Research Article: Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study

Date Published: March 28, 2017

Publisher: Public Library of Science

Author(s): Claudia K. Suemoto, Renata E. L. Ferretti-Rebustini, Roberta D. Rodriguez, Renata E. P. Leite, Luciana Soterio, Sonia M. D. Brucki, Raphael R. Spera, Tarcila M. Cippiciani, Jose M. Farfel, Alexandre Chiavegatto Filho, Michel Satya Naslavsky, Mayana Zatz, Carlos A. Pasqualucci, Wilson Jacob-Filho, Ricardo Nitrini, Lea T. Grinberg, Carol Brayne

Abstract: BackgroundClinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis.Methods and findingsIn this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y). Cognitive function was investigated using the Clinical Dementia Rating (CDR) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE); neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI). Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC) score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD), and 35% of vascular dementia (VaD). Neurofibrillary tangles (NFTs), hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (β = 1.33, 95% CI 1.20–1.46), IQCODE (β = 0.14, 95% CI 0.13–0.16), and NPI (β = 1.74, 95% CI = 1.33–2.16). Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with Lewy body/Parkinson dementia. The major limitation of our study is the lack of clinical follow-up of participants during life.ConclusionsNFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Our results confirm the high prevalence of neuropathological diagnosis in older adults and the mismatch between clinical and neuropathological diagnoses.

Partial Text: In 2010, 35.6 million people lived with dementia worldwide. This number is expected to double every 20 y and reach 115.4 million in 2050 [1]. Much of this increase will be due to a surge in dementia prevalence in low- and middle-income countries (LMICs). By 2050, 71% of people with dementia will live in LMICs, as oppose to 58% in 2010 [1]. Alzheimer disease (AD) is the leading cause of dementia worldwide, according to epidemiological studies, accounting for an average of 60% of cases in LMICs [2] and ranging from 50% to 84% of cases in Latin America [3].

Here we described neuropathological findings and clinical and neuropathological variables associated with cognitive impairment in a community-based sample of 1,092 older adults from a LMIC with broad educational attainment and admixed race background, a population profile much different compared to the samples enrolled in other neuropathologic studies conducted in developed countries. The main findings of this study were as follows:



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