title: Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study.
abstract: Clinicopathological 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.
  
  
  
  In 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.
  
  
  
  NFT 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.
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.|Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Claudia K
authors.initials: CK
authors.lastname: Suemoto
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.|Department of Medical Surgical Nursing, University of São Paulo Nursing School, São Paulo, Brazil.
authors.forename: Renata E L
authors.initials: RE
authors.lastname: Ferretti-Rebustini
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.|Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Roberta D
authors.identifier: 0000-0002-6544-7861
authors.initials: RD
authors.lastname: Rodriguez
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.|Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Renata E P
authors.identifier: 0000-0002-5878-398X
authors.initials: RE
authors.lastname: Leite
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Luciana
authors.identifier: 0000-0002-9399-8062
authors.initials: L
authors.lastname: Soterio
authors.affiliation: Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Sonia M D
authors.identifier: 0000-0002-8303-6732
authors.initials: SM
authors.lastname: Brucki
authors.affiliation: Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Raphael R
authors.identifier: 0000-0003-3066-3457
authors.initials: RR
authors.lastname: Spera
authors.affiliation: Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Tarcila M
authors.initials: TM
authors.lastname: Cippiciani
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.|Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Farfel
authors.affiliation: Department of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Chiavegatto Filho
authors.affiliation: Human Genome and Stem Cell Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors.forename: Michel Satya
authors.initials: MS
authors.lastname: Naslavsky
authors.affiliation: Human Genome and Stem Cell Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors.forename: Mayana
authors.identifier: 0000-0003-3970-8025
authors.initials: M
authors.lastname: Zatz
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.|Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pasqualucci
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.|Division of Geriatrics, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Jacob-Filho
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.|Department of Neurology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Nitrini
authors.affiliation: Brazilian Aging Brain Study Group, University of São Paulo Medical School, São Paulo, Brazil.|Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.|Memory and Aging Center, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Lea T
authors.identifier: 0000-0002-6809-0618
authors.initials: LT
authors.lastname: Grinberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000473:pathology; D001938:Brazil / Q000453:epidemiology; D003071:Cognition; D003430:Cross-Sectional Studies; D003704:Dementia / Q000453:epidemiology* / Q000473:pathology; D015140:Dementia, Vascular / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged