The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2013
Early onset dementia (EOD) poses specific challenges and issues for both the patient and (in)form... more Early onset dementia (EOD) poses specific challenges and issues for both the patient and (in)formal care. This study explores the use of (in)formal care prior to institutionalization, and its association with patient and caregiver characteristics. Participants were part of a community-based prospective longitudinal study of 215 patients and their informal caregivers. Baseline data of a subsample of 215 patient-caregiver dyads were analyzed. Analyses of covariance were performed to determine correlates of (in)formal care use assessed with the Resource Utilization in Dementia (RUD)-Lite questionnaire. Informal care had a 3:1 ratio with formal care. Supervision/surveillance constituted the largest part of informal care. In more than half of cases, patients had only one informal caregiver. The amount of informal care was associated with disease severity, showing more informal care hours in advanced disease stages. Fewer informal care hours were related to more caregiver working hours, e...
study that enrolls consenting randomly selected non-demented people aged 65 from a healthcare del... more study that enrolls consenting randomly selected non-demented people aged 65 from a healthcare delivery system. Participants were asked at enrollment and biennially regarding injuries leading to loss of consciousness (LOC), including TBI. Those endorsing TBI were asked about age at time of TBI and duration of loss of consciousness. Autopsy consent rates are 25-30%. We evaluated the following outcomes: Braak stage; CERAD grade; amyloid angiopathy; presence of cystic infarcts; presence of any microinfarcts, cerebral microinfarcts, and deep microinfarcts; atrophy ascertained by lateral ventricle diameter at the temporal pole; presence of any Lewy bodies and Lewy bodies in the substantia nigra or locus ceruleus, frontal or temporal cortex, and in the amygdala. We performed loglinear regression for each outcome, controlling for age, education, and sex. We used inverse probability weighting to account for factors associated with dying and coming to autopsy; resulting estimates are weighted back to the parent ACT study, thus giving population-relevant relative risks. Results: 529 decedents came to autopsy by 9/2013, 2 families withdrew consent and 2 had no TBI data. Of the remaining 525, 107 (20.4%) reported 1 TBI. For the 94 decedents with LOC length data, 14 (15%) had LOC >1 hour. Regression results are summarized in the The most notable finding was the strong association between TBI with LOC >1 hour with Lewy bodies, especially in frontal or temporal cortex or in substantia nigra or locus ceruleus. Conclusions: We found large associations between TBI with LOC >1 hour and Lewy bodies. There was no particular relationship between TBI exposures and neuropathological indices used to characterize Alzheimer's disease pathology, vascular pathology, or atrophy. Further assessments are warranted to determine whether tau pathologies characteristic of chronic traumatic encephalopathy seen in athletes with multiple concussions are also seen following single or multiple TBIs in a community-based cohort, and also to determine whether gene expression may be altered in brains of people who survived to older age despite TBI.
In Parkinson&... more In Parkinson's disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population.
Because of the increasing number of elderly people with dementia, the costs of dementia and demen... more Because of the increasing number of elderly people with dementia, the costs of dementia and dementia care are expected to grow rapidly in the coming decades. Cost-effectiveness results are relevant for decision making about new strategies in dementia care. To evaluate the cost-effectiveness of an integrated multidisciplinary diagnostic facility for diagnosing dementia in ambulatory psychogeriatric patients. Randomized controlled trial with an economic evaluation component. The Maastricht Evaluation of a Diagnostic Intervention for Cognitively Impaired Elderly, Maastricht University Hospital, Maastricht, the Netherlands. A total of 137 patients who received care in the multidisciplinary diagnostic facility and 93 who received usual care. Quality-adjusted life-years (QALYs) as the main outcome measure and cognition and behavioral problems as secondary outcome measures. Compared with patients receiving usual care, patients who visited the diagnostic facility gained a mean 0.05 QALY at the extra cost of euro65. The incremental cost per QALY amounted to euro1267. This point estimate lies beneath commonly accepted thresholds and is within an acceptable range of uncertainty. With regard to the secondary analyses, cost-effectiveness results showed a substantial amount of uncertainty and were therefore indecisive. On the basis of the main cost-per-QALY analysis, the use of the integrated multidisciplinary diagnostic facility is cost-effective for the diagnosis and management of dementia in ambulatory patients.
The cerebrospinal fluid (CSF) biomarkers amyloid- (A) 1-42 , T-tau, and P-tau have good diagnos... more The cerebrospinal fluid (CSF) biomarkers amyloid- (A) 1-42 , T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer's disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 32), patients with stable MCI (n = 13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n = 15), and healthy controls (n = 20). CSF was analyzed for A 1-42 , T-tau, P-tau, A X-38 , A X-40 , A X-42 , sAPP␣, and sAPP. In multivariate analysis, the core biomarkers A 1-42 , T-tau, and P-tau demonstrated a high ability to diagnose AD versus the combined groups of controls and stable MCI, with an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI 0.93-1.00, p < 0.0001). The additional biomarkers only marginally increased AUROC to 0.98 (95% CI 0.95-1.00, p < 0.0001), this increase mainly mediated by A X-42 . In conclusion, CSF biomarkers A 1-42 , T-tau, and P-tau have very high diagnostic accuracy in a well defined cohort of untreated patients, demonstrating the excellent potency of CSF biomarkers to identify pathological processes in AD when a stringent analytical protocol is used.
were not included in the optimal classification algorithm. In the N ¼ 81 imaging/gene expression ... more were not included in the optimal classification algorithm. In the N ¼ 81 imaging/gene expression dataset the hippocampal-only classifier achieved 69% diagnostic accuracy (AUC ¼ 0.63) and ventricular-only classifier achieved 69% accuracy (AUC ¼ 0.57) compared to the hippocampal-GE classifier -accuracy 78%(AUC ¼ 0.79), and the combined hippocampalventricular-GE classifier -accuracy84% (AUC ¼ 0.82). 12 expressed genes and 8 expressed genes were selected as being useful for improving classification, by the final hippocampal-GE and hippocampal-ventricular-GE combined classifiers, respectively. Conclusions: As hypothesized, NC vs. aMCI classifier performance improved when combining imaging and genetic biomarkers. Automated classifiers show great promise for diagnostic analyses and potentially for predicting future conversion to AD. Receiver Operating Characteristic (ROC) curves for the unsupervised NC vs amnestic MCI classifier using structural imaging and SNP (top row) or gene expression data (bottom row). AUC stands for area under the curve.
Informal care plays a substantial role in the provision of total care in dementia. Several review... more Informal care plays a substantial role in the provision of total care in dementia. Several reviews have been published on the predictive factors of subjective burden; however, such a review lacks information on objective burden, which refers to the amount and/or costs of informal care. The objectives of this study were to (1) give an overview of the predictive factors that are associated with the objective burden of informal care; (2) discuss whether these factors are similar to the predictive factors of subjective burden; and (3) examine whether they are modifiable. The literature in a number of international databases was systematically searched. Methodological quality and level of certainty were assessed. Ten studies were identified as relevant for the purpose of this review, describing a total of 39 predictive factors. Three factors (behavioral problems and impairments regarding daily functioning and cognition) were considered to be predictors of objective burden. Three factors were not related; 12 were potential predictors; and the results of the remaining 22 factors were inconclusive. Many factors were found to be (potential) predictors of objective burden, reflecting its complex nature. Objective and subjective burdens are 2 different relevant aspects of informal care. Interventions aimed at countering behavioral problems and impairments regarding daily functioning could reduce objective burden.
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2013
Early onset dementia (EOD) poses specific challenges and issues for both the patient and (in)form... more Early onset dementia (EOD) poses specific challenges and issues for both the patient and (in)formal care. This study explores the use of (in)formal care prior to institutionalization, and its association with patient and caregiver characteristics. Participants were part of a community-based prospective longitudinal study of 215 patients and their informal caregivers. Baseline data of a subsample of 215 patient-caregiver dyads were analyzed. Analyses of covariance were performed to determine correlates of (in)formal care use assessed with the Resource Utilization in Dementia (RUD)-Lite questionnaire. Informal care had a 3:1 ratio with formal care. Supervision/surveillance constituted the largest part of informal care. In more than half of cases, patients had only one informal caregiver. The amount of informal care was associated with disease severity, showing more informal care hours in advanced disease stages. Fewer informal care hours were related to more caregiver working hours, e...
study that enrolls consenting randomly selected non-demented people aged 65 from a healthcare del... more study that enrolls consenting randomly selected non-demented people aged 65 from a healthcare delivery system. Participants were asked at enrollment and biennially regarding injuries leading to loss of consciousness (LOC), including TBI. Those endorsing TBI were asked about age at time of TBI and duration of loss of consciousness. Autopsy consent rates are 25-30%. We evaluated the following outcomes: Braak stage; CERAD grade; amyloid angiopathy; presence of cystic infarcts; presence of any microinfarcts, cerebral microinfarcts, and deep microinfarcts; atrophy ascertained by lateral ventricle diameter at the temporal pole; presence of any Lewy bodies and Lewy bodies in the substantia nigra or locus ceruleus, frontal or temporal cortex, and in the amygdala. We performed loglinear regression for each outcome, controlling for age, education, and sex. We used inverse probability weighting to account for factors associated with dying and coming to autopsy; resulting estimates are weighted back to the parent ACT study, thus giving population-relevant relative risks. Results: 529 decedents came to autopsy by 9/2013, 2 families withdrew consent and 2 had no TBI data. Of the remaining 525, 107 (20.4%) reported 1 TBI. For the 94 decedents with LOC length data, 14 (15%) had LOC >1 hour. Regression results are summarized in the The most notable finding was the strong association between TBI with LOC >1 hour with Lewy bodies, especially in frontal or temporal cortex or in substantia nigra or locus ceruleus. Conclusions: We found large associations between TBI with LOC >1 hour and Lewy bodies. There was no particular relationship between TBI exposures and neuropathological indices used to characterize Alzheimer's disease pathology, vascular pathology, or atrophy. Further assessments are warranted to determine whether tau pathologies characteristic of chronic traumatic encephalopathy seen in athletes with multiple concussions are also seen following single or multiple TBIs in a community-based cohort, and also to determine whether gene expression may be altered in brains of people who survived to older age despite TBI.
In Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more In Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population.
Because of the increasing number of elderly people with dementia, the costs of dementia and demen... more Because of the increasing number of elderly people with dementia, the costs of dementia and dementia care are expected to grow rapidly in the coming decades. Cost-effectiveness results are relevant for decision making about new strategies in dementia care. To evaluate the cost-effectiveness of an integrated multidisciplinary diagnostic facility for diagnosing dementia in ambulatory psychogeriatric patients. Randomized controlled trial with an economic evaluation component. The Maastricht Evaluation of a Diagnostic Intervention for Cognitively Impaired Elderly, Maastricht University Hospital, Maastricht, the Netherlands. A total of 137 patients who received care in the multidisciplinary diagnostic facility and 93 who received usual care. Quality-adjusted life-years (QALYs) as the main outcome measure and cognition and behavioral problems as secondary outcome measures. Compared with patients receiving usual care, patients who visited the diagnostic facility gained a mean 0.05 QALY at the extra cost of euro65. The incremental cost per QALY amounted to euro1267. This point estimate lies beneath commonly accepted thresholds and is within an acceptable range of uncertainty. With regard to the secondary analyses, cost-effectiveness results showed a substantial amount of uncertainty and were therefore indecisive. On the basis of the main cost-per-QALY analysis, the use of the integrated multidisciplinary diagnostic facility is cost-effective for the diagnosis and management of dementia in ambulatory patients.
The cerebrospinal fluid (CSF) biomarkers amyloid- (A) 1-42 , T-tau, and P-tau have good diagnos... more The cerebrospinal fluid (CSF) biomarkers amyloid- (A) 1-42 , T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer's disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 32), patients with stable MCI (n = 13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n = 15), and healthy controls (n = 20). CSF was analyzed for A 1-42 , T-tau, P-tau, A X-38 , A X-40 , A X-42 , sAPP␣, and sAPP. In multivariate analysis, the core biomarkers A 1-42 , T-tau, and P-tau demonstrated a high ability to diagnose AD versus the combined groups of controls and stable MCI, with an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI 0.93-1.00, p < 0.0001). The additional biomarkers only marginally increased AUROC to 0.98 (95% CI 0.95-1.00, p < 0.0001), this increase mainly mediated by A X-42 . In conclusion, CSF biomarkers A 1-42 , T-tau, and P-tau have very high diagnostic accuracy in a well defined cohort of untreated patients, demonstrating the excellent potency of CSF biomarkers to identify pathological processes in AD when a stringent analytical protocol is used.
were not included in the optimal classification algorithm. In the N ¼ 81 imaging/gene expression ... more were not included in the optimal classification algorithm. In the N ¼ 81 imaging/gene expression dataset the hippocampal-only classifier achieved 69% diagnostic accuracy (AUC ¼ 0.63) and ventricular-only classifier achieved 69% accuracy (AUC ¼ 0.57) compared to the hippocampal-GE classifier -accuracy 78%(AUC ¼ 0.79), and the combined hippocampalventricular-GE classifier -accuracy84% (AUC ¼ 0.82). 12 expressed genes and 8 expressed genes were selected as being useful for improving classification, by the final hippocampal-GE and hippocampal-ventricular-GE combined classifiers, respectively. Conclusions: As hypothesized, NC vs. aMCI classifier performance improved when combining imaging and genetic biomarkers. Automated classifiers show great promise for diagnostic analyses and potentially for predicting future conversion to AD. Receiver Operating Characteristic (ROC) curves for the unsupervised NC vs amnestic MCI classifier using structural imaging and SNP (top row) or gene expression data (bottom row). AUC stands for area under the curve.
Informal care plays a substantial role in the provision of total care in dementia. Several review... more Informal care plays a substantial role in the provision of total care in dementia. Several reviews have been published on the predictive factors of subjective burden; however, such a review lacks information on objective burden, which refers to the amount and/or costs of informal care. The objectives of this study were to (1) give an overview of the predictive factors that are associated with the objective burden of informal care; (2) discuss whether these factors are similar to the predictive factors of subjective burden; and (3) examine whether they are modifiable. The literature in a number of international databases was systematically searched. Methodological quality and level of certainty were assessed. Ten studies were identified as relevant for the purpose of this review, describing a total of 39 predictive factors. Three factors (behavioral problems and impairments regarding daily functioning and cognition) were considered to be predictors of objective burden. Three factors were not related; 12 were potential predictors; and the results of the remaining 22 factors were inconclusive. Many factors were found to be (potential) predictors of objective burden, reflecting its complex nature. Objective and subjective burdens are 2 different relevant aspects of informal care. Interventions aimed at countering behavioral problems and impairments regarding daily functioning could reduce objective burden.
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