Insomnia symptom severity and cognitive performance: Moderating role of APOE genotype

Andrée Ann Baril, Alexa S. Beiser, Erlan Sanchez, Vincent Mysliwiec, Susan Redline, Daniel J. Gottlieb, George T. O'Connor, Mitzi M. Gonzales, Dibya Himali, Sudha Seshadri, Jayandra J. Himali, Matthew P. Pase

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Introduction: We evaluated whether insomnia symptom severity was associated with cognitive function, and whether this relationship was modified by biomarkers associated with Alzheimer's disease risk. Methods: We examined insomnia symptoms and neuropsychological performance 3.4 years later in 511 dementia-free Framingham Heart Study participants (62.65 ± 8.7 years, 50.9% male). Additionally, we explored insomnia symptoms combined with self-reported short habitual sleep duration and effect modification by apolipoprotein E (APOE) ε4 allele status. Results: More severe insomnia symptoms were associated with lower performance on global cognition, and immediate and delayed Logical Memory recall, especially when insomnia symptoms were combined with short sleep duration. The association between insomnia symptoms and poorer memory recall was more pronounced in APOE ε4 allele carriers. Discussion: Insomnia symptom severity was associated with worse subsequent global cognitive and memory performance, which was especially apparent in APOE ε4 allele carriers, suggesting that poor sleep might be particularly detrimental when the brain is already vulnerable to neurodegeneration.

Original languageEnglish (US)
Pages (from-to)408-421
Number of pages14
JournalAlzheimer's and Dementia
Issue number3
StatePublished - Mar 2022


  • Alzheimer's disease
  • C-reactive protein
  • aging
  • apolipoprotein E ε4
  • cognition
  • cognitive aging
  • dementia
  • inflammation
  • insomnia
  • memory
  • neuropsychology
  • sleep

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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