Prevalence and Correlates of Cognitive Impairment among the Elderly in a General Hospital

Aims: To estimate the prevalence and correlates of cognitive impairment (CI) among the elderly in a general hospital. Methods: A cross-sectional study, including 200 Brazilian inpatients aged 60 years or over, using the Mini Mental State Examination to evaluate CI (dependent variable), and the Geriatric Depression Scale and the Katz and Lawton Index to evaluate basic (BADL) and instrumental activities of daily living (IADL). Results: 56% were women, 29% were dependent for BADL and 77.5% for IADL. The prevalence of CI was 29% and, in the logistic regression, it remained associated with higher age (1 74 years old), number of previous hospitalizations (1 3) and dependency for BADL (being dependent raised the odds of being cognitively impaired). Conclusions: It is essential to train the hospital staff to properly assist these patients, and to orient and support their caregivers. Copyright (C) 2009 S. Karger AG, Basel

Long-term sertraline treatment increases expression and decreases phosphorylation of glycogen synthase kinase-3B in platelets of patients with late-life major depression

Background: Abnormal regulation of glycogen synthase kinase 3-beta (GSK3B) activity has been implicated in the pathophysiology of mood disorders. Many pharmacological agents, including antidepressants, can modulate GSK3B. The aim of the present study was to investigate the effect of short-and long-term sertraline treatment on the expression and phosphorylation of GSK3B in platelets of patients with late-life major depression. Methods: Thirty-nine unmedicated elderly adults with major depressive disorder (MOD) were initially included in this study. The comparison group comprised 18 age-matched, healthy individuals. The expression of total and Ser-9 phosphorylated GSK3B (pGSK3B) was determined by Enzyme Immunometric Assay (EIA) in platelets of patients and controls at baseline, and after 3 and 12 months of sertraline treatments for patients only. During this period, patients were continuously treated with therapeutic doses of sertraline. GSK3B activity was indirectly estimated by calculating the proportion of inactive (phosphorylated) forms (pGSK3B) in relation to the total expression of the enzyme (i.e.. GSK3B ratio). Results: Depressed patients had significantly higher levels of pGSK3B as compared to controls (p < 0.001). Within the MDD group, after 3 months of sertraline treatment no significant changes were observed in GSK3B expression and phosphorylation state, as compared to baseline levels. However, after 12 months of treatment we found a significant increase in the expression of total GSK3B (p = 0.05), in the absence of any significant changes in pGSK3B (p = 0.12), leading to a significant reduction in GSK3B ratio (p = 0.001). Conclusions: Our findings indicate that GSK3B expression was upregulated by the continuous treatment with sertraline, along with an increment in the proportion of active forms of the enzyme. This is compatible with an increase in overall GSK3B activity, which may have been induced by the long-term treatment of late-life depression with sertraline. (C) 2012 Elsevier Ltd. All rights reserved.

Ecological validity of virtual reality daily living activities screening for early dementia: longitudinal study

Background: Dementia is a multifaceted disorder that impairs cognitive functions, such as memory, language, and executive functions necessary to plan, organize, and prioritize tasks required for goal-directed behaviors. In most cases, individuals with dementia experience difficulties interacting with physical and social environments. The purpose of this study was to establish ecological validity and initial construct validity of a fire evacuation Virtual Reality Day-Out Task (VR-DOT) environment based on performance profiles as a screening tool for early dementia. Objective: The objectives were (1) to examine the relationships among the performances of 3 groups of participants in the VR-DOT and traditional neuropsychological tests employed to assess executive functions, and (2) to compare the performance of participants with mild Alzheimer’s-type dementia (AD) to those with amnestic single-domain mild cognitive impairment (MCI) and healthy controls in the VR-DOT and traditional neuropsychological tests used to assess executive functions. We hypothesized that the 2 cognitively impaired groups would have distinct performance profiles and show significantly impaired independent functioning in ADL compared to the healthy controls. Methods: The study population included 3 groups: 72 healthy control elderly participants, 65 amnestic MCI participants, and 68 mild AD participants. A natural user interface framework based on a fire evacuation VR-DOT environment was used for assessing physical and cognitive abilities of seniors over 3 years. VR-DOT focuses on the subtle errors and patterns in performing everyday activities and has the advantage of not depending on a subjective rating of an individual person. We further assessed functional capacity by both neuropsychological tests (including measures of attention, memory, working memory, executive functions, language, and depression). We also evaluated performance in finger tapping, grip strength, stride length, gait speed, and chair stands separately and while performing VR-DOTs in order to correlate performance in these measures with VR-DOTs because performance while navigating a virtual environment is a valid and reliable indicator of cognitive decline in elderly persons. Results: The mild AD group was more impaired than the amnestic MCI group, and both were more impaired than healthy controls. The novel VR-DOT functional index correlated strongly with standard cognitive and functional measurements, such as mini-mental state examination (MMSE; rho=0.26, P=.01) and Bristol Activities of Daily Living (ADL) scale scores (rho=0.32, P=.001). Conclusions: Functional impairment is a defining characteristic of predementia and is partly dependent on the degree of cognitive impairment. The novel virtual reality measures of functional ability seem more sensitive to functional impairment than qualitative measures in predementia, thus accurately differentiating from healthy controls. We conclude that VR-DOT is an effective tool for discriminating predementia and mild AD from controls by detecting differences in terms of errors, omissions, and perseverations while measuring ADL functional ability.

The feasibility of self-report advance directives among elderly patients with cognitive impairment

The central objective of this dissertation was to determine the feasibility of self-completed advance directives (AD) in older persons suffering from mild and moderate stages of dementia. This was accomplished by identifying differences in ability to complete AD among elderly subjects with increasing degrees of dementia and cognitive incompetence. Secondary objectives were to describe and compare advance directives completed by elders and identified proxy decision makers. Secondary objectives were accomplished by measuring the agreement between advance directives completed by proxy and elder, and comparing that agreement across groups defined by the elder's cognitive status. This cross-sectional study employed a structured interview to elicit AD, followed by a similar interview with a proxy decision maker identified by the elder. A stratified sampling scheme recruited elders with normal cognition, mild, and moderate forms of dementia using the Mini Mental-State Exam (MMSE). The Hopkins Competency Assessment Test (HCAT) was used for evaluation of competency to make medical decisions. Analysis was conducted on "between group" (non-demented $\leftrightarrow$ mild dementia $\leftrightarrow$ moderate dementia, and competent $\leftrightarrow$ incompetent) and "within group" (elder $\leftrightarrow$ family member) variation.^ The 118 elderly subjects interviewed were generally male, Caucasian, and of low socioeconomic status. Mean age was 77. Overall, elders preferred a "trial of therapy" regarding AD rather than to "always receive the therapy". No intervention was refused outright more often than it was accepted. A test-retest of elders' AD revealed stable responses. Eleven logic checks measured appropriateness of AD responses independent of preference. No difference was found in logic error rates between elders grouped by MMSE or HCAT. Agreement between proxy and elder responses showed significant dissimilarity, indicating that proxies were not making the same medical decisions as the elders.^ Conclusions based on these data are: (1) Self reporting AD is feasible among elders showing signs of cognitive impairment and they should be given all opportunities to complete advance directives, (2) variation in preferences for advance directives in cognitively impaired elders should not be assumed to be the effects of their impairment alone, (3) proxies do not appear to forego life-prolonging interventions in the face of increasing impairment in their ward, however, their advance directives choices are frequently not those of the elder they represent. ^

Oxidative LDL modification is increased in vascular dementia and is inversely associated with cognitive performance

It is not known whether the association between increased plasma homocysteine (Hcy) associated with LDL modification and propensity for LDL uptake by macrophages in cardiovascular disease patients holds true in vascular dementia (VaD). Plasma from 83 subjects diagnosed with Alzheimer's disease (AD), VaD, mild cognitive impairment (MCI) and from controls was analysed to examine (1) whether LDL isolated from the plasma of VaD is biochemically and functionally distinct from that isolated from AD, MCI or controls; and (2) whether such biomarkers of LDL phenotype are related to plasma folate levels, Hcy levels and/or to disease severity. Folate and vitamin B6 levels were significantly lower in VaD subjects than in controls. VaD-LDL showed increased protein carbonyl content (p <0.05) and was more susceptible to scavenging by macrophages (p <0.05) than AD- or control-LDL. Patients from the VaD cohort were more prevalent in the lowest tertile for HDL:LDL and the upper tertile for LDL oxidation; the combined parameters of HDL cholesterol, LDL oxidation and scavenging by macrophages show 87% sensitivity towards VaD detection. The association between folate deficiency, LDL modification and dysfunction in VaD but not in AD may provide a novel biomarker assessment to discriminate between the diseases.

Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease

Background - Previous Cochrane reviews have considered the use of cholinesterase inhibitors in both Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). The clinical features of DLB and PDD have much in common and are distinguished primarily on the basis of whether or not parkinsonism precedes dementia by more than a year. Patients with both conditions have particularly severe deficits in cortical levels of the neurotransmitter acetylcholine. Therefore, blocking its breakdown using cholinesterase inhibitors may lead to clinical improvement. Objectives - To assess the efficacy, safety and tolerability of cholinesterase inhibitors in dementia with Lewy bodies (DLB), Parkinson’s disease with dementia (PDD), and cognitive impairment in Parkinson’s disease falling short of dementia (CIND-PD) (considered as separate phenomena and also grouped together as Lewy body disease). Search methods - The trials were identified from a search of ALOIS, the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group (on 30 August 2011) using the search terms Lewy, Parkinson, PDD, DLB, LBD. This register consists of records from major healthcare databases (MEDLINE, EMBASE, PsycINFO, CINAHL) and many ongoing trial databases and is updated regularly. Reference lists of relevant studies were searched for additional trials. Selection criteria - Randomised, double-blind, placebo-controlled trials assessing the efficacy of treatment with cholinesterase inhibitors in DLB, PDD and cognitive impairment in Parkinson’s disease (CIND-PD). Data collection and analysis - Data were extracted from published reports by one review author (MR). The data for each 'condition' (that is DLB, PDD or CIND-PD) were considered separately and, where possible, also pooled together. Statistical analysis was conducted using Review Manager version 5.0. Main results - Six trials met the inclusion criteria for this review, in which a total of 1236 participants were randomised. Four of the trials were of a parallel group design and two cross-over trials were included. Four of the trials included participants with a diagnosis of Parkinson's disease with dementia (Aarsland 2002a; Dubois 2007; Emre 2004; Ravina 2005), of which Dubois 2007 remains unpublished. Leroi 2004 included patients with cognitive impairment and Parkinson's disease (both with and without dementia). Patients with dementia with Lewy bodies (DLB) were included in only one of the trials (McKeith 2000). For global assessment, three trials comparing cholinesterase inhibitor treatment to placebo in PDD (Aarsland 2002a; Emre 2004; Ravina 2005) reported a difference in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) score of -0.38, favouring the cholinesterase inhibitors (95% CI -0.56 to -0.24, P < 0.0001). For cognitive function, a pooled estimate of the effect of cholinesterase inhibitors on cognitive function measures was consistent with the presence of a therapeutic benefit (standardised mean difference (SMD) -0.34, 95% CI -0.46 to -0.23, P < 0.00001). There was evidence of a positive effect of cholinesterase inhibitors on the Mini-Mental State Examination (MMSE) in patients with PDD (WMD 1.09, 95% CI 0.45 to 1.73, P = 0.0008) and in the single PDD and CIND-PD trial (WMD 1.05, 95% CI 0.42 to 1.68, P = 0.01) but not in the single DLB trial. For behavioural disturbance, analysis of the pooled continuous data relating to behavioural disturbance rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.36 to -0.04, P = 0.01). For activities of daily living, combined data for the ADCS and the Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.38 to -0.02, P = 0.03). For safety and tolerability, those taking a cholinesterase inhibitor were more likely to experience an adverse event (318/452 versus 668/842; odds ratio (OR) 1.64, 95% CI 1.26 to 2.15, P = 0.0003) and to drop out (128/465 versus 45/279; OR 1.94, 95% CI 1.33 to 2.84, P = 0.0006). Adverse events were more common amongst those taking rivastigmine (357/421 versus 173/240; OR 2.28, 95% CI 1.53 to 3.38, P < 0.0001) but not those taking donepezil (311/421 versus 145/212; OR 1.24, 95% CI 0.86 to 1.80, P = 0.25). Parkinsonian symptoms in particular tremor (64/739 versus 12/352; OR 2.71, 95% CI 1.44 to 5.09, P = 0.002), but not falls (P = 0.39), were reported more commonly in the treatment group but this did not have a significant impact on the UPDRS (total and motor) scores (P = 0.71). Fewer deaths occurred in the treatment group than in the placebo group (4/465 versus 9/279; OR 0.28, 95% CI 0.09 to 0.84, P = 0.03). Authors' conclusions - The currently available evidence supports the use of cholinesterase inhibitors in patients with PDD, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales. The effect in DLB remains unclear. There is no current disaggregated evidence to support their use in CIND-PD.

The effects of centrally acting ACE inhibitors on the rate of cognitive and functional decline in dementia: a KDD approach

Alzheimer’s Disease and other dementias are one of the most challenging illnesses confronting countries with ageing populations. Treatment options for dementia are limited, and the costs are significant. There is a growing need to develop new treatments for dementia, especially for the elderly. There is also growing evidence that centrally acting angiotensin converting enzyme (ACE) inhibitors, which cross the blood-brain barrier, are associated with a reduced rate of cognitive and functional decline in dementia, especially in Alzheimer’s disease (AD). The aim of this research is to investigate the effects of centrally acting ACE inhibitors (CACE-Is) on the rate of cognitive and functional decline in dementia, using a three phased KDD process. KDD, as a scientific way to process and analysis clinical data, is used to find useful insights from a variety of clinical databases. The data used are from three clinic databases: Geriatric Assessment Tool (GAT), the Doxycycline and Rifampin for Alzheimer’s Disease (DARAD), and the Qmci validation databases, which were derived from several different geriatric clinics in Canada. This research involves patients diagnosed with AD, vascular or mixed dementia only. Patients were included if baseline and end-point (at least six months apart) Standardised Mini-Mental State Examination (SMMSE), Quick Mild Cognitive Impairment (Qmci) or Activities Daily Living (ADL) scores were available. Basically, the rates of change are compared between patients taking CACE-Is, and those not currently treated with CACE-Is. The results suggest that there is a statistically significant difference in the rate of decline in cognitive and functional scores between CACE-I and NoCACE-I patients. This research also validates that the Qmci, a new short assessment test, has potential to replace the current popular screening tests for cognition in the clinic and clinical trials.

Effectiveness of community-based nonpharmacological interventions for early-stage dementia : conclusions and recommendations

In 2007, a comprehensive review of the extant research on nonpharmacological interventions for persons with early-stage dementia was conducted. More than 150 research reports, centered on six major domains, were included: early-stage support groups, cognitive training and enhancement programs, exercise programs, exemplar programs, health promotion programs, and “other” programs not fitting into previous categories. Theories of neural regeneration and plasticity were most often used to support the tested interventions. Recommendations for practice, research, and health policy are outlined, including evidence-based, nonpharmacological treatment protocols for persons with mild cognitive impairment and early-stage dementia. A tested, community-based, multimodal treatment program is also described. Overall, findings identify well-supported nonpharmacological treatments for persons with early-stage dementia and implications for a national health care agenda to optimize outcomes for this growing population of older adults.

Behavioral and psychological symptoms and cognitive decline in patients with amnestic MCI and mild AD: a two-year follow-up study.

BACKGROUND: Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and dementia. In many cases, MCI represents an early stage of developing cognitive impairment. Patients diagnosed with MCI do not meet the criteria for dementia as their general intellect and everyday activities are preserved, although minor changes in instrumental activities of daily living (ADL) may occur. However, they may exhibit significant behavioral and psychological signs and symptoms (BPS), also frequently observed in patients with Alzheimer's disease (AD). Hence, we wondered to what extent specific BPS are associated with cognitive decline in participants with MCI or AD. METHODS: Our sample consisted of 164 participants, including 46 patients with amnestic (single or multi-domain) MCI and 54 patients with AD, as well as 64 control participants without cognitive disorders. Global cognitive performance, BPS, and ADL were assessed using validated clinical methods at baseline and at two-year follow-up. RESULTS: The BPS variability over the follow-up period was more pronounced in the MCI group than in patients with AD: some BPS improve, others occur newly or worsen, while others still remain unchanged. Moreover, specific changes in BPS were associated with a rapid deterioration of the global cognitive level in MCI patients. In particular, an increase of euphoria, eating disorders, and aberrant motor behavior, as well as worsened sleep quality, predicted a decline in cognitive functioning. CONCLUSIONS: Our findings confirm a higher variability of BPS over time in the MCI group than in AD patients. Moreover, our results provide evidence of associations between specific BPS and cognitive decline in the MCI group that might suggest a risk of conversion of individuals with amnestic MCI to AD.

Eficacia de los inhibidores selectivos de recaptación de serotonina en síntomas no cognitivos del alzhéimer: revisión sistemática

Introducción: El Alzhéimer tiene una prevalencia de 1,6% en las personas mayores de 65 años. Se caracteriza por la pérdida de memoria y otras funciones cognoscitivas, pero más del 70% de los afectados presentan síntomas no cognitivos entre los que se encuentran alteraciones del afecto, comportamiento y psicosis. Estos síntomas están asociados a mayores tasas de institucionalización, morbilidad y mortalidad. Métodos: Revisión sistemática de la literatura de artículos que proporcionaron información sobre la eficacia de los inhibidores selectivos de recaptación de serotonina en síntomas no cognitivos del Alzhéimer. Resultados: La búsqueda inicial arrojó un total de 495 resultados, 64 artículos fueron preseleccionados y 7 se incluyeron en la revisión; éstos se clasificaron como nivel de evidencia Ib; citalopram mostró ser más eficaz que el placebo y similar a antipsicóticos para síntomas comportamentales y psicóticos asociados al Alzhéimer con un perfil de efectos adversos más tolerable; sertralina no mostró eficacia en depresión y sí una mayor incidencia de efectos adversos con respecto al placebo. Discusión: Se obtuvieron resultados favorables en síntomas comportamentales y psicóticos pero no en afectivos. Las diferencias metodológicas de los estudios le dan complejidad a la interpretación de los resultados. Conclusión: La evidencia sugiere que el tratamiento con citalopram es eficaz en síntomas comportamentales y psicóticos asociados al Alzhéimer; para el tratamiento de la depresión asociado a esta demencia aún no existe un antidepresivo que pueda considerarse de elección.

Ansiedad, depresión y calidad de vida en personas adultas con VIH/SIDA y deterioro cognitivo leve

El Virus de la Inmunodeficiencia Humana (VIH) y el Síndrome de Inmunodeficiencia Adquirida (SIDA) han tenido a lo largo de los años un comportamiento epidemiológico que muestra la tendencia al aumento, de tal forma que ha llegado a considerarse como un problema de salud pública a nivel mundial. Sin embargo los tratamientos antiretrovirales han permitido que las personas con esta infección tengan una tasa de supervivencia mayor; pero ligado a esto, se han presentado efectos secundarios tales como problemas con la memoria y el funcionamiento cognitivo de estas personas. Además se ha encontrado que las personas con VIH/SIDA tienen algunas alteraciones en su área afectiva y generalmente ven afectada su calidad de vida. Este es un estudio exploratorio descriptivo que tuvo por objeto describir la ansiedad, depresión y percepción de calidad de vida en 35 pacientes con VIH/SIDA con deterioro cognitivo leve, seleccionados por conveniencia. Se aplicaron tres cuestionarios, el BDI-II para evaluar la sintomatología depresiva; el BAI para evaluar la sintomatología ansiosa y el MOS-SF30 para evaluar la calidad de vida. Además, se realizó una entrevista semiestructurada para profundizar en la evaluación de estas tres variables. Dentro de los resultados se evidenció que todos los paciente presentan algún nivel de ansiedad y de depresión, evalúan su calidad de vida en un punto medio; ni óptima ni baja. Se discuten estos y otros resultados.

Eficacia de la melatonina en insomnio primario en el adulto mayor: revisión sistemática de la literatura

Introducción: La melatonina, una sustancia cronobiótica endógena, es cada vez más empleada para el manejo de los problemas del sueño en adultos mayores por su aparente eficacia y buen perfil de eventos adversos. En este sentido, se intentó evaluar la eficacia de la melatonina en el tratamiento del insomnio primario en el adulto mayor (≥55 años) comparado con benzodiacepinas, zopiclona y placebo a la luz de la evidencia disponible en los últimos cinco años. Métodos: Revisión sistemática de la literatura. Resultados: En comparación con placebo, al parecer la melatonina mejora la calidad y los hábitos de sueño, no así la latencia de inicio de sueño en mediciones subjetivas ni objetivas (polisomnografía); a diferencia de otros medicamentos hipnóticos, no altera la arquitectura del sueño ni genera síntomas diurnos. Conclusiones: No se encontró evidencia que soporte el uso de melatonina en adultos mayores de 55 años para la reducción de la latencia de sueño, aumento del tiempo total de sueño, mejoría de la eficiencia del sueño, disminución de despertares nocturnos o mejoría de la calidad de sueño. Es necesario adelantar más estudios en comparación con placebo y otros medicamentos.