Hans Wouters

Prenatal undernutrition and cognitive function in late adulthood

At the end of World War II, a severe 5-mo famine struck the cities in the western part of The Netherlands. At its peak, the rations dropped to as low as 400 calories per day. In 1972, cognitive performance in 19-y-old male conscripts was reported not to have been affected by exposure to the famine before birth. In the present study, we show that cognitive function in later life does seem affected by prenatal undernutrition. We found that at age 56 to 59, men and women exposed to famine during the early stage of gestation performed worse on a selective attention task, a cognitive ability that usually declines with increasing age. We hypothesize that this decline may be an early manifestation of an accelerated cognitive aging process.

Psychometric properties of an interviewer-administered version of the Kessler Psychological Distress scale (K10) among Dutch, Moroccan and Turkish respondents

The Kessler Psychological Distress scale (K10) is an instrument that is widely used to screen for mental disorders, but information is lacking on its psychometric qualities in non‐Western samples. This study used a population‐based sample (N = 725) to assess the reliability and validity of the K10 across ethnic groups in an urban area. The results were generally supportive of the K10 as a reliable and valid instrument to screen for anxiety and depression in all three groups. Cronbachs alpha was high (0.93) and the results indicated the existence of a solid single factor structure. Item bias in relation to ethnic background was minor. In each group, there was good criterion validity with respect to one‐month DSM‐IV diagnosis for depressive and/or anxiety disorder. The results nevertheless highlight the importance of cross‐cultural validation, as we found different cut‐off values for ethnic subgroups to obtain optimal sensitivity and specificity for detecting depressive and/or anxiety disorders. Copyright

Three sides of the same coin: measuring global cognitive impairment with the MMSE, ADAS-cog and CAMCOG

The total scores of the ADAS‐cog, MMSE and CAMCOG, comprising various cognitive tasks, are widely used to measure a dimension of global cognitive impairment. It is unknown, however, whether this dimension is common to these instruments. This hampers comparisons when either of these instruments is used. The extent to which these instruments share a common dimension of global cognitive impairment and how their scores relate was examined.

Revising the ADAS-cog for a more accurate assessment of cognitive impairment

BackgroundTo examine whether it is appropriate to sum the cognitive part of the Alzheimer Disease Assessment Scale (ADAS-cog) items to assess cognitive impairment. This assumes items to have (1) equal measurement precision and (2) hierarchically ordered categories. MethodsRasch analysis on the basis of pooled data from 3 Randomized Controlled Trials was used to examine these assumptions and to estimate each patients level of impairment. Analyses were replicated in an independent sample. ResultsThe original ADAS-cog scoring did not fit the Rasch Model and did not reliably distinguish between impairment levels. Patients with equal test scores had different impairment levels. Similarly, patients with different test scores could have the same impairment level. Revising the ADAS-cog by (1) weighting the items by their measurement precision and (2) collapsing nonhierarchical item categories resulted in good fit and a valid one to one correspondence between sum scores and estimated impairment levels. This revealed that equal differences in ADAS-cog scores did not reflect equal differences in impairment level along the tests score range. ConclusionsIt is appropriate to summate the ADAS-cog items provided that the items are weighted and have their categories hierarchically ordered.

Quantification of anticholinergic and sedative drug load with the Drug Burden Index: a review of outcomes and methodological quality of studies

PurposeThe Drug Burden Index (DBI) is a non-invasive method to quantify patients’ anticholinergic and sedative drug burden from their prescriptions. This systematic review aimed to summarise the evidence on the associations between the DBI and clinical outcomes and methodological quality of studies.MethodsA search in PubMed and Embase (search terms: ‘drug’, ‘burden’, and ‘index’) was performed and experts were contacted. We excluded publications that did not report empirical results or clinical outcomes. Methodological quality was assessed using the Newcastle-Ottawa Scale. Potential omissions of relevant clinical outcomes and populations were studied.ResultsOf the 2998 identified publications, 21 were eligible. Overall, methodological quality of studies was good. In all but one study, adjustment was made for prevalent co-morbidity. The DBI was examined in diverse older individuals, i.e. both males and females from different settings and countries. However, no studies were conducted in other relevant patient groups, e.g. psychiatric patients. Exposure to anticholinergic and sedative drugs was thoroughly ascertained, though the specific calculation of the DBI differed across studies. Outcomes were assessed from medical records, record linkage or validated objective tests or questionnaires. Many studies found associations between the DBI and outcomes including hospitalisation, physical and cognitive function. Cognitive function and quality of life were understudied and the number and scope of longitudinal studies was limited.ConclusionsAn accumulating body of evidence supports the validity of the DBI. Longitudinal studies of cognitive function and quality of life and in other patient groups, e.g. psychiatric patients, are warranted.

Endocrine therapy for breast cancer: assessing an array of women's treatment experiences and perceptions, their perceived self-efficacy and nonadherence.

BACKGROUND Although adjuvant endocrine therapy effectively prevents breast cancer recurrence, nonadherence rates are substantial. We therefore examined associations of womens experiences and perceptions regarding the efficacy, side effects, and practical problems of endocrine therapy with nonadherence. Furthermore, we examined whether womens perceived self-efficacy moderated these associations. PATIENTS AND METHODS Two hundred forty-one breast cancer patients participated. Using the electronic Tailored Medicine Inventory, which enables skipping of irrelevant items, experiences and perceptions were assessed in a comprehensive yet feasible manner. Adherence was assessed according to self-report and evaluated for agreement with adherence estimated from pharmacy refill data. RESULTS A substantial number of women doubted the efficacy of endocrine therapy, were worried about and/or had experienced hot flushes, loss of libido, joint ache, and/or practical problems with regard to information, intake, and packaging. Experience of practical problems (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.0-5.8) and perceived self-efficacy with regard to medicine intake (OR, 0.5; 95% CI, 0.4-0.7) were associated with unintentional nonadherence. Number of side effects experienced (OR, 1.2; 95% CI, 1.05-1.4) and perceived self-efficacy with regard to learning about medication (OR, 0.6; 95% CI, 0.4-0.96) were associated with intentional nonadherence. Perceived self-efficacy did not moderate associations between womens treatment experiences and perceptions and nonadherence. CONCLUSION Endocrine therapy is challenging for many women. Targeting womens specific experiences and perceptions and improving their perceived self-efficacy is likely to decrease intentional and unintentional nonadherence.

Discontinuing inappropriate medication in nursing home residents (DIM-NHR Study): protocol of a cluster randomised controlled trial.

Introduction Nursing home residents often have a high number of comorbidities resulting in polypharmacy. Inappropriate prescribing is therefore likely to occur, which in turn is expected to worsen cognitive impairment, to increase the fall risk and to decrease residents’ quality of life. The objective of the ‘Discontinuing Inappropriate Medication in Nursing Home Residents’ (DIM-NHR) study is to examine the efficacy and cost-effectiveness of the Multidisciplinary Multistep Medication Review (3MR) that is aimed at optimising prescribing and discontinuing inappropriate medication. Methods A cluster randomised controlled trial will be conducted. Elderly care physicians and their wards (clusters) will be randomised. Data will be collected at baseline and 4 months after the 3MR has taken place. Six hundred nursing home residents will be recruited of whom more than half are expected to suffer from dementia. The 3MR will be based on consensus criteria and the relevant literature and will be performed by the patient’s elderly care physician in collaboration with a pharmacist. Analysis Primary outcomes—the difference in proportion of residents who successfully discontinued inappropriate medication between the intervention and control group at follow-up. Secondary outcomes—undertreatment, exposure to anticholinergic and sedative medicines, neuropsychiatric symptoms, cognitive function, falls, hospital admission, quality of life and cost-effectiveness. Ethics and dissemination Participant burden will be kept at a minimum. The elderly care physician will remain free to adjust medication when symptoms relapse or adverse events occur, rendering serious adverse events highly unlikely. Study findings will be published in peer-reviewed journals and a 3MR toolkit will be developed. Trial registration number This study has been registered at http://www.ClinicalTrials.gov (trial registration number: NCT01876095)

Adaptive cognitive testing in cerebrovascular disease and vascular dementia

Background/Aims: To examine whether brevity can be combined with precision in measuring global cognitive ability in patients with cerebrovascular disease (CVD) or vascular dementia (VaD). Longer tests (e.g. the CAMCOG) are precise but inefficient, whereas brief tests (e.g. the MMSE) are efficient but imprecise. Methods: A simulated computerized adaptive testing (CAT) algorithm using existing CAMCOG data from 284 patients with CVD of whom 55 were diagnosed with VaD. CAT was used to estimate each individual patient’s total score on a large precise test (the CAMCOG). CAT repeatedly selected only items of appropriate difficulty, depending on whether the previous item was (in)correctly responded to. CAT estimates were compared with total scores on the whole CAMCOG. Results: Even though there was an average test reduction of more than 40%, CAT estimates were in very high agreement with the whole test results (intraclass correlation >0.97) and had similar accuracy for the diagnosis of dementia (area under the curve = 0.94). Conclusion: CAT combines efficiency with precision in the measurement of global cognitive ability in CVD patients.

Decreasing the load? Is a Multidisciplinary Multistep Medication Review in older people an effective intervention to reduce a patient's Drug Burden Index? Protocol of a randomised controlled trial

Introduction Older people often use medications with anticholinergic or sedative side effects which increase the risk of falling and worsen cognitive impairment. The Drug Burden Index (DBI) is a measure of the burden of anticholinergic and sedative medications. Medication reviews are typically done by a pharmacist in collaboration with a general practitioner to optimise the medication use and reduce these adverse drug events. We will evaluate whether a Multidisciplinary Multistep Medication Review (3MR) is an effective intervention to reduce a patients DBI. Methods A randomised controlled trial including 160 patients from 15 community pharmacies will be conducted. Per pharmacy, 1 pharmacist will perform a structured 3MR in close collaboration with the general practitioner, including the objective to reduce the DBI. Analysis Primary outcome—the difference in proportion of patients having a decrease in DBI≥0.5 in the intervention and control groups at follow-up. Secondary outcomes—anticholinergic and sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission, and mortality. Ethics and dissemination The burden of patients will be kept at a minimum. The 3MR can be considered as usual care by the pharmacist and general practitioner. Medical specialists will be consulted, if necessary. The intervention is specifically aimed at older community-dwelling patients in an attempt to optimise prescribing, in particular, to reduce medication with anticholinergic and sedative properties. Study results will be published in peer-reviewed journals and will be distributed through information channels targeting professionals. Trial registration number NCT02317666; Pre-results.

Does Adaptive Cognitive Testing Combine Efficiency with Precision? Prospective Findings

Longer cognitive tests, such as the Alzheimers disease assessment scale (ADAS-cog) or the Cambridge cognitive examination (CAMCOG), are more precise but less efficient than briefer tests, such as the Mini Mental State Examination (MMSE). We examined if computerized adaptive testing (CAT) of cognitive impairment can combine brevity with precision by tailoring a precise test to each individual patient. We conducted a prospective study of 84 participants [normal aging, n = 41; mild cognitive impairment (MCI), n = 21; dementia, n = 22]. CAT estimated a participants ability during testing by selecting only items of appropriate difficulty from either the CAMCOG or the CAMCOG supplemented with ADAS-cog items and neuropsychological tests (the CAMCOG-Plus). After tailored testing with CAT, the remaining CAMCOG and CAMCOG-Plus items not selected by CAT were administered. The time needed to complete the CAT was compared to that needed for the whole CAMCOG and CAMCOG-Plus. Results showed that testing time reductions achieved with CAT were 37% or more compared to the whole CAMCOG and 55% or more compared to the whole CAMCOG-Plus. Estimated ability levels with CAT were in excellent agreement with those based on the whole CAMCOG and CAMCOG-Plus (intraclass correlations 0.99 and 0.98, respectively). Diagnostic accuracy of detecting mild dementia and MCI seemed better for the CAT administered tests than for the MMSE, but the differences were not significant. We conclude that adaptive testing combines brevity with precision, especially in grading the severity of cognitive impairment.