Background The clinical and neuropathological features associated with dementia in Down's syndrome (DS) are not well established. Aims To examine clinico-pathological correlations and the incidence of cognitive decline in a cohort of adults with DS. Method A total of 92 hospitalized persons with DS were followed up from 1985 to December 2000. At outset, 87 participants were dementia-free, with a median age of 38 years. Assessments included the Prudhoe Cognitive Function Test (PCFT) and the Adaptive Behavior Scale (ABS), to measure cognitive and behavioural deterioration. Dementia was diagnosed from case records and caregivers' reports. Results Eighteen (21%) patients developed dementia during follow-up, with a median age of onset 55.5 years (range 45-74). The PCFT demonstrated cognitive decline among those with a less severe intellectual disability (mild and moderate) but not among the profoundly disabled people (severe and profound). Clinical dementia was associated with neuropathological features of Alzheimer's disease, and correlated with neocortical neurofibrillary tangle densities. At the age of 60 years and above, a little more than 50% of patients still alive had clinical evidence of dementia. Conclusions Clinical dementia associated with measurable cognitive and functional decline is frequent in people with DS after middle age, and can be readily diagnosed among less severely intellectually disabled persons using measures of cognitive function such as the PCFT and behavioural scales such as the ABS. In the more profoundly disabled people, the diagnosis of dementia is facilitated by the use of behavioural and neurological criteria. In this study, the largest prospective DS series including neuropathology on deceased patients, the density of neurofibrillary tangles related more closely to the dementia of DS than senile plaques. In people with DS surviving to middle and old age, the development of dementia of Alzheimer type is frequent but not inevitable, and some people with DS reach old age without clinical features of dementia.

BACKGROUND:The amyloid precursor protein (APP) locus on chromosome 21 influences the development of Alzheimer disease.METHOD:The authors investigated the relationship between a tetranucleotide repeat on intron 7 of the APP gene and the age at onset of dementia in Down syndrome (DS).RESULTS:There was a 13-year difference in the age at onset of dementia in DS associated with the number of tetranucleotide repeat alleles in APP.CONCLUSION:APP is an important locus predicting the age at onset of dementia in people with Down syndrome.

BACKGROUND:In the clinical diagnosis of dementia in Down's syndrome (DS), it may be difficult to distinguish between cognitive deterioration and the various degrees of pre-existing intellectual disability (ID). Serial measurements of both cognitive function and behaviour are required. The aim of the present study was to evaluate the performance of non-demented adults with DS on a subject-directed instrument, the Prudhoe Cognitive Function Test (PCFT), preliminary to its serial use in a prospective study.METHODS:From 1985 to 1986, 85 non-demented hospitalized adults with DS were interviewed using the PCFT. The Adaptive Behavior Scale (ABS) was administered to the carers. The subjects' levels of ID (graded from mild through moderate, severe and profound to untestable) were based on their scores on the Stanford-Binet Intelligence Scale, as reported in the medical records, and the relationship between level of disability and performance on the PCFT and ABS, and their respective domains, was examined.RESULTS:Both scales produced a wide range of scores and the correlation between them was highly significant. Both scales correlated highly significantly with the degree of ID, but more subjects with high levels (i.e. profound to untestable) of disability obtained very low or zero scores on the PCFT and its domains than on the ABS.CONCLUSIONS:The PCFT provides a reliable quantitative measure of cognitive function in subjects with DS, and could be a useful adjunct to the diagnosis of dementia in prospective studies. However, the almost uniformly low scores obtained by those with high levels of ID suggests that its power to detect cognitive decline will be limited to those who are less disabled, while the ABS may be more useful than the PCFT in detecting deterioration in people with profound ID.

Background The Prudhoe Cognitive Function Test (PCFT) was designed to measure cognitive function in subjects with all degrees of intellectual disability (ID) and to be administered by non-specialist raters. The aim of the present study was to measure the test-retest and inter-rater reliability of the PCFT.Methods Three raters, one a specialist and two non-specialists, administered the PCFT to 14 subjects with Down's syndrome on two occasions separated by 4 weeks.Results The intra-class correlation coefficients (ICCs) between the rater pairs (n = 3) were 0.99, 0.99 and 0.98 (P < 0.01). Floor effects were recorded for two items. The ICC for test-retest reliability was 0.99 (P < 0.01).Conclusions The PCFT is a highly reliable instrument when used by either specialist or non-specialist raters. It has excellent temporal stability.

Aims and MethodFactors leading to success in the MRCPsych Part I and Part II examinations, including age, gender and original medical school of training, were examined in the 1999 MRCPsych examination entrants to determine how far they are associated with the results. The ethnic breakdown of examiners of the MRCPsych examinations was also determined and compared with the origin of all consultant psychiatrists.ResultsYounger age at taking the examination and training at a British or Irish medical school were found to be highly significant predictors of success in the MRCPsych examinations. When allowance was made for confounding variables, the gender of candidates did not contribute to success. There was no difference in ethnic background of examiners compared with consultant psychiatrists overall.Clinical ImplicationsFactors affecting trainees wishing to undertake a psychiatric career need to be more closely examined. To ensure fairness and transparency in future examinations the ethnicity of candidates taking the examination needs to be addressed.

ABSTRACT The use of psychotropic drugs in intellectual disability is reviewed with reference to psychiatric illness--including psychoses, neuroses, sleep disorders, and personality disorders--as well as to acute and chronic behaviour disorder. Aberrant sexual behaviour and other relevant conditions, namely stereotypies, autism, Down's syndrome, Lesch-Nyhan syndrome, Cornelia de Lange syndrome, and Prader-Willi syndrome, are also discussed. Recent empirical evidence from the intellectual disability literature is documented and where appropriate, recommendations are made regarding which drugs should take priority. The authors highlight the clinical importance of psychological and behavioural therapies and conclude that pharmacological treatment must be undertaken with caution for this population. In particular, physicians should make themselves especially aware of the side effects and health risks associated with psychotropic drugs. Key words: Behaviour Disorder; Developmental Disorders; Mental Retardation; Psychiatric Illness; Psychopharmacology INTRODUCTION Neuroleptic agents and other psychotropic drugs are still widely prescribed for people with intellectual disability. Between 20% and 77% of residents in institutions for intellectually disabled people receive psychotropic drugs. (1,2) The most frequent drugs employed are the neuroleptics although antidepressants, anticonvulsants, lithium, [beta]-blockers, benzodiazepines, antimuscarinic drugs, and hypnotics are also prescribed. There is occasional use of central nervous system (CNS) stimulants, opiate antagonists, and neurotransmitter-depleting agents such as the benzoquinolizine drug, tetrabenazine. Most patients receive more than one psychotropic drug. (3) The majority of people taking these drugs do not have clear psychiatric illnesses and most would be described as having a behavioural disturbance. (4,5) TREATMENT OF PSYCHIATRIC ILLNESS PSYCHOSES If the patient has a psychiatric illness that fulfils International Classification of Disease (ICD)-10 or Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for a psychiatric disorder for which drug treatment is effective, it is usual to give these drugs in the first instance. In practice, the majority of patients with intellectual disability do not fulfil the criteria indicated in standard operational texts, hampering confident diagnosis of most psychiatric illnesses, in particular psychotic disorders. Thus, it is not possible to diagnose schizophrenia in those who function below the mild intellectual disability range. (6) However, if there is evidence of affective flattening, incongruous behaviour, self-preoccupation and catatonic posturing, neuroleptic medication can have a dramatic effect, suggesting that such syndromes in those of lower intelligence are of schizophrenic origin. (7) A diagnosis of affective disorder can be made more confidently for intellectually disabled people even if they have major communication difficulties. The symptom triad of recent insomnia, loss of weight, and reduced activity usually indicates depression in the absence of a physical cause. Conversely, increasing activity accompanied by euphoria and/or irritability is suggestive of mania in the absence of other factors. The treatment of schizophrenia in intellectually disabled persons is not essentially different from the treatment of this illness in people of average intelligence. There is increased usage of the newer 'atypical' anti-psychotic drugs in people with intellectual disability because of the dangers of tardive dyskinesia (8) and akathisia (9) that are more frequent for older neuroleptics. A further hazard is the potentially fatal neuroleptic malignant syndrome, which has also been reported following treatment with atypical neuroleptics such as clozapine and risperidone. (10) There has also been a recent report of neuroleptic-induced dementia in four adults with intellectual disability. …

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Rapid cycling bipolar affective disorder has attracted renewed interest in the general adult psychiatric literature, particularly as the response to lithium prophylaxis is poor in this subgroup of patients. The present paper describes a systematic Medline/Psyclit review of case studies and small series of patients with rapid cycling bipolar affective disorder in people with intellectual disability (ID). Rapid cycling bipolar affective disorder in people with ID may differ from its occurrence in the non-ID population in terms of a relative preponderance of males, an increased likelihood of rapid cycling onset in those with an early (prepubertal) onset of affective disorder and a different response to prophylactic drugs. The efficacy of treatment and prophylaxis of rapid cycling illnesses needs further investigation in the population with ID.

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Letters pp 536 Over the past 20 years we have witnessed the closure of large residential hospitals for adults with mental handicap and an exodus from these institutions into community care. This move wasmotivated by a desire to give people with handicaps the opportunity to live as normal a life as possible.1 However, concerns have been expressed by the Department of Health,2 some psychiatrists,3 and patients themselves4 about the change. Adults with learning disability are more prone than the rest of the population to chronic health problems, including epilepsy, dementia, hepatitis, peptic ulcer, dysphagia, and problems relatedto sensory impairment.5 Age related diseases such as stroke, cardiovascular disease, and malignancy will also be of growing concern as life expectancy increases. Many may be surprised to learn that in the Netherlands mental retardation is the greatest single source of …

Criminal Behaviour and Mental HealthVolume 8, Issue 3 p. 171-177 Editorial Editorial: People with learning disabilities in the criminal justice system in England and Wales: a challenge to complacency Dr Timothy J. Howard, Corresponding Author Dr Timothy J. Howard Prudhoe Hospital, Prudhoe, Northumberland, NE42 5NTPrudhoe Hospital, Prudhoe, Northumberland, NE42 5NT, UK.Search for more papers by this authorStephen P. Tyrer, Stephen P. Tyrer Prudhoe Hospital, Prudhoe, Northumberland, NE42 5NTSearch for more papers by this author Dr Timothy J. Howard, Corresponding Author Dr Timothy J. Howard Prudhoe Hospital, Prudhoe, Northumberland, NE42 5NTPrudhoe Hospital, Prudhoe, Northumberland, NE42 5NT, UK.Search for more papers by this authorStephen P. Tyrer, Stephen P. Tyrer Prudhoe Hospital, Prudhoe, Northumberland, NE42 5NTSearch for more papers by this author First published: 14 March 2006 https://doi.org/10.1002/cbm.243Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References Baron-Cohen S. (1990) Autism: a specific cognitive disorder of 'mind-blindness'. International Review of Psychiatry 2: 81–90. 10.3109/09540269009028274 Google Scholar Bean P, Nemitz T (1995) Out of Depth and Out of Sight. Loughborough: Midlands Centre For Criminology, University Of Loughborough. 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Aluminium (Al) is an abundant terrestrial element, but toxic to tissues, including brain. The body is largely protected because systemic Al absorption is very low and in normal individuals almost all absorbed Al is excreted from the body. However gastrointestinal (Gl) absorption is enhanced by organic acids, including citrate. Aluminium and citrate Gl absorption was measured in three healthy males, aged 40–46. After overnight fast, subjects drank a 100 ml fruit drink containing 280 mg Al and 3.2 g citrate (104 and 167 mM, respectively). Al was measured in timed blood and urine samples by GFAAS and serum citrate by enzymatic assay. Blood Al peaked by an increase of 13±2.1 μg/l after 87±19 min then fell slowly over 24 h. Plasma citrate peaked after 32 min, returning to baseline by 90 min. Al was excreted at a constant rate for the first 24 h, 0.4% of the dose being excreted in urine by this time. It is unlikely that Al is absorbed as Al citrate because the blood citrate peak preceded the Al peak by 45–60 min.

BackgroundThe management of disturbed behaviour in facilities for those with learning disabilities involves a spectrum of approaches including the prescription of emergency medication, restraint and seclusion. The use of these techniques has recently come under close scrutiny.MethodAll incidents requiring emergency medication or seclusion that occurred in a large hospital for those with learning disabilities were studied over a six-months period. The precipitating factors, course and outcome of those who had received emergency medication or seclusion were then examined.ResultsIn all, 286 incidents involving 72 individuals occurred during the study period. The episodes requiring seclusion comprised 19% of all incidents. Two-thirds of the patients involved were male but six female patients accounted for 36% of all incidents. During the second part of the study, when the staff knew that the treatments used were being monitored, there was a significant reduction in use of restraint and emergency drugs given intramuscularly. Patients receiving seclusion were judged to have a better outcome one hour after the onset of the incident compared with those who received medication.ConclusionsDespite concerns about the use of seclusion, the results of this survey suggest that procedures that remove the patient from the environment contributing to the disturbance may have certain advantages in this population.

Individuals with Down's Syndrome (DS) develop the neuropathological features of senile dementia of the Alzheimer's type (SDAT) by early middle age. Because of recent evidence that gastrointestinal (GI) aluminum (Al) absorption is increased in patients with SDAT, and that Al may contribute to associated neuropathological changes, we have investigated the GI uptake of Al in patients with DS by two methods. The first measured the absorption of Al-27 at concentrations associated with antacid use, in the presence of citrate, using atomic absorption spectrometry. There was no difference between basal blood concentrations of Al-27 in 15 DS subjects (36-46 years) and 15 age-matched controls. The mean increase in Al-27 blood concentrations 60 minutes after the dose of Al was four times greater in the DS group than in controls (p < 0.001). The second measured GI absorption of Al-26 under normal dietary conditions using accelerator mass spectrometry. With Al-26 the mean Al absorption in DS subjects (n = 5) exceeded that of controls (n = 4) by a factor of 6 (p < 0.02). Although the mechanisms of enhanced absorption are unknown, the data indicate that similar abnormalities in the GI handling of Al occur in both SDAT and DS suggesting that it may be advisable to minimize dietary exposure to Al in subjects at risk of developing Alzheimer-type pathology. (C) 1997 Society of Biological Psychiatry.

Fisetin (FS) was reported to have various pharmacological activities. But due to its lower aqueous solubility and oral bioavailability, it is not in much use. As solubility and bioavailability plays and important role in the pharmacological activity, in this research work we tried to improve the oral bioavailability of fisetin. In this research work, we developed self-nanoemulsifying drug delivery system (SNEDDS) of fisetin. Developed SNEDDS were subjected for pharmacokinetic and pharmacodynamics studies against rotenone-induced Parkinson's disease (PD) model in rats. Higher Cmax and area under the curve during pharmacokinetic study indicated that SNEDDS improved the oral bioavailability of FS and also increased the mean residence time of drug in plasma. Results of behavior parameters (locomotor, muscle co-ordination and catalepsy), biochemical estimation (TBARS, nitrite, GSH, SOD and CAT) and ELISA (soluble alfa synuclein, BDNF, TNF-α and IL-6) confirmed the significantly improved (p < 0.05) neuroprotection in rats treated with FS loaded SNEDDS as compared to rats treated with naïve FS. This study suggests that SNEDDS improved the oral bioavailability of FS which further helped in improving its neuroprotective activity in rat model of PD. It further suggests the potential use of FS-SNEDDS in effective management of PD condition.