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

Abstract

Objective: 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. Methods: 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. Results: Considering 201 patients, only APOE-e4 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. Conclusion: Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.

Behavioral and Psychological Symptoms of Dementia (BPSD): Clinical Characterization and Genetic Correlates in an Italian Alzheimer’s Disease Cohort

“…The ε4 carriers showed also higher severity in aberrant motor behavior, the finding was confirmed also in other different studies [ 50 , 51 , 52 ], where they demonstrated that the APOE ε4 status increased the tendency toward this symptom.…”

Genetics and epigenetics as tools to inform the pathophysiology of neuropsychiatric disorders

“…Examples of this approach include studying the effects of specific markers on clinical symptoms, age at illness onset, differential prognosis, responsiveness to treatment, and other clinical variables. A recent study published in this journal, for instance, has identified genetic determinants of the age at onset of Alzheimer’s disease,3 and similar findings have been reported for several other disorders. In addition, several studies have acknowledged a key role of genetic and epigenetic alterations in neuroanatomical and neurocognitive alterations.…”

Apolipoprotein E e4 Allele Is Associated with Subjective Cognitive Decline: A Meta-Analysis

“…The gene is located on chromosome 19q13.2 and has 3 common alleles ( e2 , e3 , and e4 ) [7]. APOE e4 is a susceptibility gene for AD, and is associated with increased risk for developing AD and reduced age at disease onset [8, 9]. APOE e4 might be a potential risk factor for SCD.…”