Increasing emphasis has been placed on extending healthy life expectancy. Patients with dementia, cerebrovascular disease, and frailty due to old age account for 24.8%, 18.4%, and 12.1%, respectively, of people aged 65 years or more requiring nursing care.

The causes of dementia are numerous, and the most common type is Alzheimer’s disease (AD), followed by vascular dementia (VaD), and dementia with Lewy bodies. Lifestyle-related diseases such as diabetes and hypertension are involved in the onset and progression of dementia.

The term “frailty” indicates an intermediate stage between a healthy state and one where an individual will require nursing care. Frailty involves physical, mental, and psychological decline, and possibly also social factors such as solitude and financial distress.

Sarcopenia, which causes muscle loss, and a decrease in muscular strength and physical function, is the key factor in physical decline.

Dementia, sarcopenia, and frailty are closely related. The frequency of frailty is higher in patients with AD than in healthy elderly people. Cerebrovascular disease (CVD), such as lacunes and white matter lesions, is common in elderly patients with AD. Frailty is more closely associated with AD + CVD than with AD alone; and it also shows a stronger association with VaD than with AD.

The close relationship between dementia and frailty/sarcopenia is believed to constitute a vicious cycle.

Vascular dementia (VaD) is regarded as the second most common type of dementia but recent surveys suggest vascular cognitive impairment (VCI) is even more frequent in most populations worldwide. White matter hyperintensities (WMHs) detected on brain MRI are the radiological signature of cerebral small vessel disease (SVD), which is highly characteristic in subcortical ischaemic vascular dementia (SIVD), the most prevalent subtype of VaD. Vascular risk factors are strongly associated with WMHs and development of post-stroke VaD or dementia. The gliovascular unit (GVU) has a critical role in SIVD. Therefore, any component of the GVU could be a therapeutic target for VaD. When considering pharmacological approaches, more attentions ought to be paid onto pleiotropic effects of existing drugs. Autonomic dysfunction is highly prevalent in VaD patients and is a treatable factor to protect GVU from VaD pathologies. As non-pharmacological approaches for VaD, environmental enrichment (EE) and physical exercise training, particularly limited EE rather than full-time EE, have been proved to preserve GVU integrity in VaD. Glial responses, especially clasmatodendrosis, would be a novel therapeutic target for VaD. Animal models of VaD are useful to demonstrate pathophysiology, explore and establish safe and effective treatments. Nevertheless, pathophysiological substrate of VaD is heterogeneous. Multimodal combination treatments targeting GVU, implementing both pharmacological and non-pharmacological interventions, would be a promising interventional strategy to counter vascular dementia.

An 11-year-old girl underwent craniotomy for suprasellar germinoma. Thereafter, whole brain irradiation (50 Gy) was performed. Her cognitive decline progressed from the age of 35. Brain computed tomography indicated that calcification began in the basal ganglia (at the age of 25), followed by the cerebellar dentate nucleus (at the age of 34) and the cerebral cortex (at the age of 43). A late delayed complication of whole brain irradiation against a brain tumor induced microvascular injury and cognitive decline. The present case showed serial brain calcification, which may be related to the progress of microvascular injury after whole brain irradiation.