Premium
Association of Alzheimer's genetic loci with mild behavioral impairment
Author(s) -
Andrews Shea J.,
Ismail Zahinoor,
Anstey Kaarin J.,
Mortby Moyra
Publication year - 2018
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32684
Subject(s) - dementia , psychology , disease , logistic regression , cognition , clinical psychology , association (psychology) , apolipoprotein e , risk factor , etiology , cognitive decline , medicine , psychiatry , psychotherapist
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 understood, 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. Participants 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 GRS 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 and APOE* ε4 were associated with increased likelihood of affective dysregulation. Nominally significant associations were observed between MS4A4A ‐rs4938933*C and MS4A6A‐ 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 ‐rs744373*G and EPHA1 ‐rs11767557*C with higher likelihood of abnormal perception/thought content; NME8 ‐rs2718058*G with a reduced likelihood of decreased motivation. These preliminary findings suggest a common genetic etiology between MBI and traditionally recognized cognitive problems observed in AD and improve our understanding of the pathophysiological features underlying MBI.