Lifetime Risk Factors for Functional and Cognitive Outcomes in Patients with Alzheimer’s Disease

Article type: Research Article

Authors: de Oliveira, Fabricio Ferreira^{a; *} | de Almeida, Sandro Soares^b | Chen, Elizabeth Suchi^c | Smith, Marilia Cardoso^c | Naffah-Mazzacoratti, Maria da Graça^a | Bertolucci, Paulo Henrique Ferreira^a

Affiliations: [a] Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil | [b] Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil | [c] Department of Morphology and Genetics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

Correspondence: [*] Correspondence to: Fabricio Ferreira de Oliveira, MD, MSc, PhD, Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina, Departamento de Neurologia e Neurocirurgia, Rua Botucatu 740, Vila Clementino,CEP 04023-900, São Paulo, SP, Brazil. Tel.: (+55) (+11) 5576 4139; Fax: (+55) (+11) 5575 5240; Email: [email protected].

Abstract: Lifetime risk factors for cognitive and functional decline in Alzheimer’s disease (AD) are not fully understood, and were prospectively evaluated in patients with low mean schooling from São Paulo, Brazil. Consecutive outpatients with late-onset AD were assessed for APOE haplotypes and the following potential baseline predictors: gender, schooling, age at dementia onset, lifetime urban living and sanitary conditions, occupational complexity, cognitive and physical activities, cerebrovascular risk factors (obesity, lifetime alcohol use and smoking, length of arterial hypertension, diabetes mellitus, and a dyslipidemic profile), use of a pacemaker, creatinine clearance, body mass index, waist circumference, head traumas with unconsciousness, treated systemic bacterial infections, amount of surgical procedures under general anesthesia, and family history of AD. Participants were followed from October 2010 to May 2017 for baseline risk factor associations with time since dementia onset for Clinical Dementia Rating and Mini-Mental State Examination score changes. For 227 patients (154 women, 119 APOE ε 4 carriers), later AD onset (mean 73.60±6.4 years-old, earlier for APOE ε 4/ε 4 carriers, p < 0.001) was the only variable hastening all endpoints, baseline creatinine clearance and lifetime alcohol use were hazardous for earlier cognitive and functional endpoints, women had earlier cognitive endpoints only, and schooling had a cumulative protective effect over later cognitive endpoints, particularly for carriers of APOE ε 4. Exclusively for carriers of APOE ε 4, head traumas with unconsciousness were hazardous for earlier cognitive endpoints, while lifetime sanitary conditions were protective regarding later cognitive endpoints. Functional and cognitive outcomes in AD represent probable interactions between effects of brain reserve and cerebral perfusion over neurodegeneration.

Keywords: Aging, Alzheimer’s disease, cognition, dementia, educational status, neurodegenerative diseases, neuropsychiatry, risk factors

DOI: 10.3233/JAD-180303

Journal: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1283-1299, 2018