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Background/Aims: The aim of this study was to determine the consistency of neuropsychiatric subsyndromes of the Neuropsychiatric Inventory across several clinical and demographic subgroups (e.g. dementia subtypes, dementia severity, medication use, age and gender) in a large sample of outpatients with dementia. Methods: Cross-sectional data of 2,808 patients with dementia from 12 centres from the European Alzheimer’s Disease Consortium were collected. Principal component analysis was used for factor analysis. Subanalyses were performed for dementia subtypes, dementia severity, medication use, age and gender. Results: The results showed the relatively consistent presence of the 4 neuropsychiatric subsyndromes ‘hyperactivity’, ‘psychosis’, ‘affective symptoms’ and ‘apathy’ across the subanalyses. The factor structure was not dependent on dementia subtypes, age and gender but was dependent on dementia severity and cholinesterase use. The factors hyperactivity and affective symptoms were present in all subanalyses, but the presence of the factors apathy and psychosis was dependent on use of cholinesterase inhibitors and dementia severity, respectively. Conclusion: The present study provided evidence of the relative consistency of neuropsychiatric subsyndromes across dementia subtypes, age and gender, thereby stressing the importance of thinking about neuropsychiatric subsyndromes instead of separate symptoms. However, the subsyndromes apathy and psychosis were dependent on use of cholinesterase inhibitors and dementia severity. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer’s disease (AD). Methods: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer’s Disease Consortium were collected. Principal component analysis was used for factor analysis. Results: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients. Conclusion: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective To evaluate the concordance of General Practitioners (GPs) with advice for treatment after a multidisciplinary psychogeriatric assessment by the Diagnostic Observation Centre for PsychoGeriatric patients (DOC-PG). Method Concordance checklists, listing the recommendations from the multidisciplinary team, were sent to the GPs in order to establish GP concordance. Regression models were used to study the associations between various patient and GP characteristics and level of concordance. Furthermore, results of a questionnaire (to identify the level of satisfaction regarding the services provided by the DOC-PG) were compared with the level of GP concordance. Results Based on 530 recommendations, the overall GP concordance rate amounted to 71%. The most common types of advice pertained to medication, GP follow-up/advice and referral. GP concordance with advice regarding admissions was the highest, followed by advice concerning the arrangement of daycare, home care and the adaptation of medication. GP concordance was lowest for referral recommendations to other specialties and recommendations regarding psychoeducation. Concordance was higher for patients who lived alone, for patients with fewer cognitive problems, when the number of recommendations did not exceed six and in group practices. Concordance was dependent on the type of advice. Satisfaction with DOC-PG did not correlate with the level of concordance. Conclusions In general, GPs showed a high level of concordance with advice from the DOC-PG. Enhancement of GP concordance can be achieved by limiting the number of recommendations, giving detailed explanations about the purpose of recommendations and educating GPs by doing. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The goal of this study was to compare the efficacy and safety of olanzapine versus haloperidol in the treatment of agitation and aggression in patients with dementia. The subjects were 58 out-patients with dementia and agitation. After baseline assessments and, if necessary, a period of wash-out of a previous antipsychotic drug, they were randomly assigned to 5 weeks of double-blind treatment with either olanzapine or haloperidol. The first 2 weeks were used for dose titration. Subsequently, the patients received a fixed dose of either olanzapine (average dose 4.71 mg) or haloperidol (average dose 1.75 mg) from day 14 to day 35. Both olanzapine and haloperidol decreased agitation significantly (decrease in Cohen-Mansfield Agitation Inventory scores), but there was no significant difference between the two drugs. The two drugs had comparable effects on all secondary outcome measures. They were well tolerated and had a similar side-effect pattern. Our study could not demonstrate the superiority of olanzapine, compared to haloperidol, for the treatment of agitation in patients with dementia. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: transnational and psychometrically appropriate versions of instruments used in the diagnosis of dementia are essential for comparing information between different countries. The Cambridge Examination for Mental Disorders of the Elderly incorporates a brief neuropsychological test battery, Cambridge Cognitive Examination (recently revised version), which provides objective data on performance across a number of cognitive domains. Objective: to harmonise the Cambridge Cognitive Examination between seven European countries. Method: 40 patients with probable or possible Alzheimer' s disease of each of the seven countries were administered the Cambridge Cognitive Examination. The Nurse Observation Scale for Geriatrics was used to assess concordance between cognitive and behavioural measures. Results: only small differences between the various Cambridge Cognitive Examination versions were found, and patterns of correlation between Cambridge Cognitive Examination and the Nurse Observation Scale for Geriatrics were consistent. Conclusion: these findings indicate that the harmonisation of the Cambridge Cognitive Examination was successful. [ABSTRACT FROM AUTHOR]

Background Previous studies have indicated that not all subjects who meet the CAMDEX criteria of ‘minimal dementia’ progress to dementia. In the present study, predictors of outcome in minimally demented subjects were tested. Methods Forty-five subjects with minimal dementia who were participating in a population-based study were followed-up for on average 2.3 years. Variables tested as predictors of outcome were age, the apolipoprotein E (APOE) genotype, and the baseline scores on the MMSE, CAMCOG memory subscale, and fluency. Depression at baseline was tested as a predictor of reversible minimal dementia. Results At follow-up, minimal dementia turned out to be reversible in 11 subjects (24%), and persistent in ten subjects (22%). Twenty-four subjects (53%) had become demented. Predictors of outcome in multivariate analyses were age, score on the CAMCOG memory subscale, and the APOE genotype. Depression was not associated with reversible minimal dementia. Conclusions Subjects who meet the CAMDEX criteria of minimal dementia form a heterogenous group with respect to clinical outcome. Age, the score on the CAMCOG memory subscale, and the APOE genotype can improve predictive accuracy in these subjects. Copyright © 2002 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The concurrent validity of the Hamilton Rating Scale for Depression (HAMD-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS) against the DSM-IV diagnosis ‘depressive disorder’ was assessed in patients with Parkinson's disease (PD). Sixty-three non-demented Parkinson's Disease (PD) patients who attended the outpatient department of an academic hospital were diagnosed according to a standardised research protocol. This protocol consisted of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) to establish the presence or absence of ‘depressive disorder’ according to the DSM-IV criteria, as well as the HAMD-17 and the MADRS. Receiver Operating Characteristics curves (ROC curves) were obtained and the positive and negative predictive values (PPV, NPV) were calculated for different cut-off scores. Maximum discrimination between depressed and non-depressed patients was reached at a cut-off score of 13/14 for the HAMD-17, and at 14/15 for the MADRS. At lower cut-offs, like 11/12 for the HAMD-17 and 14/15 for the MADRS, the high sensitivity and NPV make these scales good screening instruments. At higher cut-offs, such as 16/17 for the HAMD-17 and 17/18 for the MADRS, the high specificity and PPV make these instruments good diagnostic instruments. The diagnostics performance of the HAMD-17 is slightly better than that of the MADRS. This study shows that it is justified to use the HAMD-17 and the MADRS to measure depressive symptoms in both non-depressed and depressed PD patients, to diagnose depressive disorder in PD, and to dichotomize patient samples into depressed and non-depressed groups. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the course of objective memory impairment in non-demented subjects who attended a memory clinic and to test predictors of outcome. Non-demented subjects (N =74) were included when they were older than 40 years and had a baseline score on the delayed recall of a word learning test below the tenth percentile. Subjects with memory impairment due to known somatic or neurological causes were excluded. The subjects were reassessed after 2 and 5 years. At the 5-year follow-up, 42% of the subjects had no memory impairment, 19% of the subjects had memory impairment without dementia, and 39% of the subjects had Alzheimer type dementia (AD). Predictors at baseline of reversible memory impairment in a multivariate analysis were age, scores on the MMSE and delayed recall, and the degree of functional impairment. Predictors at baseline of AD in a multivariate analysis were age and the score on the MMSE. The apolipoprotein E genotype and the presence of depression at baseline were not predictors of outcome. The positive predictive value was 72% for reversible memory impairment and 81% for AD. Memory impairment is often reversible and therefore its presence alone is not sufficient to consider subjects as preclinically demented. Predictive accuracy can be increased by including simple measures such as age, the scores on the MMSE and delayed recall, and the degree of functional impairment. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We examined 170 outpatients, 103 with Alzheimer’s disease, 43 with vascular dementia and 24 with various other causes, in order to investigate whether or not depressive symptoms were more like to occur in dementia patients who had some degree of awareness of their cognitive deterioration. Awareness was rated on a four-point scale that assessed discrepancies between the patient’s and the caregiver’s history. The level of awareness was significantly related to the severity of dementia but not to depression or to the score on Hamilton’s depression scales. However, the score from the item ‘psychic anxiety’ showed a weak but significant correlation with the level of awareness of one’s deficits. It is conclude that intact awareness of deterioration was not clearly related to the development of depression or depression or depressive symptoms in dementia. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about psychiatric disorders in patients attending an outpatient memory clinic, published in the October 1, 1995 issue of the "International Journal of Geriatric Psychiatry."

Background: Individuals with depression have an increased dementia risk, which might be due to modifiable risk factors for dementia. This study investigated the extent to which the increased risk for dementia in depression is explained by modifiable dementia risk factors. Methods: We used data from the English Longitudinal Study of Ageing (2008–2009 to 2018–2019), a prospective cohort study. A total of 7460 individuals were included [mean(standard deviation) age, 65.7 ± 9.4 years; 3915(54.7%) were women]. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale-8 (score ≥3) or self-reported doctor's diagnosis. Ten modifiable risk factors for dementia were combined in the 'LIfestyle for BRAin health' (LIBRA) score. Dementia was determined by physician diagnosis, self-reported Alzheimer's disease or the shortened version of the Informant Questionnaire on Cognitive Decline in the Elderly (average score ≥3.38). Structural equation modelling was used to test mediation of LIBRA score. Results: During 61 311 person-years, 306 individuals (4.1%) developed dementia. Participants aged 50–70 years with depressive symptoms had higher LIBRA scores [difference(s.e.) = 1.15(0.10)] and a 3.59 times increased dementia risk [HR(95% CI) = 3.59(2.20–5.84)], adjusted for age, sex, education, wealth and clustering at the household level. In total, 10.4% of the dementia risk was mediated by differences in LIBRA score [indirect effect: HR = 1.14(1.03–1.26)], while 89.6% was attributed to a direct effect of depressive symptoms on dementia risk [direct effect: HR = 3.14(2.20–5.84)]. Conclusions: Modifiable dementia risk factors can be important targets for the prevention of dementia in individuals with depressive symptoms during midlife. Yet, effect sizes are small and other aetiological pathways likely exist. [ABSTRACT FROM AUTHOR]

The aim of the current study was to investigate the health-related quality of life (HRQol) of the family caregiver in MCI, explore possible determinants and study possible differences with mild dementia. This secondary data analysis included 145 persons with MCI and 154 persons with dementia and their family caregivers from two Dutch cohort studies. HRQoL was measured with the VAS of the EuroQol-5D-3L version. Regressions analyses were conducted to examine potential demographic and clinical determinants of the caregiver's HRQoL. The mean EQ5D-VAS in family caregivers of persons with MCI was 81.1 (SD 15.7), and did not significantly differ from family caregivers in mild dementia (81.9 (SD 13.0)). In MCI, patient measurements were not significantly associated with caregiver mean EQ5D-VAS. Concerning caregiver characteristics, being a spouse and a lower educational level were associated with a lower mean EQ5D-VAS (in a multiple linear regression model: unstandardized B −8.075, p = 0.013 and unstandardized B −6.162, p = 0.037 resp.). In mild dementia, the NPI item irritability showed an association with caregiver EQ5D-VAS in bivariate linear regression analyses. Results indicate that especially family caregiver characteristics seem to influence family caregiver HRQoL in MCI. Future research should include other potential determinants such as burden, coping strategies and relationship quality. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers. In previous reports, we demonstrated that AD biomarkers amyloid-beta and tau, are measurable in tear fluid and are associated with disease severity and neurodegeration. This study aims to validate previous results in a larger cohort and evaluate the diagnostic accuracy of tear biomarkers to discriminate between individuals with and without neurodegeneration as determined by hippocampal atrophy. Methods: The TearAD study is an observational longitudinal multi-center study that will enroll 50 cognitively healthy controls, 50 patients with subjective cognitive decline, 50 patients with mild cognitive impairment and 50 patients with AD dementia from the memory clinic. Participants will be examined at baseline, after one year, and after two years follow-up. Study assessments include neuropsychological tests and ophthalmic examination. All participants will receive a MRI scan, and a subset of the study population will undergo cerebral spinal fluid collection and an amyloid PET scan. Tear fluid will be collected with Schirmer strips and levels of Aβ38, Aβ40, Aβ42, t-tau and p-tau in tear fluid will be determined using multiplex immunoassays. Blood samples will be collected from all participants. Images of the retina will be obtained with a standard, hyperspectral and ultra-wide field fundus camera. Additionally, macular pigment optical density will be measured with the macular pigment reflectometer, and cross-sectional images of the retina will be obtained through optical coherence tomography imaging. Discussion: The TearAD study will provide insight into the potential diagnostic use of tear biomarkers as a minimally invasive and low cost tool for the screening and diagnosis of AD. Trial registration: Retrospectively registered at clinicaltrials.gov (NCT05655793). [ABSTRACT FROM AUTHOR]

A biography of the German neuropsychiatrist Alois Alzheimer is presented. He was born on June 14, 1864 in Marktbreit am Main, Bavaria, and studied medicine in Tübingen, Berlin and Würzburg, Germany. He gave a lecture for South German neuropsychiatrists on November 3, 1906 entitled "Ueber eine eigenartige Erkrankung der Hirnrinde" which is all about a remarkable illness of the cerebral cortex.

Presents a letter to the editor referencing a study about the characteristics of the preclinical Alzheimer's disease.

The authors discuss several studies related to capacity building of early stage psychosocial dementia researchers in Europe. Topics covered include the needs and quality of life of people with dementia and their caregivers, the use and implementation of Dementia Care Mapping with the RE-AIM Framework to support care experts working in 12 group homes, and the effectiveness and acceptability of training interventions with a communication component aimed at target groups.

Background: Older patients suffering from a combination of psychiatric disorders and physical illnesses and/or dementia are called Double Care Demanding patients (DCDs). Special wards for DCDs within Dutch nursing homes (NHs) and mental health care institutions (MHCIs) offer a unique opportunity to obtain insight into the characteristics and needs of this challenging population. Methods: This observational cross-sectional study collected data from 163 DCDs admitted to either a NH or a MHCI providing specialized care for DCDs. Similarities and differences between both DCD groups are described. Results: Neuropsychiatric symptoms were highly prevalent in all DCDs but significantly more in MHCI-DCDs. Cognitive disorders were far more present in NH-DCDs, while MHCI-DCDs often suffered from multiple psychiatric disorders. The severity of comorbidities and care dependency were equally high among all DCDs. NH-DCDs expressed more satisfaction in overall quality of life. Conclusions: The institutionalized elderly DCD population is very heterogeneous. Specific care arrangements are necessary because the severity of a patient's physical illness and the level of functional impairment seem to be equally important as the patient's behavioural, psychiatric and social problems. Further research should assess the adequacy of the setting assignment and the professional skills needed to provide adequate care for elderly DCDs. [ABSTRACT FROM AUTHOR]

Municipalities in Western Europe have increasingly gained a responsibility to support their populations' healthy ageing, but are they ready to do so? In this case study, we are looking into the awareness, attitudes, capacities and mandates of 33 neighboring Belgian, Dutch, and German municipalities to support ageing people, and especially people with dementia, people with late‐life depression and informal caregivers. As part of the Senior Friendly Communities Interreg project, we conducted semi‐structured interviews with municipal policymakers and relevant stakeholders from May 2017 to January 2018. The results show that dementia was a more salient theme in municipality policies than depression; that informal caregivers were considered important but difficult for municipalities to identify; that there was a difference between how embedded these health themes were in policies versus in practice; and lastly, that conducting this assessment turned out to act as an intervention itself. We discuss the similarities and differences between the regions, and the context that needs to be taken into account for municipalities when becoming more age‐friendly. These results do not only provide an insight into the status quo of the participating municipalities with regard to becoming more age‐friendly but can provide a starting point for further development of policies in this area. Key points: The Senior Friendly Communities project stimulates age‐friendly municipality policies for people with dementia, people with late‐life depression, and informal caregivers.This paper describes the results of interviews with officials from municipalities in the Meuse‐Rhine Euroregion who participated in the Senior Friendly Communities project.The results indicate that dementia is a more salient topic in municipality policies than depression.Informal caregivers are regarded as difficult to identify for municipalities.The support of healthy ageing differs between policies and practice.Conducting assessments of municipal health policies acted as an intervention itself. [ABSTRACT FROM AUTHOR]

Background: Individuals with depression often experience widespread and persistent cognitive deficits, which might be due to brain atrophy and cerebral small vessel disease (CSVD). We therefore studied the associations between depression, markers of brain atrophy and CSVD, and cognitive functioning. Methods: We used cross-sectional data from the population-based Maastricht study (n = 4734; mean age 59.1 ± 8.6 years, 50.2% women), which focuses on type 2 diabetes. A current episode of major depressive disorder (MDD, n = 151) was assessed by the Mini-International Neuropsychiatric Interview. Volumes of cerebral spinal fluid, white matter, gray matter and white matter hyperintensities, presence of lacunar infarcts and cerebral microbleeds, and total CSVD burden were assessed by 3 T magnetic resonance imaging. Multiple linear and logistic regression analyses tested the associations between MDD, brain markers and cognitive functioning in memory, information processing speed, and executive functioning & attention, and presence of cognitive impairment. Structural equation modeling was used to test mediation. Results: In fully adjusted models, MDD was associated with lower scores in information processing speed [mean difference = −0.18(−0.28;−0.08)], executive functioning & attention [mean difference = −0.13(−0.25;−0.02)], and with higher odds of cognitive impairment [odds ratio (OR) = 1.60(1.06;2.40)]. MDD was associated with CSVD in participants without type 2 diabetes [OR = 1.65(1.06;2.56)], but CSVD or other markers of brain atrophy or CSVD did not mediate the association with cognitive functioning. Conclusions: MDD is associated with more impaired information processing speed and executive functioning & attention, and overall cognitive impairment. Furthermore, MDD was associated with CSVD in participants without type 2 diabetes, but this association did not explain an impaired cognitive profile. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment and neuropsychiatric syndromes, like depression and apathy, are frequent residual consequences of stroke. These have a large impact on quality of life and long-term prognosis. Several factors are involved in the development of these residual syndromes, although their exact role and their interrelationships remain still rather unclear. The Cognition and Affect after Stroke: a Prospective Evaluation of Risks (CASPER) study has been primarily designed to examine whether stroke-specific (e.g. lesion location, volume, type, severity), cerebrovascular and neurodegenerative (e.g. white matter changes, atrophy, microbleeds, perivascular spaces), inflammatory, endothelial, and (epi)genetic markers are associated with cognitive impairment, post-stroke depression, and post-stroke apathy, and whether they predict their course over 12 months. The secondary aims are to investigate how the above-mentioned markers interact with each other, and to determine if patients with apathy and depression after stroke differ in pathogenesis, course, and outcome (e.g. functional outcome, neurocognitive performance, quality of life). Methods/design: CASPER is a 1-year prospective clinical cohort follow-up study in 250 stroke patients recruited at the neurological in- and outpatient services at Maastricht University Medical Center (MUMC+, Maastricht, The Netherlands), and Zuyderland Medical Center (Sittard and Heerlen, The Netherlands). At baseline (3 months post-stroke), a neuropsychological assessment, neuropsychiatric interview, blood sample, and brain magnetic resonance imaging (MRI) scan are conducted. Assessment of neuropsychiatric and neurocognitive status are repeated 6 and 12 months later. Discussion: The CASPER study investigates stroke-specific, vascular, neurodegenerative, inflammatory, and genetic markers of the development of vascular cognitive impairment, depression, and apathy after stroke. This creates the possibility to study not only the contribution of these individual markers but also their joint contribution, which differentiates this study from earlier stroke cohorts who lacked long-term follow-up data, a large sample size, an extensive MRI protocol, and markers from the blood. The knowledge we derive from this study might help in identifying markers that are associated with, or can predict the onset, maintenance, and progression of vascular cognitive impairment, depression, and apathy after stroke, and could provide new insights into possibilities for treatment and rehabilitation that result in better functional outcome after stroke. Trial Registration: ClinicalTrials.gov NCT02585349. [ABSTRACT FROM AUTHOR]

Background: Strong longitudinal evidence exists that psychological distress is associated with a high morbidity and mortality risk in type 2 diabetes. Little is known about the biological and behavioral mechanisms that may explain this association. Moreover, the role of personality traits in these associations is still unclear. In this paper, we first describe the design of the psychological part of The Maastricht Study that aims to elucidate these mechanisms. Next, we present exploratory results on the prevalence of depression, anxiety and personality traits in type 2 diabetes. Finally, we briefly discuss the importance of these findings for clinical research and practice. Methods: We measured psychological distress and depression using the MINI diagnostic interview, the PHQ-9 and GAD-7 questionnaires in the first 864 participants of The Maastricht Study, a large, population-based cohort study. Personality traits were measured by the DS14 and Big Five personality questionnaires. Type 2 diabetes was assessed by an oral glucose tolerance test. Logistic regression analyses were used to estimate the associations of depression, anxiety and personality with type 2 diabetes, adjusted for age, sex and education level. Results: Individuals with type 2 diabetes had higher levels of depressive and anxiety symptoms, odds ratios (95 % CI) were 3.15 (1.49; 6.67), 1.73 (0.83-3.60), 1.50 (0.72-3.12), for PHQ-9 ≥ 10, current depressive disorder and GAD-7 ≥ 10, respectively. Type D personality, social inhibition and negative affectivity were more prevalent in type 2 diabetes, odds ratios were 1.95 (1.23-3.10), 1.35 (0.93-1.94) and 1.70 (1.14-2.51), respectively. Individuals with type 2 diabetes were less extraverted, less conscientious, less agreeable and less emotionally stable, and similar in openness to individuals without type 2 diabetes, although effect sizes were small. Conclusions: Individuals with type 2 diabetes experience more psychological distress and have different personality traits compared to individuals without type 2 diabetes. Future longitudinal analyses within The Maastricht Study will increase our understanding of biological and behavioral mechanisms that link psychological distress to morbidity and mortality in type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE Hypertension and diabetes are both risk factors for cognitive decline, and individuals with both might have an especially high risk. We therefore examined linear and nonlinear (quadratic) associations of 24-h blood pressure (BP) with cognitive performance in participants with and without type 2 diabetes. We also tested the association of nocturnal dipping status with cognitive performance. RESEARCH DESIGN AND METHODS This study was performed as part of the Maastricht Study, an ongoing population- based cohort study. Cross-sectional associations of 24-h BP (n = 713, of whom 201 had type 2 diabetes) and nocturnal dipping status (n = 686, of whom 196 had type 2 diabetes) with performance on tests for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition were tested using linear regression analysis and adjusted for demographics, vascular risk factors, cardiovascular disease, depression, and lipid-modifying and antihypertensive medication use. RESULTS After full adjustment, we found quadratic (inverted U-shaped) associations of 24-h diastolic blood pressure (DBP) with information processing speed (b for quadratic term = -20.0267, P < 0.01) and memory (immediate word recall: b = -0.0180, P < 0.05; delayed word recall: b = -0.0076, P < 0.01) in participants with diabetes, but not in those without. No clear pattern was found for dipping status. CONCLUSIONS This study shows that both low and high 24-h DBP are associated with poorer performance on tests of information processing speed and memory in individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Increased total tau (t-tau) in cerebrospinal fluid (CSF) is a key characteristic of Alzheimer's disease (AD) and is considered to result from neurodegeneration. T-tau levels, however, can be increased in very early disease stages, when neurodegeneration is limited, and can be normal in advanced disease stages. This suggests that t-tau levels may be driven by other mechanisms as well. Because tau pathophysiology is emerging as treatment target for AD, we aimed to clarify molecular processes associated with CSF t-tau levels. Methods: We performed a proteomic, genomic, and imaging study in 1380 individuals with AD, in the preclinical, prodromal, and mild dementia stage, and 380 controls from the Alzheimer's Disease Neuroimaging Initiative and EMIF-AD Multimodality Biomarker Discovery study. Results: We found that, relative to controls, AD individuals with increased t-tau had increased CSF concentrations of over 400 proteins enriched for neuronal plasticity processes. In contrast, AD individuals with normal t-tau had decreased levels of these plasticity proteins and showed increased concentrations of proteins indicative of blood–brain barrier and blood-CSF barrier dysfunction, relative to controls. The distinct proteomic profiles were already present in the preclinical AD stage and persisted in prodromal and dementia stages implying that they reflect disease traits rather than disease states. Dysregulated plasticity proteins were associated with SUZ12 and REST signaling, suggesting aberrant gene repression. GWAS analyses contrasting AD individuals with and without increased t-tau highlighted several genes involved in the regulation of gene expression. Targeted analyses of SNP rs9877502 in GMNC, associated with t-tau levels previously, correlated in individuals with AD with CSF concentrations of 591 plasticity associated proteins. The number of APOE-e4 alleles, however, was not associated with the concentration of plasticity related proteins. Conclusions: CSF t-tau levels in AD are associated with altered levels of proteins involved in neuronal plasticity and blood–brain and blood-CSF barrier dysfunction. Future trials may need to stratify on CSF t-tau status, as AD individuals with increased t-tau and normal t-tau are likely to respond differently to treatment, given their opposite CSF proteomic profiles. [ABSTRACT FROM AUTHOR]

Objectives: To explain the heterogeneity in dementia disease trajectory, we studied the influence of changing patient characteristics on disease course by comparing the association of dementia progression with baseline comorbidity and frailty, and with time-varying comorbidity and frailty.Methods: We used individual growth models to study baseline and time-varying associations in newly diagnosed dementia patients (n = 331) followed for 3 years. We measured cognition using the Mini-Mental State Examination (MMSE), daily functioning using the Disability Assessment for Dementia (DAD), frailty using the Fried criteria and comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G).Results: Although baseline comorbidity and frailty were associated with decreased daily functioning at diagnosis, their effects clearly diminished over time. In contrast, when incorporating comorbidity and frailty as time-varying covariates, comorbidity was associated with lower daily functioning, and frailty with both lower cognition and daily functioning. Being frail was associated with a 0.9-point lower MMSE score (p = 0.03) and a 14.9-point lower DAD score (p < 0.01). A 1-point increase in CIRS-G score was associated with a 1.1-point lower DAD score (p < 0.01).Conclusions: Time-varying comorbidity and frailty were more consistently associated with dementia disease course than baseline comorbidity and frailty. Therefore, modeling only baseline predictors is insufficient for understanding the course of dementia in a changing patient context. [ABSTRACT FROM AUTHOR]

Background: Increased total tau (t-tau) in cerebrospinal fluid (CSF) is a key characteristic of Alzheimer's disease (AD) and is considered to result from neurodegeneration. T-tau levels, however, can be increased in very early disease stages, when neurodegeneration is limited, and can be normal in advanced disease stages. This suggests that t-tau levels may be driven by other mechanisms as well. Because tau pathophysiology is emerging as treatment target for AD, we aimed to clarify molecular processes associated with CSF t-tau levels. Methods: We performed a proteomic, genomic, and imaging study in 1380 individuals with AD, in the preclinical, prodromal, and mild dementia stage, and 380 controls from the Alzheimer's Disease Neuroimaging Initiative and EMIF-AD Multimodality Biomarker Discovery study. Results: We found that, relative to controls, AD individuals with increased t-tau had increased CSF concentrations of over 400 proteins enriched for neuronal plasticity processes. In contrast, AD individuals with normal t-tau had decreased levels of these plasticity proteins and showed increased concentrations of proteins indicative of blood–brain barrier and blood-CSF barrier dysfunction, relative to controls. The distinct proteomic profiles were already present in the preclinical AD stage and persisted in prodromal and dementia stages implying that they reflect disease traits rather than disease states. Dysregulated plasticity proteins were associated with SUZ12 and REST signaling, suggesting aberrant gene repression. GWAS analyses contrasting AD individuals with and without increased t-tau highlighted several genes involved in the regulation of gene expression. Targeted analyses of SNP rs9877502 in GMNC, associated with t-tau levels previously, correlated in individuals with AD with CSF concentrations of 591 plasticity associated proteins. The number of APOE-e4 alleles, however, was not associated with the concentration of plasticity related proteins. Conclusions: CSF t-tau levels in AD are associated with altered levels of proteins involved in neuronal plasticity and blood–brain and blood-CSF barrier dysfunction. Future trials may need to stratify on CSF t-tau status, as AD individuals with increased t-tau and normal t-tau are likely to respond differently to treatment, given their opposite CSF proteomic profiles. [ABSTRACT FROM AUTHOR]

Background: The locus coeruleus (LC) plays a critical role in modulating emotional memory performance via widespread connections to the medial temporal lobe (MTL). Interestingly, both the LC and MTL are affected during aging. Therefore, we aimed to investigate whether worry during cognitive aging changes the relationship between memory performance and the neural activity patterns during an emotional memory task. Methods: Twenty-eight participants aged 60–83 years from the Maastricht Aging study conducted an emotional mnemonic discrimination task during a 7T fMRI-scan. We performed a robust multiple linear regression to examine the association between worry and mnemonic memory performance under different levels of arousal. Subsequently, we examined if worry modifies the relationship between neuronal activity and mnemonic memory performance. Results: We observed that under low arousal, only participants with low compared to high levels of worry benefitted from additional LC activity. Under high arousal, additional LC activity was associated with lower mnemonic memory performance. Conclusion: Our results suggest there might be an optimal involvement of the NA-system for optimal memory discrimination performance, as we observed that under low levels of worry and with lower levels of arousal, higher LC activity might be needed to achieve similar levels of optimal memory performance as achieved under higher arousal when LC activity remained lower. [ABSTRACT FROM AUTHOR]

Objectives: A psychosocial intervention for spousal carers of people with dementia promoted emotional well-being through self-monitoring and personalized feedback, as demonstrated in a previous randomized controlled trial. The mechanism behind the intervention effects is thought to lie in increased awareness of, and thus, engagement in behaviours that elicit positive emotions (PA). This secondary analysis tests the assumption by investigating momentary data on activities, affect, and stress and explores the relevance of personalized feedback compared to self-monitoring only. Methods: The intervention was based on the experience sampling method (ESM), meaning that carers self-monitored own affect and behaviours 10 times/day over 6 weeks. The experimental group received personalized feedback on behaviours that elicit PA, while the pseudo-experimental group performed self-monitoring only. A control group was also included. ESM-data of 72 carers was analysed using multilevel mixed-effects models. Results: The experimental group reported significant increases in passive relaxation activities over the 6 weeks (B = 0.28, SE = 0.12, Z = 2.43, p <.05). Passive relaxation in this group was negatively associated with negative affect (r = –0.50, p =.01) and positively associated with activity-related stress (r = 0.52, p =.007) from baseline to post-intervention. Other activities in this or the other groups did not change significantly. Conclusion: Carer's daily behaviours were only affected when self-monitoring was combined with personalized feedback. Changing one's daily behaviour while caring for a person with dementia is challenging and aligned with mixed emotions. Acknowledging simultaneously positive and negative emotions, and feelings of stress is suggested to embrace the complexity of carer's life and provide sustainable support. [ABSTRACT FROM AUTHOR]

There has been increasing interest in finding non-invasive biomarkers for neurodegenerative diseases such as Alzheimer's disease (AD). This observational study investigated AD-specific biomarkers in tear fluid. Tear fluid was collected from a total of 65 subjects, including 23 patients with subjective cognitive decline (SCD), 22 patients with mild cognitive impairment (MCI), 11 dementia patients and 9 healthy controls (HC). Levels of amyloid-beta peptides (AB38, AB40, AB42), total-tau (t-tau) and phosphorylated-tau (p-tau) were determined using multiplex immunoassays. Levels of AB40 and t-tau were detectable in the vast majority (> 94%) of tear fluid samples. Cerebrospinal fluid (CSF) was available from a subset of patients. In this group, tear t-tau levels were significantly higher in people with dementia compared to SCD patients. Tear t-tau levels were elevated in patients with neurodegeneration (classified according to the A/T/N system) compared to patients without neurodegeneration. Negative correlations were found between CSF AB42 and CSF t-tau, and between CSF AB42 and tear t-tau. In summary, this study shows the potential of tau proteins in tear fluid to be associated with disease severity and neurodegeneration. [ABSTRACT FROM AUTHOR]

The aim of this study was to gain insight into the experiences of patients and their family members regarding a neuropsychological assessment (NPA) and the diagnostic disclosure given by the medical specialist (psychiatrist, geriatrician, or their residents) at the memory clinic (MC). Patients with and without a cognitive impairment and their family members were recruited from three Dutch MCs. Four focus groups with 14 patients and 13 family members were analyzed using both inductive and deductive content analysis. Three themes were identified: uncertainty, early diagnostic paradox, and knowledge utilization. High levels of uncertainty were experienced throughout the NPA and diagnostic disclosure. The early diagnostic paradox refers to the coexistence of negative emotions, feeling distressed due to undergoing an NPA that made them aware of their cognitive complaints, and the experience of relief due to insight given by the outcome of the NPA and medical diagnosis. Knowledge utilization refers to a low retention of medical information. Clinicians can reduce uncertainty by using clear communication, limiting interruptions during an NPA, and paying attention to contextual factors. Low information retention could possibly be improved by involving a family member and using visual aids or written information during the diagnostic disclosure. Finally, participants also appreciated being provided with neuropsychological feedback on the strengths and weaknesses of their cognitive profiles and with guidance on how to manage this diagnosis in their daily lives. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of baseline and incident diabetes on change in cognitive function over 12 years.Research Design and Methods: A sample of 1,290 individuals aged ≥ 40 years at baseline, participating in the Maastricht Aging Study, were cognitively tested at baseline, after 6 years, and after 12 years. Of these, 68 participants had type 2 diabetes at baseline, and 54 and 57 had incident diabetes at the 6- and 12-year follow-up, respectively. Changes in performance on tests of information-processing speed, executive function, and verbal memory from baseline to 6- and 12-year follow-up were compared between groups using linear mixed models. Effects of diabetes on cognitive decline were adjusted for demographic variables, history of smoking, alcohol intake, and comorbid conditions, including hypertension, cardiovascular disease, BMI, and depression.Results: Participants with baseline diabetes showed larger decline in information-processing speed (estimate -7.64; P < 0.01), executive function (21.82; P < 0.01), and delayed word recall (-1.35; P < 0.05) over the 12-year follow-up compared with control subjects. No significant difference in decline was observed for immediate word recall. Compared with control subjects, participants with incident diabetes showed subtle early decline in information-processing speed only. Interestingly, they did not show larger decline in any other cognitive domain.Conclusions: Individuals with baseline type 2 diabetes show accelerated cognitive decline, particularly in information-processing speed and executive function, compared with individuals without diabetes. In incident diabetes, decline in speed becomes detectable first, and cognitive decline seems to increase with increasing exposure time. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine the effects of baseline and incident diabetes on change in cognitive function over 12 years. RESEARCH DESIGN AND METHODS--A sample of 1,290 individuals aged ≥40 years at baseline, participating in the Maastricht Aging Study, were cognitively tested at baseline, after 6 years, and after 12 years. Of these, 68 participants had type 2 diabetes at baseline, and 54 and 57 had incident diabetes at the 6- and 12-year follow-up, respectively. Changes in performance on tests of information-processing speed, executive function, and verbal memory from baseline to 6- and 12-year follow-up were compared between groups using linear mixed models. Effects of diabetes on cognitive decline were adjusted for demographic variables, history of smoking, alcohol intake, and comorbid conditions, including hypertension, cardiovascular disease, BMI, and depression. RESULTS--Participants with baseline diabetes showed larger decline in information-processing speed (estimate 27.64; P < 0.01), executive function (21.82; P < 0.01), and delayed word recall (21.35; P < 0.05) over the 12-year follow-up compared with control subjects. No significant difference in decline was observed for immediate word recall. Compared with control subjects, participants with incident diabetes showed subtle early decline in information-processing speed only. Interestingly, they did not show larger decline in any other cognitive domain. CONCLUSIONS--Individuals with baseline type 2 diabetes show accelerated cognitive decline, particularly in information-processing speed and executive function, compared with individuals without diabetes. In incident diabetes, decline in speed becomes detectable first, and cognitive decline seems to increase with increasing exposure time. [ABSTRACT FROM AUTHOR]

To date, the exact pathogenesis of dementia is still unknown. The most frequently hypothesized initiating factor is an accumulation of the protein amyloid-β in the brain, which has been associated with dementia of the Alzheimer type. Another potentially important initiating factor is a disrupted blood-brain barrier. This can initiate cerebral microangiopathy, which has frequently been associated with vascular dementia. Although amyloid-β and blood-brain barrier dysfunction have both been associated with one particular type of dementia (Alzheimer's disease and vascular dementia, respectively), they co-exist in most demented patients. In fact, increasing evidence indicates that amyloid-β and blood-brain barrier disruption may interact and facilitate each other in their effect on neurodegeneration. The present systematic analysis describes the available evidence for a significant interplay between amyloid-β and blood-brain barrier function in dementia. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to estimate the influence of environmental correlates of neuropsychiatric symptoms in nursing home patients with dementia. Methods 1289 patients in 56 Dementia Special Care Units (SCUs) in the Netherlands were assessed using the Neuropsychiatric Inventory–Nursing Home version (NPI–NH) and the Cohen-Mansfield Agitation Inventory (CMAI). Potential correlates of the neuropsychiatric symptoms studied were gender and age of the patient, dementia severity, psychoactive medication use and environmental correlates such as the number of patients per unit or per living room, staff size/patient ratio, time spent on care activities and presence of a walking circuit. Multilevel logistic regression analysis was used to estimate the relative contribution of the different factors in explaining neuropsychiatric symptoms variability. Results The prevalence of neuropsychiatric symptoms differed between SCUs, also after correcting for patient factors. Patient-related factors explained 7–21% of the total variance of neuropsychiatric symptoms. Intra Class Correlation (the correlation of symptoms of patients within SCUs) ranged from 0.039 (psychosis) to 0.163 (apathy). The variance in SCU symptom prevalence (variance between SCUs) accounted for 3.5–14.8% of the total variance in neuropsychiatric symptoms. In SCUs of which the staff spent more time on care activities did the patients show lower levels of apathy. Other environmental correlates did not predict neuropsychiatric symptoms. Conclusion The substantial variation of prevalence rates between SCUs in combination with the clustering of symptoms within SCUs is strong evidence for the environmental contribution to neuropsychiatric symptoms and the multifactorial nature of behaviour in dementia. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Nursing home residents needing both psychiatric care and nursing home care for either somatic illness or dementia combined with psychiatric disorders or severe behavioural problems are referred to as Double Care Demanding patients, or DCD patients. Integrated models of care seem to be necessary in order to improve the well-being of these residents. Objectives Two research questions were addressed. First, which integrated interventions combining both psychiatric care and nursing home care in DCD nursing home residents are described in the research literature? And second, which outcomes of integrated interventions combining both psychiatric care and nursing home care in DCD nursing home residents are reported in the literature? Method A critical review of studies was done that involved integrated interventions combining both psychiatric care and nursing home care on psychiatric disorders and severe behavioural problems in nursing home patients. A systematic literature search was performed in a number of international databases. Results Eight intervention trials, including four RCTs (2b level of evidence), were identified as relevant studies for the purpose of this review. Seven studies, three of which were RCTs, showed beneficial effects of a comprehensive, integrated multidisciplinary approach combining medical, psychiatric and nursing interventions on severe behavioural problems in DCD nursing home patients. Conclusions Important elements of a successful treatment strategy for DCD nursing home patients include a thorough assessment of psychiatric, medical and environmental causes as well as programmes for teaching behavioural management skills to nurses. DCD nursing home patients were found to benefit from short-term mental hospital admission. This review underlines the need for more rigorously designed studies to assess the effects of a comprehensive, integrated multidisciplinary approach towards DCD nursing home residents. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction The aim of the study was to assess the influence of dementia severity and gender on neuropsychiatric symptoms in demented nursing home patients. Methods Neuropsychiatric symptoms were assessed in a large sample of 1319 Dutch nursing home patients using the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory–Nursing Home version (NPI-NH). The influence of gender and severity of cognitive decline, assessed with the Global Deterioration Scale (GDS), was investigated using logistic regression analysis and subsequently corrected for possible confounders, such as age, duration of institutionalization and psychoactive medication use. Results While physically aggressive behaviour was more common in patients with very severe cognitive deterioration (GDS stage 7), disinhibition, irritability, physically non-aggressive and verbally agitated behaviour were more common in patients in GDS stage 5 or 6. Physically aggressive behaviour was more common in men, whereas female patients demonstrated more verbally agitated behaviour. With respect to other neuropsychiatric symptoms, delusions and depression were also more common in patients in GDS stage 5 and 6, while prevalences of anxiety and apathy further increased in severely demented patients (GDS stage 7). Apathy was more prevalent in male patients, while depression and anxiety were more common in females. Conclusion In nursing home patients, neuropsychiatric symptoms were associated with the severity of dementia, with most symptoms occurring in patients showing (moderately) severe cognitive decline. Only physical aggression, anxiety and apathy were more common in patients with very severe cognitive decline. Dementia severity and gender were important predictors of neuropsychiatric symptoms in this patient cohort. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between cognition and daily life functioning in dementia subtypes. Methods Cross-sectional data were used from 615 patients with dementia who were referred to the Maastricht Memory Clinic of the Maastricht University Medical Centre. Pearson correlation coefficients were calculated between the Mini-Mental State Examination (MMSE; to measure cognitive status) and the Blessed Dementia Scale (BDS; to measure daily life functioning) for the following types of dementia: Alzheimer's Disease (AD, n = 442); Vascular dementia (VaD, n = 113); frontotemporal dementia (FTD, n = 18); Parkinson's dementia (PD, n = 21); and primary progressive aphasia (PPA, n = 21). One-way ANOVA was used to test differences in age, MMSE scores and BDS scores across dementia subtypes. Results Scores on the MMSE showed strong correlation with BDS scores in cases of FTD (r = -0.80); moderate correlation in cases of AD, VaD, and PD (range r = -0.50–0.60); while no correlation was found in PPA cases. Conclusions The association between cognition and daily life functioning varied among dementia subtypes for AD, VaD, FTD and PD. Furthermore, the overall scores on both domains differ between dementia subtypes, indicating that different types of dementia are characterized by a specific pattern of cognitive status and daily life functioning. These findings underline the need for multidomain assessment in patients with dementia. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the feasibility of and clinical experiences with goal attainment scaling when used for the evaluation of cognitive rehabilitation in people with acquired brain injury. Design: A prospective observational longitudinal study. Setting: A 21-week cognitive rehabilitation programme and a cognitive programme with varying length in two different Dutch rehabilitation centres. Subjects: Forty-eight consecutive patients with acquired brain injury enrolled during a 15-month period. Interventions: Cognitive rehabilitation programme. Main measure: Goal attainment scaling; the number of goals was counted; time to set goals was recorded; the number of different domains in which goals were set was counted; goal attainment scaling score was calculated at baseline, one week after the end of the cognitive rehabilitation programme and at six months follow-up; clinical experiences that could be useful for both clinical and research practice were recorded. Results: The mean (SD) age of the patients was 46.1 (10.7) years; 29 (60%) were male; 186 goals were set with a mean (SD) number of 4 (1) goals per patient. It was possible to set at least three realistic goals per patient within 30 minutes. Most goals were set in the cognitive domain (i.e. memory and attention), followed by the behavioural domain (i.e. fatigue and aggression). Conclusion: It proved possible to set three goals within an acceptable time-frame, to involve patients in the goal-setting procedure, to set realistic goals, and to set goals within relevant domains. Based on clinical experiences, goal attainment scaling is less feasible for research when patients lack insight, or suffer from comorbidity or mood problems. [ABSTRACT FROM AUTHOR]

Background: Since evidence-based interventions are the standard, there is an urgent need for more information concerning individual ways of measuring clinically relevant outcomes of interventions in cognitive disorders such as dementia. Goal Attainment Scaling (GAS) seems to offer a meaningful outcome measure. Aim: To examine the applicability of GAS in psychogeriatric patients with cognitive disorders. Methods: A systematic review was performed on the available literature on the clinimetric aspects and the feasibility of GAS when used as an outcome measure for psychogeriatric patients with cognitive disorders. Eight databases were screened. Two authors independently reviewed all the data. Ten studies were included. Results: Mixed results were found for responsiveness, content validity, inter-rater reliability and construct/convergent validity. The involvement of patient and/or caregiver in the goal-setting procedure is possible and multiple domains can be implemented. The possibility to set at least 3 realistic goals per patient in less than 30 min is unclear and the need for involvement of a blinded assessor is not well established. Conclusion: GAS proved to be useful on important aspects of an outcome measure for psychogeriatric patients with cognitive disorders. Since other relevant aspects showed mixed results and the number of studies investigating the use of GAS in psychogeriatric patients with cognitive disorders is small, the evidence is not strong enough yet to state that GAS is an applicable outcome measure in this population. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: To examine the influence of dementia stage and psychoactive medication use on the factor structure of the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) in Dutch nursing home patients. Methods: The NPI-NH was administered to a large sample of 1,437 patients with mild to severe dementia receiving nursing home care. Exploratory factor analysis was used to examine behavioural dimensions underlying neuropsychiatric symptoms indicated by the NPI-NH across dementia stages (as assessed with the Global Deterioration Scale – GDS) and in patients with or without psychoactive medication prescribed. Results: In GDS stages 4/5, 6 and 7, a 4- or 5-factor solution was found, with factors referred to as agitation/aggression, depression, psychosis, psychomotor agitation and apathy. These symptom clusters were replicated in the group of drug-naive patients, but only partially in the group of patients on psychoactive medication. Conclusion: The factor structure of the NPI-NH in nursing home patients is consistent with the clinical taxonomy of symptoms, is relatively stable across dementia stages, and is only moderately influenced by psychoactive medication use. The division of depression and apathy into separate behavioural dimensions – also in patients with severe dementia – may have important therapeutic consequences. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective To estimate the prevalence of neuropsychiatric symptoms of dementia patients in Dutch nursing homes. Methods Cross-sectional study in a large sample of 1322 demented patients living in 59 dementia special care units (SCUs) in The Netherlands. Symptoms were observed by licensed vocational nurses during regular care-giving in a 2-week observational period prior to assessment. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory- Nursing home version (NPI-NH; frequency X severity score ≥ 4) and the Cohen-Mansfield Agitation Inventory (CMAI; symptoms occurring at least once a week). Results More than 80% of these patients suffered from at least one clinically significant symptom, as defined with the NPI-NH frequency X severity score ≥ 4. Measured with the NPH-NH agitation/aggression, apathy and irritability were the most frequently observed behaviors, with prevalences of 30–35%. Using the CMAI, 85% of the patients showed at least one symptom of agitation, of which general restlessness was observed most frequently (44%). Other frequently observed symptoms with prevalence rates of 30% were cursing or verbal aggression, constant request for attention, negativism, repetitious sentences, mannerisms, pacing, and complaining. Physically aggressive symptoms such as hitting, kicking, biting occurred less often (less than 13%). Conclusions Prevalence rates of neuropsychiatric symptoms in Dutch nursing home patients with dementia residing in SCUs are high, especially agitation and apathy. Insight into the prevalence rates of individual symptoms in patients with dementia has important practical consequences for the accurate planning of staff allotment and stresses the need for patient oriented care. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background/Aims: To establish the construct validity of the Dutch version of the Cohen-Mansfield Agitation Inventory (CMAI-D) in institutionalized patients with dementia. Methods: The CMAI-D was administered to a large sample of 1,437 patients with moderate to severe dementia, receiving nursing home or outreaching nursing home care. Exploratory factor analysis was used to examine the behavioral dimensions underlying CMAI-D observations. Results: A restricted 3-factor solution showed 3 factors, i.e. physical aggression, physically nonaggressive behavior and verbally agitated behavior, with prevalences of 62, 67 and 62%, respectively. An unrestricted factor solution revealed 3 additional behavioral dimensions: hiding/hoarding, vocal agitation and a factor of miscellaneous items (i.e. repetitious mannerisms, spitting), which occurred in 30, 28 and 35% of the patients, respectively. Conclusion: The 3-factor solution of physical aggression, physically nonaggressive behavior and verbally agitated behavior corroborates earlier findings in other patient samples and therefore establishes the construct validity in institutionalized patients with severe dementia. The robustness of these findings across different care settings suggests that agitated behaviors have a common basis. In addition, unrestricted factor analysis showed 3 other important independent behavioral symptoms in dementia, but they are in fact too small to be used as a subscale. These findings might add to the taxonomy of agitation and aggression in dementia. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate whether risk factors for depression in the general population are also markers for depression in Alzheimer's disease (AD) and to identify additional disease-specific markers for depression in AD. Patients and methods: A logistic model of five risk factors for depression in the general population was constructed using the data of 217 patients with AD, of whom 63 (29%) suffered from major depressive disorder. In a next step, five potential disease-specific markers were individually added to this model to see whether the strength and predictive power of the model would improve. Results: The multivariate model of five risk factors for depression in the general population was not a good model to predict depression in AD. In this multivariate approach, only ‘a history of depression’ was an independent marker for depression. The only disease-specific variable that improved the logistic model was ‘disability due to AD’. An interaction between these two markers became apparent. Conclusions: Of the established risk factors for depression in the general population, only ‘a history of depression’ was found to be an independent marker for depression in AD. ‘Disability due to AD’ was the only disease-related marker for depression in AD, although this marker cannot be considered specific for AD. The importance of controlling for general risk factors for depression in the search for disease-specific markers for depression in AD is stressed. [ABSTRACT FROM AUTHOR]

Background: Neuropsychological feedback is an important part of the neuropsychological assessment process. However, patients have difficulties remembering this information.Objective: The aim of this study was to develop a web-based visual tool to improve the understanding of neuropsychological results, information retention, and psychologist-patient communication.Methods: The visual tool was developed and optimized using an iterative three-phase stepwise approach to determine its usability, technology acceptance, and feasibility in a memory clinic population. Feedback from different user perspectives (patients, family members, and psychologists) was obtained in each phase using a multimethod approach (e.g. a multidisciplinary brainstorm session, think-aloud sessions, focus groups). The prototype was subsequently tested in a pilot study.Results: The first phases offered insights that led to optimization of the prototype. On a scale ranging from 0 to 100, psychologists evaluated the usability as high [88.1±7.6,70-87]. During the pilot study, both patients and significant others gave positive feedback, but information retention in patients remained low. All participants thought the benefits of the visual tool included seeing cognitive strengths and weaknesses with a translation to daily life all at one glance and receiving feedback on paper to take home. Important barriers were mentioned by psychologists, such as a limited set of tests included and no integration with hospital systems.Conclusion: Overall, patients, family members, and psychologists reported that a visual display of the cognitive profile with insights into daily life had added value to clinical practice. Feedback from the pilot study was adopted in the tool for future implementation purposes. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the course of psychotropic drug use in people with young-onset dementia and to explore possible associations with age, sex, dementia severity, dementia subtype and neuropsychiatric symptoms. Psychotropic drug use was studied in 198 community-dwelling persons participating in the Needs in Young-onset Dementia study. Data about psychotropic drug use were retrieved at baseline, as well as at 6, 12, 18 and 24 months and was classified into five groups (antiepileptics, antipsychotics, anxiolytics, hypnotics/sedatives and antidepressants) and quantified as 'present' or 'absent'. Generalized Estimating Equation modeling and chi-square tests were used to study associations between the determinants and psychotropic drug use. There was a statistically significant increase in the prevalence of psychotropic drug use from 52.3% to 62.6% during the course of the study. Almost three-quarters (72.4%) of the participants were treated with any psychotropic drug during the study, and more than one-third (37.4%) received psychotropic drugs continuously. Antipsychotics were used continuously in more than 10% of the participants and antidepressants in more than 25%. Increasing age was positively associated (p =.018) with psychotropic drug use at baseline, while apathy symptoms were negatively associated (p =.018). Despite the recommendations of various guidelines, the prolonged use of psychotropic drugs in community-dwelling people with young-onset dementia is high. Therefore, more attention is needed to timely evaluate psychotropic drug use and the introduction of self-management programs for caregivers should be encouraged to support caregivers in dealing with the neuropsychiatric symptoms caused by the dementia. [ABSTRACT FROM AUTHOR]

The Locus Coeruleus (LC) and the Substantia Nigra (SN) are small brainstem nuclei that change with aging and may be involved in the development of various neurodegenerative and psychiatric diseases. Magnetization Transfer (MT) MRI has been shown to facilitate LC and the SN visualization, and the observed contrast is assumed to be related to neuromelanin accumulation. Imaging these nuclei may have predictive value for the progression of various diseases, but interpretation of previous studies is hindered by the fact that the precise biological source of the contrast remains unclear, though several hypotheses have been put forward. To inform clinical studies on the possible biological interpretation of the LC- and SN contrast, we examined an agar-based phantom containing samples of natural Sepia melanin and synthetic Cys-Dopa-Melanin and compared this to the in vivo human LC and SN. T1 and T2* maps, MT spectra and relaxation times of the phantom, the LC and the SN were measured, and a two-pool MT model was fitted. Additionally, Bloch simulations and a transient MT experiment were conducted to confirm the findings. Overall, our results indicate that Neuromelanin-MRI contrast in the LC likely results from a lower macromolecular fraction, thus facilitating interpretation of results in clinical populations. We further demonstrate that in older individuals T1 lengthening occurs in the LC. [ABSTRACT FROM AUTHOR]

Caring for a person with dementia can be challenging over the years. To support family carers throughout their entire caregiving career, interventions with a sustained effectivity are needed. A novel 6-week mobile health (mHealth) intervention using the experience sampling method (ESM) showed positive effects on carers' well-being over a period of 2 months after the intervention. In this study, the effects after 6 months of the selfsame intervention were examined to evaluate the sustainability of positive intervention effects. The 6-week mHealth intervention consisted of an experimental group (ESM self-monitoring and personalized feedback), a pseudo-experimental group (ESM self-monitoring without feedback), and a control group (providing regular care without ESM self-monitoring or feedback). Carers' sense of competence, mastery, and psychological complaints (depression, anxiety and perceived stress) were evaluated pre- and post-intervention as well as at two follow-up time points. The present study focuses on the 6-month follow-up data (n = 50). Positive intervention effects on sense of competence, perceived stress, and depressive symptoms were not sustained over 6-month follow-up. The benefits of this mHealth intervention for carers of people living with dementia were not sustained over a long time. Similarly, other psychosocial interventions for carers of people with dementia rarely reported long-lasting effects. In order to sustainably contribute to carers' well-being, researchers and clinicians should continuously ensure flexible adjustment of the intervention and consider additional features such as ad-hoc counseling options and booster sessions. In this regard, mHealth interventions can offer ideally suited and unique opportunities. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is biologically heterogeneous, and detailed understanding of the processes involved in patients is critical for development of treatments. CSF contains hundreds of proteins, with concentrations reflecting ongoing (patho)physiological processes. This provides the opportunity to study many biological processes at the same time in patients. We studied whether Alzheimer's disease biological subtypes can be detected in CSF proteomics using the dual clustering technique non-negative matrix factorization. In two independent cohorts (EMIF-AD MBD and ADNI) we found that 705 (77% of 911 tested) proteins differed between Alzheimer's disease (defined as having abnormal amyloid, n = 425) and controls (defined as having normal CSF amyloid and tau and normal cognition, n = 127). Using these proteins for data-driven clustering, we identified three robust pathophysiological Alzheimer's disease subtypes within each cohort showing (i) hyperplasticity and increased BACE1 levels; (ii) innate immune activation; and (iii) blood-brain barrier dysfunction with low BACE1 levels. In both cohorts, the majority of individuals were labelled as having subtype 1 (80, 36% in EMIF-AD MBD; 117, 59% in ADNI), 71 (32%) in EMIF-AD MBD and 41 (21%) in ADNI were labelled as subtype 2, and 72 (32%) in EMIF-AD MBD and 39 (20%) individuals in ADNI were labelled as subtype 3. Genetic analyses showed that all subtypes had an excess of genetic risk for Alzheimer's disease (all P > 0.01). Additional pathological comparisons that were available for a subset in ADNI suggested that subtypes showed similar severity of Alzheimer's disease pathology, and did not differ in the frequencies of co-pathologies, providing further support that found subtypes truly reflect Alzheimer's disease heterogeneity. Compared to controls, all non-demented Alzheimer's disease individuals had increased risk of showing clinical progression (all P < 0.01). Compared to subtype 1, subtype 2 showed faster clinical progression after correcting for age, sex, level of education and tau levels (hazard ratio = 2.5; 95% confidence interval = 1.2, 5.1; P = 0.01), and subtype 3 at trend level (hazard ratio = 2.1; 95% confidence interval = 1.0, 4.4; P = 0.06). Together, these results demonstrate the value of CSF proteomics in studying the biological heterogeneity in Alzheimer's disease patients, and suggest that subtypes may require tailored therapy. [ABSTRACT FROM AUTHOR]

Objective: To identify determinants within 3 different domains (ie, somatic comorbidities, cognitive functioning, and neuropsychiatric symptoms [NPS]) of health-related quality of life (HRQoL) over time in memory clinic patients without dementia.Methods: This longitudinal multicenter cohort study with a 3-year observation period recruited 315 individuals (age: 69.8 ± 8.6, 64.4% males, Mini-Mental State Examination score 26.9 ± 2.6). A multivariable explanatory model was built using linear mixed effects models (forward selection per domain) to select determinants for self-perceived HRQoL over time, as measured by the EuroQoL-5D visual analogue scale (EQ VAS).Results: Mean HRQoL at study entry was 69.4 ± 15.6. The presence of agitation, appetite and eating abnormalities, and eyes/ears/nose (ie, sensory impairment) comorbidities were associated with a change in HRQoL over time. Agitation was most strongly associated with HRQoL over time.Conclusions: The association of somatic comorbidities and NPS in memory clinic patients with course of HRQoL shows that these should receive more awareness, detection, and monitoring by clinicians. [ABSTRACT FROM AUTHOR]

Background: The cerebral default mode network (DMN) can be mapped onto specific regions in the cerebellum, which are specifically vulnerable to atrophy in Alzheimer's disease (AD) patients.Objective: We set out to determine whether there are specific differences in the interaction between the cerebral and cerebellar DMN in amnestic mild cognitive impairment (aMCI) patients compared to healthy controls using resting-state functional MRI and whether these differences are relevant for memory performance.Methods: Eighteen patients with aMCI were age and education-matched to eighteen older adults and underwent 3T MR-imaging. We performed seed-based functional connectivity analysis between the cerebellar DMN seeds and the cerebral DMN.Results: Our results showed that compared to healthy older adults, aMCI patients showed lower anti-correlation between the cerebellar DMN and several cerebral DMN regions. Additionally, we showed that degradation of the anti-correlation between the cerebellar DMN and the medial frontal cortex is correlated with worse memory performance in aMCI patients.Conclusion: These findings provide evidence that the cerebellar DMN and cerebral DMN are negatively correlated during rest in older individuals, and suggest that the reduced anti-correlated impacts the modulatory role of the cerebellum on cognitive functioning, in particular on the executive component of memory functions in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]