The Association Between Biomarkers and Neuropsychiatric Symptoms Across the Alzheimer's Disease Spectrum.

OBJECTIVE: To investigate the relationship between Alzheimer's disease biomarkers and neuropsychiatric symptoms. METHODS: Data from two large cohort studies, the Dutch Parelsnoer Institute - Neurodegenerative Diseases and the Alzheimer's Disease Neuroimaging Initiative was used, including subjects with subjective cognitive decline (N = 650), mild cognitive impairment (N = 887), and Alzheimer's disease dementia (N = 626). Cerebrospinal fluid (CSF) levels of Aß42, t-tau, p-tau, and hippocampal volume were associated with neuropsychiatric symptoms (measured with the Neuropsychiatric Inventory) using multiple logistic regression analyses. The effect of the Mini-Mental State Examination (as proxy for cognitive functioning) on these relationships was assessed with mediation analyses. RESULTS: Alzheimer's disease biomarkers were not associated with depression, agitation, irritability, and sleep disturbances. Lower levels of CSF Aß42, higher levels of t- and p-tau were associated with presence of anxiety. Lower levels of CSF Aß42 and smaller hippocampal volumes were associated with presence of apathy. All associations were mediated by cognitive functioning. CONCLUSION: The association between Alzheimer's disease pathology and anxiety and apathy is partly due to impairment in cognitive functioning.

Determinants of Cross-Sectional and Longitudinal Health-Related Quality of Life in Memory Clinic Patients Without Dementia.

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.

A survey on the prevalence of apathy in elderly people referred to specialized memory centers.

BACKGROUND: Apathy is a pervasive neuropsychiatric syndrome in people with neurocognitive and psychiatric disorders. The diagnostic criteria for apathy (DCA) have been revised in 2018. OBJECTIVES: Employing the 2018 DCA, in the present study, we investigated in groups of elderly subjects suffering from different neuropsychiatric disorders (a) the apathy prevalence; (b) the most commonly affected apathy dimensions (behavior/cognition, emotion, and social interaction); (c) the sensitivity and specificity of those dimensions for apathy diagnosis; and (d) the concurrent validity of 2018 DCA compared with the 2009 DCA. METHODS: This multicenter survey included 166 subjects. Each center checked the presence of apathy in subjects belonging to the following DSM-5 diagnoses: mild neurocognitive disorders (mild NCDs); major NCDs; affective disorders (Aff D); and subjective cognitive decline (SCD). RESULTS: The frequency of apathy varied significantly based on the diagnostic groups (0% of subjects with apathy in the SCD group; 25% in the mild NCD group; 77% in the major NCD group; and 57% in the Aff. D group). All subjects with apathy fulfilled the criteria for the behavior/cognition dimension, 73.1% fulfilled the criteria for the emotion dimension, and 97.4% fulfilled the criteria for the social interaction dimension. Behavior/cognition showed the highest sensitivity, the copresence of emotion and social interaction the highest specificity. The concordance between the 2009 and the 2018 DCA indicated an almost perfect agreement. CONCLUSIONS: These results are consistent with previous reports and confirm that the social interaction dimension added to the 2018 DCA is present in most of subjects with apathy referred to specialized memory centers.

Co-occurrence of depressive symptoms and executive dysfunction after stroke: associations with brain pathology and prognosis.

OBJECTIVE: To examine, first, whether the co-occurrence of executive dysfunction (ED) and poststroke depression (PSD) shows different associations with neuroimaging markers and the course of depression and executive function, and second, whether it is associated with a different course on other cognitive domains and quality of life. METHODS: The present study included 245 stroke patients (35.9% female, mean age 67.5 years (SD=11.9). All patients completed neuropsychological and neuropsychiatric assessment 3 months poststroke, which were repeated at 6-month and 12-month follow-up. A subset (n=186) received 3-Tesla brain MRI at baseline to evaluate lesion-related imaging markers, white matter hyperintensity volume, global brain atrophy and total cerebral small vessel disease burden. RESULTS: Patients with 'depression-executive dysfunction syndrome' (DES) showed higher white matter hyperintensity volumes compared with all other groups and more frequently showed left-sided lesions compared with ED only and PSD only. They also had more frequently old infarcts and higher total cerebral small vessel disease burden compared with PSD only and patients with neither ED nor PSD, and more global brain atrophy compared with PSD only. Longitudinal analyses showed that patients with DES had a more chronic course of depressive symptoms relative to PSD only, and a stable pattern of worse cognitive performance similar to patients with ED only. CONCLUSIONS: The co-occurrence of ED and PSD is associated with a worse prognosis of depression, persistent cognitive impairment and a higher amount of vascular and degenerative brain pathology. Future studies are needed to examine whether these patients represent a more severe subtype within the PSD spectrum. CLINICAL TRIAL REGISTRATION: NCT02585349;Results.

Baseline Vascular Cognitive Impairment Predicts the Course of Apathetic Symptoms After Stroke: The CASPER Study.

OBJECTIVE: To examine the influence of vascular cognitive impairment (VCI) on the course of poststroke depression (PSD) and poststroke apathy (PSA). METHODS: Included were 250 stroke patients who underwent neuropsychological and neuropsychiatric assessment 3 months after stroke (baseline) and at a 6- and 12-month follow-up after baseline. Linear mixed models tested the influence of VCI in at least one cognitive domain (any VCI) or multidomain VCI (VCI in multiple cognitive domains) at baseline and domain-specific VCI at baseline on levels of depression and apathy over time, with random effects for intercept and slope. RESULTS: Almost half of the patients showed any VCI at baseline, and any VCI was associated with increasing apathy levels from baseline to the 12-month follow-up. Patients with multidomain VCI had higher apathy scores at the 6- and 12-month follow-up compared with patients with VCI in a single cognitive domain. Domain-specific analyses showed that impaired executive function and slowed information processing speed went together with increasing apathy levels from baseline to 6- and 12-month follow-up. None of the cognitive variables predicted the course of depressive symptoms. CONCLUSION: Baseline VCI is associated with increasing apathy levels from baseline to the chronic stroke phase, whereas no association was found between baseline VCI and the course of depressive symptoms. Health professionals should be aware that apathy might be absent early after stroke but may evolve over time in patients with VCI.

The clinical course and interrelations of dementia related symptoms.

ABSTRACTBackground:Dementia is a neurodegenerative syndrome that interferes with multiple aspects of life, including cognition, daily functioning, and behavior. Despite the large heterogeneity in symptom development, these three domains are seldom studied simultaneously. This study investigates how trajectories of these domains are interrelated within individuals over time, and how they in turn are related to dementia severity and quality of life (QoL). METHODS: We used data from a longitudinal clinical cohort study, including 331 dementia patients. Cognitive status was measured using the Mini-Mental State Examination, daily functioning was measured with the disability assessment for dementia and neuropsychiatric symptoms (NPS) were scored using the neuropsychiatric inventory. We investigated the relationships in the time course of the various dementia domains using random effects multilevel models and parallel-process growth models. RESULTS: Changes in cognition and daily functioning were highly correlated over time (r = 0.85, p < 0.01), as were changes in NPS and functioning (r = -0.60, p < 0.01), while changes in cognition and NPS were not (r = -0.20, p = 0.06). All three domains were strongly associated with dementia severity over time (p < 0.01). Decreased functioning and increased NPS were both associated with decreased QoL (ß = 2.97, p < 0.01 and ß = -2.41, p < 0.01, respectively), while cognition was not (ß = 0.01, p = 0.93). CONCLUSION: This study demonstrates the heterogeneity of dementia progression between individuals and between different dementia domains within individuals. To improve our understanding of dementia progression, future research should embrace a broader perspective encompassing multiple outcome measures along with the patient's profile, including neurological factors as well as physical, social, and psychiatric health.

Prevalence of the apolipoprotein E ε4 allele in amyloid ß positive subjects across the spectrum of Alzheimer's disease.

INTRODUCTION: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid ß (Aß) pathology. METHODS: We included 3451 Aß+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. RESULTS: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aß+ cognitively normal and Aß+ mild cognitive impairment (P < .05) but not in Aß+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education. DISCUSSION: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aß pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.

Imaging Markers of Post-Stroke Depression and Apathy: a Systematic Review and Meta-Analysis.

Several brain imaging markers have been studied in the development of post-stroke depression (PSD) and post-stroke apathy (PSA), but inconsistent associations have been reported. This systematic review and meta-analysis aims to provide a comprehensive and up-to-date evaluation of imaging markers associated with PSD and PSA. Databases (Medline, Embase, PsycINFO, CINAHL, and Cochrane Database of Systematic Reviews) were searched from inception to July 21, 2016. Observational studies describing imaging markers of PSD and PSA were included. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to examine the association between PSD or PSA and stroke lesion laterality, type, and location, also stratified by study phase (acute, post-acute, chronic). Other imaging markers were reviewed qualitatively. The search retrieved 4502 studies, of which 149 studies were included in the review and 86 studies in the meta-analyses. PSD in the post-acute stroke phase was significantly associated with frontal (OR 1.72, 95% CI 1.34-2.19) and basal ganglia lesions (OR 2.25, 95% CI 1.33-3.84). Hemorrhagic stroke related to higher odds for PSA in the acute phase (OR 2.58, 95% CI 1.18-5.65), whereas ischemic stroke related to higher odds for PSA in the post-acute phase (OR 0.20, 95% CI 0.06-0.69). Frequency of PSD and PSA is modestly associated with stroke type and location and is dependent on stroke phase. These findings have to be taken into consideration for stroke rehabilitation programs, as this could prevent stroke patients from developing PSD and PSA, resulting in better clinical outcome.

Temporal Associations between Fatigue, Depression, and Apathy after Stroke: Results of the Cognition and Affect after Stroke, a Prospective Evaluation of Risks Study.

BACKGROUND: Poststroke fatigue (PSF) is a form of pathological fatigue that can develop after stroke and has a negative impact on functional outcome. PSF is associated with poststroke depression (PSD), which in turn shows similarities with poststroke apathy (PSA). This study aimed at disentangling the temporal associations between PSF and PSD and between PSF and PSA. METHODS: A total of 250 stroke patients were included, of which 243 completed the Fatigue Severity Scale, Montgomery-Åsberg Depression Rating Scale, and Apathy Evaluation Scale at 3 months poststroke, with follow-up measurements at 6 and 12 months after initial testing. Linear mixed models and linear regressions were performed to evaluate the temporal associations between PSF and PSD, and between PSF and PSA. RESULTS: PSF was present in 119 patients (49%), of whom 62 patients also had PSD (26%), and 21 patients (9%) also had PSA. At baseline, PSF patients showed higher depression levels, which remained stable at follow-up. PSD patients had higher fatigue levels compared with no-PSD patients at baseline, which remained stable at follow-up. No association between apathy and fatigue was found at baseline and no interaction with time was found. Change in fatigue from baseline to 12-month follow-up was associated with change in depression and with change in apathy. CONCLUSIONS: Bidirectional associations were found between PSF and PSD. In treatment and rehabilitation programs, early focus on the presence of PSD and PSF is important, since these conditions tend to persist. As there are currently more treatment options for PSD, attention for PSD is important and might also have a beneficial effect on PSF.

The Cognition and Affect after Stroke - a Prospective Evaluation of Risks (CASPER) study: rationale and design.

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.

A profile of The Clinical Course of Cognition and Comorbidity in Mild Cognitive Impairment and Dementia Study (The 4C study): two complementary longitudinal, clinical cohorts in the Netherlands.

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.

Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.

IMPORTANCE: Cerebral amyloid-ß aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). DATA SOURCES: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. STUDY SELECTION: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. DATA EXTRACTION AND SYNTHESIS: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. MAIN OUTCOMES AND MEASURES: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. RESULTS: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality. CONCLUSIONS AND RELEVANCE: Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.

Optimizing the use of expert panel reference diagnoses in diagnostic studies of multidimensional syndromes.

BACKGROUND: In the absence of a gold standard, a panel of experts can be invited to assign a reference diagnosis for use in research. Available literature offers limited guidance on assembling and working with an expert panel for this purpose. We aimed to develop a protocol for an expert panel consensus diagnosis and evaluated its applicability in a pilot project. METHODS: An adjusted Delphi method was used, which started with the assessment of clinical vignettes by 3 experts individually, followed by a consensus discussion meeting to solve diagnostic discrepancies. A panel facilitator ensured that all experts were able to express their views, and encouraged the use of argumentation to arrive at a specific diagnosis, until consensus was reached by all experts. Eleven vignettes of patients suspected of having a primary neurodegenerative disease were presented to the experts. Clinical information was provided stepwise and included medical history, neurological, physical and cognitive function, brain MRI scan, and follow-up assessments over 2 years. After the consensus discussion meeting, the procedure was evaluated by the experts. RESULTS: The average degree of consensus for the reference diagnosis increased from 52% after individual assessment of the vignettes to 94% after the consensus discussion meeting. Average confidence in the diagnosis after individual assessment was 85%. This did not increase after the consensus discussion meeting. The process evaluation led to several recommendations for improvement of the protocol. CONCLUSION: A protocol for attaining a reference diagnosis based on expert panel consensus was shown feasible in research practice.

The Dutch Parelsnoer Institute--Neurodegenerative diseases; methods, design and baseline results.

BACKGROUND: The Parelsnoer Institute is a collaboration between 8 Dutch University Medical Centers in which clinical data and biomaterials from patients suffering from chronic diseases (so called "Pearls") are collected according to harmonized protocols. The Pearl Neurodegenerative Diseases focuses on the role of biomarkers in the early diagnosis, differential diagnosis and in monitoring the course of neurodegenerative diseases, in particular Alzheimer's disease. The objective of this paper is to describe the design and methods of the Pearl Neurodegenerative Diseases, as well as baseline descriptive variables, including their biomarker profile. METHODS: The Pearl Neurodegenerative Diseases is a 3-year follow-up study of patients referred to a memory clinic with cognitive complaints. At baseline, all patients are subjected to a standardized examination, including clinical data and biobank materials, e.g. blood samples, MRI and cerebrospinal fluid. At present, in total more than 1000 patients have been included, of which cerebrospinal fluid and DNA samples are available of 211 and 661 patients, respectively. First descriptives of a subsample of the data (n = 665) shows that patients are diagnosed with dementia (45%), mild cognitive impairment (31%), and subjective memory complaints (24%). DISCUSSION: The Pearl Neurodegenerative Diseases is an ongoing large network collecting clinical data and biomaterials of more than 1000 patients with cognitive impairments. The project has started with data analyses of the baseline characteristics and biomarkers, which will be the starting point of future specific research questions that can be answered by this unique dataset.

A review of current information and communication technologies: can they be used to assess apathy?

BACKGROUND: Neuropsychiatric symptoms, such as apathy, have an important impact on the quality of life of both patients diagnosed with dementia and their caregivers and represent a strong predictor of progression of the illness. Current clinical assessment methods risk bias resulting from the assessor's subjectivity, pointing to a need for additional objective and systematic assessment tools. Therefore, the use of information and communication technologies (ICT) such as actigraphy and automatized video monitoring are of interest in addition to current assessment methods. AIM: The goal of this study is to give an overview of current assessment tools for apathy in clinical practice and new approaches to assessment methods with the help ICT. METHODS: This study was conducted with the use of narrative literature overview. RESULTS: There is evidence that apart from the currently used assessment methods for apathy, new ICT approaches could provide clinicians with valuable additional information for an earlier detection and therefore more accurate diagnosis of apathy. CONCLUSIONS: There are no ICT techniques specifically designed for the assessment of apathy, but nevertheless several techniques seem to be promising and deserve more study.

Diagnosing Alzheimer's disease: a systematic review of economic evaluations.

BACKGROUND: The objective of this study is to systematically review the literature on economic evaluations of interventions for the early diagnosis of Alzheimer's disease (AD) and related disorders and to describe their general and methodological characteristics. We focused on the diagnostic aspects of the decision models to assess the applicability of existing decision models for the evaluation of the recently revised diagnostic research criteria for AD. METHODS: PubMed and the National Institute for Health Research Economic Evaluation database were searched for English-language publications related to economic evaluations on diagnostic technologies. Trial-based economic evaluations were assessed using the Consensus on Health Economic Criteria list. Modeling studies were assessed using the framework for quality assessment of decision-analytic models. RESULTS: The search retrieved 2109 items, from which eight decision-analytic modeling studies and one trial-based economic evaluation met all eligibility criteria. CONCLUSIONS: Diversity among the study objective and characteristics was considerable and, despite considerable methodological quality, several flaws were indicated. Recommendations were focused on diagnostic aspects and the applicability of existing models for the evaluation of recently revised diagnostic research criteria for AD.

Determinants of care costs of patients with dementia or cognitive impairment.

INTRODUCTION: Dementia causes a high burden on patients, caregivers, and societies. Decision analytic models to support allocation of resources are often developed making use of cost-of-illness (COI) studies. However, current COI study estimates are highly variable due to care setting and methodological issues. We aim to explore variables explaining the variation of (formal and informal) health care costs of cognitive disorders, using a broad spectrum of variables, including patient, caregiver, and social context variables. METHODS: A bottom-up COI study design was used in which a societal viewpoint and a validated method to measure and value informal care was applied. Data were analyzed using univariate, multivariate, and forward regression analyses. RESULTS: The average 1-year health care sector costs were &OV0556;26,140 ($34,505 or £17,775) and &OV0556;11,931 ($15,749 or £8113) for patient and family. The analyses indicated that cognitive functioning, caregiver burden, patient sex, and instrumental activities of daily living were significantly associated with care costs independently. CONCLUSIONS: Cognitive functioning and instrumental activities of daily living are important variables to include in health care decision models. We recommend also including caregiver burden and patient sex in decision models for health policy decision makers to fully reflect the heterogeneity of the disease progression of cognitive disorders.

Awareness and its association with affective symptoms in young-onset and late-onset Alzheimer disease: a prospective study.

BACKGROUND: It is unknown whether there are differences between young-onset dementia and late-onset dementia in awareness levels and whether awareness is differentially associated with affective symptoms in both groups. The present study assesses possible differences between young-onset (YO-AD) and late-onset Alzheimer disease (LO-AD) in awareness levels and the association between awareness and affective symptoms. METHODS: This study included 142 YO-AD and 126 LO-AD patients and their caregivers from 2 prospective studies. The participants were assessed 3 times during 1 year. Awareness was assessed using the Guidelines for the Rating of Awareness Deficits, and affective symptoms were assessed using the anxiety and depression items of the Neuropsychiatric Inventory. Population-averaged logistic regressions were used to analyze awareness and its association with affective symptoms. RESULTS: The odds for impaired awareness in LO-AD were more than double the odds in YO-AD. Intact awareness was associated with depressive symptoms but not with anxiety. This effect was more pronounced in YO-AD compared with LO-AD at baseline. High awareness at baseline did not predict incident affective symptoms. CONCLUSIONS: Caregivers and clinicians should be prepared for affective symptoms in YO-AD patients with high awareness. The higher awareness in the YO-AD group also has potential positive implications for this group.

Impact of molecular imaging on the diagnostic process in a memory clinic.

BACKGROUND: [(11)C]Pittsburgh compound B ([(11)C]PIB) and [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) PET measure fibrillar amyloid-ß load and glucose metabolism, respectively. We evaluated the impact of these tracers on the diagnostic process in a memory clinic population. METHODS: One hundred fifty-four patients underwent paired dynamic [(11)C]PIB and static [(18)F]FDG PET scans shortly after completing a standard dementia screening. Two-year clinical follow-up data were available for 39 patients. Parametric PET images were assessed visually and results were reported to the neurologists responsible for the initial diagnosis. Outcome measures were (change in) clinical diagnosis and confidence in that diagnosis before and after disclosing PET results. RESULTS: [(11)C]PIB scans were positive in 40 of 66 (61%) patients with a clinical diagnosis of Alzheimer's disease (AD), 5 of 18 (28%) patients with frontotemporal dementia (FTD), 4 of 5 (80%) patients with Lewy body dementia, and 3 of 10 (30%) patients with other dementias. [(18)F]FDG uptake patterns matched the clinical diagnosis in 38 of 66 (58%) of AD patients, and in 6 of 18 (33%) FTD patients. PET results led to a change in diagnosis in 35 (23%) patients. This only occurred when prior diagnostic certainty was <90%. Diagnostic confidence increased from 71 ± 17% before to 87 ± 16% after PET (p < .001). Two-year clinical follow-up (n = 39) showed that [(11)C]PIB and [(18)F]FDG predicted progression to AD for patients with mild cognitive impairment, and that the diagnosis of dementia established after PET remained unchanged in 96% of patients. CONCLUSIONS: In a memory clinic setting, combined [(11)C]PIB and [(18)F]FDG PET are of additional value on top of the standard diagnostic work-up, especially when prior diagnostic confidence is low.