Milder Alzheimer's disease pathology in heart failure and atrial fibrillation.
BACKGROUND
Heart failure (HF) and atrial fibrillation (AF) have been associated with a higher risk of Alzheimer's disease (AD). Whether HF and AF are related to AD by enhancing AD neuropathological changes is unknown.


METHODS
We applied network analyses and multiple logistic regression models to assess the association between HF and AF with severity of AD neuropathology in patients from the National Alzheimer's Coordinating Center database with primary neuropathological diagnosis of AD.


RESULTS
We included 1593 patients, of whom 129 had HF and 250 had AF. HF and AF patients were older and had milder AD pathology. In the network analyses, HF and AF were associated with milder AD neuropathology. In the regression analyses, age (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.93-0.95 per 1-year increase in age, P < .001) and the interaction term HF × AF (OR 0.61, 95% CI 0.40-0.91, P = .014) were inversely related to severe AD pathology, whereas APOE ε4 genotype showed a direct association (OR 1.68, 95% CI 1.31-2.16). Vascular neuropathology was more frequent in patient with HF and AF patients than in those without.


CONCLUSIONS
HF and AF had milder AD neuropathology. Patients with milder AD lived longer and had more exposure to vascular risk factors. HF and AF patients showed a higher frequency of vascular neuropathology, which could have contributed to lower the threshold for clinically evident dementia.
Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, Ontario, Canada; London Stroke, Dementia & Heart Disease Laboratory, Western University, London, Ontario, Canada. Electronic address: lucianosposato@gmail.com.
Luciano A
LA
Sposato
Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, Ontario, Canada.
Estefanía
E
Ruíz Vargas
Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, Ontario, Canada.
Patricia M
PM
Riccio
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA, USA; Department of Internal Medicine, Houston Methodist Hospital, Houston, TX, USA.
Jon B
JB
Toledo
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA, USA.
John Q
JQ
Trojanowski
Department of Epidemiology, National Alzheimer's Coordinating Center, Seattle, WA, USA.
Walter A
WA
Kukull
Ivey Business School, Western University, London, Ontario, Canada.
Lauren E
LE
Cipriano
Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, Ontario, Canada.
Antonia
A
Nucera
Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, Ontario, Canada; Canadian Institutes of Health Research (CIHR) Group on Vascular Cognitive Impairment, Department of Anatomy and Cell Biology, Western University, London, Ontario, Canada.
Shawn N
SN
Whitehead
Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, Ontario, Canada.
Vladimir
V
Hachinski
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001281:Atrial Fibrillation / Q000150:complications*; D015140:Dementia, Vascular / Q000473:pathology; D005260:Female; D006333:Heart Failure / Q000150:complications*; D006801:Humans; D008297:Male; D012307:Risk Factors
Alzheimer's disease; Atrial fibrillation; Dementia; Heart failure; Neuropathology; Vascular dementia