Browsing by Subject "Vascular dementia"

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    N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer's disease, vascular dementia and Parkinson's disease
    (Bentham Science Publishers, 2012-07) Olivares, David; Deshpande, Varun K.; Shi, Ying; Lahiri, Debomoy K.; Greig, Nigel H.; Rogers, Jack T.; Huang, Xudong; Department of Psychiatry, IU School of Medicine
    Memantine, a partial antagonist of N-methyl-D-aspartate receptor (NMDAR), approved for moderate to severe Alzheimer's disease (AD) treatment within the U.S. and Europe under brand name Namenda (Forest), Axura and Akatinol (Merz), and Ebixa and Abixa (Lundbeck), may have potential in alleviating additional neurological conditions, such as vascular dementia (VD) and Parkinson's disease (PD). In various animal models, memantine has been reported to be a neuroprotective agent that positively impacts both neurodegenerative and vascular processes. While excessive levels of glutamate result in neurotoxicity, in part through the over-activation of NMDARs, memantine-as a partial NMDAR antagonist, blocks the NMDA glutamate receptors to normalize the glutamatergic system and ameliorate cognitive and memory deficits. The key to memantine's therapeutic action lies in its uncompetitive binding to the NMDAR through which low affinity and rapid off-rate kinetics of memantine at the level of the NMDAR-channel preserves the physiological function of the receptor, underpinning memantine's tolerability and low adverse event profile. As the biochemical pathways evoked by NMDAR antagonism also play a role in PD and since no other drug is sufficiently effective to substitute for the first-line treatment of L-dopa despite its side effects, memantine may be useful in PD treatment with possibly fewer side effects. In spite of the relative modest nature of its adverse effects, memantine has been shown to provide only a moderate decrease in clinical deterioration in AD and VD, and hence efforts are being undertaken in the design of new and more potent memantine-based drugs to hopefully provide greater efficacy.
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    Neuroimaging in aging and neurologic diseases
    (Elsevier, 2019) Risacher, Shannon L.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    Neuroimaging biomarkers for neurologic diseases are important tools, both for understanding pathology associated with cognitive and clinical symptoms and for differential diagnosis. This chapter explores neuroimaging measures, including structural and functional measures from magnetic resonance imaging (MRI) and molecular measures primarily from positron emission tomography (PET), in healthy aging adults and in a number of neurologic diseases. The spectrum covers neuroimaging measures from normal aging to a variety of dementias: late-onset Alzheimer's disease [AD; including mild cognitive impairment (MCI)], familial and nonfamilial early-onset AD, atypical AD syndromes, posterior cortical atrophy (PCA), logopenic aphasia (lvPPA), cerebral amyloid angiopathy (CAA), vascular dementia (VaD), sporadic and familial behavioral-variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA), frontotemporal dementia with motor neuron disease (FTD-MND), frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), Parkinson's disease (PD) with and without dementia, and multiple systems atrophy (MSA). We also include a discussion of the appropriate use criteria (AUC) for amyloid imaging and conclude with a discussion of differential diagnosis of neurologic dementia disorders in the context of neuroimaging.
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    Novel Markers of Angiogenesis in the Setting of Cognitive Impairment and Dementia
    (IOS Press, 2020) Callahan, Christopher M.; Apostolova, Liana G.; Gao, Sujuan; Risacher, Shannon L.; Case, Jamie; Saykin, Andrew J.; Lane, Kathleen A.; Swinford, Cecily G.; Yoder, Mervin C.; Medicine, School of Medicine
    Background: Aberrant angiogenesis may play a role in the development of Alzheimer's disease and related dementia. Objective: To explore the relationship between angiogenesis activity and evidence of neurodegeneration among older adults. Methods: Cross-sectional study of 49 older adults clinically characterized as cognitively normal, mild cognitive impairment, or early Alzheimer's disease. In addition to neuroimaging, we completed assays on peripheral blood, including: vascular endothelial growth factor, tumor necrosis factor, fibroblast growth factor, and amyloid-β peptide 40. We used advanced polychromatic flow cytometry to phenotype circulating mononuclear cells to assess angiogenesis activity. Results: Although we documented differences in cognitive performance, structural changes on neuroimaging, and burden of amyloid and tau on positron emission tomography, angiogenesis activity did not vary by group. Interestingly, VEGF levels were shown to be increased among subjects with mild cognitive impairment. In ANCOVA models controlling for age, sex, intracranial volume, and monocyte subpopulations, angiogenesis activity was correlated with increased white matter hyperintensities. Conclusion: We demonstrate a significant association between angiogenesis activity and cerebrovascular disease. To better understand the potential of angiogenesis as an intervention target, longitudinal studies are needed.
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    Subjective cognitive decline and rates of incident Alzheimer's disease and non-Alzheimer's disease dementia
    (Elsevier, 2019-03) Slot, Rosalinde E. R.; Sikkes, Sietske A. M.; Berkhof, Johannes; Brodaty, Henry; Buckley, Rachel; Cavedo, Enrica; Dardiotis, Efthimios; Guillo-Benarous, Francoise; Hampel, Harald; Kochan, Nicole A.; Lista, Simone; Luck, Tobias; Maruff, Paul; Molinuevo, José Luis; Kornhuber, Johannes; Reisberg, Barry; Riedel-Heller, Steffi G.; Risacher, Shannon L.; Roehr, Susanne; Sachdev, Perminder S.; Scarmeas, Nikolaos; Scheltens, Philip; Shulman, Melanie B.; Saykin, Andrew J.; Verfaillie, Sander C. J.; Visser, Pieter Jelle; Vos, Stephanie J. B.; Wagner, Michael; Wolfsgruber, Steffen; Jessen, Frank; Radiology and Imaging Sciences, School of Medicine
    INTRODUCTION: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. METHODS: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. RESULTS: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini-Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia. DISCUSSION: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts.