase activity was detected in nuclear and mitochondrial extracts from AD subjects, while apurinic/apyrimidinic endonuclease activity was similar in all groups. Although mtDNA mutation frequency was similar in all groups, mtDNA copy number was significantly decreased in the temporal cortex of AD brains but not of high-pathology control subjects. Our results show that lower mitochondrial uracil DNA glycosylase activity does not result in increased mutagenesis, but rather in depletion of mtDNA in early-affected brain regions during AD development.

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BACKGROUND: Morphometric measurements of systemic atherosclerosis and direct quantification of visceral fat are only possible using materials from autopsy studies. However, the few autopsy studies that have investigated the association of visceral fat with atherosclerosis had small sample sizes and focused on coronary arteries of young or middle-aged White subjects. We aimed to investigate the association of pericardial fat (PF) and abdominal visceral fat (AVF) with atherosclerosis in the aorta, coronary, carotid, and cerebral arteries in a large autopsy study. MATERIALS AND METHODS: We evaluated deceased subjects aged 30 years or above. We dissected and weighted the PF and the AVF and evaluated the atherosclerotic burden in the aorta, as well as the carotid, coronary, and cerebral arteries using morphometric measurements. We also investigated the interaction of PF and AVF with age regarding the atherosclerotic burden. RESULTS: The mean age of the 240 included subjects was 64.8±15.3 years, and 63% was male. Greater PF was associated with a higher degree of aortic atherosclerosis after adjusting for confounding variables (coefficient = 4.39, 95% CI = 0.83; 7.94, p = 0.02). Greater AVF was associated with a higher coronary stenosis index (coefficient = 1.49, 95% CI = 0.15; 2.83, p = 0.03) and a greater number of coronary plaques (coefficient = 0.71, 95% CI = 0.24; 1.19, p = 0.003). We did not find an association of PF or AVF with carotid or cerebral atherosclerotic burden. We found a significant interaction of AVF (coefficient = -0.08; 95% CI = -0.14; -0.02, p = 0.009) and PF (coefficient = -0.87, 95% CI = -1.70; -0.04, p = 0.04) with age regarding carotid artery atherosclerotic burden. CONCLUSIONS: Greater AVF was associated with greater atherosclerotic burden and extent in coronary arteries, while greater PF correlated with a higher degree of atherosclerosis in the aorta.

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