Sietske A.M. Sikkes

Cognitive Rehabilitation in Patients With Gliomas: A Randomized, Controlled Trial

PURPOSEnPatients with gliomas often experience cognitive deficits, including problems with attention and memory. This randomized, controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program (CRP) on cognitive functioning and selected quality-of-life domains in patients with gliomas.nnnPATIENTS AND METHODSnOne hundred forty adult patients with low-grade and anaplastic gliomas, favorable prognostic factors, and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherlands. Patients were randomly assigned to an intervention group or to a waiting-list control group. The intervention incorporated both computer-based attention retraining and compensatory skills training of attention, memory, and executive functioning. Participants completed a battery of neuropsychological (NP) tests and self-report questionnaires on cognitive functioning, fatigue, mental health-related quality of life, and community integration at baseline, after completion of the CRP, and at 6-month follow-up.nnnRESULTSnAt the immediate post-treatment evaluation, statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures. At the 6-month follow-up, the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue. Group differences in other subjective outcomes were not significant at 6 months.nnnCONCLUSIONnThe CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue. Additional research is needed to identify which elements of the intervention are most effective.

A systematic review of Instrumental Activities of Daily Living scales in dementia: room for improvement

Background: Instrumental Activities of Daily Living (IADL) questionnaires can be helpful in diagnosing dementia and are often used for clinical follow-up and treatment evaluation in dementia patients. Despite the large number of questionnaires, their quality has received little attention. Objective: To systematically review the measurement properties of all available structured informant-based (I)ADL questionnaires, developed or validated for use in demented patients. Methods: A systematic literature search was conducted in MEDLINE, PsycINFO and EMBASE for psychometric articles on (I)ADL questionnaires. In addition, reference lists of all retrieved articles were screened. Standardised criteria were used to assess the quality of the measurement properties. When possible, investigators were contacted to obtain missing information. Two authors independently extracted studies and performed the quality assessment of the questionnaires. Findings: Thirty-two articles were selected, covering 12 (I)ADL questionnaires. Information on 52.3% of the quality aspects was not available, 32.4% of the ratings were indeterminate, 8.1% were positive, and 7.2% were negative. Out of eight measurement properties, two scales (the DAD and the Bristol ADL) received two positive ratings and were classified as of moderate quality. Five scales (ADL-PI, ADL-IS, B-ADL, CSADL and Lawton IADL) received one positive rating. Interpretation: The findings indicate that improvements in and more data on psychometric properties of (I)ADL questionnaires for dementia patients are necessary in order to justify their use.

Mild cognitive impairment and deficits in instrumental activities of daily living: a systematic review

IntroductionThere is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic review, therefore, we aimed to summarize research results regarding the performance of MCI patients in specific IADL (sub)domains compared with persons who are cognitively normal and/or patients with dementia.MethodsThe databases PsycINFO, PubMed and Web of Science were searched for relevant literature in December 2013. Publications from 1999 onward were considered for inclusion. Altogether, 497 articles were retrieved. Reference lists of selected articles were searched for potentially relevant articles. After screening the abstracts of these 497 articles, 37 articles were included in this review.ResultsIn 35 studies, IADL deficits (such as problems with medication intake, telephone use, keeping appointments, finding things at home and using everyday technology) were documented in patients with MCI. Financial capacity in patients with MCI was affected in the majority of studies. Effect sizes for group differences between patients with MCI and healthy controls were predominantly moderate to large. Performance-based instruments showed slight advantages (in terms of effect sizes) in detecting group differences in IADL functioning between patients with MCI, patients with Alzheimer’s disease and healthy controls.ConclusionIADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits. The use of assessment tools specifically designed and validated for patients with MCI is therefore strongly recommended. Furthermore, the development of performance-based assessment instruments should be intensified, as they allow a valid and reliable assessment of subtle IADL deficits in MCI, even if a proxy is not available. Another important point to consider when designing new scales is the inclusion of technology-associated IADL. Novel instruments for clinical practice should be time-efficient and easy to administer.

Do Instrumental Activities of Daily Living Predict Dementia at 1- and 2-Year Follow-Up? Findings from the Development of Screening Guidelines and Diagnostic Criteria for Predementia Alzheimer's Disease Study

To investigate whether problems in instrumental activities of daily living (IADL) can add to conventionally used clinical measurements in helping to predict a diagnosis of dementia at 1‐ and 2‐year follow‐up.

Implementation of subjective cognitive decline criteria in research studies

Subjective cognitive decline (SCD) manifesting before clinical impairment could serve as a target population for early intervention trials in Alzheimers disease (AD). A working group, the Subjective Cognitive Decline Initiative (SCD‐I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed.

Single-Subject Gray Matter Graph Properties and Their Relationship with Cognitive Impairment in Early- and Late-Onset Alzheimer's Disease

Abstract We investigated the relationships between gray matter graph properties and cognitive impairment in a sample of 215 patients with Alzheimers disease (AD) and also whether age of disease onset modifies such relationships. We expected that more severe cognitive impairment in AD would be related to more random graph topologies. Single-subject gray matter graphs were constructed from T1-weighted magnetic resonance imaging scans. The following global and local graph properties were calculated: betweenness centrality, normalized clustering coefficient γ, and normalized path length λ. Local clustering, path length, and betweenness centrality measures were determined for 90 anatomically defined areas. Regression models with as interaction term age of onset (i.e., early onset when patients were ≤65 years old and late onset when they were >65 years old at the time of diagnosis)×graph property were used to assess the relationships between cognitive functioning in five domains (memory, language, visuospatial, attention, and executive). Worse cognitive impairment was associated with more random graphs, as indicated by low γ, λ, and betweenness centrality values. Three interaction effects for age of onset×global graph property were found: Low γ and λ values more strongly related to memory impairment in early-onset patients; low beta values were significantly related to impaired visuospatial functioning in late-onset patients. For the local graph properties, language impairment showed the strongest relationship with decreased clustering coefficient in the left superior temporal gyrus across the entire sample. Our study shows that single-subject gray matter graph properties are associated with individual differences in cognitive impairment.

How Useful Is the IQCODE for Discriminating between Alzheimer’s Disease, Mild Cognitive Impairment and Subjective Memory Complaints?

Background: Informant questionnaires may be useful in diagnosing early dementia. Conflicting results were found when these questionnaires were used to differentiate patients with mild cognitive impairment (MCI) from healthy elderly subjects. We evaluated the ability of the most commonly used informant questionnaire, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), to discriminate between Alzheimer’s disease (AD), MCI and subjective memory complaints (SMC). Methods: Informants of 180 AD patients, 59 MCI patients and 89 SMC subjects who visited the Alzheimer Center of the VU University Medical Center between 2004 and 2007 completed the short Dutch version of the IQCODE. Logistic regression and receiver operating characteristic curves were used to evaluate the diagnostic ability of the IQCODE. Results: The IQCODE was able to differentiate AD from MCI and SMC, but was not able to differentiate SMC from MCI. Conclusions: The IQCODE may be helpful in diagnosing AD but is of limited use in differentiating MCI from SMC.

Long-term effects of amyloid, hypometabolism, and atrophy on neuropsychological functions.

Objective: To assess how amyloid deposition, glucose hypometabolism, and cerebral atrophy affect neuropsychological performance in patients with Alzheimer disease (AD) dementia, patients with mild cognitive impairment (MCI), and controls over time. Methods: A total of 41 patients with AD dementia, 28 patients with MCI, and 19 controls underwent [11C]–Pittsburgh compound B (11C-PiB) and [18F]-2-fluoro-2-deoxy-d-glucose (18F-FDG)–PET and MRI scans at baseline. We extracted global binding potential for 11C-PiB, the number of abnormal voxels for 18F-FDG, and gray matter volumes using SIENAX for MRI as measures of amyloid, hypometabolism, and atrophy. In addition, repeat neuropsychological testing was performed, including memory, attention, language, and executive tasks (mean follow-up 2.2 ± 0.7 years). Cross-sectional and longitudinal relationships between imaging markers and cognition were assessed using linear mixed models, including terms for the imaging markers, time, sex, age, diagnosis, and interactions for imaging marker × time and imaging marker × time × diagnosis. Results: Linear mixed models showed that baseline hypometabolism and atrophy were associated with poorer baseline performance on attention and executive functions (p < 0.05), whereas amyloid was not related to baseline cognition. Hypometabolism and amyloid were strongly associated with longitudinal decline in essentially all cognitive domains (pinteraction < 0.05), whereas atrophy was related specifically to future decline in Mini-Mental State Examination and memory (pinteraction < 0.05). Conclusion: Glucose hypometabolism and brain atrophy were associated with concurrent cognitive function, whereas brain amyloid was not. Amyloid deposition and glucose hypometabolism were predictors for decline of a wide variety of cognitive functions, while brain atrophy specifically predicted memory deterioration.

Assessment of instrumental activities of daily living in dementia: diagnostic value of the Amsterdam Instrumental Activities of Daily Living Questionnaire.

Background: Measuring impairments in “instrumental activities of daily living” (IADL) is important in dementia, but challenging due to the lack of reliable and valid instruments. We recently developed the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q; note 1). We aim to investigate the diagnostic accuracy of the A-IADL-Q for dementia in a memory clinic setting. Methods: Patients visiting the Alzheimer Center of the VU University Medical Center with their informants between 2009 and 2011 were included (N = 278). Diagnoses were established in a multidisciplinary consensus meeting, independent of the A-IADL-Q scores. An optimal A-IADL-Q cutoff point was determined, and sensitivity and specificity were calculated. Area under the curves (AUCs) were compared between A-IADL-Q and “disability assessment of dementia” (DAD). The additional diagnostic value of the A-IADL-Q to Mini-Mental State Examination (MMSE) was examined using logistic regression analyses. Results: Dementia prevalence was 50.5%. Overall diagnostic accuracy based on the AUC was 0.75 (95% confidence interval [CI]: 0.70-0.81) for the A-IADL-Q and 0.70 (95% CI: 0.63-0.77) for the DAD, which did not differ significantly. The optimal cutoff score for the A-IADL-Q was 51.4, resulting in sensitivity of 0.74 and specificity of 0.64. Combining the A-IADL-Q with the MMSE improved specificity (0.94), with a decline in sensitivity (0.55). Logistic regression models showed that adding A-IADL-Q improved the diagnostic accuracy (Z = 2.55, P = .011), whereas the DAD did not. Conclusions: In this study, we showed a fair diagnostic accuracy for A-IADL-Q and an additional value in the diagnosis of dementia. These results support the role of A-IADL-Q as a valuable diagnostic tool.

A qualitative review of instrumental activities of daily living in dementia: what's cooking?

The measurement of instrumental activities of daily living (IADL) is common in clinical practice and research into dementia. IADL are cognitively complex daily activities, such as cooking and doing finances. Their measurement is required for the diagnostic process of dementia, and also useful for the monitoring of disease progression. Since problems in IADL contribute to the disease burden of both patient and caregiver, it is a relevant outcome measure for disease-modifying and non-pharmacological interventions. Despite the widespread use of IADL instruments, an overview of its theoretical background, measurement methods, and potential sources of bias is lacking. In the current manuscript, we therefore aim to provide a selective overview of these topics.