Vascular contributions to cognitive impairment and dementia including Alzheimer's disease

Snyder, Heather M.; Corriveau, Roderick A.; Craft, Suzanne; Faber, James E.; Greenberg, Steven M.; Knopman, David S.; Lamb, Bruce T.; Montine, Thomas J.; Schaffer, Chris B.; Schneider, Julie A.; Wellington, Cheryl L.; Wilcock, Donna M.; Zipfel, Gregory J.; Zloković, Berislav V.; Bain, Lisa J.; Bosetti, Francesca; Galis, Zorina S.; Koroshetz, Walter J.; Carrillo, María C.

doi:10.1016/j.jalz.2014.10.008

Cited by 521 publications

(449 citation statements)

References 95 publications

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“…146 More specifically, several top priority objectives were recognized in the field: (1) animal models to understand the mechanistic link between cerebrovascular dysfunction and cognitive decline and to investigate the neuropathologic time course of neuronal and white matter injury. Smallvessel disease models mimicking human AD-related and mixed dementias are particularly needed; (2) biomarkers capable of detecting preclinical dementia are necessary, as early detection is the key to future therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

The neuropathology and cerebrovascular mechanisms of dementia

Raz

Knoefel

Bhaskar

2015

J Cereb Blood Flow Metab

366

284

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The prevalence of dementia is increasing in our aging population at an alarming rate. Because of the heterogeneity of clinical presentation and complexity of disease neuropathology, dementia classifications remain controversial. Recently, the National Plan to address Alzheimer's Disease prioritized Alzheimer's disease-related dementias to include: Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, and mixed dementias. While each of these dementing conditions has their unique pathologic signature, one common etiology shared among all these conditions is cerebrovascular dysfunction at some point during the disease process. The goal of this comprehensive review is to summarize the current findings in the field and address the important contributions of cerebrovascular, physiologic, and cellular alterations to cognitive impairment in these human dementias. Specifically, evidence will be presented in support of small-vessel disease as an underlying neuropathologic hallmark of various dementias, while controversial findings will also be highlighted. Finally, the molecular mechanisms shared among all dementia types including hypoxia, oxidative stress, mitochondrial bioenergetics, neuroinflammation, neurodegeneration, and bloodbrain barrier permeability responsible for disease etiology and progression will be discussed.

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Section: Discussionmentioning

confidence: 99%

The neuropathology and cerebrovascular mechanisms of dementia

Raz

Knoefel

Bhaskar

2015

J Cereb Blood Flow Metab

366

284

View full text Add to dashboard Cite

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“…WMH also occur in neuroinflammatory diseases such as multiple sclerosis (Sarbu et al, 2016), and in neurodegenerative diseases (Filley & Fields, 2016). Research into the pathological correlates of WMH in vascular dementia and sporadic and familial Alzheimer’s disease (AD) is well-established (McAleese et al, 2015, 2017; Ryan et al, 2015; Snyder et al, 2015). However, WMH are less commonly seen in frontotemporal dementia (FTD).…”

Section: Introductionmentioning

confidence: 99%

Pathological correlates of white matter hyperintensities in a case of progranulin mutation associated frontotemporal dementia

et al. 2018

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White matter hyperintensities (WMH) are often seen on MRI brain scans in frontotemporal dementia (FTD) due to progranulin (GRN) mutations, but their pathological correlates are unknown. We examined the histological changes underlying WMH in a patient with GRN mutation associated behavioral variant FTD. In vivo and cadaveric MRI showed progressive, asymmetric frontotemporal and parietal atrophy, and asymmetrical WMH predominantly affecting frontal mid-zones. We first performed segmentation and localization analyses of WMH present on cadaveric MRI FLAIR images, then selected five different brain regions directly matched to differing severities of WMH for histological analysis. We used immunohistochemistry to assess vascular pathology, degree of spongiosis, neuronal and axonal loss, TDP-43, demyelination and astrogliosis, and microglial burden and morphology. Brain regions with significant WMH displayed severe cortical and white matter pathology, and prominent white matter microglial activation and microglial dystrophy, but only mild axonal loss and minimal vascular pathology. Our study suggests that WMH in GRN mutation carriers are not secondary to vascular pathology. Whilst cortical pathology induced axonal degeneration could contribute to white matter damage, individuals with GRN mutations could develop selective white matter vulnerability and myelin loss due to chronic, regional microglial dysfunction arising from GRN haploinsufficiency.

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“…A large body of evidence derived from both clinical and experimental studies demonstrate that aging significantly impairs neurovascular coupling responses, which likely contribute to cognitive decline in the elderly (Balbi et al 2015;Fabiani et al 2013;Sorond et al 2013;Tong et al 2012;Toth et al 2014;Zaletel et al 2005;Park et al 2007). There is also growing evidence for microvascular pathophysiological alterations having a causal role in the development of cognitive decline associated with Alzheimer's disease (AD) (Tarantini et al 2016;Snyder et al 2015). …”

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confidence: 99%

Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer’s disease using functional laser speckle contrast imaging

et al. 2017

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Increasing evidence from epidemiological, clinical, and experimental studies indicates that cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including both vascular cognitive impairment (VCI) and Alzheimer's disease. Vascular contributions to cognitive impairment and dementia (VCID) include impairment of neurovascular coupling responses/functional hyperemia (Bneurovascular uncoupling^). Due to the growing interest in understanding and pharmacologically targeting pathophysiological mechanisms of VCID, there is an increasing need for sensitive, easy-to-establish methods to assess neurovascular coupling responses. Laser speckle contrast imaging (LSCI) is a technique that allows rapid and minimally invasive visualization of changes in regional cerebromicrovascular blood perfusion. This type of imaging technique combines high resolution and speed to provide great spatiotemporal accuracy to measure moment-to-moment changes in cerebral blood flow induced by neuronal activation. Here, we provide detailed protocols for the successful measurement in neurovascular coupling responses in anesthetized mice equipped with a thinned-skull cranial window using LSCI. This method can be used to evaluate the effects of anti-aging or anti-AD treatments on cerebromicrovascular health.Keywords Neurovascular coupling . Functional hyperemia . Laser speckle contrast imaging . Laser speckle contrast analysis . LASCA . Laser speckle imaging . LSI Neurovascular uncoupling in aging and Alzheimer's diseaseIt is well recognized that the brain consumes more energy than any other human organ. Over 20% of the body's total energy requirements are spent to fuel the brain, which in turn only accounts for 2% of the total body mass. Moment-to-moment regulation of cerebral blood flow (CBF) is crucial since inadequate supply of glucose and oxygen to an active region of the brain GeroScience (2017) 39:465-473

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Vascular contributions to cognitive impairment and dementia including Alzheimer's disease

Cited by 521 publications

References 95 publications

The neuropathology and cerebrovascular mechanisms of dementia

The neuropathology and cerebrovascular mechanisms of dementia

Pathological correlates of white matter hyperintensities in a case of progranulin mutation associated frontotemporal dementia

Demonstration of impaired neurovascular coupling responses in TG2576 mouse model of Alzheimer’s disease using functional laser speckle contrast imaging

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