Genetically increased risk of sleep disruption in Alzheimer's disease.
OBJECTIVE
To investigate the role of a monoamine A oxidase promoter polymorphism in sleep disruption in Alzheimer's disease (AD).


METHODS
A case-control association analysis.


METHODS
Sleep disturbance in AD is common, is extremely stressful for caregivers, and increases the risk of institutionalisation. It remains unclear why only some patients develop sleep disturbance; neuropathologic changes of AD are not typically seen in the areas of the brain responsible for sleep. We hypothesized that the risk of sleep disturbance is, at least in part, influenced by the availability of serotonin used for melatonin synthesis secondary to polymorphic variation at the enzyme monoamine oxidase A (MAO-A).


METHODS
Patients with AD diagnosed according to standard criteria.


METHODS
Data were collected using the Sleep domain of the Neuropsychiatric Inventory with Caregiver Distress. Patients' cognition and function were assessed using the Mini-Mental State Examination and the Functional Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp variable number tandem repeat of the MAO-A promoter was by standard methods.


RESULTS
Of 426 patients surveyed, 54% experienced sleep disturbance. We found that the high-activity 4-repeat allele of the MAO-A VNTR promoter polymorphism confers increased susceptibility to sleep disturbance (p = .008). A quantitative sleep disturbance score was significantly higher in the patients possessing MAO-A 4-repeat allele genotypes. APOE had no influence on the development of an altered sleep phenotype.


CONCLUSIONS
We conclude that sleep disturbance in AD is common and distressing and is associated with genetic variation at MAO-A.
Craig
David
D
Department of Geriatric Medicine, Queen's University of Belfast, Northern Ireland, United Kingdom. david.craig@qub.ac.uk
Hart
Dominic J
DJ
Passmore
A Peter
AP
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics; D020029:Base Pairing / Q000235:genetics; D016022:Case-Control Studies; D017281:Cost of Illness; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood; D008995:Monoamine Oxidase / Q000235:genetics*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012306:Risk; D012701:Serotonin / Q000502:physiology; D012892:Sleep Deprivation / Q000235:genetics* / Q000503:physiopathology
D001057:Apolipoproteins E; D012701:Serotonin; D008995:Monoamine Oxidase; D008550:Melatonin