In this installment, the leadership team at the Gerontological Advanced Practice Nurses Association (GAPNA) highlights the most important published literature that affects geriatric practice. This month, GAPNA Past-President and Director of GAPNA Leadership Institute Deborah Dunn, EdD, MSN, GNP-BC, ACNS-BC, GS-C, reviews 3 studies on the risk for dementia: the first looks at cardiometabolic multimorbidity; the second on risk for dementia and atrial cardiopathy; and the third on the link between cardiovascular disease in midlife and increased risk for Alzheimer’s disease.

Cardiometabolic multimorbidity, genetic risk and dementia: a prospective cohort study

Lancet Healthy Longev. 2022;3(6):e428-e436

Summary: Cardiometabolic multimorbidity was independently associated with the risk for dementia and extensive brain imaging differences to a greater extent than was genetic risk. Targeting cardiometabolic multimorbidity might help reduce the risk for dementia, regardless of genetic risk. The dementia risk associated with high cardiometabolic multimorbidity was 3 times greater than that associated with high genetic risk (hazard ratio [HR] 5.55, 95% CI; 3.39-9.08, P <.0001, and 1.68, 1.53-1.84, P <.0001, respectively). Participants with both high genetic risk and cardiometabolic multimorbidity index of 2 or greater had an increased risk of developing dementia (HR 5.74, 95% CI 4.26-7.74, P<0.0001), compared with those with low genetic risk and no cardiometabolic conditions. The authors also found no interaction between cardiometabolic multimorbidity and polygenic risk (P =.18). Cardiometabolic multimorbidity was independently associated with more extensive, widespread brain structural changes including lower hippocampal volume and total grey matter volume.

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Commentary by Dr Dunn: In the 2022 Alzheimer’s Disease Facts and Figures report, the prevalence of dementia in the US was clearly outlined. An estimated 6.5 million Americans are living with Alzheimer’s disease or other dementias.1 This daunting news may lead laypersons as well as health care providers to despair that with the largest population of aging Americans, the baby boomers, we are bound to see dementia cases rise because of the shear increase in number of persons with a genetic predisposition to dementia. 

Recent research calls us to question this assumption and look beyond genetic predisposition as a single impactful cause of dementia. Research on cardiometabolic multimorbidity, atrial cardiopathy, and bench research in mouse modeling of neurovascular changes, atherosclerosis, and dementia give us reason to hope and direction for intervention.

Research by Tai and colleagues suggests that clinical interventions to control cardiometabolic multimorbidities such as diabetes, stroke, and myocardial infarction are not only beneficial to cardiovascular health outcomes but also may independently reduce the incidence of dementia.2 This research provides important evidence to support our clinical work with patients who have cardiometabolic conditions and are concerned about reducing their risk for dementia.

Risk of dementia associated with atrial cardiopathy: the ARIC study

J Am Heart Assoc. 2022;11(16):e025646

Summary: The authors of this study conducted a prospective analysis of participants in the ARIC (Atherosclerosis Risk in Communities). They found that cardiopathy was significantly associated with an increased risk for dementia (adjusted HR, 1.35; 95% CI, 1.16–1.58). Atrial cardiopathy was defined if more than 1 of the following factors was present: P‐wave terminal force >5000 mV·ms in ECG lead V1, N‐terminal pro-brain natriuretic peptide >250 pg/mL, or left atrial volume index ≥34 mL/m2 by transthoracic echocardiography. The prevalence of atrial cardiopathy was 34% in the 5078 participants (mean age, 75 years; 59% women; 21% Black adults), with 763 participants developing dementia. An increased risk for dementia among those with atrial cardiopathy was also found when excluding those with atrial fibrillation (adjusted HR, 1.31; 95% CI, 1.12-1.55) or stroke (adjusted HR, 1.28; 95% CI, 1.09-1.52). The proportion of the effect mediated by atrial fibrillation was 4% (P =.005) and 9% was mediated by stroke (P =.048).

Commentary by Dr Dunn: In this study of cardiovascular risk factors and dementia risk, Johansen et al found that in community-dwelling older adults, atrial cardiopathy was an independent risk factor associated with increased risk for dementia, independent of stroke and atrial fibrillation.3 Again, this is encouraging news for clinicians who identify atrial cardiopathy in their patients. Careful monitoring and control of cardiovascular risk in patients with atrial cardiopathy may have a 2-fold benefit for patients: first, in optimizing cardiovascular health; and second, in reducing dementia risk.

Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s Disease

eLife. 2022;11:e68242

Summary: Neurovascular coupling is a critical brain mechanism where changes to blood flow accompany localized neural activity, noted the authors of this study. “The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia,” they wrote. To study the role of neurovascular coupling, the authors examined cortical hemodynamics in mouse models of Alzheimer disease (J20-AD) and atherosclerosis (PCSK9-ATH). Their novel findings suggest that “systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimer-related amyloid-plaques.”

Commentary by Dr Dunn: As clinicians, we know the importance of primary research in uncovering the mechanisms of disease. Shabir et al have highlighted a connection between cardiovascular disease in midlife and increased risk for Alzheimer disease. The authors’ research shows a linkage between cardiovascular disease and breakdown of neurovascular coupling along with increases in interleukin (IL)-1 in the brain. Shabir and colleagues plan further research to explore if an arthritis drug targeting IL-1 can reduce the brain dysfunction triggered by cardiovascular disease.4 

Helping your patients prevent and control cardiovascular conditions in midlife may not only provide good heart health but also reduce their risk for dementia. Now that’s great news!


1. 2022 Alzheimer’s disease facts and figures. Alzheimers Dement. 2022;18(4):700-789. doi:10.1002/alz.12638

2. Tai XY, Veldsman M, Lyall DM, et al. Cardiometabolic multimorbidity, genetic risk, and dementia: a prospective cohort study. Lancet Healthy Longev. 2022;3(6):e428-e436. doi:10.1016/S2666-7568(22)00117-9

3. Johansen MC, Wang W, Zhang M, et al. Risk of dementia associated with atrial cardiopathy; the ARIC study. J Am Heart Assoc. 2022;11(16):e025646. doi:10.1161/JAHA. 121.025646

4. Shabir O, Pendry B, Lee L, et al. Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s Disease. eLife. 2022;11:e68242. doi:10.7554/eLife.68242