Lewy body diseases share clinical, pathological, genetic and biochemical signatures, and are regarded as a highly heterogeneous group of neurodegenerative disorders. Inclusive of Parkinson's disease ...(PD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), controversy still exists as to whether they should be considered as separate disease entities or as part of the same disease continuum. Here we discuss emerging knowledge relating to both clinical, and neuropathological differences and consider current biomarker strategies as we try to improve our diagnostic capabilities and design of disease modifying therapeutics for this group of debilitating neurodegenerative disorders.
This article is part of the Special Issue “Synuclein”.
We discuss the difficulties and challenges facing researchers when trying to distinguish between Lewy body disorders based on the current clinical, neuropathological and genetic data. It seems clear that to unravel the complex pathogenesis behind the spectrum of diseases within the LBD spectrum, we need to focus our attention on a combined approach which may identify potential targets that are able to be translated into successful clinical trials and subsequent personalised treatment strategies for people affected by these terrible neurodegenerative diseases.
This article is part of the Special Issue “Synuclein”.
Alterations in the immune response that result in inflammation might play a role in the pathology of dementias. In order to analyze changes of the peripheral immune system associated with different ...types of dementias, we determined several innate and adaptive cell populations in whole blood using flow cytometry. We included patients with Alzheimer's disease (AD; n = 60), vascular dementia (VaD; n = 20), and frontotemporal dementia (FTD; n = 12) at the time point of diagnosis and 24 age-matched neuropsychiatric healthy persons. Monocytes and NK cells were diminished in VaD, but not in AD and FTD. B cell and T cell numbers were decreased in all investigated forms of dementia. Changes in the contribution of naïve/memory T cells were only present in AD. Correlation and regression analyses revealed associations between altered immune cell populations and Q Albumin as marker for the integrity of the blood-cerebrospinal fluid-barrier, Mini-Mental State Examination values, and age. The peripheral immune system is altered in AD, VaD, and FTD. However, each disorder presents unique changes in the investigated cell types indicating different mechanisms underlying the pathology.
Purpose of Review
Diet, physical activity, and sleep are three major modifiable lifestyle factors. This selective review examines the evidence for strong and reliable associations between these three ...lifestyle factors and risk of dementia and cognitive decline, in an effort to assist clinicians with providing more informed answers to the common questions they face from patients.
Recent Findings
Certain aspects of nutrition can decrease risk for dementia. Physical activity has also been associated with delayed or slower age-related cognitive decline. In addition, emerging evidence links sleep dysfunction and dementia, with amyloid deposition being a possible mediator.
Summary
Data from further clinical trials are needed before more definitive conclusions can be drawn regarding the efficacy of these lifestyle interventions for lowering the risk of incident dementia and cognitive decline. Nevertheless, it is reasonable to make recommendations to our patients to adopt certain dietary changes and to engage in regular physical activity to improve cardiovascular risk factors for dementia. It is also reasonable to include questions on sleep during cognitive evaluations of the elderly, given the common co-occurrence of sleep dysfunction and cognitive impairment in the elderly population.
Cognitive impairment associated with aging has emerged as one of the major public health challenges of our time. Although Alzheimer's disease is the leading cause of clinically diagnosed dementia in ...Western countries, cognitive impairment of vascular etiology is the second most common cause and may be the predominant one in East Asia. Furthermore, alterations of the large and small cerebral vasculature, including those affecting the microcirculation of the subcortical white matter, are key contributors to the clinical expression of cognitive dysfunction caused by other pathologies, including Alzheimer's disease. This scientific expert panel provides a critical appraisal of the epidemiology, pathobiology, neuropathology, and neuroimaging of vascular cognitive impairment and dementia, and of current diagnostic and therapeutic approaches. Unresolved issues are also examined to shed light on new basic and clinical research avenues that may lead to mitigating one of the most devastating human conditions.
Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are ...currently unknown.
To investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLWD.
National linked healthcare records were used to identify 1522 PLWD who attended psychological therapy services across England. Associations between various factors and therapy outcomes were explored.
People with frontotemporal dementia were more likely to experience reliable deterioration in depression/anxiety symptoms compared with people with vascular dementia (odds ratio 2.98, 95% CI 1.08-8.22;
= 0.03) or Alzheimer's disease (odds ratio 2.95, 95% CI 1.15-7.55;
= 0.03). Greater depression severity (reliable recovery: odds ratio 0.95, 95% CI 0.92-0.98,
< 0.001; reliable deterioration: odds ratio 1.73, 95% CI 1.04-2.90,
= 0.04), lower work and social functioning (recovery: odds ratio 0.98, 95% CI 0.96-0.99,
= 0.002), psychotropic medication use (recovery: odds ratio 0.67, 95% CI 0.51-0.90,
= 0.01), being of working age (recovery: odds ratio 2.03, 95% CI 1.10-3.73,
= 0.02) and fewer therapy sessions (recovery: odds ratio 1.12, 95% CI 1.09-1.16,
< 0.001) were associated with worse therapy outcomes in PLWD.
Dementia type was generally not associated with outcomes, whereas clinical factors were consistent with those identified for the general population. Additional support and adaptations may be required to improve therapy outcomes in PLWD, particularly in those who are younger and have more severe depression.
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.
Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models.
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.
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.
•A large collaborative study indicates subjective cognitive decline (SCD) is a prodrome of Alzheimer's disease and non-Alzheimer's disease dementia.•Incidence of dementia for SCD is 17.7 (95% confidence interval 15.2-20.3)/1000 person-years.•Risk factors for progression from SCD to dementia are age, lower MMSE, and APOE.•SCD in a memory clinic setting increased the risk of dementia.