Predictors of Cognitive and Functional Decline in Patients With Alzheimer Disease Dementia From Brazil

Abstract

Little is known on how risk factors for Alzheimer disease (AD) dementia affect disease progression, much less for populations with low mean schooling, whereas the transcription of APOE may be regulated by nongenetic factors. In this 44-month cohort study, 214 consecutive outpatients with late-onset AD were assessed for rates of cognitive and functional decline by way of Clinical Dementia Rating and Mini-Mental State Examination (MMSE) scores, keeping blinded assessment of APOE haplotypes. Subjects were evaluated for sex, schooling, age of dementia onset, and cerebrovascular risk factors (including Framingham risk scores). Of the 214 patients, there were 146 (68.2%) women and 113 (52.8%) APOE4+ carriers. The mean age of AD onset was 73.4±6.5 years-old, negatively correlated with time to Clinical Dementia Rating >1.0 (β=-0.132; ρ<0.001), MMSE=20 (β=-0.105; ρ<0.001), and MMSE=15 (β=-0.124; ρ=0.003), more significantly for women and APOE4+ carriers. Mean schooling was 4.18±3.7 years, correlated with time to MMSE=20 and MMSE=15 for women and APOE4+ carriers. Body mass index was correlated with time to MMSE=20 only for men (ρ=0.006). The 10-year coronary heart disease risk was correlated with time to MMSE=20 only for APOE4+ carriers (ρ=0.015). These outcomes suggest interactions among genomic effects of cognitive reserve, cerebral perfusion, and hormonal changes over mechanisms of neurodegeneration.

Sex differences in cognitive reserve: implications for Alzheimer’s Disease in women

“…This clearly demonstrates that women are able to maintain verbal memory across the lifespan better than men indicating greater resistance to AD. Interestingly, in this series of studies, the men had significantly higher education level than women, suggesting that education may not confer as strong resistance in men as women, as per studies presented earlier (Koran et al, 2017;Launer et al, 1999;Letenneur et al, 2000;Oliveira et al, 2016).…”

“…Specifically, women with high education had reduced risk of developing AD compared to women with low/moderate education, a relationship that was not observed in men (Launer et al, 1999;Letenneur et al, 2000). Furthermore, in individuals who did not carry the APOE4 allele, more years of education was associated with slower declines in Mini Mental Status Exam (MMSE) score with age in women but not men (Oliveira et al, 2016). In APOE4 carriers, more years of education was associated with slower cognitive decline, measured by the Cognitive Dementia Rating Scale, in women but not men (Oliveira et al, 2016).…”

“…Furthermore, in individuals who did not carry the APOE4 allele, more years of education was associated with slower declines in Mini Mental Status Exam (MMSE) score with age in women but not men (Oliveira et al, 2016). In APOE4 carriers, more years of education was associated with slower cognitive decline, measured by the Cognitive Dementia Rating Scale, in women but not men (Oliveira et al, 2016). Lastly, CSF levels of amyloid beta at baseline predicted more rapid decline in executive function in women compared to men (Koran et al, 2017).…”

Dementia in Latin America: Paving the way toward a regional action plan

“…Data from Brazil suggest that by modifying risk factors such as low educational attainment, physical inactivity, midlife hypertension, midlife obesity, depression, smoking, and diabetes mellitus, the country could potentially reduce the prevalence of dementia by 16.2% by 2050 19 . Prospective studies 20,21 have provided evidence on the differential effects of alcohol use, education, lifetime sanitary conditions, and cerebrovascular risk factors. Although characterizing specific risks factors affecting LACs is beyond the scope of this work, we provide a brief summary of risk factors for dementia in LACs in Supplementary Material 2.…”

Cloud-Based Brain Magnetic Resonance Image Segmentation and Parcellation System for Individualized Prediction of Cognitive Worsening

“…These best imaging predictors involve atrophy in selected brain structures, such as areas of the mesial and lateral temporal lobes, the posterior cingulate, the orbitofrontal gyri, and white matter hyperintensity [2–4]. Non-neuro-anatomical predictors [5], such as age—with younger having worse prognosis [6], baseline cognitive function [7–9], and vascular risk factors [10], are well established. However, individualized prediction ( precision medicine ) of future decline based on individual variables is difficult because each factor only weakly correlates with the outcome, and often overlaps and interacts with other factors.…”