Apolipoprotein E genotype modifies the association between midlife lung function and cognitive function in old age.
OBJECTIVE
Because poor lung function may be a risk factor for cognitive decline, we aimed to test the association of respiratory function with cognitive function and dementia later in life, as well as potential effect modification by APOE epsilon4 carrier status.


METHODS
In a prospective population-based cohort study, forced vital capacity and forced expiratory flow were measured around 1965 in 857 men aged 45-64 years (394 from Finland, 208 from The Netherlands, and 255 from Italy). The Mini-Mental State Examination scores around 1990, 1995 and 2000 were analyzed using multilevel regression models and the Clinical Dementia Rating score around 1990 using multinomial logistic regression analyses.


RESULTS
Midlife lung function was positively associated with cognitive function in old age in APOE epsilon4 non-carriers, but not in carriers (p < 0.05 for interaction). In Finland and Italy, 18.6% had questionable to mild dementia and 2.8% moderate to severe dementia after 25 years of follow-up. Dementia was inversely related to midlife lung function in APOE epsilon4 non-carriers, but not in carriers (p < 0.05 for interaction).


CONCLUSIONS
Small lung volumes were prospectively associated with an increased risk for poor cognitive function and dementia in non-carriers of the APOE epsilon4 gene.
Giltay
Erik J
EJ
Leiden University Medical Center, Department of Psychiatry, NL-2300 RC Leiden, The Netherlands. giltay@dds.nl
Nissinen
Aulikki
A
Giampaoli
Simona
S
Kromhout
Daan
D
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics*; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D003704:Dementia / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D005060:Europe / Q000453:epidemiology; D005500:Follow-Up Studies; D005540:Forced Expiratory Flow Rates; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008168:Lung / Q000502:physiology*; D008176:Lung Volume Measurements; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D014797:Vital Capacity
D053327:Apolipoprotein E4