Circulating cardiac biomarkers, structural brain changes, and dementia: Emerging insights and perspectives

Abstract

Diseases of the heart and brain are strongly linked to each other, and cardiac dysfunction is associated with cognitive decline and dementia. This link between cardiovascular disease and dementia offers opportunities for dementia prevention through prevention and treatment of cardiovascular risk factors and heart disease. Increasing evidence suggests the clinical utility of cardiac biomarkers as risk markers for structural brain changes and cognitive impairment. We propose the hypothesis that structural brain changes are the link between impaired cardiac function, as captured by blood-based cardiac biomarkers, and cognitive impairment. This review provides an overview of the literature and illustrates emerging insights into the association of markers of hemodynamic stress (natriuretic peptides) and markers of myocardial injury (cardiac troponins) with imaging findings of brain damage and cognitive impairment or dementia. Based on these findings, we discuss potential pathophysiological mechanisms underlying the association of cardiac biomarkers with structural brain changes and dementia. We suggest testable hypotheses and a research plan to close the gaps in understanding the mechanisms linking vascular damage and neurodegeneration, and to pave the way for targeted effective interventions for dementia prevention. From a clinical perspective, cardiac biomarkers open the window for early identification of patients at risk of dementia, who represent a target population for preventive interventions targeting modifiable cardiovascular risk factors to avert cognitive decline and dementia.

Relative associations of behavioral and physiological risks for cardiometabolic disease with cognition in bipolar disorder during mid and later-life: findings from the UK biobank

“…Future research would also do well to explore cardiac biomarkers and their relation to cognition and cognitive markers in BD. An association between these markers and cognition has already been established in the general population (Hosoki et al, 2023;Jensen et al, 2023;van der Velpen et al, 2017), where relevantly, troponina widely recognized indicator of heart muscle damage has been linked to individual variation in the factors associated with cognition in BD in this study; blood pressure, physical activity, and sedentary behavior (Aakre & Omland, 2019;Xue, Iqbal, Chan, & Maisel, 2014). Exploring the association of cognition and cardiac biomarkers like troponin could, therefore, help to delineate the mechanistic pathways involved in cognitive dysfunction within the disorder.…”

“…General population studies have shown age-dependent associations of cardiometabolic diseases and their risk factors with both cognitive impairment and incident dementia (Qiu & Fratiglioni, 2015). Indeed, hemodynamic and serum markers of cardiac function have been associated with structural brain changes and accelerated cognitive decline and dementia (Hosoki et al, 2023;Jensen, Zeller, Twerenbold, & Thomalla, 2023;van der Velpen, Feleus, Bertens, & Sabayan, 2017). Cognitive impairments associated with these markers, as well as with the presence of cardiometabolic diseases and their risk factors, are evident across a number of cognitive domains including executive function, processing speed, memory, attention, fluency, and global cognition (Qiu & Fratiglioni, 2015;Tahmi, Palta, & Luchsinger, 2021;van der Velpen et al, 2017;Waldstein & Wendell, 2010;Zonneveld et al, 2023).…”

Association of cardiometabolic multimorbidity with motoric cognitive risk syndrome in older adults

“…The association of heart‐related diseases (heart failure, coronary heart disease, and atrial fibrillation) with cognitive dysfunction were also commonly reported 44–46 . Many pathophysiological systems participated, regulating heart–brain interactions, including the vascular, neurohumoral, and immune systems 47,48 . The damaging impact of heart‐related disease on cognition may be driven by regional cerebral hypoperfusion that affects cognitive regulatory cerebral sites 47 …”

“… 44 , 45 , 46 Many pathophysiological systems participated, regulating heart–brain interactions, including the vascular, neurohumoral, and immune systems. 47 , 48 The damaging impact of heart‐related disease on cognition may be driven by regional cerebral hypoperfusion that affects cognitive regulatory cerebral sites. 47 …”

Echocardiographic measures of the left heart and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact adults: The CABLE study

“…Cardiac diseases could accelerate brain aging. Robust data have identified some cardiac diseases (e.g., coronary heart disease [CHD], heart failure, and atrial fibrillation [AF]) and cardiac dysfunction as risk factors of cognitive impairment and Alzheimer's disease (AD), the most common type of dementia 2–4 . AD is pathologically characterized by the accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles in the brain, which can be reflected by the cerebrospinal fluid (CSF) biomarkers (amyloid β 42 [Aβ 42 ], phosphorylated tau protein [p‐tau], and total tau protein [t‐tau]) or brain positron emission tomography imaging as early as in a preclinical stage 5 .…”