Increased prevalence of significant recurrent headache in preclinical familial Alzheimer's disease mutation carriers

Dement Geriatr Cogn Disord. 2008;25(4):380-4. doi: 10.1159/000121986. Epub 2008 Mar 29.


Background/aims: A previous study found a high prevalence of headaches in persons with familial Alzheimer's disease (FAD) due to a PSEN1 mutation. In our study we compared the prevalence of headaches between nondemented FAD mutation carriers (MCs) and non-mutation-carrying controls (NCs).

Methods: A headache questionnaire that assessed the prevalence of significant headaches and diagnosis of migraine and aura by ICHD-2 criteria was administered to 27 individuals at risk for FAD. Frequency of significant headaches, migraine, and aura were compared between MCs and NCs by chi(2) or Fisher's exact tests.

Results: Twenty-three subjects were at risk for PSEN1 mutations and 4 for an APP substitution. The majority of subjects were female (23/27). MCs were more likely to report significant recurrent headache than NCs (67 vs. 25%, p = 0.031). Forty percent of MCs had headaches that met criteria for migraine whereas 17% of NCs met such criteria. The tendency for a higher prevalence of headaches in MCs held for different PSEN1 and APP mutations but was not significant unless all families were combined.

Conclusions: In this population, headache was more common in nondemented FAD MCs than NCs. Possible mechanisms for this include cerebral inflammation, aberrant processing of Notch3, or disrupted intracellular calcium regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics*
  • Family Health
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Headache / epidemiology*
  • Headache / genetics*
  • Humans
  • Male
  • Mutation
  • Presenilin-1 / genetics*
  • Prevalence
  • Recurrence


  • Amyloid beta-Protein Precursor
  • PSEN1 protein, human
  • Presenilin-1