The Association Between Neuropathological Lesions and Body Mass Index Is Independent of Cognitive Abilities
Article type: Research Article
Authors: Ururahy, Raul dos Reisa; * | do Val, Marina Scottb | Ciciliati, Aline Maria Macagnana | Leite, Renata Elaine Paraizoc | Paes, Vitor Ribeiroc | Rodrigues, Roberta Diehlc | Grinberg, Lea Tenenholzc; d | Pasqualucci, Carlos Augustoc | Jacob Filho, Wilsona | Suemoto, Claudia Kimiee
Affiliations: [a] Division of Geriatrics – Laboratório de Investigação Médica no Envelhecimento (LIM 66), University of São Paulo Medical School, São Paulo, Brazil | [b] Escola Politécnica of the University of São Paulo, São Paulo, Brazil | [c] Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil | [d] Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA | [e] Division of Geriatrics – Laboratório de Patologia Cardiovascular (LIM 22), University of São Paulo Medical School, São Paulo, Brazil
Correspondence: [*] Correspondence to: Raul dos Reis Ururahy, MD, Division of Geriatrics, University of São Paulo Medical School, Dr. Enéas Carvalho de Aguiar Ave. 255, CEP 05403-000, São Paulo, SP, Brazil. E-mail: rreisururahy@gmail.com.
Abstract: Background:The association of moderate and severe dementia with low body mass index (BMI) is well described, but weight decline seems to also occur in individuals with preclinical neuropathologies. Considering that up to one-fifth of individuals with normal cognition meet the criteria for a dementia-related neuropathological diagnosis, autopsy studies are key to detecting preclinical neurodegenerative and cerebrovascular diseases that could be underlying weight changes. Objective:We investigated the association between dementia-related brain lesions and BMI and evaluated whether the cognitive function was a mediator of this association. Methods:In 1,170 participants, sociodemographic data, clinical history, and cognitive post-mortem evaluation were assessed with an informant. Neuropathological evaluation was performed in all cases. Linear regression models were used to investigate the association between neuropathological lesions (exposure variable) and BMI (outcome) adjusted for demographic, clinical, and cognitive variables in the whole sample, and in only those with normal cognition. Corrections for multiple comparisons were performed. In addition, a mediation analysis was performed to investigate the direct and indirect effects of cognitive abilities on the association between neuropathology and BMI. Results:Individuals with lower BMI had a higher burden of neuropathological lesions and poorer cognitive abilities. Only neurofibrillary tangles (NFT) and neuropathological comorbidity were associated with low BMI, while other neurodegenerative and cerebrovascular lesions were not. NFT were indirectly associated with BMI through cognitive abilities, and also directly, even in participants with normal cognition. Conclusions:Neurofibrillary tangles were directly associated with low BMI even in individuals with preclinical Alzheimer’s disease.
Keywords: Alzheimer’s disease, autopsy, body mass index, dementia, mediation, neuropathology
DOI: 10.3233/JAD-231366
Journal: Journal of Alzheimer's Disease, vol. 101, no. 3, pp. 773-785, 2024
Unexplained weight loss may be a possible early sign of Alzheimer's disease
What is it about?
Lesions that develop and accumulate in the brain can impair cognitive function and lead to dementia, as is commonly seen in Alzheimer’s disease, the most frequent cause of dementia worldwide. Interestingly, up to 20% of people with normal cognition (those who don’t show clear signs of brain impairment) are found to meet the criteria for one or more neuropathological diagnoses when their brains are examined after death. This suggests that these brain lesions gradually accumulate over time, eventually leading to a dementia diagnosis. Another well-known observation is that people with dementia often experience weight loss, leading to a lower body mass index (BMI) compared to healthy individuals. However, emerging research shows that weight loss can also occur in people with normal cognition, even before the onset of cognitive symptoms. This raises the possibility that weight loss may be an early sign of dementia-related changes in the brain. Our study aimed to explore the connection between dementia-related brain lesions and BMI by examining the brains of individuals during autopsies.
Why is it important?
Our study found a link between brain lesions characteristic of Alzheimer’s disease and lower BMI, not only in individuals with cognitive symptoms but also in those with normal cognition. More importantly, our analysis suggested that weight loss is associated with the presence of brain lesions independent of the cognitive symptoms they cause. This means that unexplained weight loss in older adults could be an early sign of the buildup of Alzheimer’s disease-related brain lesions, even before cognitive symptoms appear. This insight may lead to earlier detection, diagnosis, and ultimately, more effective treatments in the future.