Mild Alzheimer's Disease: AFib, Heart Failure as Promising Targets
Cardiovascular diseases may serve as biomarkers of future dementia.
Heart failure (HF) and atrial fibrillation (AF) are promising targets for the early intervention — and possible prevention — of mild forms of dementia. An inverse relationship between the presence of HF and AF and mild Alzheimer's disease (AD) was recently reported in a study published in Alzheimer's and Dementia.1
Population studies over the past decade have pointed to a higher risk of AD in association with HF and have led to more frequent diagnoses of mild AD despite relatively normal cognition.2,3 The direct correlation between AF and AD is less clear, as one study, for example, found a 40% to 50% increase in the likelihood of AD-related changes in patients with AF, although these findings were not statistically significant.4,5
In the current study, which included a cohort of 1593 patients with a primary diagnosis of nonpathologic AD (taken from the National Alzheimer's Coordinating Center [NACC] database in Seattle, Washington), the presence of HF and AF were consistently seen only in patients with mild AD pathology and greater vascular pathology. Moreover, the additive effect of both comorbidities was associated with further divergence between these values (lesser AD pathology and greater vascular pathology).
In general, cognitive function as measured by the Mini Mental Status Examination (MMSE, mean ± standard deviation) was incrementally better in patients with AD with AF only (-10.7 ± 7.4), HF only (-9.8 ± 6.6), and both AF and HF (-7.2 ± 6.6) compared with patients with AD with no AF or HF (-11.3 ± 7.6, P =.012).
Using logistic regression models, the investigators found that AD neuropathology was decreased by 5% per 1 year gained in age before death in patients without HF or AF and by 39% per year in patients who had both. In addition, a pattern of milder AD pathology was apparent in patients with both HF and AF after network analysis. This suggests that patients predisposed to milder AD pathology are likely to live longer, present later in life with cognitive changes, and have an increased risk of comorbid cardiovascular conditions due to older age.
The investigators also posed another theory; that conversely, the vascular neuropathology observed along with HF and AF may contribute to dementia, while at the same time a diagnosis of vascular neuropathology might also lower the threshold for clinical symptomatology of AD.
Regardless, the investigators do not feel that the higher risk of mild AD associated with HF and AF was likely to be mediated by primary AD mechanisms but might still play a role in secondary pathologic processes that are not yet well understood.4,6,7
Rather than demonstrating a causative nature, the investigators concluded that the study pointed to the validity of using HF and AF as possible markers for milder forms of AD and further suggested that early interventions in these cardiovascular conditions might have the potential to delay clinical signs of dementia.
- Sposato LA, Vargas ER, Riccio PM, et al. Milder Alzheimer's disease pathology in heart failure and atrial fibrillation [published online February 4, 2017]. Alzheimer's Dement. doi:10.1016/j.jalz.2016.12.002
- Qiu C, Winblad B, Marengoni A, et al. Heart failure and risk of dementia and Alzheimer disease: a population-based cohort study. Arch Intern Med. 2006;166:1003-1008.
- Jefferson AL, Beiser AS, Himali JJ, et al. Low cardiac index is associated with incident dementia and Alzheimer disease: The Framingham Heart Study. Circulation. 2015;131:1333-1339.
- Vogels RL, Scheltens P, Schroeder-Tanka JM. Cognitive impairment in heart failure: a systematic review of the literature. Eur J Heart Fail. 2007;9:440-449.
- Dublin S, Anderson ML, Heckbert SR, et al. Neuropathologic changes associated with atrial fibrillation in a population-based autopsy cohort. J Gerontol A Biol Sci Med Sci. 2014;69:609-615.
- Kalantarian S, Stern TA, Mansour M, Ruskin JN. Cognitive impairment associated with atrial fibrillation: a meta-analysis. Ann Intern Med. 2013;158:338-346.
- Duering M, Righart R, Wollenweber FA. Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts. Neurology. 2015;84:1685-1692.