Summary Down's syndrome is the most common genetic cause of learning difficulties, and individuals with this condition represent the largest group of people with dementia under the age of 50 years. ...Genetic drivers result in a high frequency of Alzheimer's pathology in these individuals, evident from neuroimaging, biomarker, and neuropathological findings, and a high incidence of cognitive decline and dementia. However, cognitive assessment is challenging, and diagnostic methods have not been fully validated for use in these patients; hence, early diagnosis remains difficult. Evidence regarding the benefits of cholinesterase inhibitors and other therapeutic options to treat or delay progressive cognitive decline or dementia is very scarce. Despite close similarities with late-onset Alzheimer's disease, individuals with Down's syndrome respond differently to treatment, and a targeted approach to drug development is thus necessary. Genetic and preclinical studies offer opportunities for treatment development, and potential therapies have been identified using these approaches.
Summary C9orf72 hexanucleotide repeat expansions are the most common cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. The clinical presentation is ...often indistinguishable from classic FTD or ALS, although neuropsychiatric symptoms are more prevalent and, for ALS, behavioural and cognitive symptoms occur more frequently. Pathogenic repeat length is in the hundreds or thousands, but the minimum length that increases risk of disease, and how or whether the repeat size affects phenotype, are unclear. Like in many patients with FTD and ALS, neuronal inclusions that contain TARDBP are seen, but are not universal, and the characteristic pathological finding is of dipeptide repeat (DPR) proteins, formed by unconventional repeat-associated non-ATG translation. Possible mechanisms of neurodegeneration include loss of C9orf72 protein and function, RNA toxicity, and toxicity from the DPR proteins, but which of these is the major pathogenic mechanism is not yet certain.
Excess body fat is associated with an increase in risk of type 2 diabetes and hypertension in adulthood and these risks can adversely affect progression of arterial disease. We aimed to assess the ...impact of lifelong patterns of adiposity on cardiovascular risk factors and carotid intima media thickness (cIMT) in later life in participants in the 1946 British birth cohort study.
The National Survey of Health and Development Study was a nationally representative sample of 5362 singleton births to married parents in England, Scotland, and Wales, stratified by social class, during 1 week in March 1946. Our present study is based on the 60% of participants still alive and with a known present address in England, Scotland, or Wales who attended a clinic assessment after invitation aged 60–64 years. We included participants with lifetime adiposity measures, cardiovascular risk factors, and cIMT measured at 60–64 years. Participants were classified as normal weight or overweight or obese at each age (36, 43, 53, and 60–64 years) in adulthood, and childhood overweight was defined. Patterns of BMI change were identified and we used BMI to define adiposity status. We used multivariable linear regression to establish the cross-sectional association of BMI category at age 60–64 years with cIMT, adjusted for various confounders.
We included 1273 (45%) of 2856 participants eligible in 2006–10 (at age 60–64 years) in this study. Compared with normal weight, overweight and obesity were associated with higher cIMT (0·029 mm, 95% CI 0·014–0·043) and systolic blood pressure (7·95 mm Hg, 5·86–10·0). Increased cIMT, systolic blood pressure, leptin, prevalence of diabetes, and reduced adiponectin were all associated with duration of exposure to adult adiposity (p<0·0001 for all). We noted little additional effect of childhood overweight. Individuals who dropped a BMI category in adulthood had lower cIMT (–0·034 mm, −0·056 to −0·013) and leptin concentrations (–0·4 ng/mL, −0·47 to −0·32), even when this change was not maintained, than did those who never lost weight.
Longer exposure to high adiposity in adulthood had a cumulative adverse effect on cardiovascular phenotype in later life. Reductions in BMI category, even if not sustained, were associated with decreases in cIMT and improvements in cardiovascular risk-factor profile, suggesting that weight loss, at any age in adulthood, is worthwhile because it might result in long-term cardiovascular benefit.
Medical Research Council and the British Heart Foundation.
Summary Parkinson's disease is a common progressive bradykinetic disorder that can be accurately diagnosed. It is characterised by the presence of severe pars-compacta nigral-cell loss, and ...accumulation of aggregated α-synuclein in specific brain stem, spinal cord, and cortical regions. The main known risk factor is age. Susceptibility genes including α-synuclein, leucine rich repeat kinase 2 ( LRRK-2 ), and glucocerebrosidase ( GBA ) have shown that genetic predisposition is another important causal factor. Dopamine replacement therapy considerably reduces motor handicap, and effective treatment of associated depression, pain, constipation, and nocturnal difficulties can improve quality of life. Embryonic stem cells and gene therapy are promising research therapeutic approaches.
Illness perception, a measure of illness representations developed from physical medicine, has recently been applied to psychosis. We investigated how illness perceptions relate to affect and ...expressed emotion (EE) in carer-patient dyads, particularly if their perceptions differed.
We interviewed 82 carer-patient dyads, after a relapse of psychosis. Carers were assessed for illness perceptions, distress, self-esteem and EE; patients for illness perceptions, depression, anxiety and self-esteem, in a cross sectional study.
Carers were more pessimistic than patients about illness persistence and consequences, and carers with low mood were particularly pessimistic about persistence and controllability. Discrepant views about illness consequences were related to greater anxiety, depression, and lower self-esteem in patients, while discrepant views on controllability were associated with greater distress, depression, and lower self-esteem in carers. Illness perceptions did not relate directly to EE.
In this sample, meta-cognitive carer representations of illness in psychosis are related to negative affective reactions in carers, but not to EE. Resolving discrepant illness perceptions between carers and patients might provide a way of improving family reactions to the health threat of psychosis.
PDF
