Association between diabetes and causes of dementia: Evidence from a clinicopathological study / Associação entre diabetes e causas de demência: evidência de um estudo clínico-patológico

ABSTRACT.Background: Diabetes mellitus is a risk factor for dementia, especially for vascular dementia (VaD), but there is no consensus on diabetes as a risk factor for Alzheimer's disease (AD) and other causes of dementia. Objective: To explore the association between diabetes and the neuropathological etiology of dementia in a large autopsy study. Methods: Data were collected from the participants of the Brain Bank of the Brazilian Aging Brain Study Group between 2004 and 2015. Diagnosis of diabetes was reported by the deceased's next-of-kin. Clinical dementia was established when CDR ≥ 1 and IQCODE > 3.41. Dementia etiology was determined by neuropathological examination using immunohistochemistry. The association of diabetes with odds of dementia was investigated using multivariate logistic regression. Results: We included 1,037 subjects and diabetes was present in 279 participants (27%). The prevalence of dementia diagnosis was similar in diabetics (29%) and non-diabetics (27%). We found no association between diabetes and dementia (OR = 1.22; 95%CI = 0.81-1.82; p = 0.34) on the multivariate analysis. AD was the main cause of dementia in both groups, while VaD was the second-most-frequent cause in diabetics. Other mixed dementia was the second-most-common cause of dementia and more frequent among non-diabetics (p = 0.03). Conclusion: Diabetes was not associated with dementia in this large clinicopathological study.

RESUMO. Introdução: Diabetes mellitus é um fator de risco para a demência, especialmente para a demência vascular (DV), mas ainda não há consenso sobre diabetes como fator de risco para a doença de Alzheimer (DA) e outras causas de demência. Objetivo: Verificar a associação entre diabetes e demência e sua etiologia neuropatológica em um grande estudo de autópsia. Métodos: Os dados foram coletados do Banco de Encéfalos Humanos do Grupo de Estudos em Envelhecimento Cerebral da FMUSP entre 2004 e 2015. O diagnóstico de diabetes foi relatado por pelos parentes do falecido. A demência clínica foi estabelecida quando CDR ≥ 1 e IQCODE > 3,41. A etiologia da demência foi determinada pelo exame neuropatológico com imuno-histoquímica. A associação de diabetes com probabilidades de demência foi investigada usando regressão logística multivariada. Resultados: Foram incluídos 1.037 sujeitos, diabetes esteve presente em 279 participantes (27%). A frequência de diagnóstico de demência foi semelhante entre diabéticos (29%) e não diabéticos (27%). Não encontramos associação entre diabetes e demência (OR = 1,22; IC 95% = 0,81-1,82; p = 0,34) na análise multivariada. DA foi a principal causa de demência em ambos os grupos, DV foi a segunda causa em diabéticos. A frequência de outra demência mista foi a segunda causa de demência e mais frequente entre os não diabéticos (p = 0,03). Conclusão: A diabetes não foi associada à demência neste grande estudo clínico-patológico.

Diabetes is Not Associated with Alzheimer's Disease Neuropathology.

BACKGROUND: Previous evidence linking diabetes to Alzheimer's disease (AD) neuropathology is mixed and scant data are available from low- and middle-income countries. OBJECTIVE: To investigate the association between diabetes and AD neuropathology in a large autopsy study of older Brazilian adults. METHODS: In this cross-sectional study, diabetes was defined by diagnosis during life or use of antidiabetic medication. A standardized neuropathological examination was performed using immunohistochemistry. The associations of diabetes with Consortium to Establish and Registry for Alzheimer Disease (CERAD) scores for neuritic plaques and Braak-Braak (BB) scores for neurofibrillary tangles were investigated using multivariable ordinal logistic regression. We investigated effect modification of education, race, and APOE on these associations. RESULTS: Among 1,037 subjects (mean age = 74.4±11.5 y; mean education = 4.0±3.7 y; 48% male, 61% White), diabetes was present in 279 subjects. Diabetes was not associated with BB (OR = 1.12, 95% CI = 0.81-1.54, p = 0.48) or with CERAD (OR = 0.97, 95% CI = 0.68-1.38, p = 0.86) scores on analyses adjusted for sociodemographic and clinical variables. We observed effect modification by the APOE allele ɛ4 on the association between diabetes mellitus and BB scores. CONCLUSION: No evidence of an association between diabetes and AD neuropathology was found in a large sample of Brazilians; however, certain subgroups, such as APOE allele ɛ4 carriers, had higher odds of accumulation of neurofibrillary tangles.

Association between diabetes and causes of dementia: Evidence from a clinicopathological study.

BACKGROUND: Diabetes mellitus is a risk factor for dementia, especially for vascular dementia (VaD), but there is no consensus on diabetes as a risk factor for Alzheimer's disease (AD) and other causes of dementia. OBJECTIVE: To explore the association between diabetes and the neuropathological etiology of dementia in a large autopsy study. METHODS: Data were collected from the participants of the Brain Bank of the Brazilian Aging Brain Study Group between 2004 and 2015. Diagnosis of diabetes was reported by the deceased's next-of-kin. Clinical dementia was established when CDR ≥ 1 and IQCODE > 3.41. Dementia etiology was determined by neuropathological examination using immunohistochemistry. The association of diabetes with odds of dementia was investigated using multivariate logistic regression. RESULTS: We included 1,037 subjects and diabetes was present in 279 participants (27%). The prevalence of dementia diagnosis was similar in diabetics (29%) and non-diabetics (27%). We found no association between diabetes and dementia (OR = 1.22; 95%CI = 0.81-1.82; p = 0.34) on the multivariate analysis. AD was the main cause of dementia in both groups, while VaD was the second-most-frequent cause in diabetics. Other mixed dementia was the second-most-common cause of dementia and more frequent among non-diabetics (p = 0.03). CONCLUSION: Diabetes was not associated with dementia in this large clinicopathological study.

INTRODUÇÃO: Diabetes mellitus é um fator de risco para a demência, especialmente para a demência vascular (DV), mas ainda não há consenso sobre diabetes como fator de risco para a doença de Alzheimer (DA) e outras causas de demência. OBJETIVO: Verificar a associação entre diabetes e demência e sua etiologia neuropatológica em um grande estudo de autópsia. Métodos: Os dados foram coletados do Banco de Encéfalos Humanos do Grupo de Estudos em Envelhecimento Cerebral da FMUSP entre 2004 e 2015. O diagnóstico de diabetes foi relatado por pelos parentes do falecido. A demência clínica foi estabelecida quando CDR ≥ 1 e IQCODE > 3,41. A etiologia da demência foi determinada pelo exame neuropatológico com imuno-histoquímica. A associação de diabetes com probabilidades de demência foi investigada usando regressão logística multivariada. RESULTADOS: Foram incluídos 1.037 sujeitos, diabetes esteve presente em 279 participantes (27%). A frequência de diagnóstico de demência foi semelhante entre diabéticos (29%) e não diabéticos (27%). Não encontramos associação entre diabetes e demência (OR = 1,22; IC 95% = 0,81-1,82; p = 0,34) na análise multivariada. DA foi a principal causa de demência em ambos os grupos, DV foi a segunda causa em diabéticos. A frequência de outra demência mista foi a segunda causa de demência e mais frequente entre os não diabéticos (p = 0,03). CONCLUSÃO: A diabetes não foi associada à demência neste grande estudo clínico-patológico.

Association between adiposity and systemic atherosclerosis: a protocol of a cross-sectional autopsy study.

INTRODUCTION: Adiposity has been associated with atherosclerosis in clinical studies. However, few autopsy studies have investigated this association, and they had only examined the coronary artery disease. Moreover, most studies had small sample sizes and were limited to middle-aged or young adults. Our aim is to investigate the association between adiposity and systemic atherosclerosis in an autopsy study. METHODS AND ANALYSIS: A sample of 240 deceased with 30 years or more will be evaluated. The sample size was calculated using the lowest correlation coefficient found in previous studies (r=0.109), assuming a power of 90% and α=0.05. We will collect information about sociodemographics, frequency of previous contact of the deceased's next of kin and cardiovascular risk factors. We will measure neck, waist and hip circumferences, weight, height and abdominal subcutaneous tissue thickness, and then we will calculate the body mass index, waist-to-hip ratio, waist-to-height ratio and body shape index. We will also weigh the pericardial and abdominal visceral fat, the heart, and we will measure the left ventricular wall thickness. We will evaluate the presence of myocardial infarction, the degree of atherosclerosis in the aorta, carotid, coronary and cerebral arteries and plaque composition in carotid, coronary and cerebral arteries. For each individual, we will fix arterial and adipose tissue samples in 10% formalin and freeze another adipose tissue sample at -80°C for future studies. ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee of University of Sao Paulo Medical School, Brazil. Results will be submitted for publication in a peer-reviewed journal.

Very low levels of education and cognitive reserve: a clinicopathologic study.

OBJECTIVE: We conducted a clinicopathologic study in a large population with very low levels of education to determine whether very few years of education could contribute to cognitive reserve and modify the relation of neuropathologic indices to dementia. METHODS: In this cross-sectional study, we included 675 individuals 50 years of age or older from the Brazilian Aging Brain Study Group. Cognitive abilities were evaluated through a structured interview with an informant at the time of autopsy, including the Clinical Dementia Rating (CDR) scale. Neuropathologic examinations were performed using immunohistochemistry and following internationally accepted criteria. Multivariate linear regression models were conducted to determine whether the association between cognitive abilities (measured by CDR sum of boxes) and years of education was independent of sociodemographic variables and neuropathologic indices, including neuritic plaques, neurofibrillary tangles, lacunar infarctions, small-vessel disease, and Lewy bodies. In addition, interaction models were used to examine whether education modified the relation between neuropathologic indices and cognition. RESULTS: Mean education was 3.9 ± 3.5 years. Formal education was associated with a lower CDR sum of boxes (ß = -0.197; 95% confidence interval -0.343, -0.052; p = 0.008), after adjustment for sociodemographic variables and neuropathologic indices. Furthermore, education modified the relationship of lacunar infarcts with cognitive abilities (p = 0.04). CONCLUSIONS: Even a few years of formal education contributes to cognitive reserve.