Increased Prevalence of Significant Recurrent Headache in Preclinical Familial Alzheimer’s Disease Mutation Carriers

<i>Background/Aims:</i> A previous study found a high prevalence of headaches in persons with familial Alzheimer’s disease (FAD) due to a <i>PSEN1</i> mutation. In our study we compared the prevalence of headaches between nondemented FAD mutation carriers (MCs) and non-mutation-carrying controls (NCs). <i>Methods:</i> 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 χ² or Fisher’s exact tests. <i>Results:</i> Twenty-three subjects were at risk for <i>PSEN1</i> mutations and 4 for an <i>APP </i>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 <i>PSEN1</i> and <i>APP</i> mutations but was not significant unless all families were combined. <i>Conclusions:</i> 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.