Dementia is one of the most pressing public health challenges of the 21st century[
1]. Despite decades of research, effective disease-modifying treatments remain elusive, and current therapies provide only modest symptomatic benefit. In this context, accumulating evidence highlights an underused yet promising strategy: preventing dementia by preventing cerebrovascular disease[
2]. Vascular and neurodegenerative pathologies are closely interconnected, both mechanistically and epidemiologically, necessitating an integrated framework for research, prevention, and policy.
Epidemiological studies have consistently demonstrated that vascular risk factors, including midlife hypertension, diabetes, obesity, and smoking, substantially increase the risk of cognitive impairment and dementia in later life[
3,
4]. These factors exert their greatest effects when present in midlife, underscoring the importance of a life-course perspective on brain health. Findings from the SPRINT-MIND (Systolic Blood Pressure Intervention Trial-Memory and Cognition in Decreased Hypertension)[
5] and FINGER (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability)[
6] trials provide proof of concept that intensive vascular risk control can reduce the incidence of mild cognitive impairment and slow cognitive decline. From a population health perspective, it is estimated that eliminating cerebrovascular disease could prevent approximately one third of dementia cases[
7].
The biological links between vascular dysfunction and neurodegeneration are increasingly well elucidated. Cerebral small vessel disease, which affects more than 70% of adults over the age of 50[
8], leads to chronic blood-brain barrier disruption, impaired cerebral perfusion, and dysfunction of glio-neuro-vascular unit. These alterations compromise perivascular clearance pathways, promoting amyloid and tau accumulation and thereby lowering the threshold for clinical cognitive impairment. Vascular dysfunction can occur early, even preceding overt cerebrovascular lesions, and may act both directly, by causing ischemic injury such as macro- and microinfarcts, and indirectly, by amplifying neurodegenerative processes.
Neuropathological studies further challenge the traditional dichotomy between “Alzheimer’s disease” and “vascular dementia”. Mixed pathologies are the rule rather than the exception in older adults[
9]: vascular lesions, including macroinfarcts, microinfarcts, arteriolosclerosis, and cerebral amyloid angiopathy, are present in up to half of ageing brains and frequently coexist with amyloid plaques and neurofibrillary tangles. These vascular pathologies act as additive “hits”, lowering the threshold at which neurodegenerative changes lead to clinical manifestations. Notably, many of these vascular changes are clinically silent; covert infarcts, white matter hyperintensities, and cerebral microbleeds are highly prevalent in community populations and can be detected through modern neuroimaging.
This convergence of evidence calls for a fundamental reframing of dementia prevention strategies. First, vascular risk factor control should be recognized as a cornerstone of dementia prevention, through midlife blood pressure control, lifestyle modification, and early detection of small vessel disease. Second, research should adopt the conceptual framework of vascular contributions to cognitive impairment and dementia (VCID)[
7,
10], which integrates vascular and neurodegenerative mechanisms across the disease continuum. Third, early biomarkers of vascular dysfunction, including advanced neuroimaging techniques and biomarkers of blood–brain barrier integrity, should be developed and implemented to identify at-risk individuals before irreversible damage occurs. Finally, public health policies should prioritize vascular brain health, leveraging existing cardiovascular prevention infrastructures to reduce the global burden of dementia.
China’s rapidly ageing population and growing burden of cerebrovascular disease make this integrated approach particularly urgent. Large-scale community cohorts with multimodal imaging and longitudinal follow-up provide unique opportunities to elucidate vascular–neurodegenerative interactions in diverse populations and to develop population-specific prevention strategies.
In summary, the vascular–neurodegenerative interface represents one of the most promising and actionable frontiers in dementia prevention. Shifting the focus from late-stage pathology to early, vascular-targeted interventions across the life course will be essential to achieving the goal of reducing the global dementia burden.
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