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

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.

Neuropathological lesions in the very old: results from a large Brazilian autopsy study

“…AD‐neuropathology was evaluated using the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) criteria for neuritic plaques , and the Braak and Braak (BB) score for neurofibrillary tangles (NFT) . Our assessment of cerebrovascular lesions consisted of gross and microscopic evaluations . We registered infarcts by topography, type, stage, size and number.…”

“…Using a well‐characterized, population‐based clinicopathological study from Brazil that features different race composition, socioeconomic factors, and educational attainment profile compared to available series from high‐income countries (HIC) , we demonstrated that even a small a percentage of African descent lower the relative risk to accumulate AD‐related neuritic plaques compared to Caucasian ancestry , suggesting that ethnicity may affect the vulnerability to neuropathological changes. Among other results retrieved from the same series, we also demonstrated that the prevalence of vascular dementia is higher in this population than in reported community‐based clinicopathological studies from HIC . Here, we sought to investigate the prevalence and impact on cognitive impairment of neuropathological changes in individuals aged 80 and older compared to a group aged from 50 to 79.…”

Alzheimer’s disease clinical variants show distinct regional patterns of neurofibrillary tangle accumulation

“…In AD, the microtubule-associated protein tau aggregates form neurofibrillary tangles (NFTs), one of the hallmark structural lesions of AD. Tau pathology is highly deleterious to synaptic function and is closely linked to cognitive decline [4,5]. The Braak and Braak staging scheme of neurofibrillary changes characterizes the stereotypic progression of regional deposition of NFT pathology from the brainstem and transentorhinal cortex, to the hippocampus, and finally to the association and primary cortices [6].…”

Combined neuropathological pathways account for age‐related risk of dementia

“…M ultiple age-related neuropathologies are increasingly recognized as contributors to dementia risk. [1][2][3][4][5][6] Although dementia is most commonly associated with Alzheimer's disease (AD) neuropathology, namely amyloid-beta plaques and neurofibrillary tangles, pure AD is relatively rare; the majority of dementia cases clinically diagnosed with probable AD show evidence of multiple neuropathologies. 4,[7][8][9][10][11] Even among pathologically confirmed AD cases, significant comorbidities are common and are frequently associated with worse clinical outcomes.…”