Dissociable Effects of Alzheimer Disease and White Matter Hyperintensities on Brain Metabolism

Haight, Thaddeus; Landau, Susan; Carmichael, Owen; Schwarz, Christopher G.; DeCarli, Charles; Jagust, William J.

doi:10.1001/jamaneurol.2013.1878

Cited by 57 publications

(51 citation statements)

References 38 publications

(44 reference statements)

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“…Other studies have observed that cerebral amyloid burden and white matter hyperintensity burden are independently associated with greater brain atrophy and hypometabolism(J. Barnes et al, 2013; Guzman et al, 2013; Haight et al, 2013), and additional studies support the view that the co-occurrence of amyloid and white matter hyperintensities is clinically relevant among those clinically diagnosed with Alzheimer's disease (Provenzano et al, 2013). To the degree that white matter hyperintensities are a manifestation of cerebrovascular dysfunction, the in vivo data can be used to support the notion that cerebrovascular injury and Alzheimer's disease may have additive or multiplicative deleterious effects on the brain that hasten cognitive deterioration.…”

Section: What Is Knownmentioning

confidence: 67%

Preventing Vascular Effects on Brain Injury and Cognition Late in Life: Knowns and Unknowns

Carmichael

2014

Neuropsychol Rev

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For some researchers, the relationship between prevalent cardiovascular risk factors and late-life cognitive decline is not worthy of further study. It is already known that effective treatment of vascular risk factors lowers risk of such major outcomes as stroke and heart attack, the argument goes; thus, any new information about the relationship between vascular risk factors and another major outcome - late-life cognitive decline-- is unlikely to have an impact on clinical practice. The purpose of this review is to probe the logic of this argument by focusing on what is known, and what is not known, about the relationship between vascular risk factors and late-life cognitive decline. The unknowns are substantial: in particular, there is relatively little evidence that current vascular risk factor treatment protocols are adequate to prevent late-life cognitive decline or the clinically silent brain injury that precedes it. In addition, there is relatively little understanding of which factors lead to differential vulnerability or resilience to the effects of vascular risk factors on silent brain injury. Differential effects of different classes of treatments are similarly unclear. Finally, there is limited understanding of the impact of clinically-silent neurodegenerative disease processes on cerebrovascular processes. Further study of the relationships among vascular risk factors, brain injury, and late-life cognitive decline could have a major impact on development of new vascular therapies and on clinical management of vascular risk factors, and there are promising avenues for future research in this direction.

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Section: What Is Knownmentioning

confidence: 67%

Preventing Vascular Effects on Brain Injury and Cognition Late in Life: Knowns and Unknowns

Carmichael

2014

Neuropsychol Rev

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“…30 This may contribute to a disruption of vascular dynamics, weakness of the arterioles, insufficient brain perfusion, increased small-vessel pulsatility, and wave reflections, all mechanisms that could alter the perivascular clearance of Aβ, 31 leading to plaque formation. 32 Our data suggest that arterial stiffness may play a central and potentially unifying role in the development of both white matter disease and Aβ deposition and provide interesting insight to the ongoing debate that Aβ and WMHs have complementary 33 or dissociable effects 34 on the presentation and conversion to AD. Future research needs to assess the role of brain vascular dynamics in the development and progression of Aβ deposition in the brain.…”

Section: Discussionmentioning

confidence: 79%

Arterial Stiffness and β-Amyloid Progression in Nondemented Elderly Adults

et al. 2014

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“…In fact, emerging data-driven models suggest that vascular disease and dysregulated inflammation are early risk factors in the pathophysiological cascade leading to AD 55 . The mechanisms of vascular disease — especially small vessel disease (SVD) — and AD-related neurodegeneration might be intricately interrelated 56 .…”

Section: Alzheimer Diseasementioning

confidence: 99%

“…As the frontal white matter is particularly vulnerable to SVD 56 , typical cognitive deficits with disease progression include executive dysfunction, with diminished attention and concentration and impaired spontaneous retrieval of stored memory. Behavioural changes such as irritability are common, and parkinsonism (frequently symmetrical) can also be noted.…”

Section: Vascular Dementiamentioning

confidence: 99%

A clinicopathological approach to the diagnosis of dementia

2017

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The most definitive classification systems for dementia are based on the underlying pathology which, in turn, is categorized largely according to the observed accumulation of abnormal protein aggregates in neurons and glia. These aggregates perturb molecular processes, cellular functions and, ultimately, cell survival, with ensuing disruption of large-scale neural networks subserving cognitive, behavioural and sensorimotor functions. The functional domains affected and the evolution of deficits in these domains over time serve as footprints that the clinician can trace back with various levels of certainty to the underlying neuropathology. The process of phenotyping and syndromic classification has substantially improved over decades of careful clinicopathological correlation, and through the discovery of in vivo biomarkers of disease. Here, we present an overview of the salient features of the most common dementia subtypes — Alzheimer disease, vascular dementia, frontotemporal dementia and related syndromes, Lewy body dementias, and prion diseases — with an emphasis on neuropathology, relevant epidemiology, risk factors, and signature signs and symptoms.

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Dissociable Effects of Alzheimer Disease and White Matter Hyperintensities on Brain Metabolism

Cited by 57 publications

References 38 publications

Preventing Vascular Effects on Brain Injury and Cognition Late in Life: Knowns and Unknowns

Preventing Vascular Effects on Brain Injury and Cognition Late in Life: Knowns and Unknowns

Arterial Stiffness and β-Amyloid Progression in Nondemented Elderly Adults

A clinicopathological approach to the diagnosis of dementia

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