Alain Robillard

Predictors of driving cessation in mild-to-moderate dementia

Background: Although physicians in most provinces are mandated to report patients whose driving ability is impaired by illness, little is known about dementia-related factors associated with driving cessation. The purpose of our study was to explore factors that may affect the likelihood of driving cessation in a sample of elderly, community-dwelling patients with dementia. Methods: A 3-year prospective study, the Canadian Outcomes Study in Dementia (COSID) has enrolled 883 patients with mild-to-moderate dementia at 32 centres across Canada. Assessment tools included the Mini-Mental State Examination (MMSE) for cognition, the Global Deterioration Scale (GDS) for staging (severity), the Functional Autonomy Measurement System (SMAF) for function, and the Neuropsychiatric Inventory (NPI) for behaviour. Factors associated with the decision to quit driving after the baseline assessment were tested with Cox survival analysis. Results: Of 719 subjects who were or had been drivers, 203 (28.2%) were still driving at baseline. Over an observation period that averaged 23 months, 97 (48.5%) of 200 patients quit driving. Factors predictive of driving cessation included GDS (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.15–2.45), MMSE score (HR 0.90, 95% CI 0.83–0.97) and NPI findings (HR 1.63 for presence of ≥ 3 behaviours, 95% CI 1.01–2.62). Among the NPI behaviours, when they were analyzed separately, agitation led to a decreased likelihood of driving cessation (p = 0.019), whereas apathy (p = 0.031) and hallucinations (p = 0.050) led to an increased likelihood. Interpretation: Cognitive impairment and behaviours such as agitation, apathy and hallucinations were significant predictors of driving cessation in patients with a mild to moderate degree of dementia. These findings should be considered when one counsels patients and their families.

Visual retinocortical function in dementia of the Alzheimer type

Background: Some histological investigations have reported anomalies in the primary visual pathways of individuals with dementia of the Alzheimer type (DAT), while others have suggested that these visual structures are spared by the disease process. Objectives: This study was conducted to address this issue of substantial controversy. We determined in vivo whether DAT alters the functioning of the primary visual pathways by evaluating pattern-reversal electroretinograms (ERGs) and cortical visual evoked potentials (VEPs). Methods: Twenty-seven individuals with mild to moderate DAT and 27 age- and sex-matched control subjects were included in the investigation. ERG and VEP recordings were obtained from all participants with the use of a clinical electrodiagnostic system. Stimulus conditions were biased towards a preferential response from the magnocellular and parvocellular subdivisions of the visual system. Results: Amplitude and latency of the ERG were not affected by DAT. The VEP amplitude was not attenuated in DAT individuals, but there was a delay in the latency of the VEPs arising from both magnocellular and parvocellular streams of visual processing. Conclusion: Our results indicate that while the inner retina appears to be spared by the disease process, the visual function is altered upstream in the retinocortical visual pathways of individuals with DAT.

Neuroretinal function is normal in early dementia of the Alzheimer type

We recently demonstrated that retinal ganglion cell function, optic nerve head parameters and the retinal nerve fiber layer thickness are not altered in early dementia of the Alzheimer type (DAT). Our current objective was to assess whether the function of cells located more distally in the retina is also unaffected by the disease. We evaluated 23 individuals with early to moderate DAT and 23 healthy age-matched subjects, all displaying clinically normal visual function. Scotopic and photopic flash electroretinograms (fERGs) and oscillatory potentials (OPs) were recorded. The amplitude and latency of the retinal potentials did not differ between DAT and control subjects. Our current results showing normal fERGs and OPs in early DAT indicate that the underlying neurons giving rise to these signals are not impaired by the disease process. These data support and extend our recent findings suggesting that visual deficits in DAT do not stem from neuroretinal dysfunction.

Normal optic nerve head topography in the early stages of dementia of the Alzheimer type

In view of the existing controversy as to whether or not the optic nerve head (ONH) is altered in Alzheimer disease, we used modern imaging technology to evaluate the ONH structure in individuals with dementia of the Alzheimer type (DAT). Real-time topographical images of the ONH were obtained with a Heidelberg retina tomograph from individuals in the early stages of DAT and age-matched controls. The various ONH parameters examined in this study did not differ significantly between DAT and age-matched subjects. These results suggest that the deficits in visual function that are known to occur in DAT are not related to ONH structural anomalies, at least in the earlier stages of the disease.

Real-life effectiveness and tolerability of the rivastigmine transdermal patch in patients with mild-to-moderate Alzheimer's disease: the EMBRACE study.

Abstract Objective: To assess the real-life effectiveness and tolerability of the rivastigmine transdermal patch in patients with mild-to-moderate Alzheimer’s disease (AD) in Canada. Research design and methods: Eighteen-month observational, prospective, multi-center, open-label study conducted on AD patients with Standardized Mini-Mental State Examination (SMMSE) score of 10–26 and Global Deterioration Scale (GDS) score of 4–6. Patients were treated with the rivastigmine transdermal patch (Exelon patch) 5 cm2 (4.6 mg/24 hours) or 10 cm2 (9.5 mg/24 hours), once daily. Main outcome measures: Primary outcome was change in SMMSE from baseline to 18 months. Secondary outcomes included change in SMMSE at 6 and 12 months and change in GDS, Assessment of Patient Ability (APA-C), Overall Patient Assessment Rating (OPAR), caregiver-reported compliance and treatment satisfaction at 6, 12, and 18 months. Results: Among the 1204 patients enrolled, 969 were included in the ITT analysis. Mean (SD) age was 80.2 (8.00) years, disease duration was 0.6 (1.26) years, 62.0% of patients were women, 80.4% were living in the community, and 69.3% were treatment naïve. Mean (SD) baseline SMMSE and GDS scores were 21.8 (3.98) and 4.2 (0.61), respectively. Over 18 months of treatment there were no clinically significant changes in SMMSE and GDS. The majority of patients showed improvement or no change in GDS, APA-C and OPAR over 18 months. The proportion with reported improvement in GDS, APA-C and OPAR was higher than the proportion that deteriorated. Compliance improved from baseline to 18 months and for 88.2% of patients caregivers preferred the transdermal patch to oral medications. Conclusions: The rivastigmine transdermal patch is effective in maintaining cognitive function over 18 months of treatment in patients with mild-to-moderate AD. The safety profile was comparable to the data in the Canadian product monograph. Lack of a comparator group is a potential limitation of the study.

Rivastigmine for Alzheimer's disease : Canadian interpretation of intermediate outcome measures and cost implications

BACKGROUND Clinical studies have shown that patients with Alzheimers disease (AD) who are treated with rivastigmine have statistically significantly better scores on 5 scales used to assess AD than control patients receiving placebo. However, the clinical meaning and cost implications of these differences are not clear. OBJECTIVE The purpose of this study was to assess the clinical meaning and cost implications of statistically significant results obtained in clinical trials of rivastigmine for the treatment of AD. Potential cost implications for the health care system, caregivers, and society are considered. METHODS Data on clinical effects of rivastigmine were obtained from published North American and European clinical studies of patients with mild to moderately severe AD receiving rivastigmine 6 to 12 mg/d (n = 828) or placebo (n = 647). Differences in scores on the Alzheimers Disease Assessment Scale-Cognitive Function, Clinicians Interview-Based Impression of Change with both clinical and caregiver information considered, Progressive Deterioration Scale, Mini-Mental State Examination (MMSE), and Global Deterioration Scale were assessed. A convenience panel of 9 Canadian specialists experienced in the treatment of AD provided their opinions on the clinical importance of the trial results. Chart review was performed to identify specific behaviors that improved, and cost implications of improvements were assessed. RESULTS The panel determined that statistically significant differences in scores on all scales except the MMSE were likely associated with functional or cognitive differences that were clinically relevant for patients, reflecting stabilization that would have beneficial consequences for caregivers and health care resource use. Subsequent chart review showed that improvement on specific scale items confirmed the physician panels opinion. Analysis of possible cost implications to society indicated that medication expenditures would be offset largely by delays in the need for paid home care and institutionalization, positive effects on caregiver health, and less time lost from work for the caregiver. CONCLUSIONS From the perspective of a Canadian specialist panel, rivastigmine treatment for AD produces clinically relevant effects for patients that are beneficial to caregivers. These effects suggest decreased use of caregiver resources and delays in the need for institutionalization, both of which reduce societal costs.