Abstract for presentation at 11th International Congress of Human Genetics

Sibling risk for the Depression of Alzheimer Disease

  • Michael Slifer, Center for Human Genetics, Duke University Medical Center, United States
  • Don Schmechel, Department of Neurology, Duke University Medical Center, United States
  • Murali Doriswamy, Department of Psychiatry, Duke University Medical Center, United States
  • John Gilbert, Center for Human Genetics, Duke University Medical Center, United States
  • Jonathan Haines, Center for Human Genetics Research, Vanderbilt University, United States
  • Dr Margaret Pericak-Vance, Center for Human Genetics, Duke University Medical Center, United States

    • Purpose: To determine if there is increased occurrence of the Depression of Alzheimer Disease (DAD)(APA Consensus Guideline, Olin et al. 2002), among siblings with Alzheimer disease (AD). Population estimates for DAD range around 30-50% (four times the rate of depression among non-demented elderly). Since DAD is phenotypically distinct, appears early in the course of cognitive impairment, and can be measured; it may be a useful feature to reduce the clinical and presumably genetic heterogeneity of AD.
    Methods: Individuals were ascertained based on AD status from the Collaborative Alzheimer Project (CAP). All who met NINDCS/ADRDA criteria for diagnosis of AD were eligible for inclusion. From this group, all siblings were selected who had adequate screening to detect the possible presence of depression on the Geriatric Depression Scale. Siblings with an onset of depression not associated with AD (i.e. early-in-life onset) were excluded.
    Results: In the CAP dataset, 331 of 904 individuals with AD had co-morbid DAD (36.6%). 78 individuals comprising 47 sibling pairs met criteria for AD and had adequate depression screening. The majority excluded (of 826) were because they had no siblings with AD or only one of the siblings was screened for possible depression. 27 of the 78 siblings met criteria for DAD (34.6%) and prevalence was not significantly different than the overall CAP prevalence (p=0.725). The odds ratio for having DAD when an AD affected sibling also had DAD was 5.11 (95% CI 1.40 to 18.54; p = 0.01). For such a common co-morbid disorder, this represents a substantial increase in absolute risk (59% vs. 23%) for depression. Dropping siblings from the sibships with more than two siblings did not appreciably change the outcome (OR = 4.90; p = 0.04).
    Conclusion: DAD is an under recognized devastating but robustly treatable co-morbid disorder. There is a strong familial component, consistent with a genetic diathesis producing an odds ratio in siblings of 5 in this dataset. DAD may represent a distinct sub-phenotype of AD. As such, it may be useful in reducing genetic heterogeneity in AD studies, facilitating identification of genetic variants governing the susceptibility to AD or DAD.

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