RESUMO
BACKGROUND: MRI in presymptomatic autosomal dominant Alzheimer's disease mutation carriers (MC) provides an opportunity to detect changes that pre-date symptoms or clinical diagnosis. We used automated cortical thickness (CTh) measurement to compare the grey matter of such a group with cognitively normal controls. METHODS: 9 presymptomatic mutation carriers (4 PSEN1, 5 APP) and 25 healthy, age and sex-matched controls underwent longitudinal volumetric MRI brain imaging. CTh measurement was performed across the whole brain using a validated, automated technique. Four regions of interest (ROI) (entorhinal cortex (ERC), parahippocampal gyrus (PHG), posterior cingulate cortex and precuneus) and two control regions (paracentral and pericalcarine) were selected on the basis of imaging data in existing Alzheimer's disease (AD) literature. Linear mixed models were used to describe normal ageing in controls and the extent to which mean CTh in cases differed from controls according to time since clinical diagnosis, adjusting for normal ageing. RESULTS: An accelerating decline in CTh was observed across all ROI in the MC group. No such decline was demonstrated in the control regions for the MC group. Relative to controls, and adjusting for normal ageing, there was evidence (p=0.05, one-sided test) of lower CTh in the posterior cingulate up to 1.8 years prior to diagnosis and in the precuneus up to 4.1 years prior to diagnosis in the MC group. DISCUSSION: Automated CTh analysis is a relatively practical, rapid and effective technique for assessing subtle structural change in AD. There is evidence that cortical thickness is reduced in mutation carriers a number of years prior to clinical diagnosis.
Assuntos
Doença de Alzheimer/patologia , Córtex Cerebral/fisiopatologia , Saúde da Família , Adulto , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Estudos de Casos e Controles , Córtex Cerebral/patologia , Progressão da Doença , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Presenilina-1/genéticaRESUMO
OBJECTIVE: To examine the cardiovascular effects of combined amylin (AMN) and leptin (LEP) treatment in lean and obese rats. RESEARCH DESIGN: Rats were instrumented for telemetry and given LEP (300 µg kg(-1) day(-1)), AMN (100 µg kg(-1) day(-1)), AMN+LEP or vehicle (VEH; 0.9% normal saline) via a subcutaneous mini-osmotic pump for 7 days. The VEH group was subdivided into ad libitum fed and pair-fed to the amount of food AMN+LEP animals ate daily. Rats were housed in metabolic chambers for analysis of cardiovascular physiology and metabolism. SUBJECTS: Male Fisher 344 × Brown Norway (FBNF1; Harlan; age=3-5 months; n=72) rats were placed on standard rodent chow (LEAN, n=41) or moderately high-fat diet (OBESE; n=31) to produce obesity. RESULTS: AMN+LEP potently reduced food intake (LEAN: 57% OBESE: 59%) and abdominal fat mass (LEAN: 56% OBESE: 41%). Pair-fed rats displayed bradycardia and metabolic suppression. In contrast, AMN+LEP increased heart rate and oxygen consumption above levels in LEP or AMN-treated rats. LEP reduced blood pressure in both lean and obese rats but AMN had no effect. LEP-induced reductions in blood pressure were not altered by AMN+LEP treatment. Thus, AMN+LEP treatment decreased food intake, body fat and blood pressure in lean and obese rats. CONCLUSION: We conclude that the potent anti-adiposity actions of AMN+LEP are due in part to prevention of the bradycardia and metabolic suppression typically observed with negative energy balance. Furthermore, the hypotensive actions of peripheral LEP treatment are observable in spite of the potent AMN+LEP activation of anorexic and thermogenic mechanisms in the central nervous system.
Assuntos
Adiposidade/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/farmacologia , Leptina/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos F344RESUMO
Visual hallucinations (VH) are a cardinal neuropsychiatric symptom and often have important diagnostic implications. The interpretation of VH is influenced by the patient's social and cultural milieu, but the impact of socio-cultural factors on the interpretation, presentation and detection of VH has been little studied. When patients exhibit VH and other neuropsychiatric phenomena, appropriate sensitivity to the role of cultural factors is an important determinant of the success of the medical consultation. We discuss this issue using three illustrative cases.
Assuntos
Cultura , Alucinações/etiologia , Idoso , Feminino , Alucinações/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , ReligiãoRESUMO
We report the case of a 40 year-old woman who, at 38 years of age, developed insidious memory loss and, subsequently, progressive dementia satisfying criteria for probable Alzheimer's disease (AD) (NINCDS-ADRDA) [Neurology 1984; 34: 939]. Analysis of the presenilin 1 gene (PSEN1) revealed a 496_498delCTT mutation at codon 166. The amnestic presentation and absence of other features contrasts with the majority of other documented deletions which have been associated with spastic paraparesis. They are, however, consistent with the reported clinical phenotype in the majority of PSEN1 exon 6 mutations so far reported.
Assuntos
Doença de Alzheimer/genética , Presenilina-1/genética , Deleção de Sequência , Adulto , Idade de Início , Éxons/genética , Feminino , Humanos , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Linhagem , Presenilina-1/químicaRESUMO
Mature male Sprague-Dawley (SD) and Long-Evans (LE) rats were instrumented with telemetry transmitters for measurement of heart rate (HR) and housed in room calorimeters for assessment of food intake and oxygen consumption (Vo(2)) at standard laboratory temperatures (23 degrees C) to examine physiological responses to caloric restriction (CR; 60% of baseline ad libitum calories for 2 wk) and refeeding. Ad libitum controls had stable food intake (84-88 kcal/day) and gained weight at rates of 3-4 g/day. Groups from both strains assigned to CR exhibited similar patterns of weight loss and reductions in Vo(2) and HR. Upon refeeding, SD rats exhibited a mild, transient hyperphagic response (1 day) accompanied by sustained suppression of Vo(2) and HR that remained evident 8 days after refeeding. In contrast, LE rats exhibited sustained daily hyperphagia that persisted 8 days after refeeding and was accompanied by a complete restoration of HR and Vo(2). The lower HR and Vo(2) observed during refeeding in SD rats were not due to reduced locomotor activity. The results reveal a strain-dependent divergent response to recovery from CR. We conclude that during recovery from CR, homeostatic stimulation of appetite or suppression of energy expenditure may occur selectively to restore body weight.