The global number of dementia cases is expected to increase to 152 million by 2050, particularly in low- and middle-income countries, significantly impacting individuals, families, and economies.

Various organizations and academic groups have proposed indicators for addressing dementia. The World Health Organization (WHO) indicators focus on early detection, prevention, public health measures, and national policies for dementia, especially from an international perspective. From an academic perspective, the Lancet Commission, which began in 2017 and updated in 2020 and 2024, proposes a comprehensive life course model for dementia prevention. Additionally, the American Heart Association (AHA) expands its cardiovascular health strategy to include dementia prevention through its Life’s Essentials 8 guidelines. Therefore, this review outlines and compares these guidelines and strategies against dementia.

In Japan, the Basic Law for the Promotion of Dementia Measures, enacted in 2023, emphasizes social initiatives alongside individual health management. This study also indicates that with the advent of disease-modifying drugs for Alzheimer’s disease in countries including Japan, the need for early detection and comprehensive care may increase.

According to the estimation of Japan’s population composition, the number of individuals over 65 years is expected to rise significantly, with one in four predicted to be 75 years or older by 2070. This demographic trend has increased the focus on dementia prevention. Fourteen modifiable risk factors, including hypertension, diabetes, smoking, and obesity are linked to dementia. Cerebral small-vessel disease (SVD), associated with vascular risk factors, plays a critical role in dementia progression. SVD, which affects small blood vessels in the brain, leads to brain damage including white matter lesions and microbleeds, detectable through magnetic resonance imaging. Recent research demonstrates that SVD progression contributes to cognitive decline and dementia, particularly in individuals with Alzheimer’s disease (AD), as both often coexist and impact cognitive function. Although the effect of SVD on AD progression remains debatable, managing vascular risk factors is crucial for preventing both SVD and dementia. Early detection and management of SVD may delay the onset of dementia and slow cognitive decline, emphasizing the need for preventive healthcare strategies for aging populations.

Background: Diabetes mellitus (DM) is a risk factor for both vascular dementia and Alzheimer’s disease (AD). We previously reported that tau phosphorylation is increased in the brain of a diabetic AD mouse model, which can be an underlying mechanism linking DM and AD. However, the key molecules mediating the tau phosphorylation by DM remain unknown. Here, using a phosphoproteomic approach, we aimed to identify candidate kinases that regulate tau phosphorylation by DM.

Method and Results: We generated diabetic tau-transgenic (TauTg) mice by high-fat diet (HFD) feeding and conducted a phosphoproteomic analysis of their brain tissues. Phosphoproteome profiling of the brains from the diabetic and non-diabetic TauTg mice were compared. We identified 30 kinases whose levels of phosphorylation were significantly altered in the brains of the diabetic TauTg mice. Molecular networking analysis found that six of the 30 kinases were associated with tau phosphorylation. Among the six kinases, the decrease in the phosphorylation levels of CaMK2α, which reflected the severity of diabetic conditions, was associated with the exacerbation of accumulation of phosphorylated tau in the brains of TauTg mice.

Conclusions: Tau-related kinases that potentially mediate DM-induced tau phosphorylation were identified using a phosphoproteomic approach. These kinases could be therapeutic targets for preventing AD in patients with DM.

Background: We previously reported that each taxifolin (TAX) and cilostazol (CSZ) have neuroprotective pleiotropic effects that target amyloid β, and that TAX is clinically associated with cognitive improvement. Thus, TAX and CSZ combination therapy could amplify cognitive improvement.

Methods and Results: In this retrospective longitudinal study, we collected data from 29 patients diagnosed with mild cognitive impairment and mild dementia who received TAX (300 mg/day) and regularly underwent the Montreal Cognitive Assessment (MoCA) or Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale–Cognitive Subscale 13 (ADAS-Cog). The total MMSE scores were converted to the total MoCA score based on the established calculation method. The total MoCA and ADAS-Cog score changes were compared between the nontreatment (pre-TAX) period (180 ± 100 days) and the following treatment (on-TAX) period (180 ± 100 days) in patients taking CSZ (TAX/CSZ group, n = 6) and those not taking CSZ (TAX group, n = 23). Increase in the mean total MoCA scores was significantly greater during the on-TAX period than the non-TAX period in the TAX group (0.96 vs. –1.30, p = 0.016) and in the TAX/CSZ group (1.83 vs. –1.83, p = 0.011). Furthermore, the increase during the on-TAX period tended to be greater in the TAX/CSZ group than in the TAX group (1.83 vs. 0.96, p = 0.21). However, the changes in mean total ADAS-Cog score were comparable between the on-TAX and the non-TAX periods in the TAX group (p = 0.21) and the TAX/CSZ group (p = 0.44).

Conclusion: TAX and CSZ combination therapy could serve as a novel strategy for maintaining brain health during aging.

Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID) are the leading causes of dementia, and are characterized by distinct yet overlapping pathophysiological mechanisms. AD is characterized by amyloid-beta plaques, neurofibrillary tangles, and neurodegeneration, whereas VCID arises from vascular damage, including small vessel disease and blood-brain barrier disruption. Biomarkers have revolutionized dementia research and offer tools for early diagnosis, monitoring, and therapeutic evaluation. Cerebrospinal fluid (CSF) biomarkers, such as amyloid-beta (Aβ) 42/Aβ40 ratio and phosphorylated tau, provide reliable indicators of AD pathology, while emerging markers like microtubule binding region (MTBR)-tau243 offer insights into disease progression. Blood-based biomarkers, including plasma Aβ42/Aβ40 ratio, phosphorylated tau, neurofilament light chain (NfL), and glial fibrillary acidic protein, represent scalable, non-invasive alternatives. In VCID, biomarkers like matrix metalloproteinases, soluble platelet-derived growth factor receptor-β and inflammatory markers reflect vascular pathology and neurodegeneration. Advances in detection technologies such as single-molecule arrays have improved sensitivity and precision, facilitating their integration into clinical practice. However, challenges remain, including assay variability, limited accessibility, and high costs. Harmonization of protocols and integration of multimodal biomarkers, including CSF, blood, and imaging data, offer a holistic approach to diagnostics. Biomarkers are central to personalized medicine, enabling tailored interventions and improving the outcomes of patients with dementia. Ongoing innovation holds promise for advancing the understanding and management of these complex disorders.

Recent progress in cerebrovascular research has revealed new aspects of the pathogenesis of vascular dementia. Newly uncovered molecular mechanisms underlying the physiological and pathological functions of cerebrovasculature have provided an evolving landscape for understanding the pathogenesis of vascular dementia. These findings have, in turn, promoted the development of biomarkers for predicting, diagnosing, and assessing the severity of vascular dementia. Furthermore, the recent approval of an anti-amyloid antibody treatment against Alzheimer’s disease has brought researchers’ attention to the interplay between Alzheimer’s amyloid-β and cerebrovasculature, as amyloid-related imaging abnormalities occurred in a certain number of patients receiving the therapy. Cerebral amyloid angiopathy, the deposition of amyloid-β in the brain’s blood vessels, may play a role in the interplay between Alzheimer’s and vascular dementia. Here, we review recent developments in research on vascular dementia related to the findings concerning imaging, biofluid, and digital biomarkers for diseases.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are typically presented before the age of 30 years. This case report describes a rare late-onset MELAS in a 55-year-old woman with the m.3243A>G mutation. The patient presented with aphasia, perseveration, and headache. She had diabetes mellitus but did not show common MELAS features like short stature. The diagnosis was confirmed through MRI, elevated lactate and pyruvate levels in the serum and cerebrospinal fluid, and genetic testing. Levetiracetam treatment improved her symptoms and taurine prevented the recurrence of stroke-like attacks. This case highlights the importance of considering MELAS as a differential diagnosis in patients with atypical stroke-like symptoms for appropriate treatment, even in middle-aged patients.