Comorbidity and dementia: a scoping review of the literature.

BACKGROUND: Evidence suggests that amongst people with dementia there is a high prevalence of comorbid medical conditions and related complaints. The presence of dementia may complicate clinical care for other conditions and undermine a patient's ability to manage a chronic condition. The aim of this study was to scope the extent, range and nature of research activity around dementia and comorbidity. METHODS: We undertook a scoping review including all types of research relating to the prevalence of comorbidities in people with dementia; current systems, structures and other issues relating to service organisation and delivery; patient and carer experiences; and the experiences and attitudes of service providers. We searched AMED, Cochrane Library, CINAHL, PubMed, NHS Evidence, Scopus, Google Scholar (searched 2012, Pubmed updated 2013), checked reference lists and performed citation searches on PubMed and Google Scholar (ongoing to February 2014). RESULTS: We included 54 primary studies, eight reviews and three guidelines. Much of the available literature relates to the prevalence of comorbidities in people with dementia or issues around quality of care. Less is known about service organisation and delivery or the views and experiences of people with dementia and their family carers. There is some evidence that people with dementia did not have the same access to treatment and monitoring for conditions such as visual impairment and diabetes as those with similar comorbidities but without dementia. CONCLUSIONS: The prevalence of comorbid conditions in people with dementia is high. Whilst current evidence suggests that people with dementia may have poorer access to services the reasons for this are not clear. There is a need for more research looking at the ways in which having dementia impacts on clinical care for other conditions and how the process of care and different services are adapting to the needs of people with dementia and comorbidity. People with dementia should be included in the debate about the management of comorbidities in older populations and there needs to be greater consideration given to including them in studies that focus on age-related healthcare issues

Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

BACKGROUND: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. OBJECTIVES: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. METHODS: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. RESULTS: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. CONCLUSION: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer’s disease (AD), vascular dementia (VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27th, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787–0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576–0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556–0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620–1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818–0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383–1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449–0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475–1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD

The association between cognition and dual-tasking among older adults: the effect of motor function type and cognition task difficulty

Hossein Ehsani,1,2 Martha Jane Mohler,1–3 Kathy O’Connor,4 Edward Zamrini,4,5 Coco Tirambulo,2 Nima Toosizadeh1–3 1Department of Biomedical Engineering, University of Arizona, Tucson, AZ, USA; 2Arizona Center on Aging, Department of Medicine, University of Arizona, Tucson, AZ, USA; 3Division of Geriatrics, General Internal Medicine and Palliative Medicine, Department of Medicine, University of Arizona, Tucson, AZ, USA; 4Neurology Department, Banner Sun Health Research Institute, Sun City, AZ, USA; 5Department of Neurology, University of Utah, Salt Lake City, UT, USA Background: Dual-task actions challenge cognitive processing. The usefulness of objective methods based on dual-task actions to identify the cognitive status of older adults has been previously demonstrated. However, the properties of select motor and cognitive tasks are still debatable. We investigated the effect of cognitive task difficulty and motor task type (walking versus an upper-extremity function [UEF]) in identifying cognitive impairment in older adults. Methods: Older adults (≥65 years) were recruited, and cognitive ability was measured using the Montreal Cognitive Assessment (MoCA). Participants performed repetitive elbow flexion under three conditions: 1) at maximum pace alone (Single-task); and 2) while counting backward by ones (Dual-task 1); and 3) threes (Dual-task 2). Similar single- and dual-task gait were performed at normal speed. Three-dimensional kinematics were measured for both motor functions using wearable sensors. Results: One-hundred older adults participated in this study. Based on MoCA score <20, 21 (21%) of the participants were considered cognitively impaired (mean age =86±10 and 85±5 for cognitively impaired and intact participants, respectively). Within ANOVA models adjusted with demographic information, UEF dual-task parameters, including speed and range-of-motion variability were significantly higher by 52% on average, among cognitively impaired participant (p<0.01). Logistic models with these UEF parameters plus age predicted cognitive status with sensitivity, specificity, and area under curve (AUC) of 71%, 81% and 0.77 for Dual-task 1. The corresponding values for UEF Dual-task 2 were 91%, 73% and 0.81, respectively. ANOVA results were non-significant for gait parameters within both dual-task conditions (p>0.26). Conclusion: This study demonstrated that counting backward by threes within a UEF dual-task experiment was a pertinent and challenging enough task to detect cognitive impairment in older adults. Additionally, UEF was superior to gait as the motor task component of the dual-task. The UEF dual-task could be applied as a quick memory screen in a clinical setting. Keywords: wearable motion sensor, gait, upper-extremity function, biomechanics, MCI, Alzheimer’s diseas