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

Ringman J.M.a, b · Romano J.D.g · Medina L.D.a, b · Rodriguez-Agudelo Y.h · Schaffer B.a, b · Varpetian A.e · Ortiz F.a, c, f · Fitten L.J.a, c, f · Cummings J.L.a, b, d · Baloh R.W.b
aAlzheimer’s Disease Research Center, bUCLA Department of Neurology, cGreater Los Angeles Veterans Affairs Healthcare System, Sepulveda Campus, and dPsychiatry and Biobehavioral Science, UCLA, Los Angeles, Calif., eDepartment of Neurology, Keck School of Medicine, USC, Rancho Los Amigos National Rehabilitation Center, Downey, Calif., fNeuropsychiatry Research Memory Clinic, Olive-View UCLA Medical Center, Sylmar, Calif., and gVirginia Commonwealth University Medical School, Richmond, Va., USA; hDepartment of Neuropsychology, National Institute of Neurology and Neurosurgery, Mexico City, Mexico Dement Geriatr Cogn Disord 2008;25:380–384 (DOI:10.1159/000121986)


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 χ2 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.


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