RESUMEN
A blood-based biomarker to complement the clinical and neuropsychological assessments used to evaluate the risk of individuals with mild cognitive impairment (MCI) developing Alzheimer's disease (AD) would be invaluable. Previous pilot studies by our group identified elevated platelet membrane ß-secretase activity in patients with AD and MCI, as compared to controls, and this activity was influenced by membrane cholesterol levels. The present study investigated baseline platelet membrane ß-secretase activity and cholesterol levels in 97 MCI participants and 85 controls and explored whether these parameters differed in individuals with stable MCI, as compared to those who subsequently developed AD. To evaluate signal specificity, ß-secretase activity assays were conducted in the presence and absence of beta-site amyloid-ß protein precursor-cleaving enzyme (BACE) inhibitors. Baseline platelet membrane ß-secretase activity did not differ significantly in MCI participants, as compared to controls, and platelet membrane cholesterol levels were significantly lower in the MCI group. The longitudinal study indicated that the activities inhibited by two different BACE inhibitors did not predict conversion to AD; however, the activity that was not affected by BACE inhibitors was significantly (40%) higher in individuals with stable MCI, as compared with those who subsequently developed AD. These findings indicated that further research into the source of this activity could contribute to a measure facilitating prediction of the risk of conversion from MCI to AD.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Secretasas de la Proteína Precursora del Amiloide/sangre , Plaquetas/enzimología , Disfunción Cognitiva/fisiopatología , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Colesterol/sangre , Estudios Transversales , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: Mild cognitive impairment (MCI) has clinical value in its ability to predict later dementia. A better understanding of cognitive profiles can further help delineate who is most at risk of conversion to dementia. We aimed to (1) examine to what extent the usual MCI subtyping using core criteria corresponds to empirically defined clusters of patients (latent profile analysis [LPA] of continuous neuropsychological data) and (2) compare the two methods of subtyping memory clinic participants in their prediction of conversion to dementia. METHODS: Memory clinic participants (MCI, n = 139) and age-matched controls (n = 98) were recruited. Participants had a full cognitive assessment, and results were grouped (1) according to traditional MCI subtypes and (2) using LPA. MCI participants were followed over approximately 2 years after their initial assessment to monitor for conversion to dementia. RESULTS: Groups were well matched for age and education. Controls performed significantly better than MCI participants on all cognitive measures. With the traditional analysis, most MCI participants were in the amnestic multidomain subgroup (46.8%) and this group was most at risk of conversion to dementia (63%). From the LPA, a three-profile solution fit the data best. Profile 3 was the largest group (40.3%), the most cognitively impaired, and most at risk of conversion to dementia (68% of the group). DISCUSSION: LPA provides a useful adjunct in delineating MCI participants most at risk of conversion to dementia and adds confidence to standard categories of clinical inference.
RESUMEN
OBJECTIVES: A healthy lifestyle may help maintain cognitive function and reduce the risk of developing dementia. This study employed a focus group approach in order to gain insight into opinions of mild cognitive impairment (MCI) patients, caregivers (CG) and health professionals (HP) regarding lifestyle and its relationship with cognition. The qualitative data were used to design, develop and pilot test educational material (EM) to help encourage lifestyle behaviour change. METHOD: Data gathering phase: structured interviews were conducted with HP (n = 10), and focus groups with MCI patients (n = 24) and CG (n = 12). EM was developed and pilot tested with a new group of MCI patients (n = 21) and CG (n = 6). RESULTS: HP alluded to the lack of clinical trial evidence for a lifestyle and MCI risk link. Although they felt that lifestyle modifications should be recommended to MCI patients, they appeared hesitant in communicating this information and discussions were often patient-driven. MCI patients lacked awareness of the lifestyle cognition link. Participants preferred EM to be concise, eye-catching and in written format, with personal delivery of information favoured. Most pilot testers approved of the EM but were heterogeneous in terms of lifestyle, willingness to change and support needed to change. CONCLUSION: MCI patients need to be made more aware of the importance of lifestyle for cognition. EM such as those developed here, which are specifically tailored for this population would be valuable for HP who, currently, appear reticent in initiating lifestyle-related discussions. Following further evaluation, the EM could be used in health promotion activities targeting MCI patients.
Asunto(s)
Disfunción Cognitiva/psicología , Conductas Relacionadas con la Salud , Promoción de la Salud/métodos , Estilo de Vida , Anciano , Anciano de 80 o más Años , Actitud del Personal de Salud , Cuidadores/psicología , Cognición , Dieta , Femenino , Grupos Focales , Humanos , Entrevistas como Asunto , Masculino , Actividad Motora , Pruebas Neuropsicológicas , Evaluación de Resultado en la Atención de Salud , Desarrollo de Programa , Investigación Cualitativa , Encuestas y CuestionariosRESUMEN
Hippocampus and amygdala changes have been implicated in the pathophysiology and symptomatology of both schizophrenia (SCZ) and bipolar disorder (BD). However relationships between illness course, neuropathological changes and variations in symptomatology remain unclear. This investigation examined the associations between hippocampus and amygdala volumes and symptom dimensions in schizophrenia and bipolar disorder patients after their first episode of psychosis. Symptom severity was associated with decreases in hippocampus/amygdala complex volume across groups. In keeping with previous work bilateral hippocampus and amygdala volume reductions were also identified in the SCZ patients while in BD patients only evidence of amygdala inflation reached significance. The study concludes that there appear to be important relationships between volume changes in the hippocampus and amygdala and dimensions and severity of symptomatology in psychosis. Structural alterations are apparent in both SCZ and BD after first episode of psychosis but present differently in each illness and are more severe in SCZ.
Asunto(s)
Amígdala del Cerebelo/patología , Trastorno Bipolar/patología , Hipocampo/patología , Trastornos Psicóticos/patología , Esquizofrenia/patología , Adulto , Amígdala del Cerebelo/fisiopatología , Trastorno Bipolar/fisiopatología , Femenino , Hipocampo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/fisiopatología , Esquizofrenia/fisiopatología , Adulto JovenRESUMEN
Schizophrenia (SCZ) and bipolar disorder (BP) are associated with neuropathological brain changes, which are believed to disrupt connectivity between brain processes and may have common properties. Patients at first psychotic episode are unique, as one can assess brain alterations at illness inception, when many confounders are reduced or absent. SCZ (N=25) and BP (N=24) patients were recruited in a regional first episode psychosis MRI study. VBM methods were used to study gray matter (GM) and white matter (WM) differences between patient groups and case by case matched controls. For both groups, deficits identified are more discrete than those typically reported in later stages of illness. SCZ patients showed some evidence of GM loss in cortical areas but most notable were in limbic structures such as hippocampus, thalamus and striatum and cerebellum. Consistent with disturbed neural connectivity WM alterations were also observed in limbic structures, the corpus callosum and many subgyral and sublobar regions in the parietal, temporal and frontal lobes. BP patients displayed less evidence of volume changes overall, compared to normal healthy participants, but those changes observed were primarily in WM areas which overlapped with regions identified in SCZ, including thalamus and cerebellum and subgyral and sublobar sites. At first episode of psychosis there is evidence of a neuroanatomical overlap between SCZ and BP with respect to brain structural changes, consistent with disturbed neural connectivity. There are also important differences however in that SCZ displays more extensive structural alteration.
Asunto(s)
Trastorno Bipolar/patología , Mapeo Encefálico , Encéfalo/patología , Esquizofrenia/patología , Adolescente , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To compare the performance of patients with mild-moderate Alzheimer's disease (AD) and vascular dementia (VaD) on tests of information processing and attention. METHOD: Patients with AD (n=75) and VaD (n=46) were recruited from a memory clinic along with dementia-free participants (n=28). They underwent specific tests of attention from the Cognitive Drug Research battery, and pen and paper tests including Colour Trails A and B and Stroop. All patients had a CT brain scan that was independently scored for white-matter change/ischaemia. RESULTS: Attention was impaired in both AD and VaD patients. VaD patients had more impaired choice reaction times and were less accurate on a vigilance test measuring sustained attention. Deficits in selective and divided attention occurred in both patient groups and showed the strongest correlations with Mini Mental State Examination scores. CONCLUSION: This study demonstrates problems with the attentional network in mild-moderate AD and VaD. The authors propose that attention should be tested routinely in a memory clinic setting.
Asunto(s)
Enfermedad de Alzheimer/epidemiología , Atención , Trastornos del Conocimiento/epidemiología , Demencia Vascular/epidemiología , Anciano , Trastornos Cerebrovasculares/epidemiología , Trastornos del Conocimiento/diagnóstico , Demencia Vascular/diagnóstico , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Substance misuse is a common comorbid problem in people presenting with first-episode psychosis and is associated with a poor short-term outcome. AIMS: The aim of this study is to examine differences in baseline characteristics and 1-year outcome between individuals with first-episode psychosis who have never misused substances, those who stop misusing substances after initial presentation and those who persistently misuse substances over the 1-year assessment period. METHOD: Patients were recruited to the Northern Ireland First Episode Psychosis Study (n = 272). Clinical assessments were performed at baseline and at 1 year (n = 194) and data were collected from the case notes. RESULTS: Individuals with persistent substance misuse had more severe depression, more positive symptoms, poorer functional outcome and greater rates of relapse at 1 year than those who stopped and those who had never misused substances. There were no differences in outcome between people who had never misused substances and those who stopped misusing after presentation. CONCLUSIONS: These results support assertive intervention targeted at comorbid substance misuse in individuals with first-episode psychosis.
Asunto(s)
Trastornos Mentales/epidemiología , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Trastorno Bipolar/epidemiología , Comorbilidad , Trastorno Depresivo/epidemiología , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente/psicología , Cooperación del Paciente/estadística & datos numéricos , Escalas de Valoración Psiquiátrica , Recurrencia , Esquizofrenia/epidemiología , Psicología del Esquizofrénico , Trastornos Relacionados con Sustancias/psicología , Adulto JovenRESUMEN
BACKGROUND: Researching psychotic disorders in unison rather than as separate diagnostic groups is widely advocated, but the viability of such an approach requires careful consideration from a neurocognitive perspective. AIMS: To describe cognition in people with bipolar disorder and schizophrenia and to examine how known causes of variability in individual's performance contribute to any observed diagnostic differences. METHOD: Neurocognitive functioning in people with bipolar disorder (n = 32), schizophrenia (n = 46) and healthy controls (n = 67) was compared using analysis of covariance on data from the Northern Ireland First Episode Psychosis Study. RESULTS: The bipolar disorder and schizophrenia groups were most impaired on tests of memory, executive functioning and language. The bipolar group performed significantly better on tests of response inhibition, verbal fluency and callosal functioning. Between-group differences could be explained by the greater proclivity of individuals with schizophrenia to experience global cognitive impairment and negative symptoms. CONCLUSIONS: Particular impairments are common to people with psychosis and may prove useful as endophenotypic markers. Considering the degree of individuals' global cognitive impairment is critical when attempting to understand patterns of selective impairment both within and between these diagnostic groups.
Asunto(s)
Trastorno Bipolar/psicología , Trastornos del Conocimiento/psicología , Psicología del Esquizofrénico , Adolescente , Adulto , Atención , Trastorno Bipolar/diagnóstico , Estudios de Casos y Controles , Trastornos del Conocimiento/diagnóstico , Femenino , Humanos , Inteligencia , Masculino , Recuerdo Mental , Persona de Mediana Edad , Pruebas Neuropsicológicas , Conducta Verbal , Adulto JovenRESUMEN
Rapid tryptophan (Trp) depletion (RTD) has been reported to cause deterioration in the quality of decision making and impaired reversal learning, while leaving attentional set shifting relatively unimpaired. These findings have been attributed to a more powerful neuromodulatory effect of reduced 5-HT on ventral prefrontal cortex (PFC) than on dorsolateral PFC. In view of the limited number of reports, the aim of this study was to independently replicate these findings using the same test paradigms. Healthy human subjects without a personal or family history of affective disorder were assessed using a computerized decision making/gambling task and the CANTAB ID/ED attentional set-shifting task under Trp-depleted (n=17; nine males and eight females) or control (n=15; seven males and eight females) conditions, in a double-blind, randomized, parallel-group design. There was no significant effect of RTD on set shifting, reversal learning, risk taking, impulsivity, or subjective mood. However, RTD significantly altered decision making such that depleted subjects chose the more likely of two possible outcomes significantly more often than controls. This is in direct contrast to the previous report that subjects chose the more likely outcome significantly less often following RTD. In the terminology of that report, our result may be interpreted as improvement in the quality of decision making following RTD. This contrast between studies highlights the variability in the cognitive effects of RTD between apparently similar groups of healthy subjects, and suggests the need for future RTD studies to control for a range of personality, family history, and genetic factors that may be associated with 5-HT function.