Factor structure and measurement invariance of the cognitive failures questionnaire across the adult life span.

The Cognitive Failures Questionnaire (CFQ) is designed to assess a person's proneness to committing cognitive slips and errors in the completion of everyday tasks. Although the CFQ is a widely used instrument, its factor structure remains an issue of scientific debate. The present study used data of a representative sample (N = 1,303, 24-83 years of age) from the Maastricht Aging Study (MAAS) to test and compare factor solutions for the CFQ previously reported in the literature by means of confirmatory factor analysis of ordered categorical variables. A three-factor model of the CFQ from an exploratory factor analysis was tested for increasing levels of measurement invariance across six age groups. Factor (co-)variances remained stable across the age groups, mean differences were observed for the factor Forgetfulness with higher means for older participants, and the factor Distractibility where participants older than 60 years of age had lower means.

Age-dependent differences in attentional processes in ADHD and disruptive behavior disorder.

The aim of this study was to analyze age-dependent differences in attentional performance in subjects aged 8-16 years with attention deficit/hyperactivity disorder (ADHD) with or without disruptive behavior disorders (DBD). Age effects were investigated in three different groups (ADHD [N = 118], ADHD + DBD [N = 105], and controls [N = 105]) on a sustained attention and a Go-No-Go paradigm. Attentional competencies increased with age and children in the two clinical groups performed worse than control children on both tasks. However, these group differences between ADHD, ADHD + DBD, and controls decreased with increasing age. Thus, age-related differences must be considered in neuropsychological studies.

Association between apolipoprotein E4 and cognitive decline in elderly adults.

OBJECTIVE: To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2-year (range 0.7-4.2) follow-up for memory (Picture-Word Recall), speed of information processing (Stroop and Letter-Digit Coding), global cognitive function (Mini-Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E(4) versus those without E(4) had poorer memory performance (mean score difference -0.20 (95% confidence interval (CI)=-0.31 to -0.09) for immediate recall and -0.32 (95% CI=-0.48 to -0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI=1.20-4.28); Letter-Digit score, -0.36, (95% CI=-0.77-0.05). Subjects with apolipoprotein E(4) showed a greater decline in immediate (-0.22, 95% CI=-0.33 to -0.11) and delayed (-0.30, 95% CI=-0.46 to -0.15) memory scores but no significant change in speed of information processing (Stroop, P=.17; Letter-Digit, P=.06). Memory scores decreased 2.5% from baseline in those without E(4), 4.3% in E(4) heterozygotes (P=.01 for immediate and P=.03 for delayed, vs no E(4)) and 8.9% to 13.8% in E(4) homozygotes (P=.04 for immediate and P=.004 for delayed, vs heterozygotes). Apolipoprotein E(4) was associated with greater decline in instrumental activities of daily living (P<.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E(4) is associated with more-rapid cognitive decline and may, therefore, predispose to dementia.

The influence of neuropsychological functioning on neuropsychiatric problems in dementia.

Although much is known about the relationship between neuropsychiatric problems and the severity of cognitive impairments, relatively little is known about the association with specific cognitive impairments. The aim of this study was to determine whether specific cognitive impairments are predictive of neuropsychiatric problems. One hundred twenty-six patients were evaluated every 6 months for 2 years. In particular, a low level of language expression was related to higher levels of overall neuropsychiatric problems and to psychosis. Impairment of abstract reasoning was related to psychosis and aberrant motor behavior.

Ten-year risk of dementia in subjects with mild cognitive impairment.

OBJECTIVE: To investigate the 10-year risk of dementia in subjects with mild cognitive impairment (MCI) ages 40 to 85 years. METHODS: We selected subjects from a memory clinic if they met one of the following definitions of MCI: cognitive complaints (n = 181), aging-associated cognitive decline (AACD) (n = 163), mild functional impairment (n = 86), or amnestic MCI (n = 64). Subjects were reassessed after 2, 5, and 10 years. The risk of dementia was calculated with Kaplan-Meier statistics. Analyses were conducted in the entire sample and in subgroups of subjects aged 40 to 54 years, 55 to 69 years, and 70 to 85 years. RESULTS: The 10-year risk of dementia was 0.27 (95% CI 0.20 to 0.34) in subjects with cognitive complaints, 0.28 (95% CI 0.21 to 0.35) in subjects with AACD, 0.44 (95% CI 0.32 to 0.56) in subjects with mild functional impairment, and 0.48 (95% CI 0.35 to 0.61) in subjects with amnestic MCI. Ninety-one percent of the demented subjects had probable AD. The risk of dementia increased with increasing age for all MCI definitions (p < 0.001). Depending on the MCI definition used, the risk for dementia ranged from 0 to 0.06 in subjects aged 40 to 54 years, from 0.37 to 0.52 in subjects aged 55 to 69 years, and from 0.77 to 1.0 in subjects aged 70 to 85 years. CONCLUSIONS: The majority of subjects with MCI do not progress to dementia at the long term. Age strongly influences the dementia risk. MCI often represents the predementia stage of a neurodegenerative disorder in elderly subjects but rarely in younger subjects.

Functional MRI of task switching in children with Specific Language Impairment (SLI).

The objective of this study was to examine executive functioning in children with Specific Language Impairment (SLI) using functional MRI. Six children with SLI and seven control children participated in this study and received a task-switching paradigm. No specific deficit in executive control was observed at the behavioral level in children with SLI. However, the neuroimaging data did show remarkable differences between the SLI and control children. The children with SLI recruited frontal and cingulate areas, normally associated with executive control, even when the task did not require them in the children without SLI. This might indicate that the task was more demanding for the SLI group and that compensatory mechanisms were engaged for successful task performance.

The influence of risperidone on attentional functions in children and adolescents with attention-deficit/hyperactivity disorder and co-morbid disruptive behavior disorder.

This study aims to examine the influence of risperidone on various attentional functions, including intensity and selectivity aspects of attention plus inhibitory control in children with attention deficit/hyperactivity disorder (ADHD) with co-morbid Disruptive Behavior Disorders (DBD) and normal IQ. Children with ADHD and DBD, aged 8-15 years, were treated with risperidone (mean daily dose: 1.5 mg; n = 23) and examined with three attentional paradigms before and after a 4-week treatment period. Age- and IQ-matched normal controls (n = 23) were also tested without medication on the same two occasions. No influence of the medication could be detected for any neuropsychological variable, neither as a positive enhancement nor as adverse side effects. However, clinical symptoms of ADHD and DBD assessed on the IOWA Conners Scale significantly improved after the 4-week treatment period. Divergent behavioral and cognitive effects of risperidone on ADHD symptoms were observed, with a significant reduction in behavioral symptoms, whereas no positive treatment effects were found on laboratory tasks of impulsivity. Thus, the cognitive effects of risperidone seem to differ from the cognitive effects of stimulant treatments in children with ADHD + DBD. However, no negative impact of risperidone was observed on attentional functions either, i.e., there was no slowing of cognitive speed.

Homocysteine in relation to cognitive performance in pathological and non-pathological conditions.

Elevated serum homocysteine has been associated with increased risk of Alzheimer's disease. Furthermore, elevated homocysteine levels are related to cognitive dysfunction in the elderly. The aim of the present study was to explore the disease specificity of the relation between serum total homocysteine levels and cognitive function. For this, we summarize data from several studies on homocysteine levels in both normal and pathological conditions performed in our laboratories and evaluate possible mechanisms of effects of elevated homocysteine levels in the central nervous system. Total homocysteine levels were measured in serum of: 1) healthy aging individuals; 2) patients with Alzheimer's and Parkinson's disease and patients with other cognitive disorders; and 3) patients with multiple sclerosis. Increased serum homocysteine concentration was related to worse cognitive performance over a 6-year period in the normal aging population (r=-0.36 to -0.14, p<0.01 for the Word learning tests; r=0.76, p<0.05 for the Stroop Colored Word test). Homocysteine was only increased in patients with Parkinson's disease on L-Dopa therapy (18.9 vs. 16.5 micromol/L in healthy controls), and not in dementia patients. Homocysteine was elevated in patients with progressive multiple sclerosis (15.0 micromol/L, n=39, compared to 12.0 micromol/L in 45 controls) and correlated to both cognitive and motor function (r=-0.33 and -0.33, p<0.05, respectively). The relationship between homocysteine and cognitive function in non-pathological and pathological situations indicates that changes in its levels may play a role in cognitive functioning in a broad spectrum of conditions.

The influence of sertraline on attention and verbal memory in children and adolescents with anxiety disorders.

This study investigated the cognitive side effects of a 6-week course of sertraline treatment on verbal memory and attention in children and adolescents. Children with various anxiety disorders (social phobia, generalized and separation anxiety disorder; n = 28), between 8 and 17 years of age, received a standardized, computerized neuropsychological assessment before treatment and another 6 weeks after treatment onset with sertraline (daily dose range between 25 and 100 mg). The patient group was compared to healthy controls (n = 28), who were matched for age and IQ and were also tested twice over a 6-week period. Sertraline did not have any negative effects on attentional performance (p > 0.05) but did increase response speed in a divided attention paradigm (p = 0.02). By contrast, performance of the interference part of a verbal memory task decreased (p = 0.05). The described results also remained stable over a 12-week period after treatment onset. Thus, the cognitive side effects of sertraline seemed to differ slightly between pediatric patients and those described in adult patient groups, should, therefore, be carefully assessed.

Cerebral small-vessel disease and decline in information processing speed, executive function and memory.

Cerebral small-vessel disease is common in older people and may contribute to the development of dementia. The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospective, population-based Rotterdam Scan Study. Participants were 60-90 years of age and free from dementia at baseline in 1995-1996. White matter lesions (WML), cerebral infarcts and generalized brain atrophy were assessed on the baseline MRI. We performed neuropsychological testing at baseline and repeatedly in 1999-2000 and in 2001-2003. We used random-effects models for repeated measures to examine the association between quantitative MRI measures and rate of decline in measures of global cognitive function, information processing speed, executive function and memory. There were a total of 2266 assessments for the 832 participants in the study, with an average time from the initial to last assessment of 5.2 years. Increasing severity of periventricular WML and generalized brain atrophy and the presence of brain infarcts on MRI were associated with a steeper decline in cognitive function. These structural brain changes were specifically associated with decline in information processing speed and executive function. The associations between MRI measures of cerebral small-vessel disease and cognitive decline did not change after additional adjustment for vascular risk factors or depressed mood. After exclusion of participants with an incident stroke, some of the associations of periventricular WML, brain infarcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant. This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline. Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function.

The course of neuropsychiatric symptoms in dementia. Part II: relationships among behavioural sub-syndromes and the influence of clinical variables.

BACKGROUND: Although several studies have mentioned associations between neuropsychiatric symptoms, there have been no prospective studies determining interrelations among behavioural sub-syndromes. OBJECTIVES: To investigate the influence of several clinical variables on the course of neuropsychiatric symptoms, and to determine interrelationships between the behavioural sub-syndromes. METHODS: One hundred and ninety-nine patients with dementia were assessed every six months for two-years, using the Neuropsychiatric Inventory (NPI) to evaluate neuropsychiatric symptoms. RESULTS: Age, sex, and socioeconomic status were not associated with a specific neuropsychiatric symptom. Greater cognitive impairment was related to more severe psychosis, and dementia stage influenced the course of total NPI problems. There were strong interrelations among most behavioural sub-syndromes. The sub-syndrome hyperactivity was of influence on the development of psychosis, but not vice versa. Neither was the sub-syndrome mood/apathy of influence on the course of psychosis. CONCLUSIONS: While different neuropsychiatric symptoms have their own specific correlates, there is a strong interrelationship between behavioural sub-syndromes. The data have implications for clinicians and the nosology of neuropsychiatric symptoms in dementia.

Cross-national comparison and validation of the Alzheimer's Disease Assessment Scale: results from the European Harmonization Project for Instruments in Dementia (EURO-HARPID).

BACKGROUND: The Alzheimer's Disease Assessment Scale (ADAS) is often used in international multicenter trials. Use across countries presupposes correct translation and adaptation of the scale, and maintenance of its psychometric properties. OBJECTIVES: To compare the various translations of the ADAS used in Western Europe, to design internationally harmonized translations and to validate these. SETTING: International cooperative study in eight European countries. METHODS: An inventory was made of existing versions of the ADAS-Cog used in eight European countries, and adaptations were made. The concurrent validity of the harmonized versions of the ADAS was tested in 283 patients with probable or possible Alzheimer's disease. The Nurses Observation Scale for Geriatrics (NOSGER), CAMCOG-R and MMSE was used to assess concordance between cognitive and behavioral measures. RESULTS: Differences between the versions mainly involved object naming, items for verbal memory, such as the number of trials allowed, the imagery value of the words selected as targets or distractors, and the number of parallel versions. These differences were eliminated by adapting and harmonizing the various versions of the ADAS-Cog. Thereafter, only small differences between the different countries were found, and patterns of correlation between ADAS-Cog, and the NOSGER, CAMCOG-R and MMSE were consistent. CONCLUSIONS: The study underlines the need to use harmonized versions of instruments for rating dementia in multinational studies. The findings indicate that the harmonization of the ADAS-Cog was successful.

Do caregiver management strategies influence patient behaviour in dementia?

OBJECTIVES: Little is known about the effectiveness of caregiver management strategies on the functioning of the demented patient. However, identification of specific caregiver strategies may provide useful information on the management and manifestation of behavioural problems in dementia. METHODS: Ninety-nine patients with dementia and their informal caregivers were followed up for one year. Interviews were used to assess differences in caregiver management strategies. Behavioural disturbances in the patient were measured with the Neuropsychiatric Inventory (NPI). Repeated measures analysis were carried out to investigate the relationship between caregiver management strategies and patient behaviour. RESULTS: Three caregiver management strategies were identified, based on whether caregivers accepted, or not, the caregiving situation and dementia related problems. Caregivers characterized by non-acceptance were typified as 'Non-adapters'; caregivers characterized by acceptance were further subdivided into two groups typified as 'Nurturers' and 'Supporters'. Caregiver characteristics such as sex, education and personality were important determinants of management strategies. MANOVA showed that non-adapters reported significantly more hyperactivity symptoms in patients and felt less competent than did supporters. CONCLUSIONS: Caregiver management strategies would appear to be associated with behavioural problems in dementia, and are important in predicting patient behaviour and caregiver burden. Intervention programmes should aim at teaching caregivers adequate management strategies.

Cross-national comparisons of the Cambridge Cognitive Examination-revised: the CAMCOG-R: results from the European Harmonization Project for Instruments in Dementia.

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

Behavioural disturbances in dementia patients and quality of the marital relationship.

OBJECTIVES: To investigate the relationship between behavioural problems in patients with dementia and changes in the marital relationship. METHODS: Fifty-three spouse caregivers of patients with dementia participated in the study. Questionnaires and interviews were used to examine caregiver perception of changes in the quality of their relationship. Behavioural disturbances in the patient were measured with the NeuroPsychiatric Inventory (NPI). RESULTS: Caregivers experienced a deterioration of their relationship, yet at the same time most felt closer to their spouse now than in the past. Regression analysis revealed that patient behavioural problems were, independent of patient cognitive status or functional impairment, associated with deterioration in the quality of the relationship between patient and caregiver. Patient apathy rather than depressive mood was associated with this deterioration. Apathy diminished the amount and reciprocity of interactions between partners. CONCLUSIONS: These results show that passive behaviour rather than excessive behaviour has most impact on the deterioration of the marital relationship. Intervention programmes should target relationship problems when problem behaviour, especially apathy, is present in patients with dementia.

Course of minimal dementia and predictors of outcome.

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.

Periventricular cerebral white matter lesions predict rate of cognitive decline.

The prospect of declining cognitive functions is a major fear for many elderly persons. Cerebral white matter lesions, as commonly found with magnetic resonance imaging, have been associated with cognitive dysfunction in cross-sectional studies. Only a few longitudinal studies using small cohorts confirmed these findings. We examined the relation between severity of white matter lesions and cognitive decline over a nearly 10-year period in 563 elderly subjects sampled from the general nondemented Dutch population. Severity of white matter lesions was scored for periventricular and subcortical regions separately using an extensive semiquantitative scale. Cognitive function was measured by the Mini-Mental State Examination at regular time intervals during 1990 to 2000, and magnetic resonance imaging scans were made in 1995 to 1996. More severe white matter lesions were associated with more rapid cognitive decline over a mean follow-up period of 7.3 years (standard deviation, 1.5). After adjusting for age, gender, educational level, measures of depression, and brain atrophy and infarcts, subjects with severe periventricular white matter lesions experienced cognitive decline nearly three times as fast (0.28 Mini-Mental State Examination points/year [95% confidence interval, 0.20-0.36]) as the average (0.10 points/year [95% confidence interval, 0.09-0.11]). There was no independent relationship between severity of subcortical white matter lesions and rate of cognitive decline.

Postoperative cognitive dysfunction versus complaints: a discrepancy in long-term findings.

This review describes the discrepancy in findings between postoperative cognitive performance and postoperative cognitive complaints long time after an operation under general anesthesia. Shortly (from 6 hr to 1 week) after an operation a decline in cognitive performance is reported in most studies. However, long time (from 3 weeks to 1-2 years) after an operation this is rarely found although some patients are still reporting cognitive complaints. In general this kind of research is suffering from severe methodological problems (use of insensitive tests, lack of control groups, lack of parallel tests, different definitions of cognitive decline). However, these problems cannot totally explain the discrepancy in findings in the long term. Thus, there are patients who have persistent cognitive complaints long time after an operation, that cannot be measured with cognitive tests. More psychological factors such as fixation on short-term cognitive dysfunction, mood, coping style, and personality are possible explanations for these cognitive complaints in the long term. As a consequence, these factors should be a topic in future research elucidating the persistence of these cognitive complaints long time after an operation under general anesthesia.

Diagnostic accuracy of the Preclinical AD Scale (PAS) in cognitively mildly impaired subjects.

The Preclinical AD Scale (PAS) is a newly developed scale for the diagnosis of preclinical Alzheimer's disease (AD). The PAS combines six markers of preclinical AD, namely age, MMSE score, functional impairment, cognitive test performance, medial temporal lobe atrophy, and the apolipoprotein E (APOE) genotype. The aim of the study was to investigate whether the PAS can accurately identify subjects with preclinical AD who become demented during a 2 or 5 year follow-up from among subjects with mild cognitive impairment for other reasons. We also investigated whether a step-wise scoring of the PAS could reduce the number of elaborate or expensive diagnostic procedures. The PAS was scored retrospectively in two independent samples of non-demented subjects with mild cognitive impairment older than 55 years (average age 65.6 years), who were selected from a memory clinic population. In the first sample, the follow-up was 5 years (5-year follow-up sample; n=69). In the second sample, the follow-up was 2 years (2-year follow-up sample; n=23). The PAS item medial temporal lobe atrophy was not scored in the 5-year follow-up sample. A PAS cut-off score of 4/5 could best identify subjects with AD-type dementia at follow-up (n=25) in the 5-year follow-up sample with a sensitivity of 80% and a positive predictive value of 77%. A PAS cut-off score of 5/6 could best identify subjects with AD-type dementia at follow-up (n=8) in the 2-year follow-up sample with a sensitivity of 88% and a positive predictive value of 70%. The positive predictive value could be increased to 94% in the 5-year follow-up sample and to 80% in the 2-year follow-up sample by using higher cut-off scores, but this reduced the sensitivity. Step-wise scoring of the PAS had the same diagnostic accuracy as the total PAS score and reduced the number of cognitive assessments by 22 to 38%, the number of assessments of medial temporal lobe atrophy by 57 to 74%, and the number of APOE genotypings by 74%. It is concluded that the PAS is a useful scale to identify subjects with preclinical AD who will become demented during the next 2 or 5 years. Step-wise scoring of the PAS can reduce the number of elaborate or expensive diagnostic procedures considerably.