Alzheimer's Disease–Related Dementias Summit 2016: National research priorities

Corriveau, Roderick A.; Koroshetz, Walter J.; Gladman, Jordan T.; Jeon, Sophia; Babcock, Debra; Bennett, David A.; Carmichael, S. Thomas; Dickinson, Susan; Dickson, Dennis W.; Emr, Marian; Fillit, Howard; Greenberg, Steven M.; Hutton, Michael; Knopman, David S.; Manly, Jennifer J.; Marder, Karen; Moy, Claudia S.; Phelps, Creighton H.; Scott, Pamela Sharkey; Seeley, William W.; Sieber, Beth Anne; Silverberg, Nina; Sutherland, Margaret; Taylor, Angela; Torborg, Christine L.; Waddy, Salina P.; Gubitz, Amelie K.; Holtzman, David M.

doi:10.1212/wnl.0000000000004717

Cited by 119 publications

(93 citation statements)

References 55 publications

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“…Post-stroke cognitive impairment (PSCI), the rate of which doubled between 1990 and 2000, likely due to decreased stroke mortality [1], is an important component of vascular contributions to cognitive impairment and dementia (VCID) spectrum disorders [2]. PSCI, along with sensorimotor deficits that develop after the ischemic brain injury, makes stroke a major cause of adult disability with more than 60% of its victims struggling to perform daily activities and losing their independence [3].…”

Section: Introductionmentioning

confidence: 99%

Microglia knockdown reduces inflammation and preserves cognition in diabetic animals after experimental stroke

Jackson

Dumanli

Johnson

et al. 2020

J Neuroinflammation

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Introduction: Unfortunately, over 40% of stroke victims have pre-existing diabetes which not only increases their risk of stroke up to 2-6 fold, but also worsens both functional recovery and the severity of cognitive impairment. Our lab has recently linked the chronic inflammation in diabetes to poor functional outcomes and exacerbated cognitive impairment, also known as post-stroke cognitive impairment (PSCI). Although we have shown that the development of PSCI in diabetes is associated with the upregulation and the activation of pro-inflammatory microglia, we have not established direct causation between the two. To this end, we evaluated the role of microglia in the development of PSCI.Methods: At 13 weeks of age, diabetic animals received bilateral intracerebroventricular (ICV) injections of short hairpin RNA (shRNA) lentiviral particles targeting the colony stimulating factor 1 receptor (CSF1R). After 14 days, animals were subjected to 60 min middle cerebral artery occlusion (MCAO) or sham surgery. Adhesive removal task (ART), novel object recognition (NOR), and 2-trial Y-maze were utilized to evaluate sensorimotor and cognitive function. Tissue from freshly harvested brains was analyzed by flow cytometry and immunohistochemistry.Results: CSF1R silencing resulted in a 94% knockdown of residential microglia to relieve inflammation and improve myelination of white matter in the brain. This prevented cognitive decline in diabetic animals. Conclusion: Microglial activation after stroke in diabetes may be causally related to the development of delayed neurodegeneration and PSCI.

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Section: Introductionmentioning

confidence: 99%

Microglia knockdown reduces inflammation and preserves cognition in diabetic animals after experimental stroke

Jackson

Dumanli

Johnson

et al. 2020

J Neuroinflammation

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“…Such efforts to better characterize the molecular pathways relevant to human cerebral small vessel disease is crucial for the development of diagnostic and therapeutic interventions (26).…”

Section: Discussionmentioning

confidence: 99%

“…In the spontaneously hypertensive rat model of cerebral small vessel disease, the OPC population is increased in association with vascular changes and delays in OPC maturation may be mediated by endothelial secretion of HSP90 (25). Both the diagnosis and treatment of cerebral small vessel disease would be advanced by identifying additional molecular pathways active in cerebral endothelia and driven by chronic cardiovascular risk factors (26).…”

Section: Text: Introductionmentioning

confidence: 99%

Endothelial CXCL5 negatively regulates myelination and repair after white matter stroke

Xiao

Kumar

Burguet

et al. 2019

Preprint

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Significance Statement: Chronic cardiovascular risk factors damage cerebral small vessels yet the molecular pathways induced in injured cerebral endothelial cells that lead to tissue injury are unknown. Obesity-induced endothelial expression of CXCL5 in brain white matter disrupts normal myelination by forcing oligodendrocyte progenitor cells to associate with the cerebral vasculature and impedes brain repair after stroke.

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“…Recent consensus statements by the NIA, NINDS, and others have all advocated an increased focus on ADRD prevention, primarily focusing on three overarching risk factors: physical inactivity, 'Western' dietary patterns (e.g. high intake of saturated fat and complex carbohydrates, and low intake of fruits and vegetables), and poorly controlled CVD, [109,292,293] all of which strongly influence metabolic function. The presence of common CVD risk factors, particularly HTN and obesity, have a robust and adverse impact on neurocognitive outcomes.…”

Section: Metabolic Dysfunctionmentioning

confidence: 99%

Pathways of Prevention: A Scoping Review of Dietary and Exercise Interventions for Neurocognition

Smith

2019

BPL

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Alzheimer's disease and related dementias (ADRD) represent an increasingly urgent public health concern, with an increasing number of baby boomers now at risk. Due to a lack of efficacious therapies among symptomatic older adults, an increasing emphasis has been placed on preventive measures that can curb or even prevent ADRD development among middle-aged adults. Lifestyle modification using aerobic exercise and dietary modification represents one of the primary treatment modalities used to mitigate ADRD risk, with an increasing number of trials demonstrating that exercise and dietary change, individually and together, improve neurocognitive performance among middle-aged and older adults. Despite several optimistic findings, examination of treatment changes across lifestyle interventions reveals a variable pattern of improvements, with large individual differences across trials. The present review attempts to synthesize available literature linking lifestyle modification to neurocognitive changes, outline putative mechanisms of treatment improvement, and discuss discrepant trial findings. In addition, previous mechanistic assumptions linking lifestyle to neurocognition are discussed, with a focus on potential solutions to improve our understanding of individual neurocognitive differences in response to lifestyle modification. Specific recommendations include integration of contemporary causal inference approaches for analyzing parallel mechanistic pathways and treatment-exposure interactions. Methodological recommendations include trial multiphase optimization strategy (MOST) design approaches that leverage individual differences for improved treatment outcomes.

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Alzheimer's Disease–Related Dementias Summit 2016: National research priorities

Cited by 119 publications

References 55 publications

Microglia knockdown reduces inflammation and preserves cognition in diabetic animals after experimental stroke

Microglia knockdown reduces inflammation and preserves cognition in diabetic animals after experimental stroke

Endothelial CXCL5 negatively regulates myelination and repair after white matter stroke

Pathways of Prevention: A Scoping Review of Dietary and Exercise Interventions for Neurocognition

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