Neuropsychiatric symptoms and Apolipoprotein E: Associations with eventual Alzheimer's disease development.
Alzheimer's disease (AD) is the result of neurodegeneration, which manifests clinically as deficits in memory, thinking, and behavior. It was hypothesized that neuropsychiatric symptoms and the apolipoprotein E genotype increase the likelihood of Alzheimer's disease development.



Utilizing data from the National Alzheimer's Coordinating Center, information from evaluations of 11,453 cognitively intact participants was analyzed. Survival analysis was used to explore relationships between individual neuropsychiatric symptoms as determined by the Neuropsychiatric Inventory Questionnaire, apolipoprotein E, and eventual AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic (additive and multiplicative) interactions.



This study provided evidence for an increased hazard of developing AD among participants with any of the symptoms assessed by the NPI-Q. The hazard of developing AD was almost thirteen times higher for ε4 carriers with delusions and eleven times greater for those with apathy and disinhibition. Statistically significant hazards (p>0.001) were also realized by ε4 carriers with hallucinations; agitation; depression; anxiety; elation; apathy; irritability; and motor, sleep, and appetite disturbances.



Findings suggest that neuropsychiatric symptoms are associated with eventual AD diagnosis among a group of cognitively asymptomatic participants at baseline. Many studies begin with a group of participants already impacted by AD diagnosis. The longitudinal analysis of a group of participants who, at baseline, demonstrated no observable signs of AD was a strength of this study. This investigation contributes to the literature exploring an increased hazard of AD due to potential modifiable risk factors and genetic biomarkers such as apolipoprotein E.
Florida International University, Robert Stempel College of Public Health and Social Work, School of Social Work, 11200 S.W. 8th Street, AHC5 564, Miami, FL 33199, USA. Electronic address: sburke@fiu.edu.
Shanna L
SL
Burke
Simmons College School of Social Work, Boston, MA 02115-5820, USA; Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, USA; Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, USA. Electronic address: peter.maramaldi@simmons.edu.
Peter
P
Maramaldi
Simmons College School of Social Work, Boston, MA 02115-5820, USA; Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, USA. Electronic address: Tamara.cadet@simmons.edu.
Tamara
T
Cadet
National Alzheimer's Coordinating Center (NACC) University of Washington, Department of Epidemiology Box 357236, Seattle, WA 98195-7236, USA. Electronic address: Kukull@u.washington.edu.
Walter
W
Kukull
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology*; D001007:Anxiety / Q000523:psychology; D057565:Apathy; D053327:Apolipoprotein E4 / Q000235:genetics*; D003702:Delusions / Q000523:psychology; D003863:Depression / Q000523:psychology; D001068:Feeding and Eating Disorders; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007508:Irritable Mood; D008297:Male; D011595:Psychomotor Agitation; D012893:Sleep Wake Disorders / Q000523:psychology
D053327:Apolipoprotein E4
Agitation; Alzheimer’s disease; Anxiety; Apathy; Apoe ε4; Apolipropotein e; Appetite disturbance; Delusions; Disinhibition; Elation; Hallucinations; Irritability; Motor disturbance; Neuropsychiatric symptoms; Sleep disturbance