Increased prevalence of significant recurrent headache in preclinical familial Alzheimer's disease mutation carriers.
OBJECTIVE
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.
Ringman
John M
JM
Alzheimer's Disease Research Center, UCLA, Los Angeles, CA 90095-7226, USA. jringman@mednet.ucla.edu
Romano
Joseph D
JD
Medina
Luis D
LD
Rodriguez-Agudelo
Yaneth
Y
Schaffer
Barbara
B
Varpetian
Arousiak
A
Ortiz
Freddy
F
Fitten
L Jamie
LJ
Cummings
Jeffrey L
JL
Baloh
Robert W
RW
D000328:Adult; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006261:Headache / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D053764:Presenilin-1 / Q000235:genetics*; D015995:Prevalence; D012008:Recurrence
D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1