Clinical and imaging features of mixed Alzheimer and vascular pathologies.

Helena C Chui,Liliana Ramirez-Gomez

doi:10.1186/s13195-015-0104-7

Helena C Chui, Liliana Ramirez-Gomez

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https://doi.org/10.1186/s13195-015-0104-7

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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.

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Alzheimer disease (AD) and vascular dementia are recognized as the two most prevalent forms of dementia in late life
AD, Alzheimer disease; AGECAT, Automated Geriatric Examination for Computer Assisted Taxonomy; BLSA, Baltimore Longitudinal Aging Study; CASI, Cognitive Abilities Screening Instrument; CC75 + C, Cambridge City Over-75 s Cohort; CERAD, Consortium to Establish a Registry for Alzheimer Disease; CFAS, Cognitive Function and Ageing Study; CVA, cerebrovascular accident; HAAS, Honolulu Asia Aging Study; MAP, Rush Memory and Aging Project; Microscopic brain infarct (MBI), microscopic brain infarct; MMSE, Mini-Mental State Exam; MRC, Medical Research Council; NIA, National Institute on Aging; NINDS-AIREN, National Institute of Neurological Disorders and StrokeAssociation Internationale pour la Recherche et l’Enseignement en Neurosciences; Religious Orders Study (ROS), Rush Religious Order Study; SD, standard deviation; VBI, vascular brain injury; VCI, vascular cognitive impairment
AD, Alzheimer disease; ADDTC, Alzheimer’s Disease Diagnostic and Treatment Centers; CERAD, Consortium to Establish a Registry for Alzheimer Disease; CI, confidence interval; CIND, Cognitive impairment not meeting criteria for dementia; Clin Dx, clinical diagnosis; CN, cognitively normal; CVD-PS, cerebrovascular disease-parenchymal score; Dem, dementia; EXEC, executive score; GLOB, global cognition score; MEM, memory score; NINDS-ADRDA, National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l’Enseignement en Neurosciences; NSP, non-significant pathology; NVMEM, non-verbal memory; OR, odds ratio; Path Dx, pathological diagnosis; VBI, vascular brain injury; White matter hyperintensity (WMH), white matter hyperintensity

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Introduction

Alzheimer disease (AD) and vascular dementia are recognized as the two most prevalent forms of dementia in late life. AD, Alzheimer disease; AGECAT, Automated Geriatric Examination for Computer Assisted Taxonomy; BLSA, Baltimore Longitudinal Aging Study; CASI, Cognitive Abilities Screening Instrument; CC75 + C, Cambridge City Over-75 s Cohort; CERAD, Consortium to Establish a Registry for Alzheimer Disease; CFAS, Cognitive Function and Ageing Study; CVA, cerebrovascular accident; HAAS, Honolulu Asia Aging Study; MAP, Rush Memory and Aging Project; MBI, microscopic brain infarct; MMSE, Mini-Mental State Exam; MRC, Medical Research Council; NIA, National Institute on Aging; NINDS-AIREN, National Institute of Neurological Disorders and StrokeAssociation Internationale pour la Recherche et l’Enseignement en Neurosciences; ROS, Rush Religious Order Study; SD, standard deviation; VBI, vascular brain injury; VCI, vascular cognitive impairment.

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