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“Key Points Cognitive enhancers demonstrate long-term benefit in the treatment of mixed Alzheimer’s disease (AD) and cerebrovascular disease Among cerebrovascular diseases, the small vessel subtype may demonstrate greater benefit with cognitive enhancers Randomized clinical trials of AD patients selleck chemicals llc with small vessel cerebrovascular disease are urgently needed in view of the high prevalence of small vessel cerebrovascular disease in AD 1 Introduction Alzheimer’s disease (AD) is a major cause of dementia, with a global prevalence of
3.9 % in people older than 60 years [1]. The failure of anti-amyloid clinical trials necessitates exploration of other biological SU5402 nmr factors that can potentially delay the onset and progression of AD [2]. Cerebrovascular disease can modify Astemizole the clinical expression and treatment response in AD [3]. Small vessel cerebrovascular disease (svCVD) is prevalent among patients with AD, resulting in mixed AD [4, 5]. On neuroimaging, AD patients with svCVD will demonstrate white matter hyperintensity (WMH) and lacunes [6]. WMH has been strongly associated with other markers of vascular disease [7, 8], greater cognitive impairment in AD, and higher risk of progression from mild cognitive impairment to AD [9–11]. The Honolulu-Asia Aging Study has demonstrated the role of co-prevalent brain lesions such as amyloid pathology, brain atrophy, and microvascular infarcts in AD, hence the importance of recognizing and treating patients with AD and svCVD [12]. Cholinergic dysfunction is well recognized in AD, and acetylcholinesterase inhibitors have shown benefit on cognitive and functional outcomes in AD [13–16]. Similarly, WMH has been shown to impair cholinergic function in the brain [17].