Showing papers in "Dementia and geriatric cognitive disorders extra in 2013"
TL;DR: Overall, patients with dementia who lived at special care units (SCUs) showed a significantly more challenging behavior, more agitation/aggression, more depression and anxiety, more cases of global cognitive impairment and a better psychosocial functioning.
Abstract: Background: Special care facilities for patients with dementia gain increasing attention. However, an overview of studies examining the differences between care f
2,872 citations
TL;DR: The results suggest that functional activity of the bilateral superior parietal lobules is closely related to performance time on the TMT-A, which might be a promising index of dysfunction of the superiorParietal area among mild AD patients.
Abstract: Background/Aims: The Trail Making Test (TMT) has long been used to investigate deficits in cognitive processing speed and executive function in humans. However, t
2,862 citations
TL;DR: In advanced stages of both diseases, the pattern of functional deficits associated with parietal and temporal lobe functions (attention, visuoconstruction and language) is similar, however, specific differences, already present in the early stage (recognition errors in AD, associated with mediobasal temporal lobe functioning, and depressed mood in PDD), are also observed in the late stage.
Abstract: Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are associated with severe cognitive decline, but it is still unclear to what extent they become functionally more similar over time. Methods: We compared amnestic mild cognitively impaired (aMCI; n = 29) patients to mild cognitively impaired (MCI) PD patients (n = 25), and patients with AD (n = 34) to patients with PD dementia (PDD; n = 15) with respect to cognitive functioning and mood. Results: aMCI patients were impaired in episodic memory, while MCI PD patients showed deficits in visuoconstruction and attention. AD and PDD patients showed comparable deficits on tests for language, attention and visuoconstruction. However, unlike PDD patients but similar to aMCI patients, AD patients showed a characteristic memory impairment, especially commission errors on recognition tasks, whereas PDD patients scored higher on the depressive mood questionnaire. Conclusions: In advanced stages of both diseases, the pattern of functional deficits associated with parietal and temporal lobe functions (attention, visuoconstruction and language) is similar. However, specific differences, already present in the early stage (recognition errors in AD, associated with mediobasal temporal lobe functioning, and depressed mood in PDD, associated with non-motor basal ganglia loops), are also observed in the late stage.
711 citations
TL;DR: The results suggest that a cognitive stimulation treatment for PWDs would improve not only their cognition, but also behavioral symptoms.
Abstract: Background/Aims: This study explores the effective outcomes of a structured cognitive stimulation treatment to improve cognition and behavioral symptoms in people with dementia (PWDs), using a randomized controlled clinical trial. Methods: Thirty PWDs were divided into three groups: experimental (treated with cognitive stimulation), placebo (treated with occupational therapy), and control (continuing with the usual activities of the nursing home). Assessment, at baseline and after a period of 8 weeks, was performed using the Clinical Dementia Rating Scale, activities of daily living, Mini-Mental State Examination, Esame Neuropsicologico Breve 2, Geriatric Depression Scale and Behavioral Pathology in Alzheimer’s Disease Scale. Results: Only the experimental group improved its performance in cognitive tests (p < 0.05) and showed a significant decrease in behavioral symptoms (p < 0.01) after the treatment. Conclusions: The results suggest that a cognitive stimulation treatment for PWDs would improve not only their cognition, but also behavioral symptoms.
492 citations
TL;DR: Extensive variation was observed in conversion rates due to the population sampled, diagnostic criteria, and duration, and because many studies did not account for loss to follow-up.
Abstract: Background: The purpose of this study was to summarize published estimates for conversion from mild cognitive impairment or amnestic mild cognitive impairment to Alzheimer’s dementia. We carried out a systematic review of English language publications to identify cohort studies published since January 2006 that reported the risk or rate of conversion. Summary: Thirty-two cohort studies were identified, of which 14 reported annualized conversion rates (ACRs). Conversions over 1 year ranged from 10.2 to 33.6% (5 studies, median: 19.0%), and over 2 years from 9.8 to 36.3% (7 studies, median: 18.6%). ACRs ranged from 7.5 to 16.5% (7 studies, median: 11.0%) per person-year for studies recruiting from clinics, and from 5.4 to 11.5% (7 studies, median: 7.1%) for community samples. Key Message: Extensive variation was observed in conversion rates due to the population sampled, diagnostic criteria, and duration, and because many studies did not account for loss to follow-up. © 2013 S. Karger AG, Basel
251 citations
TL;DR: There is a multifactorial influence on institutionalization of dementia patients by sociodemographic, health-related, and psychological aspects as well as the care situation, thus validating the predictor model by Luppa et al.
Abstract: Background: Institutionalization is the most important milestone in the care of dementia patients This study was aimed at identifying relevant predictors of institutionalization in a broad empirical context and interpreting them on the basis of the predictor model proposed by Luppa et al [Dement Geriatr Cogn Disord 2008;26:65-78] Methods: At the start of this study, 357 patients with mild to moderate dementia were examined by their general practitioners, and a telephone interview was conducted with their caregivers Four years later, the outcomes ‘institutionalization' and ‘death' were determined from health insurance data Forty-one variables were examined for their predictive influence by univariate and multivariate Cox regression Results: The risk of institutionalization increased significantly (p ≤ 005) with older ages of patients [hazard ratio (HR) = 105] and caregivers (HR = 103), a higher educational level of the caregiver (HR = 183), greater use of community health services (HR = 159), greater caregiver burden (HR = 102), and when the caregiver and patient lived apart (HR = 197) Conclusion: The results show that there is a multifactorial influence on institutionalization of dementia patients by sociodemographic, health-related, and psychological aspects as well as the care situation, thus validating the predictor model by Luppa et al [Dement Geriatr Cogn Disord 2008;26:65-78] Caregiver burden was found to be the strongest predictor accessible to interventions
98 citations
TL;DR: Automatic volume measurement can be used to delineate the characteristic changes in CSF space in patients with INPH and is useful in the diagnosis of INPH.
Abstract: Objectives: To measure the cerebrospinal fluid (CSF) space volume in idiopathic normal pressure hydrocephalus (INPH), we developed a software that allows us to automatically measure the regional CSF space and compared the volumes of the ventricle systems (VS), Sylvian fissures (SF) and sulci at high convexity and midline (SHM) among INPH patients, Alzheimer’s disease (AD) patients and healthy volunteers (HVs). Methods: Fifteen INPH patients, 15 AD patients and 15 HVs were retrospectively selected for this study. 3D-T1 MR images were obtained. We improved upon an automatic gray matter volume system to measure CSF spaces, adopting new regions for the template of INPH-characteristic CSF spaces and measured them. The VS, SF and SHM volumes were calculated relative to the intracranial volume. Results: The relative SHM volume of the INPH group (0.0237 ± 0.0064) was the smallest among the 3 groups (AD: 0.0477 ± 0.0109, HV: 0.0542 ± 0.0045). The VS (0.0499 ± 0.0135) and SF (0.0187 ± 0.0037) volumes of the INPH group were significantly larger than those of the AD (VS: 0.0311 ± 0.0075, SF: 0.0146 ± 0.0026) and HV groups (VS: 0.0167 ± 0.0065, SF: 0.0111 ± 0.017). Conclusion: Automatic volume measurement can be used to delineate the characteristic changes in CSF space in patients with INPH and is useful in the diagnosis of INPH.
82 citations
TL;DR: The MoCA-CS has good reliability and validity, and is a useful cognitive screening instrument for detecting VCI in the Chinese population, and the results indicate that 1 point should be added for subjects with less than 6 years of education, and that the optimal cutoff score for detectingVCI-ND is 26/27.
Abstract: Background/Aims: The goal of this study was to examine the reliability and validity of the Changsha version of the Montreal Cognitive Assessment (MoCA-CS) in ischemic cerebrovascular disease patients of Hunan Province, China, and to explore the optimal cutoff score for detecting vascular cognitive impairment-no dementia (VCI-ND) and vascular dementia (VD) Methods: Three hundred and thirty-eight ischemic cerebrovascular disease patients (131 with normal cognition, 111 with VCI-ND, and 96 with VD) and 132 healthy controls were recruited All participants accepted examination by the MoCA-CS, Mini-Mental State Examination (MMSE), and other related scales A detailed neuropsychological battery was used for making a final cognitive diagnosis SPSS 160 statistical software was used for reliability, validity examination, and optimal cutoff score detection Results: Cronbach’s α of the MoCA-CS was 0884, and test-retest and interrater reliability of the MoCA-CS were 0966 and 0926, respectively MoCA-CS scores were highly correlated with MMSE scores (r = 0867) and simplified intelligence quotients (r = 0822) The results indicate that 1 point should be added for subjects with less than 6 years of education, and that the optimal cutoff score for detecting VCI
53 citations
TL;DR: Context recall, an element of episodic memory, refers to remembering the context in which an event has occurred, such as from whom or to whom information has been transmitted.
Abstract: Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a gradual loss of memory. Specifically, context aspects of memory are impaired in AD. Our review sheds light on the neurocognitive mechanisms of this memory component that forms the core of episodic memory function. Summary: Context recall, an element of episodic memory, refers to remembering the context in which an event has occurred, such as from whom or to whom information has been transmitted. Key Messages: Our review raises crucial questions. For example, (1) which context element is more prone to being forgotten in the disease? (2) How do AD patients fail to bind context features together? (3) May distinctiveness heuristic or decisions based on metacognitive expectations improve context retrieval in these patients? (4) How does cueing at retrieval enhance reinstating of encoding context in AD? By addressing these questions, our work contributes to the understanding of the memory deficits in AD.
45 citations
TL;DR: Investigating correlates of cognitive complaints and cognitive test performance in patients with subjective (SCI) and mild (MCI) cognitive impairment suggests that depressive symptoms areassociated with cognitive complaints, while degenerative changes are associated with objective cognitive decline in high-risk predementia states.
Abstract: Aims: To improve early diagnosis of dementia disease, this study investigates correlates of cognitive complaints and cognitive test performance in patients with subjective (SCI) and mild (MCI) cognitive impairment. Methods: Seventy patients from a memory clinic, aged 45-79, with a score of 2 (n = 23) or 3 (n = 47) on the Global Deterioration Scale, were included. CSF biomarkers [Aβ42, total tau (T-tau) and phosphorylated tau (P-tau)], depressive symptoms, cognitive performance, and complaints were examined. Results: Correlation analysis showed that cognitive complaints increased with decreasing cognitive performance in SCI and decreased with decreasing performance in MCI. Linear regression models revealed that cognitive complaints were associated with depressive symptoms in both groups of patients, while cognitive performance was associated with CSF Aβ42 and P-tau in SCI and with T-tau and P-tau in MCI. Conclusion: These results suggest that depressive symptoms are associated with cognitive complaints, while degenerative changes are associated with objective cognitive decline in high-risk predementia states.
39 citations
TL;DR: Cerebral microbleeds in DLB patients showed less impairment on 123I-metaiodobenzylguanidine myocardial scintigraphy (MIBG) images, supporting the notion of an inverse relationship between vascular lesions and Lewy body pathology.
Abstract: Background: Cerebral microbleeds (MBs) have been well investigated in Alzheimer’s disease (AD), but not very extensively in non-AD dementias or in dementia with Lewy bodies (DLB). Aims: To elucidate the clinical significance of MBs in DLB. Methods: We compared the prevalence, locations and risk factors for MBs in 59 DLB and 81 AD patients. We visually counted MBs in each of the cortical and subjacent areas (frontal, temporal, parietal and occipital), the basal ganglia and the thalamus, and the brainstem and the cerebellar hemispheres on 1.5-tesla T2 * -weighted gradient-recalled-echo MRI images. White matter lesions were semiquantified in fluid-attenuated inversion recovery images according to the Fazekas rating scale. Results: While the prevalence of MBs was comparable, MBs tended to be more abundant in DLB than in AD in all brain areas with the exception of the occipital lobes. The number of MBs was positively associated with the severity of white matter lesions but not with other vascular risk factors in either AD or DLB. The presence of MBs could be associated with cognitive impairment at onset. MB-positive DLB patients showed less impairment on 123 I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy) images, supporting the notion of an inverse relationship between vascular lesions and Lewy body pathology. Conclusion: It was suggested that an intricate association between Lewy body pathology, AD-type pathologies and vascular lesions seems to be related to the initial symptoms and results of MIBG scintigraphy in DLB.
TL;DR: Results suggest that a better 6MWD performance may be related to better memory function and the maintenance of gray matter volume in older adults with MCI.
Abstract: Background/Aims: High fitness levels play an important role in maintaining memory function and delaying the progression of structural brain changes in older people at risk of developing dementia. However, it is unclear which specific regions of the brain volume are associated with exercise capacity. We investigated whether exercise capacity, determined by a 6-min walking distance (6MWD), is associated with measures of logical and visual memory and where gray matter regions correlate with exercise capacity in older adults with mild cognitive impairment (MCI). Methods: Ninety-one community-dwelling older adults with MCI completed a 6-min walking test, structural magnetic resonance imaging scanning, and memory tests. The Wechsler Memory Scale-Revised Logical Memory and Rey-Osterrieth Complex Figure Tests were used to assess logical and visual memory, respectively. Results: The logical and visual memory tests were positively correlated with the 6MWD (p < 0.01). Poor performance in the 6MWD was correlated with a reduced cerebral gray matter volume in the left middle temporal gyrus, middle occipital gyrus, and hippocampus in older adults with MCI. Conclusions: These results suggest that a better 6MWD performance may be related to better memory function and the maintenance of gray matter volume in older adults with MCI.
TL;DR: Routine incorporation of weighted comparison or other similar net benefit measures into diagnostic accuracy studies merits consideration to better inform clinicians of the relative value of cognitive screening instruments.
Abstract: Background/Aims: There are many cognitive screening instruments available to clinicians when assessing patients' cognitive function, but the best way to compare the diagnostic utility of these tests is uncertain. One method is to undertake a weighted comparison which takes into account the difference in sensitivity and specificity of two tests, the relative clinical misclassification costs of true- and false-positive diagnosis, and also disease prevalence. Methods: Data were examined from four pragmatic diagnostic accuracy studies from one clinic which compared the Mini-Mental State Examination (MMSE) with the Addenbrooke's Cognitive Examination-Revised (ACE-R), the Montreal Cognitive Assessment (MoCA), the Test Your Memory (TYM) test, and the Mini-Mental Parkinson (MMP), respectively. Results: Weighted comparison calculations suggested a net benefit for ACE-R, MoCA, and MMP compared to MMSE, but a net loss for TYM test compared to MMSE. Conclusion: Routine incorporation of weighted comparison or other similar net benefit measures into diagnostic accuracy studies merits consideration to better inform clinicians of the relative value of cognitive screening instruments.
TL;DR: A high frequency of neuropsychiatric symptoms is detected; however, these symptoms seem not to be specific to C9ORF72-associated FTLD, which should be considered in cases of middle-age-onset psychosis.
Abstract: Background: The most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) has been linked to a hexanucleotide repeat expansion in the C9ORF72 gene. The frequency of the C9ORF72 expansion in Finland is among the highest in the world. Methods: We assessed 73 Finnish patients with FTLD in order to examine the clinical characteristics associated with the expanded C9ORF72. Demographic and clinical features were evaluated. As a potential disease modifier, the apolipoprotein E (APOE) genotype was also assessed. Neuropathological analysis was available on 2 expansion carriers and 1 non-carrier. Results: The C9ORF72 expansion was present in 20 of 70 (29%) probands. Significant associations with the C9ORF72 expansion were observed for concomitant ALS and positive family history of dementia or ALS. Psychoses were detected in both carriers and non-carriers (21 vs. 10%, p = 0.25). The APOE e4 allele did not cluster among expansion carriers. Numerous p62-positive neuronal inclusions were detected in the cerebellar cortex of the 2 expansion carriers. Conclusion: In line with the suggested C9ORF72 core phenotype, we also detected a high frequency of neuropsychiatric symptoms; however, these symptoms seem not be specific to C9ORF72-associated FTLD. FTLD should be considered in cases of middle-age-onset psychosis.
TL;DR: The 4 SNPs studied here did not influence the risk for AD in a Japanese population and could not find any synergetic associations between these SNPs, APO E4 and AD.
Abstract: Background and Aims: Similar clinical and pathological features have been observed in Alzheimer's disease (AD) and Parkinson's disease with dementia (PDD). Both t
TL;DR: The ongoing ARTEMIDA study will evaluate the efficacy and safety of Actovegin for the symptomatic treatment of post-stroke cognitive impairment (PSCI) and will explore whetheractovegin has any disease-modifying effect by assessing whether any changes are sustained after treatment.
Abstract: Background: No drug treatment to date has shown convincing clinical evidence of restoring cognitive function or preventing further decline after stroke. The ongoing ARTEMIDA study will evaluate the efficacy and safety of Actovegin for the symptomatic treatment of post-stroke cognitive impairment (PSCI) and will explore whether Actovegin has any disease-modifying effect by assessing whether any changes are sustained after treatment. Design: ARTEMIDA is a 12-month, multicentre trial in patients (planned a total of 500, now recruited) with cognitive impairment following ischaemic stroke. The study consists of a baseline screening (≤7 days after stroke), after which eligible patients are randomised to Actovegin (2,000 mg/day for up to 20 intravenous infusions followed by 1,200 mg/day orally) or placebo for a 6-month double-blind treatment period. Patients will be followed up for a further 6 months, during which time they will be treated in accordance with standard clinical practice. The primary study endpoint is change from baseline in the Alzheimer's Disease Assessment Scale, cognitive subscale, extended version. Secondary outcomes include: Montreal Cognitive Assessment; dementia diagnosis (ICD-10); National Institutes of Health Stroke Scale; Barthel Index; EQ-5D; Beck Depression Inventory, version II, and safety. Conclusion: There is a clear need for effective treatments for PSCI. ARTEMIDA should provide important insights into the use of a novel drug therapy for PSCI.
TL;DR: Nondemented early-stage PD patients presented with extensive mild cognitive deficits including prominent memory impairment, which was inconsistent with expected isolated frontostriatal dysfunction previously attributed to dopamine depletion and highlights the need to further characterize extranigral sources of mild cognitive impairment in PD.
Abstract: Aim: The aim of this study was to identify mild cognitive deficits in Parkinson’s disease (PD) prior to extensive neurodegeneration and to evaluate the extent to which dopamine depletion and other disease-related predictors can explain cognitive profiles. Methods: Neuropsychological performances of 40 nondemented early-stage PD patients and 42 healthy controls were compared across on or off dopaminergic medications. Stepwise regression evaluated cognitive predictors of early-stage PD and disease-related predictors of PD cognition (levodopa dose, disease duration, Unified Parkinson’s Disease Rating Scale score, sleep, quality of life, and mood) across on and off states. Results: Neuropsychological performance was lower in PD patients across cognitive domains with significant memory, naming, visuomotor, and complex attention/executive deficits, but with intact visuospatial, simple attention, and phonemic fluency functions. However, medication effects were absent except for simple attention. Regression analyses revealed age, working memory, and memory recall to be the best cognitive predictors of PD, while age, quality of life, disease duration, and anxiety predicted PD cognition in the off state. Conclusion: Nondemented early-stage PD patients presented with extensive mild cognitive deficits including prominent memory impairment. The profile was inconsistent with expected isolated frontostriatal dysfunction previously attributed to dopamine depletion and this highlights the need to further characterize extranigral sources of mild cognitive impairment in PD.
TL;DR: It is suggested that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.
Abstract: Background/Aims: In recent years, the relationship between chronic kidney disease (CKD) and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD) is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years) were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2). SVD was evaluated by the presence and severity of silent brain infarcts (SBIs) and white matter lesions (WMLs) on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017) and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026) after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.
TL;DR: The trial did not show a significant difference between usual care and the intervention on depressive symptoms in PWD or their family caregivers and the intent-to-treat difference was not significant.
Abstract: Background/Aim: A three-component tailored psychosocial 12-month assessor-blinded randomized controlled trial to reduce depression in people with dementia (PWD) and carers was conducted. Methods: A total of 230 home-dwelling dyads of PWD and their carers were randomized to usual care or intervention consisting of three components over 12 months. Primary outcomes were the difference between the baseline and 12-month score on the Cornell Scale of Depression in Dementia (CSDD) in the PWD and on the Geriatric Depression Scale (GDS) in the carers. Results: The intent-to-treat difference between the baseline and 12month change score was not significant between the intervention and control groups for the CSDD (p = 0.95) or GDS (p = 0.82). Conclusions: The trial did not show a significant difference between usual care and the intervention on depressive symptoms in PWD or their family care
TL;DR: The changes in diffusion metrics of white matter long association tracts suggest that the loss of integrity of the networks connecting fronto-temporal areas to parietal and occipital areas contributes to cognitive impairment.
Abstract: Introduction: Executive dysfunction occurs in many patients with amyotrophic lateral sclerosis (ALS), but it has not been well studied in primary lateral sclerosis (PLS). The aims of this study were to (1) compare cognitive function in PLS to that in ALS patients, (2) explore the relationship between performance on specific cognitive tests and diffusion tensor imaging (DTI) metrics of white matter tracts and gray matter volumes, and (3) compare DTI metrics in patients with and without cognitive and behavioral changes. Methods: The Delis-Kaplan Executive Function System (D-KEFS), the Mattis Dementia Rating Scale (DRS-2), and other behavior and mood scales were administered to 25 ALS patients and 25 PLS patients. Seventeen of the PLS patients, 13 of the ALS patients, and 17 healthy controls underwent structural magnetic resonance imaging (MRI) and DTI. Atlas-based analysis using MRI Studio software was used to measure fractional anisotropy, and axial and radial diffusivity of selected white matter tracts. Voxel-based morphometry was used to assess gray matter volumes. The relationship between diffusion properties of selected association and commissural white matter and performance on executive function and memory tests was explored using a linear regression model. Results: More ALS than PLS patients had abnormal scores on the DRS-2. DRS-2 and D-KEFS scores were related to DTI metrics in several long association tracts and the callosum. Reduced gray matter volumes in motor and perirolandic areas were not associated with cognitive scores. Conclusion: The changes in diffusion metrics of white matter long association tracts suggest that the loss of integrity of the networks connecting fronto-temporal areas to parietal and occipital areas contributes to cognitive impairment.
TL;DR: Maintenance of the first prescribed ChEI was supported when some benefit was perceived by the patient or caregiver, even in cases of nonserious adverse events, including Alzheimer's disease or Lewy body dementia.
Abstract: Background: Cholinesterase inhibitors (ChEI) are widely used in dementia, but there is a lack of practice guidelines in case of intolerance or absence of perceived effect. Methods: Two hundred and forty patients (mean age 77 years, SD 6.3, 66% female) with Alzheimer's disease or Lewy body dementia were prescribed a ChEI and evaluated annually under conditions of standard practice. Of these, 152 patients maintained, 36 switched, and 52 abandoned ChEI treatment. Results: Less behavioural disturbance and less cognitive deterioration were observed, respectively, at the 3- and 4-year follow-up assessments in the patients who maintained the first prescribed ChEI (p Conclusions: Maintenance of the first prescribed ChEI was supported when some benefit was perceived by the patient or caregiver, even in cases of nonserious adverse events.
TL;DR: The dichotic digit free recall test showed a significant decline in the AD group compared with the controls (left ear), and the short time span was long enough to disclose a central auditory processing decline in AD.
Abstract: Background/Aims: Central auditory function can be studied to monitor the progression of mild cognitive impairment to dementia. Our aim was to address this issue in a prospective longitudinal setting. Methods: Tests of central hearing function were performed on 70 subjects with either Alzheimer's disease (AD) or mild cognitive impairment, and in controls with subjective memory complaints but normal cognition. The time span until follow-up was 1.5 years. Results: The dichotic digit free recall test showed a significant decline in the AD group compared with the controls (left ear). Conclusion: The short time span was long enough to disclose a central auditory processing decline in AD.
TL;DR: Dysregulation of pre-mRNA splicing from an altered expression of RNA splice-regulatory proteins may act as the convergence point underlying aberrant gene expression changes in Alzheimer's disease.
Abstract: Background/Aims: Dysregulation of pre-mRNA splicing from an altered expression of RNA splice-regulatory proteins may act as the convergence point underlying aberrant gene expression changes in Alzheimer's disease (AD). Methods: Two microarray datasets from a control/AD postmortem brain cohort of 31 subjects - 9 controls and 22 AD subjects (National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database) - were used. Results: Between the two microarray studies, the expression of six splice-regulatory protein genes showed concordant changes in AD. These genes were then correlated with gene expression changes of transcripts reported to be altered in AD. Amyloid beta (A4) precursor protein and tropomyosin receptor kinase B transcripts were found to correlate significantly with the same splice-regulatory proteins in the two studies. Conclusion: This study highlights a susceptibility network that can potentially link a number of susceptibility genes.
TL;DR: The SED-11Q reliably differentiated nondemented from demented individuals when completed by an informant, and thus is practical as a rapid screening tool in general practice, as well as in the community setting, to decide whether to seek further diagnostic confirmation.
Abstract: The aim of this study was to develop a brief informant-based questionnaire, namely the Symptoms of Early Dementia-11 Questionnaire (SED-11Q), for the screening of early dementia. 459 elderly individuals participated, including 39 with mild cognitive impairment in the Clinical Dementia Rating scale (CDR) 0.5, 233 with mild dementia in CDR 1, 106 with moderate dementia in CDR 2, and 81 normal controls in CDR 0. Informants were required to fill out a 13-item questionnaire. Two items were excluded after analyzing sensitivities and specificities. The final version of the SED-11Q assesses memory, daily functioning, social communication, and personality changes. Receiver operator characteristic curves assessed the utility to discriminate between CDR 0 (no dementia) and CDR 1 (mild dementia). The statistically optimal cutoff value of 2/3, which indicated a sensitivity of 0.84 and a specificity of 0.90, can be applied in the clinical setting. In the community setting, a cutoff value of 3/4, which indicated a sensitivity of 0.76 and a specificity of 0.96, is recommended to avoid false positives. The SED-11Q reliably differentiated nondemented from demented individuals when completed by an informant, and thus is practical as a rapid screening tool in general practice, as well as in the community setting, to decide whether to seek further diagnostic confirmation.
TL;DR: The results suggest that it may indeed be relevant to include short and easily administered measures of social cognition in the differential diagnosis of early bvFTD and AD.
Abstract: Background: Traditional cognitive tests used in clinical practice may not be sensitive enough for the early differentiation of behavioral variant frontotemporal dementia (bvFTD) from Alzheimer’s disease (AD). A growing body of literature has shown that deficits in various aspects of social cognition can be found in bvFTD. Aim: The objective of this study is to investigate whether short and easily administered tests of social cognition are useful in providing clinical information which might aid in the differentiation of bvFTD from AD in the early stages of bvFTD. Methods: 11 patients diagnosed with bvFTD and 10 patients diagnosed with AD completed a neuropsychological assessment comprising global, executive and social cognitive tasks. Results: Measures of global cognitive function showed no significant difference between the two groups, whereas even the short social cognitive measures (the Reading the Mind in the Eyes Test and the Emotion Hexagon) showed significant group differences, reflecting a poorer performance by the bvFTD group. Conclusion: Our results suggest that it may indeed be relevant to include short and easily administered measures of social cognition in the differential diagnosis of early bvFTD and AD.
TL;DR: A sample of 42 subjects with mild AD underwent clinical and cognitive evaluation and participated in a 6-month study with 2 experimental groups, finding that client-centered, global, cognitive therapy stimulated many cognitive functions and thus led to a better performance in language processing and ADL/IADL.
Abstract: Background/Aims: Many studies have shown that not only pharmacological treatment but also cognitive stimulation in the early stages of Alzheimer's disease (AD) improves language processing and (other) cognitive functions, stabilizes Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) functions and increases the subjective quality of life (wherein a combination of pharmacological intervention and cognitive stimulation could provide greater relief of clinical symptoms than either intervention given alone). Today, it is no longer the question of whether cognitive stimulation helps but rather what kind of stimulation helps more than others. Methods: A sample of 42 subjects with mild AD (all medicated with an acetylcholinesterase inhibitor and well adjusted) underwent clinical and cognitive evaluation and participated in a 6-month study with 2 experimental groups (i.e. ‘client-centered' global stimulation vs. cognitive training) and a control group. Since the test performance also depends on the individual test, we used a wide variety of tests; we z-transformed the results and then calculated the mean value for the global cognitive status (using the Mini-Mental State Examination) as well as for the single functional areas. Results: Between-group differences were found, they were overall in favor of the experimental groups. Different functional areas led to different treatment and test patterns. Client-centered, global, cognitive therapy stimulated many cognitive functions and thus led to a better performance in language processing and ADL/IADL. The subjective quality of life increased as well. The cognitive training (of working memory) improved only the ADL/IADL performance (more, however, than client-centered, global, cognitive stimulation) and stabilized the level of performance in the other three functional areas.
TL;DR: It is suggested that elevated plasma tHcy might be a sensitive marker for the vascular disease process in patients with VaD and that the level also is a reflection of changes in the other main determinants of plasma t Hcy.
Abstract: Background: Patients with vascular dementia (VaD) exhibit particularly elevated levels of plasma total homocysteine (tHcy) compared to patients with other psychogeriatric diseases. Methods: We investigated the main determinants (age, renal impairment, cobalamin/folate status and presence of extracerebral vascular disease) of plasma tHcy in 525 patients with VaD. Furthermore, 270 patients with depression were used as a reference group to reveal the potential specificity of elevated plasma tHcy in patients with VaD. Results: Elevated plasma tHcy levels in patients with VaD could only partly be attributed to cobalamin/folate deficiency or renal impairment. Plasma tHcy might also be related to the vascular disease process since patients with depression and vascular disease exhibited similar plasma tHcy levels to patients with VaD. Conclusion: Our findings suggest that elevated plasma tHcy might be a sensitive marker for the vascular disease process in patients with VaD and that the level also is a reflection of changes in the other main determinants of plasma tHcy.
TL;DR: Cognitive decline is an independent predictor of new LTCI requirement certifications and the severity of cognitive decline in elderly adults is positively associated with receiving an L TCI requirement certification in Japan.
Abstract: Aim: The purpose of this prospective cohort study is to examine whether cognitive decline is an independent predictor of new long-term care insurance (LTCI) requirement certifications in Japan. Methods: A total of 5,765 community-dwelling older Japanese adults who, at baseline, were independent in terms of their activities of daily living participated in this study and were followed up for 18 months. The outcome measure was the number of new LTCI requirement certifications during the 18-month period of the study. We collected demographic information through questionnaires and assessed cognitive skills with the Cognitive Performance Scale (CPS). The participants were divided into 3 groups according to CPS scores (0, 1, and 2 or greater). Results: During the 18-month period, 399 subjects (6.9%) became newly certified for LTCI services. In a multivariate Cox proportional hazards model, older participants with a CPS score of 1 (adjusted HR: 1.39, 95% CI: 1.08-1.77) and 2 or greater (adjusted HR: 2.27, 95% CI: 1.74-2.96) were significantly more likely to receive an LTCI certification compared to those with a CPS score of 0. Conclusions: Cognitive decline is an independent predictor of new LTCI requirement certifications and the severity of cognitive decline in elderly adults is positively associated with receiving an LTCI requirement certification in Japan.
TL;DR: It is suggested that WMLs in parietal lobes and tau pathology likely have independent but synergistic effects on the reduction of the cognitive reserve capacity of the brain.
Abstract: Background: White matter lesions (WMLs) are a common finding in patients with dementia. This study investigates the relationship between WMLs, hyperphosphorylated tau (P-tau) in cerebrospinal fluid (CSF) and apolipoprotein E (APOE) e4 genotype in prodromal Alzheimer’s disease (AD). Methods: Baseline levels of tau, P-tau and β-amyloid 1–42 in CSF, the presence of WMLs in the brain, and the APOE genotype were ascertained in 159 patients with mild cognitive impairment (MCI) and 38 cognitively healthy controls. Results: After 5.7 years, 58 patients had developed AD. In this group, patients with normal levels of CSF P-tau had higher levels of WMLs in the parietal regions than those with pathological P-tau levels (p < 0.05). Also, patients without APOE e4 alleles had more WMLs in the parietal lobes than those with at least one allele (p < 0.05). MCI patients with pathological P-tau levels and parietal WMLs showed a greater risk of developing AD than those with just one of the two pathological parameters. Conclusions: We suggest that WMLs in parietal lobes and tau pathology likely have independent but synergistic effects on the reduction of the cognitive reserve capacity of the brain. In patients with a more low-grade AD pathology, WMLs in the parietal lobes might increase the risk of developing dementia.
TL;DR: Owing to the protocol of the interviews, assessments and structured observations gathered during the two visits, CDR-NI provides valid and reliable assessment of MCI and dementia in community-living elderly subjects without an informant.
Abstract: Background: The Clinical Dementia Rating (CDR) scale is widely used to assess cognitive impairment in Alzheimer's disease. It requires collateral information from a reliable informant who is not available in many instances. We adapted the original CDR scale for use with elderly subjects without an informant (CDR-NI) and evaluated its reliability and validity for assessing mild cognitive impairment (MCI) and dementia among community-dwelling elderly subjects. Method: At two consecutive visits 1 week apart, nurses trained in CDR assessment interviewed, observed and rated cognitive and functional performance according to a protocol in 90 elderly subjects with suboptimal cognitive performance [Mini-Mental State Examination (MMSE) Results: The CDR-NI scores (0, 0.5, 1) showed good internal consistency (Crohnbach's a 0.83-0.84), inter-rater reliability (κ 0.77-1.00 for six domains and 0.95 for global rating) and test-retest reliability (κ 0.75-1.00 for six domains and 0.80 for global rating), good agreement (κ 0.79) with the clinical assessment status of MCI (n = 37) and dementia (n = 4) and significant differences in the mean scores for MMSE, MOCA and Instrumental Activities of Daily Living (ANOVA global p Conclusion: Owing to the protocol of the interviews, assessments and structured observations gathered during the two visits, CDR-NI provides valid and reliable assessment of MCI and dementia in community-living elderly subjects without an informant.