Cited by 124Dementia and Cognitive Impairment ResearchNeurological Disease Mechanisms and TreatmentsAlzheimer's disease research and treatments

Clinical and imaging features of mixed Alzheimer and vascular pathologies

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Chui, Helena C, Ramirez-Gomez, Liliana·2015·Alzheimer's Research & Therapy

Abstract

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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  • Almost a quarter of AD patients develop Parkinsonian features, but the relative contribution of substantia nigra tangles and Lewy bodies to this presentation is unresolved.

    “Almost a quarter of AD patients develop Parkinsonian features, but the relative contribution of substantia nigra tangles and Lewy bodies to this presentation is unresolved [122].”

    From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [122]

    The section on weighting pathological lesions discusses tangles and Lewy bodies in relation to cognitive decline, not Parkinsonian features. Searches for Parkinsonian features, substantia nigra tangles, and the claimed near-quarter prevalence found no passage in our copy addressing either part of the claim. (LLM, conf=0.76)

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Authors
Chui, H. C., & Ramirez-Gomez, L.
Affiliations
University of Southern California (US)
Corresponding author
Chui, Helena C
Venue
Alzheimer's Research & Therapy
Published
2015-02-27
Volume
7
Issue
1
Pages
21-21
ISSN
1758-9193 (ISSN-L)
OpenAlex
W2104703797
Cited by
124
References
70
Citations by year
2026: 11 · 2025: 7 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 13 · 2020: 8 · 2019: 16 · 2018: 10 · 2017: 12 · 2016: 15 · 2015: 9 · 2014: 1
FWCI
12.46
Type
journal article
Language
en
Open access
Locations
  • Alzheimer s Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (P50AG005142, P01AG012435)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease, vascular brain injury, vascular cognitive impairment, dementia, microinfarcts, white matter hyperintensities, cerebral amyloid angiopathy, arteriosclerosis, amyloid PET, cerebrospinal fluid biomarkers, structural MRI, cognitive impairment, vascular risk factors, hippocampal atrophy, amnesia

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