The effect of subsyndromal symptoms of depression and white matter lesions on disability for individuals with mild cognitive impairment

R. Scott Mackin, Philip Insel, Duygu Tosun, Susanne G. Mueller, Norbert Schuff, Diana Truran-Sacrey, Sky T. Raptentsetsang, Jun Young Lee, Clifford R. Jack, Paul S. Aisen, Ronald C. Petersen, Michael W. Weiner

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Objective: To assess the effect of subsyndromalsymptomsof depression (SSD) onratings of disability for individualswith mild cognitive impairment (MCI). Methods: Data from 405 MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Participants were evaluated at baseline and at 6-month intervals over 2 years. Severity of depressive symptoms was rated utilizing the Geriatric Depression Scale. Disability was assessed utilizing the Functional Assessment Questionnaire (FAQ). Other clinical variables included white matter lesion (WML) and intracranial brain (ICV) volumes derived from magnetic resonance imaging, ratings of overall cognitive function (Alzheimer's Disease Assessment Scale, ADAS), and apolipoprotein E (ApoE) status. Demographic variables included age, education, and gender. Results: SSD individuals had a lower volume of WML and higher frequency of ApoE ε4 alleles than nondepressed participants but the two groups did not differwith respect to other clinical or demographic variables. At baseline, SSD individuals were 1.77 times more likely to have poorer FAQ scores than individuals with no symptoms of depression after controlling for the effect of cognitive functioning, ICV, WML, and ApoE status. The presence of SSD at baseline was not associated with a poorer course of disability outcomes, cognitive functioning, or conversion to dementia over 24 months. Conclusions: SSD demonstrated a significant impact on disability for MCI individuals, who are also at high risk for functional limitations related to neurodegenerative disease. Therefore, the treatment of SSD may represent a significant avenue to reduce the burden of disability in this vulnerable patient population.

Original languageEnglish (US)
Pages (from-to)906-914
Number of pages9
JournalAmerican Journal of Geriatric Psychiatry
Issue number9
StatePublished - Sep 2013


  • ApoE
  • Dementia
  • Disability
  • Longitudinal
  • Mild cognitive impairment
  • Subsyndromal depression
  • Subthreshold depression
  • White matter lesions

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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