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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]

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]

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: Abnormal insulin signaling in the brain has been linked to Alzheimer's disease (AD).Objective: To evaluate whether cerebrospinal fluid (CSF) insulin levels are associated with cognitive performance and CSF amyloid-β and Tau. Additionally, we explore whether any such association differs by sex or APOE ɛ4 genotype.Methods: From 258 individuals participating in the Parelsnoer Institute Neurodegenerative Diseases, a nationwide multicenter memory clinic population, we selected 138 individuals (mean age 66±9 years, 65.2% male) diagnosed with subjective cognitive impairment (n = 45), amnestic mild cognitive impairment (n = 44), or AD (n = 49), who completed a neuropsychological assessment, including tests of global cognition and memory performance, and who underwent lumbar puncture. We measured CSF levels of insulin, amyloid-β1-42, total (t-)Tau, and phosphorylated (p-)Tau.Results: CSF insulin levels did not differ between the diagnostic groups (p = 0.136). Across the whole study population, CSF insulin was unrelated to cognitive performance and CSF biomarkers of AD, after adjustment for age, sex, body mass index, diabetes status, and clinic site (all p≥0.131). Importantly, however, we observed effect modification by sex and APOE ɛ4 genotype. Specifically, among women, higher insulin levels in the CSF were associated with worse global cognition (standardized regression coefficient -0.483; p = 0.008) and higher p-Tau levels (0.353; p = 0.040). Among non-carriers of the APOE ɛ4 allele, higher CSF insulin was associated with higher t-Tau (0.287; p = 0.008) and p-Tau (0.246; p = 0.029).Conclusion: Our findings provide further evidence for a relationship between brain insulin signaling and AD pathology. It also highlights the need to consider sex and APOE ɛ4 genotype when assessing the role of insulin. [ABSTRACT FROM AUTHOR]

Aims/Hypothesis: Accumulating evidence suggests an association between coronary heart disease and risk for cognitive impairment or dementia, but no study has systematically reviewed this association. Therefore, we summarized the available evidence on the association between coronary heart disease and risk for cognitive impairment or dementia. Methods: Medline, Embase, PsycINFO, and CINAHL were searched for all publications until 8th January 2016. Articles were included if they fulfilled the inclusion criteria: (1) myocardial infarction, angina pectoris or coronary heart disease (combination of both) as predictor variable; (2) cognition, cognitive impairment or dementia as outcome; (3) population-based study; (4) prospective (≥1 year follow-up), cross-sectional or case-control study design; (5) ≥100 participants; and (6) aged ≥45 years. Reference lists of publications and secondary literature were hand-searched for possible missing articles. Two reviewers independently screened all abstracts and extracted information from potential relevant full-text articles using a standardized data collection form. Study quality was assessed with the Newcastle-Ottawa Scale. We pooled estimates from the most fully adjusted model using random-effects meta-analysis. Results: We identified 6,132 abstracts, of which 24 studies were included. A meta-analysis of 10 prospective cohort studies showed that coronary heart disease was associated with increased risk of cognitive impairment or dementia (OR = 1.45, 95%CI = 1.21–1.74, p<0.001). Between-study heterogeneity was low (I2 = 25.7%, 95%CI = 0–64, p = 0.207). Similar significant associations were found in separate meta-analyses of prospective cohort studies for the individual predictors (myocardial infarction, angina pectoris). In contrast, meta-analyses of cross-sectional and case-control studies were inconclusive. Conclusion/Interpretation: This meta-analysis suggests that coronary heart disease is prospectively associated with increased odds of developing cognitive impairment or dementia. Given the projected worldwide increase in the number of people affected by coronary heart disease and dementia, insight into causal mechanisms or common pathways underlying the heart-brain connection is needed. [ABSTRACT FROM AUTHOR]

Background: Heterogeneous disease trajectories of mild cognitive impairment (MCI) and dementia are frequently encountered in clinical practice, but there is still insufficient knowledge to understand the reasons and mechanisms causing this heterogeneity. In addition to correlates of the disorder, patient characteristics such as their health status, social environment, comorbidities and frailty may contribute to variability in trajectories over time. The current paper outlines the study design and the study population of and provides an overview of the data collected in the Clinical Course of Cognition and Comorbidity in Mild Cognitive Impairment (4C-MCI cohort, n = 315) and Dementia (4C-Dementia cohort, n = 331) Study. Methods: The two complementary longitudinal cohorts part of the 4C study began enrolment in March 2010. Participants were prospectively recruited from three collaborating Dutch Alzheimer Centers, with three annual follow-up assessments after baseline. Extensive neuropsychological assessments, and detailed profiling of comorbidities, health and frailty at each follow up were the key features of the 4C study. As such, the 4C study was designed to study if and how patients' comorbidities and frailty are associated with the course of MCI and dementia measured with a comprehensive and multidimensional set of outcomes including cognition, daily functioning, quality of life, behavioral disturbances, caregiver burden, institutionalization and death and whether the effects of medical health and frailty differ between MCI and dementia stages of cognitive disorders. Conclusion: Sampled in a clinical setting, the 4C study complements population-based studies on neurodegenerative disorders in terms of the type of assessment (e.g. comorbidity, frailty, and functional status were repeatedly assessed). The 4C study complements available clinical cohorts of MCI and dementia patients, because the exclusion criteria were kept to a minimum, to obtain a sample that is representative for the average patient visiting a memory clinic. [ABSTRACT FROM AUTHOR]

Background: Limited information is available on short-term prognosis of Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF) in addition to routine diagnostic workup.Objective: This study aims to investigate the added prognostic value of AD CSF biomarkers.Methods: In a prospective cohort study, clinical experts predicted cognitive and functional symptoms in 114 memory clinic patients by assessing comprehensive routine diagnostic test information (patient history, and physical, neurological, psychiatric, neuropsychological, and MRI examinations), without and with CSF biomarkers. The reference standard was the 'observed clinically relevant decline' using baseline and 1- and 2-year follow-up information.Results: Decline over a 2-year period was observed in 51% of all participants (3% in SMC, 48% in MCI, 90% in mild dementia). In the total sample, the accuracy of predicted decline did not differ significantly between routine assessment without (79% correctly predicted) and with (74% correctly predicted) CSF biomarkers. Subgroup analyses revealed 25 (83%) correct predictions in SMC, 30 (68%) in MCI, and 35 (88%) in dementia without the use of CSF; and 21 (70%), 27 (61%), and 36 (90%), respectively, with the use of CSF in addition to the routine assessment.Conclusion: AD CSF biomarkers did not increase accuracy of 2-year prognosis of cognitive and functional decline when added to routine diagnostic workup. This suggests that the standard diagnostic workup without CSF biomarkers allows fairly accurate predictions for the short-term course of symptoms. Routine AD biomarkers in CSF have limited prognostic value over 2 years in persons with a suspected cognitive disorder. [ABSTRACT FROM AUTHOR]

Background: The relation between psychological distress, personality traits, and cognitive decline in cognitively impaired patients remains unclear.Objective: To investigate the effect of psychological distress and personality traits on cognitive functioning in subjects with mild cognitive impairment (MCI); and to investigate the predictive accuracy of these factors for the development of dementia.Methods: MCI patients (n = 343, age: 60.9±9.9 years, 38% female, and MMSE score: 28.1±1.9) were included from the Maastricht memory clinic. All patients underwent a standardized neuropsychological assessment (including tests for measuring mental speed (Trail Making Test (TMT) part A and Stroop Color Word Test (SCWT) part I), executive functioning (TMT part B and SCWT part III), memory (15-Word Learning Tests), and verbal fluency (1-minute animals)), CT or MRI, and blood assessment. The Dutch Personality Questionnaire (DPQ) and the 90-items Symptom Check List (SCL-90) were used to measure personality traits and psychological distress. Conversion to dementia was assessed two, five, and ten years after baseline. The mean follow-up period was 6.7±3.4 years.Results: The Psychoneuroticism score of the SCL-90 was associated with slower performances on SCWT part I and TMT part A. The subdomain Neuroticism of the DPQ was also associated with slower scores on the TMT part A. At follow-up, 85 (25.9%) subjects had developed dementia. The SCL-90 total score, and the subscales, Anxiety, Somatization, Insufficiency in thought and action, and Sleeping problems were associated with a decreased risk for developing (AD-type) dementia.Conclusion: Psychological distress negatively affected information processing speed, but was not associated with an increased risk of developing dementia in patients with MCI. [ABSTRACT FROM AUTHOR]

Subjects with Alzheimer's disease (AD) show impaired learning strategies. Whether impaired learning strategies are already present in subjects with prodromal AD remains unknown. The aim of the present study was to investigate the predictive accuracy of learning strategies for AD in subjects with Mild Cognitive Impairment (MCI). Subjects with MCI (n = 202) were selected from the Maastricht Memory Clinic. Subjects were reassessed over a period of 10 years. Fifty-five of the 202 subjects converted to AD. Learning strategies investigated were subjective organization and serial clustering. Lower scores of subjective organization were associated with a higher risk for AD (OR = 2.1, p = .002). Serial clustering did not predict AD. Prodromal AD is characterized by a decreased use of effortful learning strategies. This finding may have implications for the early detection of AD in MCI subjects and for the development of cognitive training programs. [ABSTRACT FROM PUBLISHER]

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]