Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.
We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E ε4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E ε4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.
*Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital Departments of †Neurology ‡Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Natacha
N
Lorius
Joseph J
JJ
Locascio
Dorene M
DM
Rentz
Keith A
KA
Johnson
Reisa A
RA
Sperling
Anand
A
Viswanathan
Gad A
GA
Marshall
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology* / Q000523:psychology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology* / Q000523:psychology; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014652:Vascular Diseases / Q000175:diagnosis* / Q000453:epidemiology* / Q000523:psychology