Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer's disease dementia

• Published in: Revista brasileira de psiquiatria Vol. 39; no. 2; pp. 95 - 103
• Main Authors: Oliveira, Fabricio F de, Chen, Elizabeth S, Smith, Marilia C, Bertolucci, Paulo H
• Format: Journal Article
• Language: English
• Published: Brazil Associação Brasileira de Psiquiatria 01.04.2017; Associação Brasileira de Psiquiatria (ABP)
• Subjects: Age of Onset; Aged; Aged, 80 and over; Alleles; Alzheimer disease; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Apolipoproteins E - genetics; cerebrovascular disorders; Cerebrovascular Disorders - genetics; Cerebrovascular Disorders - metabolism; Cerebrovascular Disorders - physiopathology; Cholesterol Ester Transfer Proteins - genetics; Cross-Sectional Studies; dementia; Female; Gene Dosage; Genetic Association Studies; genetics; Genotype; Humans; Late Onset Disorders; Linear Models; Lipoproteins, LDL - genetics; Liver X Receptors - genetics; Male; Middle Aged; neuropsychiatry; Neuropsychological Tests; Original; Peptidyl-Dipeptidase A - genetics; Psychiatric Status Rating Scales; PSYCHIATRY; Reference Values; Risk Factors; neuropsychiatry; dementia; genetics; cerebrovascular disorders; Alzheimer disease
• ISSN: 1516-4446; 1809-452X; 1809-452X
• DOI: 10.1590/1516-4446-2016-1991

To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer's disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage. Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121. Considering 201 patients, only APOE-ɛ4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior. Both ACE polymorphisms were associated with less intense frontally mediated behaviors. Regarding LDLR variants, carriers of the A allele of rs11669576 had less anxiety and more aberrant motor behavior, whereas carriers of the A allele of rs5930 had less delusions, less anxiety, more apathy, and more irritability. CETP variants that included G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviors, while severely impaired carriers of the T allele of rs2695121 had more anxiety and more aberrant motor behavior. Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.