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. 2024;101(3):773-785.
doi: 10.3233/JAD-231366.

The Association Between Neuropathological Lesions and Body Mass Index Is Independent of Cognitive Abilities

Raul Dos Reis Ururahy  1 , Marina Scott do Val  2 , Aline Maria Macagnan Ciciliati  1 , Renata Elaine Paraizo Leite  3 , Vitor Ribeiro Paes  3 , Roberta Diehl Rodrigues  3 , Lea Tenenholz Grinberg  3   4 , Carlos Augusto Pasqualucci  3 , Wilson Jacob Filho  1 , Claudia Kimie Suemoto  5
Affiliations

The Association Between Neuropathological Lesions and Body Mass Index Is Independent of Cognitive Abilities

Raul Dos Reis Ururahy et al. J Alzheimers Dis. 2024.

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.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflict of interest to report.

Figures

Fig. 1.
Fig. 1.
Mediation analysis for the association between the Neuropathological Comorbidity (NPC) Score and Braak staging for neurofibrillary tangles (Braak NFT) with Body Mass Index (BMI), considering a direct and indirect effect mediated by cognitive abilities, evaluated by Clinical Dementia Rating sum of boxes (CDR-SOB). (A) Findings for the whole sample; and (B) Findings when considering only individuals with normal cognition.
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References

    1. Kivipelto M, Ngandu T, Fratiglioni L, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 2005; 62: 1556–1560. - PubMed
    1. Whitmer RA, Gustafson DR, Barrett-Connor E, et al. Central obesity and increased risk of dementia more than three decades later. Neurology 2008; 71: 1057–1064. - PubMed
    1. Gustafson D, Rothenberg E, Blennow K, et al. An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med 2003; 163: 1524–1528. - PubMed
    1. Hayden KM, Zandi PP, Lyketsos CG, et al. Vascular risk factors for incident Alzheimer disease and vascular dementia: the Cache County study. Alzheimer Dis Assoc Disord 2006; 20: 93–100. - PubMed
    1. Rosengren A, Skoog I, Gustafson D, et al. Body mass index, other cardiovascular risk factors, and hospitalization for dementia. Arch Intern Med 2005; 165: 321–326. - PubMed