The course of post-stroke apathy in relation to cognitive functioning: a prospective longitudinal cohort study.

Apathy is common after stroke and has been associated with cognitive impairment. However, causality between post-stroke apathy and cognitive impairment remains unclear. We assessed the course of apathy in relation to changes in cognitive functioning in stroke survivors. Using the Apathy Scale (AS) and cognitive tests on memory, processing speed and executive functioning at six- and 15 months post-stroke we tested for associations between (1) AS-scores and (change in) cognitive scores; (2) apathy course (persistent/incident/resolved) and cognitive change scores. Of 117 included participants, 29% had persistent apathy, 13% apathy resolving over time and 10% apathy emerging between 6-15 months post-stroke. Higher AS-scores were cross-sectionally and longitudinally associated with lower cognitive scores. Relations between apathy and cognitive change scores were ambiguous. These inconsistent relations between apathy and changes in cognition over time suggest that post-stroke apathy does not directly impact cognitive performance. Both these sequelae of stroke require separate attention.

[Screening of dementia in first generation migrants]. / Screening op dementie bij eerstegeneratiemigranten.

The number of patients with dementia is increasing over time. There is evidence that the prevalence in ethnic minority groups is even higher. Diagnosing dementia in first generation non-western migrants is often difficult due to language and cultural barriers, low education, and illiteracy. In this article we recommend the use of two validated screening tools (the RUDAS, Rowland Universal Dementia assessment scale and the IQCODE, Informant Questionnaire of Cognitive Decline in the elderly) elucidated by two case descriptions.

Long-term neurologic and cognitive outcome and quality of life in adults after pneumococcal meningitis.

OBJECTIVES: To perform a cross-sectional cohort study on long-term neurologic, cognitive and quality-of-life outcome in adults surviving pneumococcal meningitis. METHODS: Adult survivors of community-acquired pneumococcal meningitis from a Dutch nationwide prospective cohort study were evaluated 1 to 5 years after acute illness. The control group consisted of partners or proxies of patients. Neurologic examination was performed and cognitive domains were tested with the Vienna Test System Cognitive Basic Assessment Test set (VTS COGBAT). The Research and Development (RAND)-36 and adapted Cognitive and Emotional Consequences of Stroke (CLCE)-24 questionnaires assessed perceived cognitive functioning and quality of life. Differences between group scores were tested with multivariate analyses of variance. RESULTS: A total of 80 pneumococcal meningitis patients and 69 controls were evaluated. After a median of 2 years (interquartile range, 2-3) after acute illness, 27 (34%) of 79 patients had persistent neurologic sequelae, most commonly hearing loss (21/79, 27%). On overall neuropsychologic evaluation, patients performed worse than the controls (MANCOVA; p 0.008), with alertness (z score -0.33, p 0.011) and cognitive flexibility (z score -0.33, p 0.027) as the most affected domains. Cognitive impairment was present in 11 (14%) of 79 patients. CLCE-24 questionnaires revealed cognitive impairment on all domains, most commonly for cognitive speed (53/75, 71%), attention (45/75, 60%) and memory (46/75, 61%). Patients had lower quality-of-life scores than controls (item physical functioning, (median) patients vs. controls, 80 vs. 95, p < 0.001; social functioning, (median) 81 vs. 100, p 0.003; perceived health, (mean) 59 vs. 70, p 0.005), which correlated with cognitive complaints (R = 0.66, p < 0.001). CONCLUSIONS: Adults after pneumococcal meningitis are at high risk of long-term neurologic and neuropsychologic deficits impairing daily life activities and quality of life.

Predicting Progression to Parkinson's Disease Dementia Using Multivariate Normative Comparisons.

OBJECTIVE: Parkinson's disease with mild cognitive impairment (PD-MCI) is a risk factor for progression to PD dementia (PDD) at a later stage of the disease. The consensus criteria of PD-MCI use a traditional test-by-test normative comparison. The aim of this study was to investigate whether a new multivariate statistical method provides a more sensitive tool for predicting dementia status at 3- and 5-year follow-ups. This method allows a formal evaluation of a patient's profile of test scores given a large aggregated database with regression-based norms. METHOD: The cognitive test results of 123 newly diagnosed PD patients from a previously published longitudinal study were analyzed with three different methods. First, the PD-MCI criteria were applied in the traditional way. Second, the PD-MCI criteria were applied using the large aggregated normative database. Last, multivariate normative comparisons (MNCs) were made using the same aggregated normative database. The outcome variable was progression to dementia within 3 and 5 years. RESULTS: The MNC was characterized by higher sensitivity and higher specificity in predicting progression to PDD at follow-up than the two PD-MCI criteria methods, although the difference in classification accuracy did not reach statistical significance. CONCLUSION: We conclude that MNCs could allow for a more accurate prediction of PDD than the traditional PD-MCI criteria, because there are encouraging trends in both increased sensitivity and increased specificity. (JINS, 2019, 25, 678-687).

Universal Scale of Intelligence Estimates (USIE): Representing Intelligence Estimated From Level of Education.

In clinical neuropsychology, it is often necessary to estimate a patient's premorbid level of cognitive functioning in order to evaluate whether his scores on cognitive tests should be considered abnormal. In practice, test results from before the onset of brain pathology are rarely available, and the patient's level of education is used instead as an estimate of his premorbid level. Unfortunately, level of education may be expressed on many different scales of education, which are difficult to use interchangeably. Here, we introduce a new scale that has the capacity to replace existing scales and can be used interchangeably with any of them: the Universal Scale of Intelligence Estimates (USIE). To achieve this, we propose to map all levels of existing educational scales to standard IQ scores. This USIE point estimate is supplemented with an estimation interval. We assert that USIE offers some important benefits for clinical practice and research.

[Validation of the Seven Minute Screen for use in a memory clinic]. / Validering van de Seven Minute Screen voor gebruik in de geheugenpolikliniek.

Cognitive tests play a crucial part in the assessment of dementia. In 1998 the Seven Minute Screen was developed by Solomon and colleagues. The test was originally designed to distinguish between Alzheimer's disease (AD) and normal ageing, and research showed that the instrument is highly sensitive to AD. Subsequent research also proved the diagnostic accuracy of the Seven Minute Screen in the detection of other common types of dementia, such as vascular dementia, frontotemporal dementia and dementia with Lewy bodies. This article reports new research on the predictive validity of the Seven Minute Screen using 289 cognitively intact subjects, 175 patients with MCI and 563 patients with dementia in the setting of a memory clinic. In addition, a comparison is made with the Mini Mental State Examination (MMSE). The study demonstrates that the Seven Minute Screen is a valuable screening instrument for all common types of dementia, and it has added value to the MMSE. The sensitivity for dementia is 96 % and the specificity 93 %, in comparison to 69 and 98 % for the MMSE (< 24). The sensitivity for the various types of dementia is consistently high, ranging from 92 % for a subcortical dementia to 97 % for AD. The Seven Minute Screen requires little training, and combines a short administration time with a high diagnostic accuracy. This makes the Seven Minute Screen useful for application in memory clinics.

Prevalence of mild cognitive impairment and dementia in older non-western immigrants in the Netherlands: a cross-sectional study.

OBJECTIVE: In the Netherlands, persons of Turkish, Moroccan and Surinamese descent form the largest groups of non-western immigrants. A high prevalence of mild cognitive impairment (MCI) and dementia has been described in immigrant populations in the United States of America and the United Kingdom. We determined the prevalence of MCI and dementia in older community-dwelling adults from the largest non-western immigrant groups in the Netherlands. METHODS: Participants, aged 55 years and older, of Turkish, Moroccan (Arabic or Berber), Surinamese (Creole or Hindustani) or Dutch descent were recruited via their general practitioners. Cognitive deficits were assessed using the Cross-Cultural Dementia screening instrument, which was validated in poorly educated people from different cultures. Differences in prevalence rates of MCI and dementia between the immigrant groups and a native Dutch group were analysed using chi-square tests. RESULTS: We included 2254 participants. Their mean age was 65.0 years (standard deviation, 7.5), and 44.4% were male. The prevalence of MCI was 13.0% in Turkish, 10.1% in Moroccan-Arabic, 9.4% in Moroccan-Berber and 11.9% in Surinamese-Hindustani participants, compared to 5.9% in Surinamese-Creoles and 3.3% in native Dutch. The prevalence of dementia was 14.8% in Turkish, 12.2% in Moroccan Arabic, 11.3% in Moroccan Berber and 12.6% in Surinamese-Hindustani participants, compared to 4.0% in Surinamese-Creoles and 3.5% in native Dutch. CONCLUSIONS: MCI and dementia were three to four times more prevalent in the majority of non-western immigrant groups when compared to the native Dutch population. These differences are important for planning and improving healthcare facilities. Copyright © 2016 John Wiley & Sons, Ltd.

Prose memory impairment in amyotrophic lateral sclerosis patients is related to hippocampus volume.

BACKGROUND AND PURPOSE: Thirty per cent of amyotrophic lateral sclerosis (ALS) patients have non-motor symptoms, including executive and memory deficits. The in vivo anatomical basis of memory deficits in ALS has not been elucidated. In this observational study, brain atrophy in relation to memory function was investigated in ALS patients and controls. METHODS: Twenty-six ALS patients without dementia and 21 healthy volunteers matched for gender, age and education level underwent comprehensive neuropsychological evaluation and T1- and T2-weighted 3 T magnetic resonance imaging scanning of the brain. Grey and white matter brain volumes were analysed using voxel-based morphometry and age related white matter changes were assessed. The most frequently abnormal memory test (<2 SD below normative data corrected for age, gender and education) was correlated with regional brain volume variations by multiple regression analyses with age, gender and total grey matter volumes as covariates. RESULTS: Immediate and delayed story recall scores were abnormal in 23% of ALS patients and correlated to bilateral hippocampus grey matter volume (r = 0.52 for both memory tests; P < 0.05; corrected for age, gender and total grey matter volume). This correlation was not found in healthy controls with similar age, education, anxiety and depression levels and white matter changes. CONCLUSIONS: Prose memory impairment is a frequent finding in this cohort and is associated with hippocampus volume in ALS patients without dementia. These findings complement previous hippocampus changes in imaging studies in ALS and suggest involvement of the hippocampus in cognitive dysfunction of ALS.

Evolution of mild cognitive impairment in Parkinson disease.

OBJECTIVE: We examined the development of Parkinson disease (PD)-mild cognitive impairment (MCI) in patients with newly diagnosed PD over 5 years using recently proposed consensus criteria, and we assessed the reliability of the criteria. METHODS: Patients with PD (n = 123) underwent extensive neuropsychological testing at baseline and after 3 (n = 93) and 5 years (n = 59). Two neuropsychologists independently applied the PD-MCI criteria to examine the interrater and intrarater reliability. RESULTS: At baseline, 35% of patients had PD-MCI. Three years later, 53% of the patients had PD-MCI. At 5-year follow-up, 20 patients who had PD-MCI at an earlier assessment had converted to PD dementia and 50% of the remaining patients without dementia had MCI. The interrater reliability (kappa) was 0.91. The intrarater reliabilities were 0.85 and 0.96. CONCLUSION: Approximately one-third of patients with newly diagnosed PD fulfill the consensus criteria for PD-MCI; after 5 years, this proportion is approximately 50% of patients without dementia. The criteria have good interrater and intrarater reliability.

Monoaminergic dysfunction in recreational users of dexamphetamine.

Preclinical studies suggest that dexamphetamine (dAMPH) can lead to monoaminergic neurotoxicity. This exploratory study aimed to investigate effects of recreational dAMPH use on the dopamine (DA) and noradrenaline (NA) systems in humans. To that purpose, eight male abstinent dAMPH (26.0 ± 4.0 years) users and 10 age- and IQ-matched male healthy control subjects (23.0 ± 3.8) underwent neuropsychological testing sensitive to DAergic function and single photon emission computed tomography (SPECT) scanning with [(123)I]FP-CIT to determine striatal DA transporter (DAT) binding. In addition, changes in cerebral blood flow (CBF) induced by the DA/NA reuptake inhibitor methylphenidate (MPH) were measured using pharmacological magnetic resonance imaging (phMRI). Performance of dAMPH users was significantly worse on executive function and verbal memory tasks. Striatal DAT binding ratios were on average lower in dAMPH users (near-significant, p=0.05). In addition, CBF in control subjects decreased significantly in response to MPH in gray matter and basal ganglia, among which the striatum, thalamus and hippocampus by 10% to 29%. However, in dAMPH users the CBF response was blunted in most brain areas studied, only decreasing in the hippocampus and orbitofrontal cortex. When comparing groups, CBF response was found to be significantly different in the thalamus with a decrease for healthy controls and a blunted response in dAMPH users. Collectively, our findings of a blunted hemodynamic response in monoaminergic regions, in combination with indications for lower striatal DAT binding and poorer behavioral measures are likely to represent DAergic dysfunction in dAMPH users, although NAergic dysfunction may also play a role.

Symptoms of apathy are associated with progression from mild cognitive impairment to Alzheimer's disease in non-depressed subjects.

BACKGROUND: Apathy is a common symptom in various neuropsychiatric diseases including mild cognitive impairment (MCI) and dementia. Apathy may be associated with an increased risk of cognitive decline. The objective of this study was to investigate if apathy predicts the progression from MCI to Alzheimer's disease (AD). METHODS: The Alzheimer's Disease Neuroimaging Initiative is a prospective multicentre cohort study. At baseline, 397 patients with MCI without major depression were included. Clinical data and the Geriatric Depression Scale at baseline were used. Apathy was defined based on the 3 apathy items of the 15-item Geriatric Depression Scale. The main outcome measure was the association of apathy with progression from MCI to AD. RESULTS: During an average follow-up of 2.7 years (SD 1.0), 166 (41.8%) patients progressed to AD. The presence of symptoms of apathy without symptoms of depressive affect increased the risk of progression from MCI to AD (hazard ratio = 1.85, 95% CI = 1.09-3.15). Apathy in the context of symptoms of depressive affect or symptoms of depressive affect alone, without apathy, did not increase the risk of progression to AD. CONCLUSIONS: Symptoms of apathy, but not symptoms of depressive affect, increase the risk of progression from MCI to AD. Apathy in the context of symptoms of depressive affect does not increase this risk. Symptoms of apathy and depression have differential effects on cognitive decline.

Increased risk of mortality associated with social isolation in older men: only when feeling lonely? Results from the Amsterdam Study of the Elderly (AMSTEL).

BACKGROUND: Loneliness has a significant influence on both physical and mental health. Few studies have investigated the possible associations of loneliness with mortality risk, impact on men and women and whether this impact concerns the situation of being alone (social isolation), experiencing loneliness (feeling lonely) or both. The current study investigated whether social isolation and feelings of loneliness in older men and women were associated with increased mortality risk, controlling for depression and other potentially confounding factors. METHOD: In our prospective cohort study of 4004 older persons aged 65-84 years with a 10-year follow-up of mortality data a Cox proportional hazard regression analysis was used to test whether social isolation factors and feelings of loneliness predicted an increased risk of mortality, controlling for psychiatric disorders and medical conditions, cognitive functioning, functional status and sociodemographic factors. RESULTS: At 10 years follow-up, significantly more men than women with feelings of loneliness at baseline had died. After adjustment for explanatory variables including social isolation, the mortality hazard ratio for feelings of loneliness was 1.30 [95% confidence interval (CI) 1.04-1.63] in men and 1.04 (95% CI 0.90-1.24) in women. No higher risk of mortality was found for social isolation. CONCLUSIONS: Feelings of loneliness rather than social isolation factors were found to be a major risk factor for increasing mortality in older men. Developing a better understanding of the nature of this association may help us to improve quality of life and longevity, especially in older men.

[Diagnosis of dementia in non-western elderly migrants in memory clinics: obstacles and solutions]. / Dementiediagnostiek bij oudere migranten op de geheugenpolikliniek: obstakels en oplossingen.

In the next decade the number of non-western elderly immigrants will double in the Netherlands. Because of specific risk factors (hypertension, diabetes), the number of elderly immigrants with dementia will probably increase. Memory clinics are not well prepared for these patients, because health professionals lack knowledge about important obstacles in intercultural dementia diagnostics. They should consider language barriers, cultural differences, low level of education and illiteracy, as well as ignorance about dementia, shame and special care expectations of patients and their families. We give recommendations to improve communication, (neuropsychological) testing and counseling in clinical practice.

Validation of symptom validity tests using a "child-model" of adult cognitive impairments.

Validation studies of symptom validity tests (SVTs) in children are uncommon. However, since children's cognitive abilities are not yet fully developed, their performance may provide additional support for the validity of these measures in adult populations. Four SVTs, the Test of Memory Malingering (TOMM), the Word Memory Test (WMT), the Amsterdam Short-Term Memory (ASTM) test, and the Word Completion Memory Test (WCMT), along with several neuropsychological instruments were administered to 48 Dutch school children aged 7-12. All children scored above the established adult cut-offs on the TOMM and the WMT. They could pass the ASTM test if their reading skills were at a level equivalent to that of 9 year olds. All children passed our criterion of a negative WCMT score. However, the WCMT does seem sensitive to the level of verbal fluency. Implications for the applicability of these SVTs in adult populations are discussed.

Meta-analysis of CSF and MRI biomarkers for detecting preclinical Alzheimer's disease.

BACKGROUND: Abnormal levels of biomarkers in cerebrospinal fluid (CSF) and atrophy of medial temporal lobe (MTL) structures on magnetic resonance imaging (MRI) are being used increasingly to diagnose early Alzheimer's disease (AD). We evaluated the claim that these biomarkers can detect preclinical AD before behavioural (i.e. memory) symptoms arise. METHOD: We included all relevant longitudinal studies of CSF and MRI biomarkers published between January 2003 and November 2008. Subjects were not demented at baseline but some declined to mild cognitive impairment (MCI) or to AD during follow-up. Measures of tau and beta-amyloid in CSF, MTL atrophy on MRI, and performance on delayed memory tasks were extracted from the papers or obtained from the investigators. RESULTS: Twenty-one MRI studies and 14 CSF studies were retrieved. The effect sizes of total tau (t-tau), phosphorylated tau (p-tau) and amyloid beta 42 (a beta 42) ranged from 0.91 to 1.11. The effect size of MTL atrophy was 0.75. Memory performance had an effect size of 1.06. MTL atrophy and memory impairment tended to increase when assessed closer to the moment of diagnosis, whereas effect sizes of CSF biomarkers tended to increase when assessed longer before the diagnosis. CONCLUSIONS: Memory impairment is a more accurate predictor of early AD than atrophy of MTL on MRI, whereas CSF abnormalities and memory impairment are about equally predictive. Consequently, the CSF and MRI biomarkers are not very sensitive to preclinical AD. CSF markers remain promising, but studies with long follow-up periods in elderly subjects who are normal at baseline are needed to evaluate this promise.

Reference data for the word memory test.

Many studies have evaluated the utility of the Word Memory Test (WMT) as a symptom validity test. However, there is a lack of reference data for the WMT conventional memory subtests. The present study examined the demographic characteristics that influence performance on these subtests, in order to develop demographically corrected reference data. For this purpose, we administered the Dutch version of the WMT to 115 healthy Dutch controls, aged 20-80 years. Furthermore, we demonstrated the equivalence of the English and Dutch language versions of the WMT. Stepwise linear regression analyses of the combined Canadian and Dutch samples (N = 155) showed that the memory scores declined with increasing age. Participants with lower levels of education performed worse than more highly educated subjects. Reference data stratified by age and level of education are presented for use in research and clinical settings.

Determinants of disability and quality of life in mild to moderate Parkinson disease.

OBJECTIVE: To identify factors that independently contribute to disability and quality of life (QoL) in patients with mild to moderate Parkinson disease (PD). METHODS: A group of 190 patients with PD recruited from outpatient clinics and the Dutch Parkinson's Disease Association participated in this cross-sectional study. Data on demographic and clinical factors, motor symptoms, cognitive functions, affective symptoms, comorbidity, and social support were collected during neurologic and neuropsychological examinations. Disability was rated using the Schwab and England Activities of Daily Living Scale (SE-ADL), the AMC Linear Disability Score (ALDS), and the Functional Independence Measure (FIM). QoL was assessed with the Parkinson's Disease Quality of Life questionnaire (PDQL) and the Medical Outcome Study Short Form (SF-36). Multiple linear regression analyses were conducted to identify determinants of disability and poor QoL. RESULTS: Axial impairment (postural instability and gait difficulty) explained the largest proportion of variance in disability. Bradykinesia and comorbidity contributed to disability, but to a lesser extent. Self-reported mood symptoms and axial impairment were the two factors most closely associated with poorer QoL, but comorbidity and bradykinesia additionally contributed to the explanatory power. Semantic fluency and psychomotor skills were the only cognitive variables related to some aspects of functional outcome. CONCLUSION: Axial impairment is strongly associated with disability in patients with mild to moderate Parkinson disease (PD). Self-report indices of mood status and axial impairment are identified as the main determinants of poor quality of life (QoL). The results of this study may help to identify patients with PD at risk for functional dependence and reduced QoL.

[Letter fluency: psychometric properties and Dutch normative data]. / Letterfluency: psychometrische eigenschappen en Nederlandse normen.

Normative data were collected for a Dutch version of the Controlled Oral Word Association Test (COWAT) in 200 healthy subjects between 17 and 89 years of age. The COWAT is a letterfluency task that is widely used in clinical neuropsychology. Fluency is an important aspect of executive functioning. The psychometric properties of the Dutch version of the test were largely comparable to those of the original COWAT. Its reliability is 0.80, and its scores are significantly related to level of education and/or vocabulary, but not to age or gender. A regression formula is provided by which the raw scores can be corrected for level of education.

Specific effects of ecstasy and other illicit drugs on cognition in poly-substance users.

BACKGROUND: A large number of studies, reviews and meta-analyses have reported cognitive deficits in ecstasy users. However most ecstasy users are polydrug users, and therefore it cannot be excluded that these deficits are (partly) the result of drugs other than ecstasy. The current study, part of the Netherlands XTC Toxicity (NeXT) study, investigates the specific sustained effects of ecstasy relative to amphetamine, cocaine and cannabis on the brain using neuropsychological examination. METHOD: A stratified sample of 67 subjects with such a variation in type and amount of drug use was included that correlations between the consumption of the various drugs were relatively low allowing stepwise linear multiple regression analyses to differentiate between the effects of ecstasy and those of other substances. Subjects were assessed with neuropsychological tests measuring attention, working memory, verbal and visuospatial memory, and visuospatial ability. RESULTS: Ecstasy use [mean 327 (S.D.=364) tablets in lifetime] had a specific significant dose-related negative effect on verbal delayed recall after adjusting for the use of other drugs. CONCLUSIONS: These findings strongly suggest a specific sustained negative effect of ecstasy use on verbal memory. The clinical relevance is not immediately clear, because test performance generally remained within the normal range. However the magnitude of the effect is substantial (d>0.5) and long-term consequences cannot be excluded.