In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment

Geraldo F Busatto; Fabio Henrique de Gobbi Porto; Daniele de Paula Faria; Paula Squarzoni; Artur Martins Coutinho; Alexandre Teles Garcez; Pedro Gomes Penteado Rosa; Naomi Antunes da Costa; Cleudiana Lima Carvalho; Leticia Torralbo; Jullie Rosana de Almeida Hernandes; Carla Rachel Ono; Sonia Maria Dozzi Brucki; Ricardo Nitrini; Carlos Alberto Buchpiguel; Fabio Luis Souza Duran; Orestes Vicente Forlenza

doi:10.1002/dad2.12122

In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment

Alzheimers Dement (Amst). 2020 Dec 8;12(1):e12122. doi: 10.1002/dad2.12122. eCollection 2020.

Authors

Geraldo F Busatto¹, Fabio Henrique de Gobbi Porto¹, Daniele de Paula Faria², Paula Squarzoni¹, Artur Martins Coutinho², Alexandre Teles Garcez², Pedro Gomes Penteado Rosa¹, Naomi Antunes da Costa¹, Cleudiana Lima Carvalho¹, Leticia Torralbo¹, Jullie Rosana de Almeida Hernandes¹, Carla Rachel Ono², Sonia Maria Dozzi Brucki³, Ricardo Nitrini³, Carlos Alberto Buchpiguel², Fabio Luis Souza Duran¹, Orestes Vicente Forlenza⁴

Affiliations

¹ Laboratory of Psychiatric Neuroimaging (LIM 21) Department of Psychiatry Faculdade de Medicina FMUSP Universidade de Sao Paulo Sao Paulo Brazil.
² Laboratory of Nuclear Medicine (LIM43) Department of Radiology and Oncology Faculdade de Medicina FMUSP Universidade de Sao Paulo Sao Paulo Brazil.
³ Department of Neurology Faculdade de Medicina FMUSP Universidade de Sao Paulo Sao Paulo Brazil.
⁴ Laboratory of Neuroscience (LIM 27) Department of Psychiatry Faculdade de Medicina FMUSP Universidade de Sao Paulo Sao Paulo Brazil.

Abstract

Introduction: Reduced cognitive reserve (CR) due to very low educational (VLE) levels may influence high dementia rates in low-middle income environments, leading to decreased cognitive resilience (RES) to Alzheimer´s disease (AD) pathology. However, in vivo findings in VLE groups confirming this prediction are lacking.

Methods: Cognitively impaired patients (with clinically defined AD dementia or amnestic mild cognitive impairment) and cognitively unimpaired older adults (n = 126) were recruited for a positron emission tomography (PET) and magnetic resonance imaging (MRI) investigation in Brazil, including 37 VLE individuals (≤5 years of education). A CR score was generated combining educational attainment and vocabulary knowledge. RES indices to AD pathology were calculated using standardized residuals from linear regression models relating current cognitive performance (episodic memory or overall cognition) to amyloid beta (Aβ) burden Pittsburgh compound-B ([11C]PiB-PET).

Results: Aβ burden was lower in VLE relative to highly-educated subjects (controlling for age, sex, and Mini-Mental Status Exam [MMSE] scores) in the overall cognitively impaired sample, and in dementia subjects when the three clinically defined groups were evaluated separately. In bivariate regression analyses for the overall sample, the RES index based on a composite cognitive score was predicted by CR, socioeconomic status, and hippocampal volume (but not white matter hyperintensities or intracranial volume [ICV]); in the multivariate model, only CR retained significance (and similar results were obtained in the Aβ-positive subsample). In the multivariate model for the overall sample using the RES index based on memory performance, CR, hippocampal volume, and ICV were significant predictors, whereas only CR retained significance in Aβ-positive subjects.

Discussion: Lower CR consistently predicted less resilience to AD pathology in older adults from a low-middle income environment.

Keywords: Alzheimer's disease; biomarkers; cognitive reserve; cognitive resilience; dementia; low education.