Kenneth Day

Bio: Kenneth Day is an academic researcher from Newcastle University. The author has contributed to research in topics: Down syndrome & Dementia. The author has an hindex of 8, co-authored 12 publications receiving 624 citations.

Male mentally handicapped sex offenders.

Abstract: BACKGROUND Sex offences are overrepresented in the mentally handicapped, but information about the characteristics and offence behaviour of this group is limited. METHOD A retrospective case note survey was made of 47 male patients referred for antisocial sexual behaviour. RESULTS Of 191 offences and/or incidents committed, 55.5% were heterosexual, 24% indecent exposure, 12.4% homosexual, 13.6% serious and 3.6% involved physical assault. Average age of the offenders was 23.9 years, with a mean IQ of 59.5, and there was a high prevalence of family psychopathology, psychiatric illness, minor physical disabilities, sexual experience, impaired relationship skills and sexual recidivism. Recidivists showed a low specificity for offence type and age and sex of victim. Categorical analysis differentiated a 'sex offences only' group from a 'sex plus other offences' group in the key areas of psychopathology, offence behaviour and outcome; this was supported by factor analysis. CONCLUSION The finding of two subgroups of mentally handicapped male sex offenders has important implications for prevention, assessment and treatment.

Psychiatric disorder in the middle-aged and elderly mentally handicapped.

Abstract: In a study of 357 long-stay hospital residents aged 40 years and over, 30% had significant psychiatric disorder, while a retrospective survey of 215 new admissions over a seven-year period to a psychiatric unit for the mentally handicapped revealed that 20% of patients were aged 40 years and over. Both similarities and differences were found in the overall pattern of disorders between the two groups and a non-handicapped population in a comparable age-range.

A hospital-based treatment programme for male mentally handicapped offenders.

Abstract: The paper describes a special hospital-based treatment programme for male mentally handicapped offenders, comprising a package of practical and personal skills training coupled with a socialisation programme based on token-economy strategies within a controlled and structured environment Twenty patients admitted to the programme and followed up after discharge for an average of 33 years were studied in detail All had committed serious or persistent offences and showed a high level of psychosocial pathology A good or fair response to the treatment programme was made by 85%, and 65% were judged well adjusted or reasonably well adjusted at last follow-up contact A good outcome was associated with more than two years' in-patient care, a good response to the treatment programme and stable residential placement, regular occupation and regular supervision and support in the community Offenders against the person (sex and assault) had a better prognosis than and showed other interesting differences from property offenders (property and arson)

Apolipoprotein E epsilon 2 allele promotes longevity and protects patients with Down's syndrome from dementia.

Abstract: Although individuals with Down's syndrome nearly always develop the clinical and pathological features of Alzheimer's disease, some clearly do not become demented despite living into their sixth and seventh decades. Genetic variation at the apolipoprotein E locus has recently been shown to be an important determinant of Alzheimer's disease, with the epsilon 4 allele having been shown to be associated with the disease and, at least in some cases, the epsilon 2 allele being negatively associated with the disease. Here we show, in a series of clinically assessed individuals with Down's syndrome, that the epsilon 2 allele of ApoE is associated with both longevity and the absence of clinical evidence of dementia. These data show that the clinical phenotype of Down's syndrome can be modulated by genes on chromosomes other than chromosome 21. The importance of this observation to the pathogenesis of Alzheimer's disease, both in Down's syndrome and in general, is discussed.

Detection of Lewy bodies in Trisomy 21 (Down's syndrome).

Abstract: The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropatho-logical diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a cliniconeuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neu-rohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression.

Lewy Bodies Contain Altered α-Synuclein in Brains of Many Familial Alzheimer's Disease Patients with Mutations in Presenilin and Amyloid Precursor Protein Genes

Abstract: Missense mutations in the α-synuclein gene cause familial Parkinson's disease (PD), and α-synuclein is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease (AD). To determine whether α-synuclein is a component of LBs in familial AD (FAD) patients with known mutations in presenilin ( n = 65) or amyloid precursor protein ( n = 9) genes, studies were conducted with antibodies to α-, β-, and γ-synuclein. LBs were detected with α- but not β- or γ-synuclein antibodies in 22% of FAD brains, and α-synuclein-positive LBs were most numerous in amygdala where some LBs co-localized with tau-positive neurofibrillary tangles. As 12 (63%) of 19 FAD amygdala samples contained α-synuclein-positive LBs, these inclusions may be more common in FAD brains than previously reported. Furthermore, α-synuclein antibodies decorated LB filaments by immunoelectron microscopy, and Western blots revealed that the solubility of α-synuclein was reduced compared with control brains. The presence of α-synuclein-positive LBs was not associated with any specific FAD mutation. These studies suggest that insoluble α-synuclein aggregates into filaments that form LBs in many FAD patients, and we speculate that these inclusions may compromise the function and/or viability of affected neurons in the FAD brain.

Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline.

Abstract: Alzheimer's disease (AD), the most prevalent age-related neurodegenerative disorder, is characterized pathologically by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles. Interestingly, up to 50% of AD cases exhibit a third prevalent neuropathology: the aggregation of α-synuclein into Lewy bodies. Importantly, the presence of Lewy body pathology in AD is associated with a more aggressive disease course and accelerated cognitive dysfunction. Thus, Aβ, tau, and α-synuclein may interact synergistically to promote the accumulation of each other. In this study, we used a genetic approach to generate a model that exhibits the combined pathologies of AD and dementia with Lewy bodies (DLB). To achieve this goal, we introduced a mutant human α-synuclein transgene into 3xTg-AD mice. As occurs in human disease, transgenic mice that develop both DLB and AD pathologies (DLB-AD mice) exhibit accelerated cognitive decline associated with a dramatic enhancement of Aβ, tau, and α-synuclein pathologies. Our findings also provide additional evidence that the accumulation of α-synuclein alone can significantly disrupt cognition. Together, our data support the notion that Aβ, tau, and α-synuclein interact in vivo to promote the aggregation and accumulation of each other and accelerate cognitive dysfunction.

Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies.

Abstract: Objective: To determine the validity of a clinical diagnosis of probable or possible dementia with Lewy bodies (DLB) made using International Consensus criteria. Background: Validation studies based on retrospective chart reviews of autopsy-confirmed cases have suggested that diagnostic specificity for DLB is acceptable but case detection rates as low as 0.22 have been suggested. Methods: We evaluated the first 50 cases reaching neuropathologic autopsy in a cohort to which Consensus clinical diagnostic criteria for DLB, National Institute for Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria for AD, and National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria for vascular dementia (VaD) had been prospectively applied. Results: Twenty-six clinical diagnoses of DLB, 19 of AD, and 5 of VaD were made. At autopsy, 29 DLB cases, 15 AD, 5 VaD, and 1 progressive supranuclear palsy were identified. The sensitivity and specificity of a clinical diagnosis of probable DLB in this sample were 0.83 and 0.95. Of the five cases receiving a false-negative diagnosis of DLB, significant fluctuation was present in four but visual hallucinations and spontaneous motor features of parkinsonism were generally absent. Thirty-one percent of the DLB cases had additional vascular pathology and in two cases this contributed to a misdiagnosis of VaD. No correlations were found between the distribution of Lewy bodies and clinical features. Conclusion: The Consensus criteria for DLB performed as well in this prospective study as those for AD and VaD, with a diagnostic sensitivity substantially higher than that reported by previous retrospective studies. DLB occurs in the absence of extrapyramidal features and in the presence of comorbid cerebrovascular disease. Fluctuation is an important diagnostic indicator, reliable measures of which need to be developed further.

The four ages of Down syndrome.

Abstract: Background: Down syndrome (DS) affects ∼1 per 650-1000 live births and is the most common known genetic cause of intellectual disability. A highly significant change in the survival of people with DS has occurred during the last two generations, with life expectancy estimates increasing from 12 to nearly 60 years of age. Subjects and Methods: Detailed information on 1332 people in Western Australia with DS was abstracted from a specialist statewide database for the period 1953-2000 and electronically linked with three other state or national health and mortality data sources and the state Birth Defects Registry. Results: Over the last 25 years the percentage of women over 35 years giving birth increased from 4.8 to 18.6%, accompanied by an increase in the overall prevalence of DS from 1.1 to 2.9 per 1000 births. Four life stages of DS were identified: prenatal, childhood and early adulthood, adulthood, and senescence. Although pneumonia, or other types of respiratory infections, was the most common cause of death across the entire lifespan, ranging from 23% of deaths in adulthood to 40% in senescence, each life stage exhibited a particular profile of comorbidities. Congenital heart defects were common causes in childhood (13%) and adulthood (23%), whereas in senescence coronary artery disease (10%) and cardiac, renal, and respiratory failure (9%) were leading causes of mortality. Conclusions: A major re-appraisal in attitudes towards DS is required to ensure that the medical and social needs of people with the disorder are adequately met across their entire lifespan. In particular, specific recognition of the comorbidities that can arise at different ages is needed, accompanied by the provision of appropriate levels of care and management.