Marie-Pierre Fortin

Effects of Anticholinergic Drugs on Verbal Episodic Memory Function in the Elderly

BackgroundAn increasing number of medications that are frequently prescribed to elderly patients have been identified as having weak but definite anticholinergic properties. Few epidemiological studies have evaluated the impact of these drugs on verbal episodic memory using sensitive and specific neuropsychological testing in an elderly population presenting with cognitive impairment.ObjectivesThe aim of this study was to assess the effect of drugs with anticholinergic properties on verbal episodic memory function in elderly patients presenting for memory evaluation.Study DesignWe performed a retrospective, cross-sectional study that included 134 consecutive elderly outpatients who attended the daycare memory unit of Centre Hospitalier Sud, Lyon, France. We searched the MEDLINE database (1973–2008) to identify drugs with anticholinergic properties. All drugs with well known anticholinergic activity, mild reported anticholinergic effects or in vitro anticholinergic activity were included in the study.MeasurementsWe used the Free and Cued Selective Reminding (FCSR) test to evaluate verbal episodic memory.ResultsThe mean±SD number of drugs with anticholinergic properties taken by the subjects was 0.64±0.82. Fifty percent of the subjects (n = 67) had a prescription for at least one drug with anticholinergic properties and 16% (n = 21) had a prescription for two or more. Drugs with anticholinergic properties most frequently prescribed in our cohort were cardiovascular (furosemide, hydrochlorothiazide, digoxin), antidepressant (paroxetine, sertraline, fluoxetine) and antispasmodic (oxybutynin chloride) drugs. The number of drugs with anticholinergic properties that subjects were taking was associated with reduced performance on tasks that assessed verbal memory (p < 0.05). Neuropsychological test batteries revealed a significant unfavourable effect of use of drugs with anticholinergic activity on episodic verbal memory. Tests evaluating other cognitive functions were not affected by use of drugs with anticholinergic activity. These associations remained following multivariate analysis adjusting for age, sex, education level, number of anticholinergic drugs, number of co-morbidities, diagnosis, behavioural symptoms and depressive symptoms.ConclusionClinicians should assess the current use of drugs with anticholinergic properties in the elderly, particularly in patients presenting for memory evaluation. In such cases, use of other therapeutic alternatives should be considered.

Clinical Impact of a Second FDG-PET in Atypical/Unclear Dementia Syndromes.

Diagnosis of atypical/unclear dementia is often difficult and this delays treatment initiation. Several authors have shown that beyond standard dementia workup, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) reduces the number of unclear diagnoses, leads to earlier treatment, and has a beneficial impact on families. However, it is not uncommon that the FDG-PET findings are equivocal in this setting. For those cases, a repeat FDG-PET may clarify the diagnosis and prevent treatment delay. We retrospectively assessed the clinical impact of a repeat FDG-PET in 59 patients with atypical/unclear dementia syndromes and inconclusive initial FDG-PET. Changes in primary diagnosis, diagnostic confidence, and management following the second FDG-PET were examined. Conducting a second FDG-PET reduced the number of unclear diagnoses from 80% to 34% , led to diagnostic change in 24% of cases, and treatment modification in 22% of patients. Overall, the clinical impact was higher when initial diagnostic confidence was low and the second FDG-PET repeated ≥12 months after the first one. In tertiary care memory clinic settings, when diagnostic incertitude persists despite extensive evaluation and an equivocal FDG-PET, repeating the FDG-PET 12 months later can greatly clarify the diagnosis and improve management.

Validation of the Dépistage Cognitif de Québec: A New Cognitive Screening Tool for Atypical Dementias

Objective This study aimed to validate and provide normative data for the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a new cognitive screening tool for atypical dementias. Method The DCQ was developed by expert behavioral neurologists and clinical neuropsychologists based on updated criteria for Alzheimers disease, primary progressive aphasia, and behavioral variant frontotemporal dementia. It targets five relevant domains: Memory, Visuospatial, Executive, Language, and Behavior. Validation was performed in a population-based sample of 410 healthy French-speaking Canadians aged between 50 and 89 years old. Normative data were derived from a subsample of 285 participants. Results Mean DCQ total score (out of 100) was 89.17 (SD = 7.36). Pearsons correlation coefficient showed a strong and significant correlation (r = .71, p < .001) with the Montreal Cognitive Assessment. Internal consistency for the cognitive domains assessed by Cronbachs alpha was satisfactory (.74). Test-retest reliability was adequate (Pearsons coefficient = . 70, p < .001) and interrater reliability, excellent (intraclass correlation = .99, p < .001). Normative data shown in percentiles were stratified by age and education. Conclusions This study suggests that the DCQ is a valid and reliable cognitive screening test. Application of the DCQ on populations with atypical dementias is underway to derive sensitivity and specificity values for various dementias.

DÉ́PISTAGE COGNITIF DE QUÉBÉC (DCQ): VALIDATION AND NORMATIVE DATA FOR A NOVEL COGNITIVE SCREENING TOOL FOR ATYPICAL DEMENTIAS

Mental State Examination, the original version of the MoCA, and the quality of life scale CASP-19. A multiple regression analysis was performed to verify the influence of age and education and the predictive capacity of the original version of the test on its alternative version. Results: Cronbach’s alpha coefficient was .76. Elimination of any of the items of the 2 version of MoCA never reduces the reliability to below .73. Convergent validity was .65 (p<.001), and divergent validity was .03 (p1⁄40.79). Correlation between the 1 and the 2 version of MoCA was significant and high (r1⁄40.86). There was a negative effect of age (b 1⁄4–0.141, p < 0.01) and a positive effect of education (b 1⁄4–0.549, p < 0.001), but these two effects did not remained significant when the total score of the original form of MoCA was included in the regression model (b1⁄4–0.691, p < 0.001) (Figure1). Conclusions: Our preliminary results showed good psychometrical properties for the 2nd alternative form of the Spanish version and strong relations between forms. Further analyses are required in order to guarantee the use of the alternate Spanish version of the MoCA test in clinical follow-ups and longitudinal studies.

Clinical utility of amyloid PET in the differential diagnosis of atypical dementias and its impact on caregivers

not available. PL-04-02 BIOCHEMICALLY BASED QUANTITATIVE NEUROPATHOLOGY IN CLINICAL

Clinical utility of amyloid imaging in the differential diagnosis of atypical/unclear dementias and its impact on caregivers

Recent studies have supported a role for amyloid positron emission tomography (PET) imaging in distinguishing Alzheimer’s disease (AD) pathology from other pathological protein accumulations leading to dementia. We investigated the clinical utility of amyloid PET in the differential diagnosis of atypical dementia cases and its impact on caregivers. Using the amyloid tracer 18F-NAV4694, we prospectively scanned 28 patients (mean age 59.3 y, s.d. 5.8; mean MMSE 21.4, s.d. 6.0) with an atypical dementia syndrome. Following a comprehensive diagnostic workup (i.e., history taking, neurological examination, blood tests, neuropsychological evaluation, MRI, and FDG-PET), no certain diagnosis could be arrived at. Amyloid PET was then conducted and classified as positive or negative. Attending physicians were asked to evaluate whether this result led to a change in diagnosis or altered management. They also reported their degree of confidence in the diagnosis. Caregivers were met after disclosure of amyloid PET results and completed a questionnaire/interview to assess the impact of the scan. Our cohort was evenly divided between positive (14/28) and negative (14/28) 18F-NAV4694 cases. Amyloid PET resulted in a diagnostic change in 9/28 cases (32.1%: 17.8% changed from AD to non-AD, 14.3% from non-AD to AD). There was a 44% increase in diagnostic confidence. Altered management occurred in 71.4% (20/28) of cases. Knowledge of amyloid status improved caregivers’ outcomes in all domains (anxiety, depression, disease perception, future anticipation, and quality of life). This study suggests a useful additive role for amyloid PET in atypical cases with an unclear diagnosis beyond the extensive workup of a tertiary memory clinic. Amyloid PET increased diagnostic confidence and led to clinically significant alterations in management. The information gained from that test was well received by caregivers and encouraged spending quality time with their loved ones.