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.
Diabetes is associated with cognitive impairment and greater risk for dementia, but the role of gamma-glutamyltransferase (γ-GT) in dementia has not been elucidated. We determined incident dementia ...including Alzheimer's disease and vascular dementia, analyzing data from participants aged 40 years or older in the National Health Insurance Database, collected by the National Health Insurance Service in Korea, from January 2009 to December 2015. During a median follow-up of 7.6 years, 272,657 participants were diagnosed as having dementia. Higher serum γ-GT was associated with increased risk of dementia (HR = 1.22, 95% CI = 1.20-1.24), and had a strong positive association with early onset dementia (HR = 1.32, 95% CI = 1.24-1.40). An additive impact of higher γ-GT on dementia was observed regardless of glycemic status, and prevalent diabetes with the highest γ-GT quartile had a 1.8-fold increased dementia risk (HR = 1.82, 95% CI = 1.78-1.85). This effect of γ-GT concentration in diabetes was more prominent in individuals with vascular dementia (HR = 1.94, 95% CI = 1.84-2.04). In subgroup analysis, young age, male sex, and relatively healthy subjects with a higher γ-GT quartile had more increased dementia risk. In conclusion, γ-GT concentration as well as glycemic status could be a future risk factor for dementia in the general population.
Currently, there are few studies considering possible modifiable risk factors of frontotemporal dementia (FTD).
In this retrospective case-control study, we evaluated whether a history of traumatic ...brain injury (TBI) associates with a diagnosis of FTD or modulates the clinical phenotype or onset age in FTD patients.
We compared the prevalence of prior TBI between individuals with FTD (N = 218) and age and sex-matched AD patients (N = 214) or healthy controls (HC; N = 100). Based on the patient records, an individual was categorized to the TBI+ group if they were reported to have suffered from TBI during lifetime. The possible associations of TBI with age of onset and disease duration were also evaluated in the whole FTD patient group or separately in the sporadic and genetic FTD groups.
The prevalence of previous TBI was the highest in the FTD group (19.3%) when compared to the AD group (13.1%, p = 0.050) or HC group (12%, p = 0.108, not significant). Preceding TBI was more often associated with the sporadic FTD cases than the C9orf72 repeat expansion-carrying FTD cases (p = 0.003). Furthermore, comparison of the TBI+ and TBI- FTD groups indicated that previous TBI was associated with an earlier onset age in the FTD patients (B = 3.066, p = 0.010).
A preceding TBI associates especially with sporadic FTD and with earlier onset of symptoms. The results of this study suggest that TBI may be a triggering factor for the neurodegenerative processes in FTD. However, understanding the precise underlying mechanisms still needs further studies.
Background and purpose
Data on epilepsy in dementia, particularly on its risk factors, are scarce. Confounding comorbidities and the rising incidence of epilepsy in older age have hampered studies in ...this field. The occurrence and risk factors for epilepsy in the Swedish Dementia Registry (SveDem), a large cohort of patients with dementia, have been examined.
Methods
Information on epilepsy and seizure‐related diagnoses, comorbidities and survival were extracted for all individuals in SveDem (n = 81 192) and three randomly selected age‐ and gender‐matched controls from the population register, excluding all with a dementia diagnosis (n = 223 933). The risk of epilepsy following dementia diagnosis was estimated with Kaplan–Meier curves, and Cox proportional hazard modelling was used to identify risk factors and adjust for comorbidities.
Results
A diagnosis of epilepsy was found more frequently amongst dementia patients 4.0%, 95% confidence interval (CI) 3.8–4.1 than controls (1.9%, 95% CI 1.9–2.0). The risk of incident epilepsy after dementia was 2.1% (95% CI 1.9–2.3) at 5 years and 4.0% (95%CI 3.4–4.6) at 10 years, compared to 0.8% (95% CI 0.8–0.8) and 1.6% (95% CI 1.4–1.8) respectively for controls. The risk was greatest for early‐onset Alzheimer's disease. In multivariate analysis, dementia was associated with a hazard ratio of 2.52 (95% CI 2.31–2.74) for epilepsy. Young age, male sex, stroke, brain trauma, brain tumour and low Mini‐Mental State Examination score significantly increased the risk.
Conclusions
Dementia, particularly young‐onset Alzheimer's disease, increases the risk of subsequent epilepsy. Further studies are needed to determine optimal management and the impact of epilepsy on prognosis.
Depression and the risk for dementia Kessing, Lars Vedel
Current opinion in psychiatry,
2012-November, 2012-Nov, 2012-11-00, 20121101, Letnik:
25, Številka:
6
Journal Article
Recenzirano
PURPOSE OF REVIEWDepression is associated with increased risk of subsequent development of dementia; however, the nature of the association is still poorly understood. The purpose of the review was ...based on recent studies to discuss whether depression is a prodromal state of dementia or an independent risk factor for dementia, as well as to discuss how the type of depression, the type of dementia, and antidepressant treatment influence the association.
RECENT FINDINGSFindings from recent studies suggest that some forms of depressive illness, for example early-onset depression before age 65 years and recurrent depression, may constitute long-term risk factors for development of dementia, whereas the onset of more recent depressive symptoms may reflect a prodromal phase of dementia. It is not clear whether specific subtypes of depression correspond to specific types of dementia. Recent studies suggest that long-term treatment with antidepressants may decrease the risk of developing some types of dementia, depending on the type of depressive disorder.
SUMMARYThis review has shown that the type of depression and dementia, as well as the effect of drug treatment, has to be considered to improve knowledge on the association between depression and dementia.
: Early-onset dementia (EOD) is defined as dementia with symptom onset before 65 years. The role of environmental risk factors in the etiology of EOD is still undefined. We aimed at assessing the ...role of environmental risk factors in EOD etiology, taking into account its different clinical types.
: Using a case-control study, we recruited all EOD cases referred to Modena hospitals from 2016 to 2019, while the referent population was drawn from cases' caregivers. We investigated residential history, occupational and environmental exposures to chemicals and lifestyle behaviors through a self-administered questionnaire. We computed the odds ratios of EOD risk (overall and restricting to the Alzheimer's dementia (AD) or frontotemporal dementia (FTD) diagnoses) and the corresponding 95% confidence intervals using an unconditional logistic regression model.
: Fifty-eight EOD patients (19 FTD and 32 AD) and 54 controls agreed to participate. Most of the investigated exposures, such as occupational exposure to aluminum, pesticides, dyes, paints or thinners, were associated with an increased odds ratio (OR) for FTD but not for AD. Long-term use of selenium-containing dietary supplements was associated with increased OR for EOD and, particularly, for FTD. For both EOD forms, smoking and playing football showed an increased odds ratio, while cycling was associated with increased risk only in FTD. Overall sports practice appeared to be a protective factor for both types.
: Our results suggest a role of environmental and behavioral risk factors such as some chemical exposures and professional sports in EOD etiology, in particular with reference to FTD. Overall sports practice may be associated with a reduced EOD risk.
ObjectivesIn patients with gout, maintaining too low serum uric acid (SUA) level with urate-lowering therapy is a concern because uric acid is thought to be neuroprotective. However, the relation ...between SUA and dementia remains debated. This study aimed to investigate the impact of SUA level on the incidence of dementia.MethodsWe assessed the longitudinal association between SUA level and incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria) in a large cohort of healthy older people from the community (Three-City Dijon cohort). Additionally, we investigated the relation between SUA level and MRI markers of brain ageing (white matter hyperintensity volume (WMHV), lacunes and hippocampal volume).ResultsThe study sample comprised 1598 people (mean (SD) age 72.4(4.1) years, 38.3% male). During the 13,357 person-years of follow-up (median duration: 10.1 years), dementia developed in 110 participants (crude incidence rate: 8.2/1000 person-years). After multiple adjustments, the multivariate HR with the highest (≥75th percentile) versus lowest SUA level was 1.79 (95% CI 1.17 to 2.73; p=0.007). The association was stronger with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to 10.41), p=0.015) than Alzheimer’s disease (HR=1.55 (95% CI 0.92 to 2.61), p=0.10). There was a non-significant trend towards an association between high SUA level and extensive WMHV (p=0.10), a biomarker of small vessel disease, but not hippocampal volume (p=0.94) or lacunes (p=0.86). The association between SUA level and vascular or mixed dementia might be affected by interim strokes.ConclusionsRisk of dementia, especially vascular or mixed dementia, may be increased with high SUA levels in elderly people.
The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires ...an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists.
GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index BMI, high fasting plasma glucose, smoking, and a diet high in sugar-sweetened beverages).
In 2016, the global number of individuals who lived with dementia was 43·8 million (95% uncertainty interval UI 37·8–51·0), increased from 20.2 million (17·4–23·5) in 1990. This increase of 117% (95% UI 114–121) contrasted with a minor increase in age-standardised prevalence of 1·7% (1·0–2·4), from 701 cases (95% UI 602–815) per 100 000 population in 1990 to 712 cases (614–828) per 100 000 population in 2016. More women than men had dementia in 2016 (27·0 million, 95% UI 23·3–31·4, vs 16.8 million, 14.4–19.6), and dementia was the fifth leading cause of death globally, accounting for 2·4 million (95% UI 2·1–2·8) deaths. Overall, 28·8 million (95% UI 24·5–34·0) DALYs were attributed to dementia; 6·4 million (95% UI 3·4–10·5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages.
The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide.
Bill & Melinda Gates Foundation.
This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later ...life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment.
Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee.
The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury-not solely stroke-ranging from mild cognitive impairment through fully developed dementia. Dysfunction of the neurovascular unit and mechanisms regulating cerebral blood flow are likely to be important components of the pathophysiological processes underlying VCI. Cerebral amyloid angiopathy is emerging as an important marker of risk for Alzheimer disease, microinfarction, microhemorrhage and macrohemorrhage of the brain, and VCI. The neuropathology of cognitive impairment in later life is often a mixture of Alzheimer disease and microvascular brain damage, which may overlap and synergize to heighten the risk of cognitive impairment. In this regard, magnetic resonance imaging and other neuroimaging techniques play an important role in the definition and detection of VCI and provide evidence that subcortical forms of VCI with white matter hyperintensities and small deep infarcts are common. In many cases, risk markers for VCI are the same as traditional risk factors for stroke. These risks may include but are not limited to atrial fibrillation, hypertension, diabetes mellitus, and hypercholesterolemia. Furthermore, these same vascular risk factors may be risk markers for Alzheimer disease. Carotid intimal-medial thickness and arterial stiffness are emerging as markers of arterial aging and may serve as risk markers for VCI. Currently, no specific treatments for VCI have been approved by the US Food and Drug Administration. However, detection and control of the traditional risk factors for stroke and cardiovascular disease may be effective in the prevention of VCI, even in older people.
Vascular contributions to cognitive impairment and dementia are important. Understanding of VCI has evolved substantially in recent years, based on preclinical, neuropathologic, neuroimaging, physiological, and epidemiological studies. Transdisciplinary, translational, and transactional approaches are recommended to further our understanding of this entity and to better characterize its neuropsychological profile. There is a need for prospective, quantitative, clinical-pathological-neuroimaging studies to improve knowledge of the pathological basis of neuroimaging change and the complex interplay between vascular and Alzheimer disease pathologies in the evolution of clinical VCI and Alzheimer disease. Long-term vascular risk marker interventional studies beginning as early as midlife may be required to prevent or postpone the onset of VCI and Alzheimer disease. Studies of intensive reduction of vascular risk factors in high-risk groups are another important avenue of research.
The occurrence of repeat-associated non-ATG (RAN) translation, an atypical form of translation of expanded repeats that results in the synthesis of homopolymeric expansion proteins, is becoming more ...widely appreciated among microsatellite expansion disorders. Such disorders include amyotrophic lateral sclerosis and frontotemporal dementia caused by a hexanucleotide repeat expansion in the
C9ORF72
gene (c9FTD/ALS). We and others have recently shown that this bidirectionally transcribed repeat is RAN translated, and the “c9RAN proteins” thusly produced form neuronal inclusions throughout the central nervous system of c9FTD/ALS patients. Nonetheless, the potential contribution of c9RAN proteins to disease pathogenesis remains poorly understood. In the present study, we demonstrate that poly(GA) c9RAN proteins are neurotoxic and may be implicated in the neurodegenerative processes of c9FTD/ALS. Specifically, we show that expression of poly(GA) proteins in cultured cells and primary neurons leads to the formation of soluble and insoluble high molecular weight species, as well as inclusions composed of filaments similar to those observed in c9FTD/ALS brain tissues. The expression of poly(GA) proteins is accompanied by caspase-3 activation, impaired neurite outgrowth, inhibition of proteasome activity, and evidence of endoplasmic reticulum (ER) stress. Of importance, ER stress inhibitors, salubrinal and TUDCA, provide protection against poly(GA)-induced toxicity. Taken together, our data provide compelling evidence towards establishing RAN translation as a pathogenic mechanism of c9FTD/ALS, and suggest that targeting the ER using small molecules may be a promising therapeutic approach for these devastating diseases.
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