Agitation is a common and distressing symptom in patients with Alzheimer's disease. Cholinesterase inhibitors improve cognitive outcomes in such patients, but the benefits of these drugs for ...behavioral disturbances are unclear.
We randomly assigned 272 patients with Alzheimer's disease who had clinically significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day (128 patients) or placebo (131 patients) for 12 weeks. The primary outcome was a change in the score on the Cohen-Mansfield Agitation Inventory (CMAI) (on a scale of 29 to 203, with higher scores indicating more agitation) at 12 weeks.
There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks (estimated mean difference in change the value for donepezil minus that for placebo, -0.06; 95% confidence interval CI, -4.35 to 4.22). Twenty-two of 108 patients (20.4%) in the placebo group and 22 of 113 (19.5%) in the donepezil group had a reduction of 30% or greater in the CMAI score (the value for donepezil minus that for placebo, -0.9 percentage point; 95% CI, -11.4 to 9.6). There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory, the Neuropsychiatric Inventory Caregiver Distress Scale, or the Clinician's Global Impression of Change.
In this 12-week trial, donepezil was not more effective than placebo in treating agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00142324 ClinicalTrials.gov.).
Despite research efforts in the past 20 years, scientific evidence about screening and treatment for depression in diabetes remains incomplete and is mostly focused on North American and European ...health-care systems. Validated instruments to detect depression in diabetes, although widely available, only become effective and thus recommended if subsequent treatment pathways are accessible, which is often not the case. Because of the well known adverse effects of the interaction between depression and diabetes, treatment goals should focus on the remission or improvement of depression as well as improvement in glycaemic control as a marker for subsequent diabetes outcome. Scientific evidence evaluating treatment for depression in type 1 and type 2 diabetes shows that depression can be treated with moderate success by various psychological and pharmacological interventions, which are often implemented through collaborative care and stepped-care approaches. The evidence for improved glycaemic control in the treatment of depression by use of selective serotonin reuptake inhibitors or psychological approaches is conflicting; only some analyses show small to moderate improvements in glycaemic control. More research is needed to evaluate treatment of different depression subtypes in people with diabetes, the cost-effectiveness of treatments, the use of health-care resources, the need to account for cultural differences and different health-care systems, and new treatment and prevention approaches.
Denisova Cave in the Siberian Altai (Russia) is a key site for understanding the complex relationships between hominin groups that inhabited Eurasia in the Middle and Late Pleistocene epoch. DNA ...sequenced from human remains found at this site has revealed the presence of a hitherto unknown hominin group, the Denisovans
, and high-coverage genomes from both Neanderthal and Denisovan fossils provide evidence for admixture between these two populations
. Determining the age of these fossils is important if we are to understand the nature of hominin interaction, and aspects of their cultural and subsistence adaptations. Here we present 50 radiocarbon determinations from the late Middle and Upper Palaeolithic layers of the site. We also report three direct dates for hominin fragments and obtain a mitochondrial DNA sequence for one of them. We apply a Bayesian age modelling approach that combines chronometric (radiocarbon, uranium series and optical ages), stratigraphic and genetic data to calculate probabilistically the age of the human fossils at the site. Our modelled estimate for the age of the oldest Denisovan fossil suggests that this group was present at the site as early as 195,000 years ago (at 95.4% probability). All Neanderthal fossils-as well as Denisova 11, the daughter of a Neanderthal and a Denisovan
-date to between 80,000 and 140,000 years ago. The youngest Denisovan dates to 52,000-76,000 years ago. Direct radiocarbon dating of Upper Palaeolithic tooth pendants and bone points yielded the earliest evidence for the production of these artefacts in northern Eurasia, between 43,000 and 49,000 calibrated years before present (taken as AD 1950). On the basis of current archaeological evidence, it may be assumed that these artefacts are associated with the Denisovan population. It is not currently possible to determine whether anatomically modern humans were involved in their production, as modern-human fossil and genetic evidence of such antiquity has not yet been identified in the Altai region.
This paper reviews the literature concerning the neural correlates of the self, the relationship between self and memory and the profile of memory impairments in Alzheimer’s disease (AD) and explores ...the relationship between the preservation of the self and anosognosia in this condition. It concludes that a potential explanation for anosognosia in AD is a lack of updating of personal information due to the memory impairments characteristic of this disease. We put forward the hypothesis that anosognosia is due in part to the “petrified self.”
Abstract Objective Chronic neurological conditions (CNCs) affect over one million people in the UK alone. Individuals with CNCs endure an increased prevalence of comorbid depression and anxiety. Poor ...mental health exacerbates the cost of the treatment and management of CNCs. CBT is recommended for the treatment of depression. However the application of CBT to individuals with CNCs may be limited by disease characteristics (e.g. mobility issues restricting therapy attendance and reducing engagement with behavioural activation, as well as difficulties challenging the veracity of disease-related negative thoughts that may reflect accurate appraisals). The objective of this review is to assess the clinical effectiveness of cognitive and behavioural interventions for depressive symptoms in individuals with non-acquired, medically explained CNCs. Data sources Searches of The Cochrane Controlled Trials Register, PubMed, and PsychINFO were conducted. Results All studies suggested that CBT is an effective treatment for depression comorbid to CNCs, however when CBT was compared to an active therapy control condition, between group differences were unstable. Conclusion CBT has promise for the treatment for depression in such conditions; however treatment protocols and outcome measures should be adapted for this population. Future trials should control for non-specific effects of therapy and, as much as possible, introduce blinding into methodologies.
Persistent postconcussional symptoms (PCS) can be a source of distress and disability following traumatic brain injury (TBI). Such symptoms have been viewed as difficult to treat but may be amenable ...to psychological approaches such as cognitive-behavioural therapy (CBT).
To evaluate the effectiveness of a 12-session individualised, formulation-based CBT programme.
Two-centre randomised waiting list controlled trial with 46 adults with persistent PCS after predominantly mild-to-moderate TBI (52% with post-traumatic amnesia (PTA)≤24 hours), but including some with severe TBIs (20% with PTA>7 days).
Improvements associated with CBT were found on the primary outcome measures relating to quality of life (using the Quality of Life Assessment Schedule and the Brain Injury Community Rehabilitation Outcome Scale). Treatment effects after covarying for treatment duration were also found for PCS and several secondary outcomes, including measures of anxiety and fatigue (but not depression or post-traumatic stress disorder (PTSD)). Improvements were more apparent for those completing CBT sessions over a shorter period of time, but were unrelated to medicolegal status, injury severity or length of time since injury.
This study suggests that CBT can improve quality of life for adults with persistent PCS and potentially reduce symptoms for some, in the context of outpatient brain injury rehabilitation services.
ISRCTN49540320.
Non-motor symptoms are present in Parkinson's disease (PD) and a key determinant of quality of life. The Non-motor Symptoms Scale (NMSS) is a validated scale that allows quantifying frequency and ...severity (burden) of NMS. We report a proposal for using NMSS scores to determine levels of NMS burden (NMSB) and to complete PD patient classification.
This was an observational, cross-sectional international study of 935 consecutive patients. Using a distribution of NMSS scores by quartiles, a classification based on levels from 0 (no NMSB at all) to 4 (very severe NMSB) was obtained and its relation with Hoehn and Yahr (HY) staging, motor and health-related quality of life scales was analyzed. Concordance between NMSB levels and grouping based on clinician's global impression of severity, using categorical regression, was determined. Disability and HRQoL predictors were identified by multiple regression models.
The distribution of motor and QoL scales scores by HY and NMSB levels was significantly discriminative. The difference in the classification of cases for both methods, HY and NMSB, was significant (gamma = 0.45; ASE = 0.032). Concordance between NMSB and global severity-based levels from categorical regression was 91.8%, (kappaw = 0.97). NMS score was predictor of disability and QoL.
Current clinical practice does not address a need for inclusion of non-motor scores in routine assessment of PD in spite of the overwhelming influence of NMS on disability and quality of life. Our data overcome the problems of "pure motor assessment" and we propose a combined approach with addition of NMSB levels to standard motor assessments.
To test the effects of a novel cognitive-behavioral therapy (CBT)-based intervention delivered by a nurse therapist to patients with Parkinson disease (PD) with clinically significant impulse control ...behaviors (ICB).
This was a randomized controlled trial comparing up to 12 sessions of a CBT-based intervention compared to a waiting list control condition with standard medical care (SMC). A total of 27 patients were randomized to the intervention and 17 to the waiting list. Patients with a Mini-Mental State Examination score of <24 were excluded. The coprimary outcomes were overall symptom severity and neuropsychiatric disturbances in the patients and carer burden and distress after 6 months. Secondary outcome measures included depression and anxiety, marital satisfaction, and work and social adjustment in patients plus general psychiatric morbidity and marital satisfaction in carers.
There was a significant improvement in global symptom severity in the CBT intervention group vs controls, from a mean score consistent with moderate to one of mild illness-related symptoms (χ(2) = 16.46, p < 0.001). Neuropsychiatric disturbances also improved significantly (p = 0.03), as did levels of anxiety and depression and adjustment. Measures of carer burden and distress showed changes in the desired direction in the intervention group but did not change significantly. General psychiatric morbidity did improve significantly in the carers of patients given CBT.
This CBT-based intervention is the first to show efficacy in ICB related to PD in terms of patient outcomes. The hoped-for alleviation of carer burden was not observed. The study demonstrates the feasibility and potential benefit of a psychosocial treatment approach for these disturbances at least in the short term, and encourages further larger-scale clinical trials.
The study provides Class IV evidence that CBT plus SMC is more effective than SMC alone in reducing the severity of ICB in PD, based upon Clinical Global Impression assessment (χ(2) = 16.46, p < 0.001): baseline to 6-month follow-up, reduction in symptom severity CBT group, 4.0-2.5; SMC alone group, 3.7-3.5.
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