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Review
. 2025 Jul 21;272(8):522.
doi: 10.1007/s00415-025-13257-z.

The heart-brain axis: neurocognitive frailty in heart failure

Olayiwola Bolaji  1 , Yasemin Bahar  2 , Sameer Lohana  3 , Abdul Rasheed Bahar  4 , Ibiyo Lawrence  5 , Sula Mazimba  6
Affiliations
Review

The heart-brain axis: neurocognitive frailty in heart failure

Olayiwola Bolaji et al. J Neurol. .

Abstract

Heart failure (HF) and neurocognitive frailty (NCF) represent an increasingly recognized clinical intersection with profound implications for patient outcomes. Recent epidemiological data reveal that 40-60% of HF patients experience cognitive impairment, with prevalence increasing proportionally with disease severity. This cognitive-functional decline manifests as structural brain abnormalities, deficits in multiple cognitive domains, and reduced physical capabilities, collectively compromising self-care, increasing healthcare utilization, and elevating mortality risk by up to twofold. This comprehensive review examines the complex bidirectional relationship between HF and NCF, synthesizing current evidence on pathophysiological mechanisms, clinical assessment approaches, and management strategies. The pathophysiology involves interrelated processes, including cerebral hypoperfusion, blood-brain barrier disruption, neuroinflammation, oxidative stress, and neurohumoral dysregulation-all contributing to accelerated brain aging and functional decline. Clinical assessment requires a multidimensional approach utilizing validated cognitive and frailty tools, biomarkers, neuroimaging, and functional measures. Management necessitates integrated strategies spanning optimized pharmacotherapy, device-based interventions, cognitive rehabilitation, structured exercise, nutritional support, and coordinated multidisciplinary care. Emerging evidence suggests that early intervention may attenuate cognitive decline and improve outcomes. As the prevalence of both conditions continues to rise, future research directions should focus on standardized assessment protocols, novel therapeutic targets, and innovative care delivery models to address this challenging clinical syndrome and improve quality of life for this vulnerable population.

Keywords: Cerebral hypoperfusion; Cognitive frailty; Cognitive impairment; Heart failure; Multidisciplinary care; Neurocognitive frailty.

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Conflict of interest statement

Declarations. Conflict of interest: The authors disclose non-financial interests. Consent to participate: Not applicable. Human ethics and consent to participate: Not applicable.

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