scholarly journals Therapeutic Issues in Vascular Dementia: Studies, Designs and Approaches

Author(s):  
Sandra E. Black

Vascular dementia (VaD) is a heterogeneous disorder resulting from various cerebrovascular diseases (CVD) causing cognitive impairment that reflects severity and location of damage. Epidemiological studies suggest VaD is the second commonest cause of dementia, but autopsy series report that pure VaD is infrequent, while combined CVD and Alzheimer's Disease(AD) is likely the commonest pathological-dementia correlate. Both diseases share vascular risk factors and benefit from their treatment. The most widely used diagnostic criteria for VaD are highly specific but not sensitive. Vascular Cognitive Impairment (VCI) is a dynamic, evolving concept that embraces VaD, Vascular Cognitive Impairment No Dementia (VCIND) and mixed AD and CVD. Clinical trials to date have focused on probable and possible VaD with beneficial effects evident for different drug classes, including cholinergic agents and NMDA agonists. Limitations have included use of cognitive tools suitable for AD that are insensitive to executive dysfunction. Disease heterogeneity has not been adequately controlled and subtypes require further study. Diagnostic VaD criteria now 13 years old need updating. More homogeneous subgroups need to be defined and therapeutically targeted to improve cognitive-behavioural outcomes including optimal control of vascular risk factors. More sensitive testing of executive function outlined in recent VCI Harmonization criteria and longer trial duration are needed to discern meaningful effects. Imaging criteria must be well-defined, with centralized review and standardized protocols. Serial scanning with quantification of tissue atrophy and lesion burden is becoming feasible, and cognitive interventions, including rehabilitation pharmacotherapy, with drugs strategically coupled to cognitive -behavioural treatments, hold promise and need further development.

Author(s):  
Victoria J. Williams ◽  
Steven E. Arnold ◽  
David H. Salat

Throughout the lifespan, common variations in systemic health and illness contribute to alterations in vasculature structure and function throughout the body, significantly increasing risk for cardiovascular and cerebrovascular disease (CVD). CVD is a prevalent cause of mortality in late life; it also promotes brain alterations, contributing to cognitive decline and, when severe, vascular dementia. Even prior to diseased states, individual variation in CVD risk is associated with structural and functional brain alterations. Yet, how cumulative asymptomatic alterations in vessel structure and function contribute to more subtle changes in brain tissue integrity and function that emerge in late life is unclear. Finally, vascular risk factors are associated with the clinical progression of neurodegenerative diseases such as Alzheimer’s disease (AD); however, recent theory posits that vascular degeneration may serve a contributory role in these conditions. This chapter reviews how lifespan changes in vascular health contribute to degenerative changes in neural tissue and the subsequent development of cognitive impairment and/or vascular dementia. It first discusses associations between vascular risk factors and cognition and also how declining vascular health may lead to cognitive impairment and dementia. Next, it identifies basic aspects of cerebrovascular anatomy and physiology sustaining tissue health and discusses how vulnerabilities of this system contribute to neurodegenerative changes. Finally, it reviews evidence of vascular contributions to AD and presents ideas for future research to better understand the full spectrum of cerebrovascular contributions to brain aging, cognitive decline, and dementia.


2021 ◽  
Author(s):  
Uma Sundar ◽  
Amita Mukhopadhyay ◽  
Sheelakumari Raghavan ◽  
Ramshekhar Menon ◽  
Chandrasekharan Kesavadas ◽  
...  

Background: It is important to establish criteria to define Vascular Cognitive Impairment (VCI) in India as VCI is an image-based diagnosis and MRI changes resulting from age with prevalent vascular risk factors may confound MRI interpretation. Objective: To establish normative community data for MRI volumetry including white matter hyperintensity volume (WMHV), correlated with age-stratified cognitive scores and vascular risk factors in adults ≥40 years old. Materials and Methods: We screened 2651 individuals without known neurological morbidity, living in Mumbai and nearby rural areas, using validated Marathi translations of Kolkata Cognitive Battery (KCB) and Geriatric depression score (GDS). We stratified 1961 persons with GDS ≤9 by age and cognitive score, and randomly selected ten percent from each subgroup for MRI brain volumetry. Crude volumes were standardized to reflect percentage of intracranial volume. Results: MRI volumetry studies were done in 199 individuals (F/M = 90/109; 73 with BMI ≥ 25; 44 hypertensives; 29 diabetics; mean cognitive score 76.5). Both grey and white matter volumes decreased with increasing age. WMHV increased with age and hypertension. Grey matter volume decreased with increasing WMHV. Positive predictors of cognition included standardized hippocampal volume (HCV), urban living, education, and BMI, while WMHV and age were negative predictors. Urban dwellers had higher cognitive scores than rural, and (paradoxically) smaller HCV. Conclusions: Further study is warranted into sociodemographic and biological factors that mutually influence cognition. Our findings contribute to baseline diagnostic criteria for VCI and could help in early diagnosis and control of cognitive decline and its key risk factors.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Angelia C Kirkpatrick ◽  
Julie A Stoner ◽  
Fabiola M Donna-Ferreira ◽  
George C Malatinszky ◽  
Adreinne M Elias ◽  
...  

Background: Rates of cardiovascular disease and stroke are elevated in Native Americans, and a greater propensity to develop vascular cognitive impairment (VCI) rather than Alzheimer-type dementia has been inferred, supporting a need for further research in VCI in this population. We determined rates and patterns of memory loss among Native American veterans with multiple vascular risk factors. Methods: Native American veterans ≥50 years old with ≥2 vascular risk factors, including smoking history, hyperlipidemia, diabetes, coronary artery disease, or peripheral arterial disease, were recruited between September 2015 and May 2016. The Montreal Cognitive Assessment (MoCA) and the Beck Depression Inventory-II were used to screen for cognitive impairment and depression. Patients with MoCA scores <26 were referred for imaging studies, memory loss serology, neuropsychiatric testing and clinical assessment by a memory loss physician. Final cognitive status was assigned by blinded adjudication. Results: We recruited 60 Native Americans aged 50-86 (mean±SD: 64±7.1 years); 90% were male, 95% had at least high-school education, and 69% had some college or advanced degrees. Risk factors included hypertension (92%), hyperlipidemia (88%), diabetes (47%), and prior/current smoking (78%). Eight (13%) with severe depression were excluded, leaving 23/51 with abnormal MoCA scores (44%, 95%CI 30%-59%). All with cognitive impairment were male compared to 83% among non-impaired subjects (p=0.059). Fifteen completed additional evaluation for memory loss, including 4/15 with normal MoCA scores who requested evaluation based on symptoms. Results were adjudicated as normal (4), or as having non-amnestic MCI (4), vascular MCI (5), and vascular dementia (2). MoCA correctly identified cognitive status in 86% (Kappa 0.66, 95%CI 0.23-1.00). Conclusions: Native American veterans have high rates of vascular cognitive impairment, which exceed rates of cognitive impairment documented in previously published older non-Native American cohorts. These results highlight the need for improved vascular risk reduction among Native American veterans. Further study is needed to identify ways to improve care in this underserved and understudied population.


Neurology ◽  
2011 ◽  
Vol 77 (19) ◽  
pp. 1729-1736 ◽  
Author(s):  
F. W. Unverzagt ◽  
L. A. McClure ◽  
V. G. Wadley ◽  
N. S. Jenny ◽  
R. C. Go ◽  
...  

Neurology ◽  
2013 ◽  
Vol 80 (23) ◽  
pp. 2112-2120 ◽  
Author(s):  
M. Ganguli ◽  
B. Fu ◽  
B. E. Snitz ◽  
T. F. Hughes ◽  
C.-C. H. Chang

Author(s):  
L.M. Bonner ◽  
A. Hanson ◽  
G. Robinson ◽  
E. Lowy ◽  
S. Craft

Dementia prevention is highly important. Improved control of vascular risk factors has the potential to decrease dementia risk, but may be difficult. Therefore, we developed and piloted a care management protocol for Veterans at risk for dementia. We enrolled 32 Veterans with diabetes and hypertension, at least one of which was poorly controlled, and cognitive impairment. Participants were randomly assigned to a 6-month care management intervention or to usual care. At enrollment, 6-months and 12-months, we assessed cognitive performance, mood, and diabetes and hypertension control. At follow-up, diastolic blood pressure was lower in intervention participants at 6 months (p=.041) and 12 months (p=.022); hemoglobin A1c, global mental status and mood did not differ between groups. Recall of a distractor list (p=.006) and logical memory long-delay recall (p=.036) were better at 6 months in the intervention group (p=.006). Care management may contribute to improved control of dementia risk factors.


2020 ◽  
Vol 12 ◽  
Author(s):  
Liying Zhuang ◽  
Huafu Ni ◽  
Junyang Wang ◽  
Xiaoyan Liu ◽  
Yajie Lin ◽  
...  

Background: Several vascular risk factors, including hypertension, diabetes, body mass index, and smoking status are found to be associated with cognitive decline and the risk of Alzheimer's disease (AD). We aimed to investigate whether an aggregation of vascular risk factors modulates the amplitude of low-frequency fluctuation (ALFF) in patients with mild cognitive impairment (MCI).Methods: Forty-three MCI patients and twenty-nine healthy controls (HCs) underwent resting-state functional MRI scans, and spontaneous brain activity was measured by the ALFF technique. The vascular risk profile was represented with the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score, and each group was further divided into high and low risk subgroups. Two-way ANOVA was performed to explore the main effects of diagnosis and vascular risk and their interaction on ALFF.Results: The main effect of diagnosis on ALFF was found in left middle temporal gyrus (LMTG) and left superior parietal gyrus (LSPG), and the main effect of risk on ALFF was detected in left fusiform gyrus (LFFG), left precuneus (LPCUN), and left cerebellum posterior lobe (LCPL). Patients with MCI exhibited increased ALFF in the LMTG and LSPG than HCs, and participants with high vascular risk showed increased ALFF in the LFFG and LCPL, while decreased ALFF in the LPCUN. An interaction between diagnosis (MCI vs. HC) and FHS-CVD risk (high vs. low) regarding ALFF was observed in the left hippocampus (LHIP). HCs with high vascular risk showed significantly increased ALFF in the LHIP than those with low vascular risk, while MCI patients with high vascular risk showed decreased ALFF in the LHIP than HCs with high vascular risk. Interestingly, the mean ALFF of LHIP positively correlated with word recall test in HCs with high vascular risk (rho = 0.630, P = 0.016), while negatively correlated with the same test in MCI patients with high vascular risk (rho = −0.607, P = 0.001).Conclusions: This study provides preliminary evidence highlighting that the aggregation of vascular risk factors modulates the spontaneous brain activity in MCI patients, and this may serve as a potential imaging mechanism underlying vascular contribution to AD.


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