The co-occurrence of both
Alzheimer disease (AD) pathology and
vascular brain injury (VBI) is very common, especially amongst the oldest of old. In neuropathologic studies, the prevalence of AD, VBI, and mixed AD/VBI lesions ranks ahead of Lewy bodies and
hippocampal sclerosis. In the modern era of structural magnetic resonance imaging (MRI) and
amyloid positron emission tomography (PET) imaging, this review examines 1) the prevalence of mixed AD and VBI pathology, 2) the significance of these pathologies for
cognitive impairment (AD and vascular
cognitive impairment (VCI)), and 3) the diagnosis and treatment of mixed AD/VCI. Although epidemiologic studies report that vascular risk factors for
arteriosclerosis increase the risk of incident AD, both autopsy and
amyloid PET studies indicate that AD and VBI contribute additively, but independently, to the risk of
dementia. The literature confirms the
malignancy of AD and highlights the adverse effects of microinfarcts on cognitive function. For the clinical diagnosis of mixed AD/VCI, the presence of AD can be recognized by neuropsychological profile, structural imaging, cerebrospinal fluid
biomarkers, and
glucose PET and
amyloid PET imaging. The diagnosis of VBI, however, still hinges predominantly on the structural MRI findings. Severe
amnesia and
atrophy of the hippocampus are characteristic of early AD, whereas the cognitive profile for VCI is highly variable and dependent on size and location of VBI. The cognitive profile of mixed AD/VBI is dominated by AD. With the notable exception of microinfarcts (which elude in vivo detection),
infarcts,
hemorrhages, and white matter hyperintensities on structural MRI currently represent the best markers for the presence VBI. Better markers that reflect the health and reactivity of intracerebral blood vessels are needed. For prevention and treatment, the type of underlying
cerebrovascular disease (for example,
arteriosclerosis or
cerebral amyloid angiopathy) should be considered. It is likely that reduction of vascular risk factors for
arteriosclerosis can significantly reduce vascular contributions to
mixed dementia.