Stroke-heart syndrome associated with increased risk of incident dementia

Patients with stroke-heart syndrome (SHS) may have increased risk of dementia in the early phase after a stroke, but this risk can be lowered to a level similar to those without SHS if adherent care is given, researchers from the University of Hong Kong (HKU) and their international collaborators have found.

The population-based, propensity score–matched, retrospective cohort study of 130,605 patients (mean age, 70.3 years; male, 55.3 percent) with first-ever ischaemic stroke (IS) found that 9.7 percent of the cohort developed new-onset cardiovascular (CV) complications within 30 days poststroke (ie, SHS). [Alzheimer’s Dement 2025;21:e70716]

At 1-year poststroke, the development of SHS was associated with a 19 percent increased risk (adjusted subdistribution hazard ratio [aSHR], 1.19; 95 percent confidence interval [CI], 1.03–1.37) of incident dementia (composite of Alzheimer’s disease [AD], vascular dementia and unspecified dementia) and a 39 percent increased risk (aHR, 1.39; 95 percent CI, 1.30–1.50) of all-cause mortality. Females were found to be at higher risk of SHS-associated dementia than males (SHR [95 percent CI], 1.27 [1.06–1.53] vs 1.12 [0.90–1.39]; p=0.01 and 0.32, respectively).

Among the various subtypes of dementia, development of SHS was associated with a significantly higher risk of vascular dementia (aSHR, 1.30; 95 percent CI, 1.10–1.53; p=0.002), but the risk increases were nonsignificant for AD and unspecified dementia.

Of note, poststroke management with adherent care (appropriate antithrombotic therapy and optimal care for comorbidities) was associated with a lower risk of incident dementia, similar to that in patients without SHS who received adherent care (aSHR [95 percent CI]: patients with SHS with adherent care, 0.68 [0.53–0.89]; patients without SHS with adherent care, 0.68 [0.56–0.84]).

The increased risk of dementia associated with SHS showed a gradual reduction with each successive year of follow-up and became nonsignificant at 3 years poststroke. This is consistent with previous studies and is possibly attributable to stabilization of the acute vascular insult and resolution of inflammation. [Lancet Neurol 2019;18:248-258; Neurology 2025;104:e210131; Eur Stroke J 2024;10:541-551]

“Our findings emphasize the possible bidirectional relationship of the brain–heart axis and highlight the cumulative impact of these conditions,” wrote the authors. While the exact cascade of events of this brain–heart axis has yet to be elucidated, the authors postulated that the “two-hit hypothesis” might explain the increased risk of dementia associated with SHS.

“After IS, microinfarction, excitotoxicity, oxidative stress, blood–brain barrier dysfunction, and focal neuronal atrophy may represent the ‘first hit’ that leaves the brain in a vulnerable state,” explained the authors. “In patients with SHS, autonomic dysregulation, coupled with systemic release of catecholamines and inflammatory cytokines, may then mount the ‘second hit’ that impairs cerebral perfusion, leading to more extensive tissue damage. This may explain the higher risk of dementia, particularly vascular dementia, that was observed in the first year poststroke.”

“Given the shared risk factors between IS, SHS, and dementia, optimizing care for these comorbidities would be fundamental in mitigating the consequences of deleterious brain–heart interactions,” suggested the authors. “[T]his may be addressed through the ABC-stroke pathway, an integrated care approach to optimize the management of stroke and associated heart disease, outlined in the position paper of the European Society of Cardiology [ESC] Council on Stroke.” [Eur Heart J 2022;43:2442-2460]