LARGE VESSEL CEREBROVASCULAR DISEASE AND DEMENTIA Intracranial atherosclerosis

With the rapid increase in the prevalence of dementia worldwide there has been significant research into modifiable risk factors for dementia. In this regard cerebrovascular diseases (CVD) represent a potential therapeutic target in the fight against the epidemic of dementia. Both large vessel CVD and small vessel disease in the form of chronic lacunes, white matter hyperintensity, microbleeds, and perivascular spaces have been strongly associated with the risk of developing dementia. These CVD factors may initiate or accelerate the amyloid and tau cascades resulting in greater rates of neurodegeneration and dementia. Understanding the precise mechanisms for the interaction between CVD and neurodegeneration will allow development of potential interventional targets. These CVD risk factors may be of particular relevance to the Asian population where a high burden of small vessel CVD has been demonstrated in Asian patients with dementia. Neurology Asia 2016; 21(2) : 103 – 111 Address correspondence to: A/Prof Nagaendran Kandiah, Senior Consultant Neurologist, Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433. Tel: 0065 6357 7199, Email: nagaendran_kandiah@nni.com. sg INTRODUCTION Dementia is a clinical syndrome characterized by chronic and progressive deterioration of mental functioning and impaired daily functioning.Cerebrovascular disease (CVD) has been observed to be attributable to two of the leading causes of dementia worldwide – Alzheimer’s disease (AD) and vascular dementia (VaD). In a recent study by Kandiah et al., severity of AD was associated with increased burden of CVD pathology. CVD comprises of a group of vascular pathologies that compromises cerebrovascular circulation, resulting in hypoperfusion and ischemic injury. One subtype called cerebral small-vessel disease affects the small perforating arterioles, capillaries, and venules, leading to damage in the brain parenchyma. We highlight the global prevalence of dementia, particularly AD and VaD; risk factors for CVD and their contributory role; role of large vessel CVD in the progression of dementia; role and pathophysiology of cerebral small-vessel disease; and the current treatment and preventive measures. INCIDENCE AND PREVALENCE OF DEMENTIA The prevalence of dementia is constantly on the rise worldwide. As of 2010, 35.6 million people have been diagnosed. This figure is projected to double every 20 years and reach 115.4 million by 2050, with low-to-middle income regions of the world expected to bear the brunt of the burden. Regional differences in prevalence rates of dementia may be attributed to poorer allocation of resources towards prevention strategies, discrepancies in diagnostic assessment, low community outreach, and cultural stigma. The incidence rate of dementia is approximately 4.6 million cases a year, with China and its western-Pacific neighbors expected to confer the greatest proportion of new cases. A pooledanalysis of eight population-based studies in Europe reported that AD and VaD contribute 60-70% and 15-20% of new cases of dementia respectively, with increased rate of incidence until the age of 85. After which, incidence rates increased for women only, highlighting sexrelated differences in survivability. CEREBROVASCULAR RISK FACTORS Approximately half of all AD cases worldwide can be attributed to cerebrovascular risk factors (CVRF) such as hypertension, diabetes mellitus, hyperlipidemia, smoking, alcohol intake, and obesity. Approximately 9% of all cases of dementia may be preventable if increased REVIEW ARTICLE Neurology Asia June 2016 104 measures had been taken to reduce the global prevalence of CVRF.