Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker‐based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood‐brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.

Background/Aims: To evaluate the psychometric properties of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease (SVD). Methods: 40 SVD patients and 40 matched controls were recruited. Concurrent and criterion validity, inter-rater and test-retest reliability, internal consistency of the HK-MoCA were examined and clinical observations were made. Results: Performance on the HK-MoCA was significantly predicted by both executive (β = 0.23, p = 0.013) and non-executive (β = 0.64, p < 0.001) composite scores. It differentiated SVD patients from controls (area under the curve = 0.81, p < 0.001) with an optimal cutoff at 21/22. Reliability, internal consistency and clinical utility were good. Conclusion: The HK-MoCA is a useful cognitive screening instrument for use in SVD patients.

Background and Purpose—: The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization working group proposed a brief cognitive protocol for screening of vascular cognitive impairment. We investigated the validity, reliability, and feasibility of the Montreal Cognitive Assessment 5-minute protocol (MoCA 5-minute protocol) administered over the telephone. Methods—: Four items examining attention, verbal learning and memory, executive functions/language, and orientation were extracted from the MoCA to form the MoCA 5-minute protocol. One hundred four patients with stroke or transient ischemic attack, including 53 with normal cognition (Clinical Dementia Rating, 0) and 51 with cognitive impairment (Clinical Dementia Rating, 0.5 or 1), were administered the MoCA in clinic and a month later, the MoCA 5-minute protocol over the telephone. Results—: Administration of the MoCA 5-minute protocol took 5 minutes over the telephone. Total score of the MoCA 5-minute protocol correlated negatively with age ( r =−0.36; P <0.001) and positively with years of education ( r =0.41; P <0.001) but not with sex (ρ=0.03; P =0.773). Total scores of the MoCA and MoCA 5-minute protocol were highly correlated ( r =0.87; P 0.05 for difference; Cohen d for group difference, 0.80–1.13). It differentiated cognitively impaired patients with executive domain impairment from those without (areas under receiver operating characteristics curve, 0.89; P <0.001; Cohen d =1.7 for group difference). Thirty-day test–retest reliability was excellent (intraclass correlation coefficient, 0.89). Conclusions—: The MoCA 5-minute protocol is a free, valid, and reliable cognitive screen for stroke and transient ischemic attack. It is brief and highly feasible for telephone administration.

Background Cerebral small vessel disease (SVD) has been suggested to be more common in Asians compared with Caucasians. However, data from population-based studies in Asia are lacking. We report on the prevalence, risk factors and consequences of SVD from contemporary studies in three Asian countries using 3-Tesla MRI for the evaluation of SVD. Methods Clinical, cognitive and 3-Tesla brain MRI assessments were performed among participants of three studies from Singapore, Hong Kong and Korea. SVD markers include white matter hyperintensities (WMHs) using the modified Fazekas scale, lacunes and microbleeds. Cognition was assessed using the Mini Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Adjustments were made for age, sex and cardiovascular risk factors. Results A total of 1797 subjects were available for analysis (mean age: 70.1±6.3 years and 57% women). The prevalence of confluent WMH was 36.6%, lacunes, 24.6% and microbleeds, 26.9%. Presence of all three SVD markers showed a steeper increase with increasing age rising from 1.9% in the lowest to 46.2% in the highest 5-year age strata. The major risk factors for the increased severity of SVD markers were advancing age and hypertension. Moreover, increasing severity of SVD markers was independently associated with worse performance on MMSE and MoCA. Conclusion Elderly Asians have a high burden of SVD which was associated with cognitive dysfunction. This suggests that SVD markers should be a potential target for treatment in clinical trials so as to delay progression of cerebrovascular disease and potentially cognitive decline.