Association of Alzheimer's genetic loci with mild behavioral impairment

Mild behavioral impairment (MBI) describes the emergence of later ‐life neuropsychiatric symptoms (NPS) as an at‐risk state for incident cognitive decline and dementia, and for some as a potential manifestation of prodromal dementia. How NPS mechanistically link to the development of mild cognitive impairment and Alzheimer's disease (AD) is not fully understoo d, with potential mechanisms including shared risk factors related to both NPS and cognitive impairment, or AD pathology promoting NPS. This is the first exploratory study to examine whether AD genetic loci as a genetic risk score (GRS), or individually, are a shared risk factor with MBI. Participan ts were 1,226 older adults (aged 72–79; 738 males; 763 normal cognition) from the Personality and Total Health Through Life project. MBI was approximated in accordance with Criterion 1 of the ISTAART‐AA diagnostic criteria using a transformation algorithm for the neuropsychiatric inventory. A GR S was constructed from 25 AD risk loci. Binomial logistic regression adjusting for age, gender, and education examined the association between GRS and MBI. A higher GRS andAPOE*ε4 were associated with increased likelihood of affective dysregulation. Nominally significant associations were observed betweenMS4A4A‐rs4938933*C andMS4A6A ‐rs610932*G with a reduced likelihood of affective dysregulation;ZCWPW1‐rs1476679*C with a reduced likelihood of social inappropriateness and abnormal perception/thought content;BIN1‐rs74...
Source: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research