Hege Kersten

Cognitive Effects of Reducing Anticholinergic Drug Burden in a Frail Elderly Population: A Randomized Controlled Trial

BACKGROUND Observational studies report a relationship between anticholinergic drug scale (ADS) score and cognitive function. This study investigated whether a reduced ADS score improved cognitive function in a frail elderly population. METHODS This randomized, controlled, single-blinded trial, recruited long-term residents with an ADS score of greater than or equal to 3 from 22 nursing homes in Norway. The participants were randomly allocated (1:1) to intervention or control. The intervention was a pharmacist-initiated reduction of ADS score after multidisciplinary drug reviews. Primary end point was Consortium to Establish a Registry for Alzheimers Disease 10-wordlist test for immediate recall. Secondary end points were Mini-Mental Sate Examination, delayed recall and recognition of words, saliva flow, and serum anticholinergic activity (SAA).The participants were retested after 4 and 8 weeks, and the study groups were compared after adjusting for baseline differences. RESULTS Eighty-seven patients were included. The median ADS score was reduced by 2 units (p < .0001) in the intervention group and remained unchanged in the control group. After 8 weeks, the adjusted mean difference in immediate recall was 0.54 words between the intervention and control group (95% confidence interval [CI]: -0.91, 2.05; p = .48). The study groups did not differ significantly in any of the other cognitive end points, salvia flow, or SAA at either follow-up (p > .18). CONCLUSION Pharmacist-initiated drug changes significantly reduced ADS score but did not improve cognitive function in nursing home residents. Moreover, the drug changes did not reduce SAA or mouth dryness significantly, which might indicate limited applicability of the ADS score to prevent prescription risks in this population.

Anticholinergic Drug Burden in Older People's Brain – How well is it Measured?

Concurrent use of several drugs with potential anticholinergic properties is highly prevalent in the elderly. Methods to determine the overall anticholinergic drug burden have been developed to estimate the risk of central anticholinergic adverse effects. The objective of this MiniReview was to critically appraise the clinical utility of the methods used to assess the anticholinergic drug burden in older peoples brain. We evaluated the in vitro method used to measure the anticholinergic activity in a patients serum and the four anticholinergic drug scales: Anticholinergic Risk Scale, Anticholinergic Cognitive Burden, Drug Burden Index and Anticholinergic Drug Scale. Medline searches of the literature from January 1988 to January 2013 were performed. Studies that related anticholinergic drug burden to central adverse outcomes in elderly people were included, while case reports and studies of single substances were excluded. Despite the consistently reported association between a high anticholinergic drug burden and negative cognitive and psychomotor outcomes in older patients, there are discrepancies in the literature. Furthermore, no significant cognitive improvements after the anticholinergic drug burden was reduced have been shown in randomized controlled trials. It is reasonable to question whether the estimated anticholinergic drug burden can predict the overall brain effects of multiple anticholinergic agents in older people.

Higher anticholinergic drug scale (ADS) scores are associated with peripheral but not cognitive markers of cholinergic blockade. Cross sectional data from 21 Norwegian nursing homes

AIM This study evaluated a presumed gradual decline in cognitive function in nursing home residents when the anticholinergic drug scale (ADS) score increased above 3. METHOD The study population was recruited from 21 nursing homes in Norway. Criteria for inclusion were ADS score ≥ 3 and no severe dementia, defined as Clinical Dementia Rating (CDR) score < 3. Primary cognitive end points were CERAD 10-word lists for recall and Mini Mental State Examination (MMSE). Secondary end points were activity of daily living (ADL), mouth dryness and serum anticholinergic activity (SAA). The patients were stratified into subgroups according to ADS score, i.e. a reference group with score 3 and test groups with scores 4, 5 or ≥6. End points were compared by analyses of covariance (ancova). RESULTS Overall, 230 of the 1101 screened nursing home residents (21%) had an ADS score ≥3. After exclusion 101 residents were recruited and among these, 87 managed to participate in the study. No significant differences were detected in cognitive function or ADL when ADS increased above 3 (P > 0.10), but in vivo (mouth dryness) and in vitro (SAA) measures of peripheral anticholinergic activity were significantly higher in patients with an ADS score ≥6 (P < 0.01). CONCLUSION The present study does not support a progressive decline in cognitive function with ADS score above 3. This might indicate that the ADS score model has limited potential to predict the clinical risk of central anticholinergic side effects in frail elderly patients receiving multiple anticholinergic drugs.

Evaluation of Brain Anticholinergic Activities of Urinary Spasmolytic Drugs Using a High-Throughput Radio Receptor Bioassay

OBJECTIVES: To compare the brain anticholinergic activities of five urinary spasmolytic drugs (USDs).

Clinical impact of potentially inappropriate medications during hospitalization of acutely ill older patients with multimorbidity

Abstract Objective: To identify potentially inappropriate medications (PIMs), to compare drug changes between geriatric and other medical wards, and to investigate the clinical impact of PIMs in acutely hospitalized older adults. Setting and subjects: Retrospective study of 232 home-dwelling, multimorbid older adults (aged ≥75 years) acutely admitted to Vestfold Hospital Trust, Norway. Main outcome measures. PIMs were identified by Norwegian general practice (NORGEP) criteria and Beers’ 2012 criteria. Clinical correlates were laboratory measures, functional and mental status, physical frailty, and length of stay. Results: Mean (SD) age was 86 (5.7) years, and length of stay was 6.5 (4.8) days. During the stay, the mean number of drugs used regularly changed from 7.8 (3.6) to 7.9 (3.6) (p = 0.22), and drugs used pro re nata (prn) changed from 1.4 (1.6) to 2.0 (1.7) (p < 0.001). The prevalence of any PIM changed from 39.2% to 37.9% (p = 0.076), while anticholinergics and benzodiazepines were reduced significantly (p ≤ 0.02). The geriatric ward reduced drug dosages (p < 0.001) and discontinued PIMs (p < 0.001) significantly more often than other medical wards. No relations between number of PIMS and clinical outcomes were identified, but the concomitant use of ≥3 psychotropic/opioid drugs was associated with reduced hand-grip strength (p ≤ 0.012). Conclusion: Hospitalization did not change polypharmacy or PIMs. Drug treatment was more appropriate on the geriatric than other medical wards. No clinical impact of PIMs was observed, but prescribers should be vigilant about concomitant prescription of ≥3 psychotropics/opioids. KEY POINTS Acute hospitalization of older patients with multimorbidity did not increase polypharmacy or potentially inappropriate medications. Prescription of anticholinergics and benzodiazepines was significantly reduced. The geriatric ward reduced drug dosages and discontinued potentially inappropriate medications more frequently than the other medical wards.

Young Onset Dementia study â A Prospective Cohort Study of Quality ofLife and Specific Needs in Persons with Young Onset Dementia and theirFamilies

Background: Young-Onset Dementia (YOD) causes challenges and concerns that are likely to affect quality of life and generate specific needs for health care, which may be different from what is observed in late onset dementia. The knowledge about the impact of YOD, in particular Fronto Temporal Dementia (FTD), on the affected families is scarce, and previous studies have underscored the importance of differentiating between diagnostic subgroups of YOD in future research. Accordingly, the aims of this study are to identify and compare factors influencing quality of life between persons with young onset FTD and Alzheimer’s Dementia (AD) and their families as the condition progresses. An additional aim is to compare the use of health care services among younger and older persons with dementia, and to investigate the life-stage specific needs for health care services in persons with YOD. Methods/Design: This is a two-year observational Nordic multicentre cohort study of community-dwelling persons with YOD and their families. Two diagnostic subgroups, each consisting of 75 dyads with AD and 75 dyads with FTD with symptom debut 70 years. Participants are recruited from nine Nordic memory clinics. Comprehensive assessments are made at baseline, 12 and 24 months, supplemented with telephone follow-ups at 6 and 18 months. Primary outcome measure is Quality of life measured by Quality of Life in Alzheimer’s Disease (QoL-AD) and EuroQol-5D (EQ-5D). Secondary outcome measures are needs for health care services measured by Camberwell Assessment of Needs in the Elderly (CANE) and Resource Utilization in Dementia Lite (RUD Lite). The inclusion period is from February 2014 to February 2015, with follow-up data collection until February 2017. Conclusion: The sample size, the outcome measures, and the explanatory factors chosen in this study will provide new knowledge of quality of life in families with young onset FTD and AD, and contribute to tailoring the health care services to the life stage-specific needs of families with YOD. ClinicalTrials.gov identifier: NCT02055092

Brief Tests such as the Clock Drawing Test or Cognistat Can Be Useful Predictors of Conversion from MCI to Dementia in the Clinical Assessment of Outpatients

Background: The identification of patients with mild cognitive impairment (MCI) who are at high risk of conversion to dementia is a challenging clinical task. Aims: To investigate whether simple cognitive screening tests can predict the conversion from MCI to dementia and to study the impact of different patient characteristics on the progression rate. Methods: A retrospective, longitudinal study of 90 outpatients diagnosed with MCI at a psychogeriatric clinic in Norway was conducted. Baseline scores on the Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), and Neurobehavioral Cognitive Status Examination (Cognistat) were related to ICD-10 diagnosis during 46 months. The influence of demographic, life situational, and clinical data were analyzed. Results: Sixty-four patients were diagnosed with dementia, significantly more females (82%) than males (50%) (p < 0.01). Low scores on the CDT [adjusted hazard ratio (HR) = 0.85; 95% CI 0.73-0.97; p = 0.020] and Cognistat (adjusted HR = 0.78; 95% CI 0.65-0.93; p = 0.007) significantly predicted the conversion from MCI to dementia, whereas the MMSE score did not. Conclusions: A high proportion of patients converted from MCI to dementia within 46 months, and females seem to be at higher risk. CDT and Cognistat significantly predicted the conversion from MCI to dementia and are therefore considered appropriate tests in clinical practice.

Association Between Inherited CYP2D6/2C19 Phenotypes and Anticholinergic Measures in Elderly Patients Using Anticholinergic Drugs

Background: To compare measures of anticholinergic activity between metabolic phenotypes of the polymorphic enzymes cytochrome P450 2D6 (CYP2D6) and CYP2C19 in the elderly patients exposed to anticholinergic agents. Methods: Long-term nursing home patients (n = 80) with an anticholinergic drug scale (ADS) score ≥3 were recruited from 22 nursing homes in Norway. Based on pharmacogenetic analyses of mutations encoding absent CYP2D6 or CYP2C19 metabolism, patients were divided into subgroups of poor metabolizers (PMs) (n = 8) and extensive metabolizers (n = 72). Serum anticholinergic activity (SAA) was determined by a validated, 96-well format radio receptor assay and adjusted for ADS score. Unadjusted and adjusted SAAs, mouth dryness, and cognitive function (Mini-Mental State Examination and verbal recall tests from Consortium to Establish a Registry for Alzheimer Disease) were compared between the subgroups with Mann–Whitney tests. Results: The study population was represented by 78% women, 68% had mild to moderate dementia, and mean age was 86 years. More than 80% used more than 1 anticholinergic agent, and their median ADS score was 4. The subpopulation of PMs had significantly higher median SAA than the extensive metabolizers (10.3 versus 4.2 pmol atropine equivalents per milliliter, P = 0.012). This difference remained significant after adjusting for ADS score (P = 0.013). No significant differences in mouth dryness and cognitive function were observed between the subgroups (P > 0.3). Conclusions: These preliminary findings suggest that elderly CYP2D6/CYP2C19 PMs with a high anticholinergic drug burden are at increased risk of elevated SAA. Whether PMs are also more prone to experience anticholinergic side effects needs to be further studied in larger patient populations.

Progression of Alzheimer's Disease: A Longitudinal Study in Norwegian Memory Clinics

BACKGROUND The course of Alzheimers disease (AD) varies considerably between individuals. There is limited evidence on factors important for disease progression. OBJECTIVE The primary aim was to study the progression of AD, as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). Secondary aims were to investigate whether baseline characteristics are important for differences in progression, and to examine the correlation between progression assessed using three different instruments: CDR-SB (0-18), the cognitive test Mini-Mental State Examination (MMSE, 0-30), and the functional measure Instrumental Activities of Daily Living (IADL, 0-1). METHODS The Progression of AD and Resource use (PADR) study is a longitudinal observational study in three Norwegian memory clinics. RESULTS In total, 282 AD patients (mean age 73.3 years, 54% female) were followed for mean 24 (16-37) months. The mean annual increase in CDR-SB was 1.6 (SD 1.8), the mean decrease in MMSE score 1.9 (SD 2.6), and the mean decrease in IADL score 0.13 (SD 0.14). Of the 282 patients, 132 (46.8%) progressed slowly, with less than 1 point yearly increase in CDR-SB. Cognitive test results at baseline predicted progression rate, and together with age, ApoE, history of hypertension, and drug use could explain 17% of the variance in progression rate. The strongest correlation of change was found between CDR-SB and IADL scores, the weakest between MMSE and IADL scores. CONCLUSION Progression rate varied considerably among AD patients; about half of the patients progressed slowly. Cognitive test results at baseline were predictors of progression rate.

Quality of Life in People with Young-Onset Alzheimer’s Dementia and Frontotemporal Dementia

Aims: The aims of this study were to compare quality of life (QOL) in people with young-onset Alzheimer’s (AD) and frontotemporal (FTD) dementia, explore variables associated with QOL, and compare QOL in young-onset dementia (YOD) and late-onset dementia (LOD). Methods: Cross-sectional data from a Nordic multicenter study of 50 community-dwelling participants with AD and 38 with FTD were included. A comparison group consisted of 100 people with LOD. QOL was measured using self-reported Euro-QOL 5-Dimension and the proxy version of Quality of Life in Alzheimer’s Disease (QOL-AD) questionnaire. Neuropsychiatric symptoms and needs were assessed using the Cornell Scale for Depression in Dementia (CSDD), Neuropsychiatric Inventory (NPI), and Camberwell Assessment of Needs in the Elderly. Multiple linear regression and multilevel modeling was used to determine variables associated with QOL. Results: We found no differences between the two YOD groups in QOL. The variables associated with QOL were scores on the CSDD, NPI, and unmet needs. The proxy QOL-AD score in YOD was significantly higher compared to LOD (median 36.0 [IQR 10.0] vs. 33.0 [IQR 9.0]). Conclusion: The QOL in Nordic people with YOD was better compared to people with LOD. Our results show depressive symptoms to be associated with QOL irrespective of age and diagnosis.