As of 2016, 50 million people worldwide had received a diagnosis of Alzheimer’s Disease (AD) [1]. For this vast number, the neurodegenerative component of the condition is unfortunately not the only significant consequence. Preliminary research had suggested a link between medical comorbidities and cognitive impairment [2], and subsequent research has only affirmed this link and discovered several common comorbidities of AD including diabetes, depression, and inflammatory bowel disease [1]. Whilst the most apparent impact of AD might be neural, one would be remiss to discount its impact on the heart – and I don’t mean just emotionally. Importantly, cardiovascular issues comprise both major risk factors for the development of AD and comorbidities of developing AD.
Santiago and Potashkin’s review reports the ways in which cardiovascular problems can be risk factors for the development of AD [1]. Symptoms of cardiovascular disease, like heightened blood pressure and hypertension, have been correlated to the formation of neuritic plaques and white matter lesions, symptoms of AD. They also reference studies that found an association between the use of anti-hypertensive drugs and lower incidence of AD. Lacunar strokes are silent brain infarcts that have been linked to an increased risk of cognitive decline. Atrial fibrillation has also been associated with a higher chance of AD, particularly in women. The exact mechanism behind this is unknown but it is theorized that the cerebral hypoperfusion and low cardiac output ensuing from atrial fibrillation could contribute to neurodegeneration. Lastly, epidemiological studies have found a correlation between coronary heart disease (CHD) and AD. The resultant atherosclerosis in intra and extracranial vessels is thought to lead to cognitive impairment and dementia.
Scientists have posited the APOE gene alleles as a reason for this frequent and strong correlation between vascular and/or cerebrovascular symptoms and AD [3]. The expression of the ε4 allele of this gene results in increased cholesterol absorption, which evolutionarily allowed humans to survive in harsher climates. However, humans today live a more sedentary lifestyle, which has created different phenotypic expressions of this allele relating to cerebrovascular diseases and AD. It is to be noted that this hypothesis remains a hypothesis and needs to be investigated further owing to the complex nature of the relationship between cardiovascular diseases and AD.
Whilst the connection between cardiovascular diseases and AD is evident, scientists differ on the extent of influence. Pachalska and colleagues correlated more severe vascular factors with more intense cognitive disturbances in ideational praxis, orientation, spoken language ability, comprehension of spoken language, and word-finding difficulty in spontaneous speech [4]. Contrastingly, Carotuneto and colleagues’ data suggest that vascular factors do not have an influence on disease progression, in early or late onset dementia [5]. This discrepancy calls for more representative sampling and further follow-ups on AD patients with cardiovascular diseases.
Research has also linked other elements of vasculature to AD. In their review, Love and Miners highlight the commonalities between cerebrovascular disease and AD [6]. They note that in Aβ amyloid angiopathy, a cerebrovascular disease which can lead to AD, the inadequate blood supply and ischemia is more a function of non-structural vascular dysfunction than structural abnormalities. Broce and colleagues have found associations between altered expression of the MBLAC1, SPI1, MINK1 and DDB2 genes – genes that have traditionally been linked to cardiovascular disease – and AD, indicating yet another connection [7]. Additionally, Iadecola’s review cites studies that have found that vascular lesions reduce the threshold of cognitive impairment and consequently increase the risk of developing more severe AD symptoms [8].
The extant research shows increasing connections between the cardiovascular system and AD suggesting that yes, the brain and heart are intimately connected in the case of AD. The hope is that physicians and patients can arm themselves with this knowledge to feel better prepared in the face of an Alzheimer’s diagnosis and act accordingly.
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References
1. Santiago, J. A., &; Potashkin, J. A. (2021). The Impact of Disease Comorbidities in Alzheimer’s Disease. Frontiers in Aging Neuroscience, 13. https://doi.org/10.3389/fnagi.2021.631770
2. Doraiswamy, P. M., Leon, J., Cummings, J. L., Marin, D., & Neumann, P. J. (2002). Prevalence and Impact of Medical Comorbidity in Alzheimer’s Disease. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 57(3). https://doi.org/10.1093/gerona/57.3.m173
3. Santos, C. Y., Snyder, P. J., Wu, W. C., Zhang, M., Echeverria, A., &; Alber, J. (2017). Pathophysiologic relationship between Alzheimer’s disease, cerebrovascular disease, and cardiovascular risk: A review and synthesis. Alzheimer’s &; Dementia: Diagnosis, Assessment &; Disease Monitoring, 7(1), 69–87. https://doi.org/10.1016/j.dadm.2017.01.005
4. Pąchalska, M., Bidzan, L., Bidzan, M., &; Góral-Półrola, J. (2015). Vascular Factors and Cognitive Dysfunction in Alzheimer Disease. Medical Science Monitor, 21, 3483–3489. https://doi.org/10.12659/msm.894550
5. Carotenuto, A., Rea, R., Colucci, L., Ziello, A. R., Molino, I., Carpi, S., Traini, E., Amenta, F., &; Fasanaro, A. M. (2012). Late and early onset dementia: What is the role of vascular factors? A retrospective study. Journal of the Neurological Sciences, 322(1-2), 170–175. https://doi.org/10.1016/j.jns.2012.07.066
6. Love, S., &; Miners, J. S. (2015). Cerebrovascular disease in ageing and Alzheimer’s disease. Acta Neuropathologica, 131(5), 645–658. https://doi.org/10.1007/s00401-015-1522-0
7. Broce, I. J., Tan, C. H., Fan, C. C., Jansen, I., Savage, J. E., Witoelar, A., Wen, N., Hess, C. P., Dillon, W. P., Glastonbury, C. M., Glymour, M., Yokoyama, J. S., Elahi, F. M., Rabinovici, G. D., Miller, B. L., Mormino, E. C., Sperling, R. A., Bennett, D. A., McEvoy, L. K., … Desikan, R. S. (2018). Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease. Acta Neuropathologica, 137(2), 209–226. https://doi.org/10.1007/s00401-018-1928-6
8. Iadecola, C. (2010). The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathologica, 120(3), 287–296. https://doi.org/10.1007/s00401-010-0718-6
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