-
Experimental Neurology Oct 2015Vascular dementia (VaD) is the second leading form of dementia after Alzheimer's disease (AD) plaguing the elderly population. VaD is a progressive disease caused by... (Review)
Review
Vascular dementia (VaD) is the second leading form of dementia after Alzheimer's disease (AD) plaguing the elderly population. VaD is a progressive disease caused by reduced blood flow to the brain, and it affects cognitive abilities especially executive functioning. VaD is poorly understood and lacks suitable animal models, which constrain the progress on understanding the basis of the disease and developing treatments. This review article discusses VaD, its risk factors, induced cognitive disability, various animal (rodent) models of VaD, pathology, and mechanisms of VaD and treatment options.
Topics: Alzheimer Disease; Animals; Cognition Disorders; Dementia, Vascular; Disease Models, Animal; Disease Progression; Humans; Hypertension; Metabolic Diseases; Risk Factors
PubMed: 25987538
DOI: 10.1016/j.expneurol.2015.05.006 -
Journal of Cachexia, Sarcopenia and... Oct 2022The fat-to-muscle mass ratio (FMR), which integrates the antagonistic effects of fat and muscle mass, has been proposed as a useful indicator to assess disease risk...
BACKGROUND
The fat-to-muscle mass ratio (FMR), which integrates the antagonistic effects of fat and muscle mass, has been proposed as a useful indicator to assess disease risk independent of overall obesity. However, little is known about the association between FMR and dementia risk. We aimed to prospectively investigate the sex-specific associations between total and regional FMR and incident dementia.
METHODS
A total of 491 420 participants (223 581 men and 267 839 women; mean age 56.7 ± 8.2 and 56.3 ± 8.0 years old, respectively) free of dementia at baseline from the UK Biobank were included. Fat mass and muscle mass were measured using a bioelectrical impedance assessment device. Cox regression analyses were used to examine the associations of total and regional FMR with incident all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). The shape of the associations of the continuous scale of FMR and incident dementia were examined using restricted cubic spline analysis.
RESULTS
During a median 8.65 years of follow-up, we documented 2 225 incident all-cause dementia cases, including 836 AD and 468 VD cases. There was an L-shaped association between whole body FMR and all-cause dementia risk in both sexes after adjusting body mass index (BMI) and other covariates (P for non-linear <0.001 in men and women), where all-cause dementia risk decreased steeply with increasing FMR and levelled off at around the medians (0.35 in men, 0.61 in women) with a hazard ratio (HR) of 0.78 (95% CI: 0.64, 0.96; P = 0.019) and 0.60 (0.47, 0.77; <0.001) per 1 standard deviation (SD) increase in men and women, respectively. Compared with other body parts, FMR of the leg showed the strongest inverse associations [HR (95% CI; P) per 1 SD below the medians: 0.60 (0.48, 0.75; <0.001); 0.61 (0.47, 0.79; <0.001) in men and women, respectively]. Specifically, the inverse associations of whole body FMR on all-cause dementia risk were significant only among participants over the age of 60 (P for trend <0.001). Multivariable adjusted Cox models showed inverse associations of whole body FMR with AD in men only (P for trend = 0.003), whereas no statistically significant decrease was detected in VD among men and women.
CONCLUSIONS
Our analyses provide strong evidence for L-shaped associations of total and regional FMR with the development of dementia among participants aged 60 years or older independent of overall obesity.
Topics: Aged; Alzheimer Disease; Body Mass Index; Dementia, Vascular; Female; Humans; Male; Middle Aged; Muscles; Obesity
PubMed: 35856185
DOI: 10.1002/jcsm.13054 -
Biochimica Et Biophysica Acta May 2016Vascular cognitive impairment and vascular dementia are composed of cognitive deficits resulted from a range of vascular lesions and pathologies, including both ischemic... (Review)
Review
Vascular cognitive impairment and vascular dementia are composed of cognitive deficits resulted from a range of vascular lesions and pathologies, including both ischemic and hemorrhagic. However the contribution of spontaneous intracerebral hemorrhage presumed due to small vessel diseases on cognitive impairment is underestimated, in contrast to the numerous studies about the role of ischemic vascular disorders on cognition. In this review we summarize recent findings from clinical studies and appropriate basic science research to better elucidate the role and possible mechanisms of intracerebral hemorrhage in cognitive impairment and dementia. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
Topics: Animals; Cerebral Hemorrhage; Cognitive Dysfunction; Dementia, Vascular; Disease Models, Animal; Humans
PubMed: 26692171
DOI: 10.1016/j.bbadis.2015.12.011 -
Journal of Medicine and Life 2019Dementia represents one of the greatest global challenges for health and social care in this century. More than 50 million people worldwide suffer from dementia, and... (Review)
Review
Dementia represents one of the greatest global challenges for health and social care in this century. More than 50 million people worldwide suffer from dementia, and this number is predicted to triple by 2050. Ageing is often associated with cognitive impairment. Therefore, prevention of cognitive impairment is an imperative. Dementia includes a heterogeneous group of disorders, the most common being Alzheimer's disease and vascular dementia. Most cardiovascular risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, atrial fibrillation and smoking are not exclusive risk factors for vascular dementia but also for Alzheimer's disease. The ApoE4 allele is the single non-modifiable risk factor for Alzheimer's disease. Today we know that an important, modifiable risk factor is education. Better education means better protection against dementia. A large number of dementia cases are potentially preventable by early intervention. Early changes in the blood vessel wall can be detected by early ultrasound methods or early biomarkers. These methods allow us to detect changes before the disease becomes clinically evident. Early disease detection enables timely management, and studies have shown that careful control of vascular risk factors can postpone the onset or even reverse disease progression.
Topics: Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Dementia, Vascular; Disease Progression; Humans; Risk Factors
PubMed: 32025250
DOI: 10.25122/jml-2019-0088 -
BMJ Open Oct 2021It is unclear whether kidney disease is a risk factor for developing dementia. We examined the association between kidney disease and risk of future dementia.
OBJECTIVES
It is unclear whether kidney disease is a risk factor for developing dementia. We examined the association between kidney disease and risk of future dementia.
DESIGN AND SETTING
Nationwide historical registry-based cohort study in Denmark based on data from 1 January 1995 until 31 December 2016.
PARTICIPANTS
All patients diagnosed with kidney disease and matched general population cohort without kidney disease (matched 1:5 on age, sex and year of kidney disease diagnosis).
PRIMARY AND SECONDARY OUTCOME MEASURES
All-cause dementia and its subtypes: Alzheimer's disease, vascular dementia and other specified or unspecified dementia. We computed 5-year cumulative incidences (risk) and hazard ratios (HRs) for outcomes using Cox regression analyses.
RESULTS
The study cohort comprised 82 690 patients with kidney disease and 413 405 individuals from the general population. Five-year and ten-year mortality rates were twice as high in patients with kidney disease compared with the general population. The 5-year risk for all-cause dementia was 2.90% (95% confidence interval: 2.78% to 3.08%) in patients with kidney disease and 2.98% (2.92% to 3.04%) in the general population. Compared with the general population, the adjusted HRs for all-cause dementia in patients with kidney disease were 1.06 (1.00 to 1.12) for the 5-year follow-up and 1.08 (1.03 to 1.12) for the entire study period. Risk estimates for dementia subtypes differed substantially and were lower for Alzheimer's disease and higher for vascular dementia.
CONCLUSIONS
Patients diagnosed with kidney disease have a modestly increased rate of dementia, mainly driven by vascular dementia. Moreover, patients with kidney disease may be underdiagnosed with dementia due to high mortality and other comorbidities of higher priority.
Topics: Cohort Studies; Dementia; Dementia, Vascular; Denmark; Humans; Kidney Diseases; Registries; Risk Factors
PubMed: 34686557
DOI: 10.1136/bmjopen-2021-052652 -
BMC Medicine Aug 2016Cerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular... (Review)
Review
BACKGROUND
Cerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease.
DISCUSSION
Here, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue.
CONCLUSION
Elucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses.
Topics: Aged; Alzheimer Disease; Autopsy; Brain; Cerebrovascular Disorders; Comorbidity; Dementia; Dementia, Vascular; Humans; Prevalence
PubMed: 27600683
DOI: 10.1186/s12916-016-0676-5 -
Stroke and Vascular Neurology Jul 2019Maintaining normal learning and memory functions requires a high degree of coordination between neural and vascular cells. Basic and clinical studies have shown that... (Review)
Review
Maintaining normal learning and memory functions requires a high degree of coordination between neural and vascular cells. Basic and clinical studies have shown that brain microvasculature dysfunction activates inflammatory cells in the brain, leading to progressive neuronal loss and eventually dementia. This review focuses on recent studies aimed at identifying the molecular events that link cerebral microvascular dysfunction to neurodegeneration, including oxidative/nitrosative stress, cellular metabolic dysfunction, inflammatory signalling and abnormal synaptic plasticity. A better understanding of the coupling between vasculature and brain neurons and how this coupling is disrupted under pathological conditions is of great significance in identifying new diagnostic and treatment targets for dementia for which no new drugs have been approved since 2003.
Topics: Animals; Cerebral Arteries; Cerebrovascular Circulation; Cerebrovascular Disorders; Cognition; Dementia, Vascular; Humans; Memory; Microcirculation; Nerve Degeneration; Neurons; Neurovascular Coupling
PubMed: 31338222
DOI: 10.1136/svn-2018-000213 -
Neurology Aug 2022Nonalcoholic fatty liver disease (NAFLD) and dementia share common risk factors including metabolic disorders. However, whether NAFLD is associated with dementia risk is...
BACKGROUND AND OBJECTIVES
Nonalcoholic fatty liver disease (NAFLD) and dementia share common risk factors including metabolic disorders. However, whether NAFLD is associated with dementia risk is unclear. We investigated the association between NAFLD and dementia risk as well as the role of cardiovascular complications including heart disease and stroke.
METHODS
In this population-based matched cohort study, we identified all Swedish patients aged 65 years or older with NAFLD identified from the National Patient Register (NPR) between 1987 and 2016. These were matched with up to 10 reference individuals from the general population on age, sex, and municipality at the year of diagnosis. Incident dementia diagnosis was derived from the NPR or the Cause of Death Register until 2016. Adjusted hazard ratios (aHRs) and 95% CIs were estimated with Cox regression models.
RESULTS
A total of 2,898 patients with NAFLD and 28,357 matched controls were identified (median age at entry, interquartile range [IQR], 70 [8]; 55.1% female). During a median follow-up of 5.5 years (IQR: 8.5 years), 145 (5.0%) patients with NAFLD and 1,291 (4.6%) reference individuals were diagnosed with dementia. Compared with the reference individuals, patients with NAFLD had higher rates of dementia (aHR 1.38, 95% CI 1.10-1.72) and vascular dementia (aHR 1.44, 95% CI 0.96-2.23, = 0.07). Comorbid NAFLD and either heart disease (aHR 1.50 95% 1.08-2.05) or stroke (aHR 2.60 95% CI 1.95-3.47) conferred a greater risk of dementia.
DISCUSSION
NAFLD had a modest association with increased rates of dementia. This was stronger among patients with NAFLD diagnosed with cardiovascular comorbidities.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that nonalcoholic fatty liver disease is associated with the development of vascular and nonvascular dementia.
Topics: Cohort Studies; Dementia, Vascular; Female; Heart Diseases; Humans; Male; Non-alcoholic Fatty Liver Disease; Risk Factors; Stroke
PubMed: 35831178
DOI: 10.1212/WNL.0000000000200853 -
Journal of Neurochemistry Mar 2018The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that... (Review)
Review
The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that leads to brain atrophy years before symptoms manifest. Currently, no cure exists and extensive efforts are being made to mitigate cognitive impairment in late life in order to reduce the burden on patients, caregivers, and society. The most common type of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) often co-exists in the brain and shares common, modifiable risk factors, which are targeted in numerous secondary prevention trials. There is a growing need for non-pharmacological interventions and infrastructural support from governments to encourage psychosocial and behavioral interventions. Secondary prevention trials need to be redesigned based on the risk profile of individual subjects, which require the use of validated and standardized clinical, biological, and neuroimaging biomarkers. Multi-domain approaches have been proposed in high-risk populations that target optimal treatment; clinical trials need to recruit individuals at the highest risk of dementia before symptoms develop, thereby identifying an enriched disease group to test preventative and disease modifying strategies. The underlying aim should be to reduce microscopic brain tissue loss by modifying vascular and lifestyle risk factors over a relatively short period of time, thus optimizing the opportunity for preventing dementia in the future. Collaboration between international research groups is of key importance to the optimal use and allocation of existing resources, and the development of new techniques in preventing dementia. This article is part of the Special Issue "Vascular Dementia".
Topics: Biomarkers; Brain; Dementia, Vascular; Humans; Life Style; Risk Factors
PubMed: 28734089
DOI: 10.1111/jnc.14132 -
The Journal of Nutrition, Health & Aging Apr 2012The objective of this review was to elucidate the relationship between VaD and various nutritional factors based on epidemiological studies. (Review)
Review
OBJECTIVE
The objective of this review was to elucidate the relationship between VaD and various nutritional factors based on epidemiological studies.
BACKGROUND
Vascular dementia (VaD) is the second most common type of dementia. The prevalence of VaD continues to increase as the US population continues to grow and age. Currently, control of potential risk factors is believed to be the most effective means of preventing VaD. Thus, identification of modifiable risk factors for VaD is crucial for development of effective treatment modalities. Nutrition is one of the main modifiable variables that may influence the development of VaD.
METHODS
A systematic review of literature was conducted using the PubMed, Web of Science, and CINAHL Plus databases with search parameters inclusive of vascular dementia, nutrition, and vascular cognitive impairment (VCI).
RESULTS
Fourteen articles were found that proposed a potential role of specific nutritional components in VaD. These components included antioxidants, lipids, homocysteine, folate, vitamin B12, and fish consumption. Antioxidants, specifically Vitamin E and C, and fatty fish intake were found to be protective against VaD risk. Fried fish, elevated homocysteine, and lower levels of folate and vitamin B12 were associated with increased VaD. Evidence for dietary lipids was inconsistent, although elevated midlife serum cholesterol may increase risk, while late-life elevated serum cholesterol may be associated with decreased risk of VaD.
CONCLUSION
Currently, the most convincing evidence as to the relationship between VaD and nutrition exists for micronutrients, particularly Vitamin E and C. Exploration of nutrition at the macronutrient level and additional long term prospective cohort studies are warranted to better understand the role of nutrition in VaD disease development and progression. At present, challenges in this research include limitations in sample size, which was commonly cited. Also, a variety of diagnostic criteria for VaD were employed in the studies reviewed, indicating the need for constructing a correct nosological definition of VaD for consistency and conformity in future studies and accurate clinical diagnosis of VaD.
Topics: Animals; Antioxidants; Ascorbic Acid; Cholesterol; Cognition Disorders; Dementia, Vascular; Diet; Disease Progression; Fishes; Folic Acid; Humans; Meat; Nutritional Status; Prevalence; Risk Factors; Vitamin B 12; Vitamin E
PubMed: 22499449
DOI: 10.1007/s12603-012-0042-z