Cerebrovascular Disease, Amyloid Plaques, and Dementia

Amyloid plaques are depositions of amyloid β (Aβ) protein in the cerebral parenchyma and considered as one of the neuropathological diagnostic hallmarks of Alzheimer’s disease (AD).1 Cerebrovascular disease (CVD) is also highly prevalent among the elderly and is commonly found in patients with AD.2 Autopsy studies conducted during the past 2 decades show that amyloid plaques frequently coexist with CVD, and the 2 may interact to modulate the risks and expression of clinical dementia.2 Neuropathological examinations show that between 6% and 47% individuals with dementia had coexisting AD and CVD pathologies (Table).3–20 Indeed, mixed pathologies may account for the majority of dementia cases (38%).11View this table:Table. Pathology Findings in DementiaAlthough autopsy study is considered the gold standard for determining the underlying pathology of dementia, it has inherent limitations with correlating pathological and clinical findings. In particular, uncertainties exist with regard to the temporal relationship between the development of brain lesions and dementia syndrome because of the time lag between dementia onset and autopsy. Moreover, the exact severity or extent of certain manifestations of CVD, in particular, white matter changes (WMC), is difficult to quantify in autopsy studies.21 Also, heterogeneity in the definition of CVD lesions (eg, lacunar infarct) might contribute to inconsistency in assessments between neuropathologists.21Clinical in-vivo study investigating the relationship between amyloid plaques and cognitive impairment has only been made possible a decade ago with the advent of amyloid imaging, such as Carbon-11-labeled Pittsburgh Compound B (PiB) positron emission tomography (PET). Other amyloid ligands, such as flutemetamol (GE-067), florbetaben (BAY-94–9172, AV-1), and florbetapir (AV-45) have also become available to the market in recent years.22 Amyloid PET can detect comorbid amyloid deposition in patients with high vascular burden.23 We reviewed the potential interactions between CVD and amyloid plaques …