Highlights from the Third Canadian Colloquium on Dementia

Ron Keren, MD, FRCPC, Third CCD Chair Clinical Director, University Health Network and Whitby Mental Health Centre Memory Clinics; Assistant Professor, University of Toronto, Toronto, ON.

The Third Canadian Colloquium on Dementia (CCD) was held at the Ottawa Westin, October 27-29, 2005. Over 500 registrants gathered from across Canada and from around the world to participate in this two-and-a-half day event that featured presentations from key international and national experts on dementia. An audience comprised primarily of specialists involved in the diagnosis and management of individuals with dementing disorders was exposed to a broad range of topics delivered in plenary sessions, debates, workshops, and clinicopathological vignettes. The CCD has grown from 150 to 500 registrants over the span of four years, confirming the importance of a national conference on dementia geared primarily towards physicians in this field.
The composition of the third CCD’s organizing committee reflected a broad representation of specialists and their national organizations, including the Canadian Academy of Geriatric Psychiatry (CAGP), the Canadian Geriatrics Society (CGS), the Canadian Neurological Society (CNS), and the Consortium of Canadian Centres for Clinical Cognitive Research (C5R), as well as representatives from neuropsychology and family medicine. The program of the third CCD was tailored to the guidelines of the Royal College of Physicians and Surgeons for accredited group learning. The content of the program was driven by a needs assessment completed at the second CCD.

Program Highlights
The third CCD was opened with a colourful presentation by Dr. Jock Murray from Dalhousie University titled “When the National Leader Becomes Forgetful.” Dr. Murray was the only non-American invited to participate in the Working Group on Disability in US Presidents formed by President Clinton. Dr. Murray gave a historical account of international leaders whose medical conditions affected their abilities to lead. Dr. Murray explained that, historically, when leaders became seriously ill they were dealt with by the “Captive King Syndrome”; they remained in office and their illness was kept hidden while those around the leader took charge. Under these circumstances the judgements of their physicians were political rather than medical. Dr. Murray pointed out that physicians have often been part of the problem by feeling a duty towards the leader as opposed to society. “They believe that their leader sick is better than the competition well.”

Dr. Murray’s presentation was followed by Dr. Peter St. George-Hyslop from the University of Toronto. Dr. St. George-Hyslop, a regular speaker at the CCD, gave an update on research pertaining to Ab-directed therapies for Alzheimer’s disease (AD) based on evidence from the amyloid cascade theory of AD. Dr. St. George-Hyslop explained that A‚ is formed through the misprocessing of the amyloid precursor protein. This pathological pathway involves both beta and gamma secretases. Subsequently, attempts are being made to inhibit these two enzymes in the hopes of diminishing the accumulation of Ab. While appearing to be very hopeful strategies, Dr. St-George Hyslop pointed out that a number of serious obstacles related to the development of these therapies have been observed in transgenic mice. He also discussed the potential clearance of Ab through the Ab vaccines and reviewed the follow-up studies on the phase 2a vaccine trial that was abruptly discontinued due to the occurrence of encephalitis in a number of the subjects receiving the vaccine. Unfortunately, results of the cognitive outcome measures in patients who developed an immune response in the study were not statistically significant. However, as Dr. St. George-Hyslop pointed out, due to the early discontinuation of the study the subjects did not receive the full complement of A‚ injections. Despite these discouraging results, Dr. St. George-Hyslop believes that the A‚ vaccine still holds promise as a therapeutic agent for AD, through active immunization with a modified A‚ protein or passive immunization with monoclonal antibodies. Lastly, Dr. St. George-Hyslop discussed another A‚-directed therapy that would inhibit the development of neurotoxic A‚ protofibrils. While addressing the importance of A‚ in the development of AD, Dr. St.-George Hyslop pointed out that the clinical symptoms of AD are more highly correlated with tau pathology than with beta amyloid: “You can be chock full of amyloid and not have dementia.” Nevertheless, A‚ is still considered to be the likely cause of a cascade of events leading to the development of the tangles and neuronal death that are present in AD.

Presentations by Dr. Serge Gauthier (McGill University) and Dr. Kenneth Rockwood (Dalhousie University) as well as a workshop lead by Dr. Gary Naglie (University of Toronto) highlighted current therapies for AD and how their benefits are measured in clinical drug trials. Both Drs. Rockwood and Naglie discussed the recent literature critiquing the cholinesterase inhibitors (ChEIs), pointing out that despite numerous successful RCTs these treatments have not been fully embraced. While the buzz in the audience suggested that this might be explained in part by ageism, both Drs. Rockwood and Naglie believe that the choice of outcome measures may be a factor. Dr. Rockwood reviewed some of his recent research on the Goal Attainment Scale (GAS) and Dr. Naglie reviewed the importance of Quality of Life scales as well as milestone scales, such as the time to placement in long-term care.

Dr. Donald Stuss (University of Toronto) and Dr. Ron Peterson (Mayo Clinic College of Medicine) gave presentations on the predementia stages, normal aging, and mild cognitive impairment. Dr. Stuss discussed factors that affect our memory, such as the time of day. He discussed “morningness-eveningness” distributions, reporting on evidence that shows that college students are mostly evening types with very few morning types whereas older adults are morning types with very few evening types. Dr. Stuss also reported that difficulties with retrieval appear to be a common manifestation of aging. In closing, Dr. Stuss pointed out that wisdom does not deteriorate with aging and that cognitive rehabilitation can be used to overcome some of the observed deficits associated with aging.

Two presentations on depression were delivered by Dr. Ira Katz (University of Pennsylvania) and Dr. Lilian Thorpe (University of Saskatchewan). Dr. Katz reviewed his work on depression in long-term care (LTC). He showed that the ratings of depression with residents and staff were totally uncorrelated. Dr. Katz concluded that screening and recognition for depression should be based on hearing the resident’s voice whenever possible. In discussing the treatment of depression in LTC, Dr. Katz pointed out that over the years there has been a dramatic increase in the use of antidepressants (from 12.6-24.9% of cases); however, there has been no improvement in getting treatment to work. He concluded by suggesting that minor depression in LTC should be treated with watchful waiting and by activating the facility resources such as care strategies, routines, preferences, activities, and family involvement. Dr. Thorpe’s presentation focused on depression in dementia. She discussed the heterogenic and overlapping etiologies of depression in dementia as well as the diagnostic challenges in differentiating between the overlapping symptoms of depression and dementia. For example, Dr. Thorpe mentioned that the core depressive symptoms of guilt and worthlessness are significantly less common in dementia. In closing, Dr. Thorpe gave an excellent review of the evidence for the pharmacological treatment of depression in dementia.

Dr. Mary Mittelman, New York University School of Medicine, presented her research on caregiver interventions in dementia through the NYU Caregiver Intervention Study. Dr. Mittelman’s research has shown that psychosocial interventions can lead to a decline in caregiver symptoms of depression, an improvement in the caregiver’s reaction to problem behaviours, and a delay of almost one year to LTC placement.

Drs. Anthony Lang (University of Toronto) and Clive Ballard (University of Newcastle upon Tyne) reviewed the latest literature on Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). Both speakers emphasized that these two conditions have been arbitrarily differentiated from each other based on the “one-year clause,” while in all likelihood they are different clinical manifestations of the same disease. Dr. Lang described a new face to Parkinson’s disease. PD is not a single disease as has been previously conceived. The new face of PD recognizes that the pathology of PD extends beyond the substantia nigra. Once the motor features of the disease are eliminated, the patient is left with clinical features such as apathy, dementia, and postural instability. Dr. Lang concluded that major advances and improvement in current responses to symptomatic therapies are less likely to come from a focus on dopamine deficiency in the substantia nigra than they are from attention to the nondopaminergic features. Dr. Ballard gave an excellent update on DLB, discussing the difficulties in making a clinical diagnosis with the current diagnostic criteria having high specificity but low sensitivity. The high prevalence of tau pathology in DLB substantially contributes to the variability in its clinical presentation. As Dr. Ballard put it, “the more tau present, the less likely the patient will be diagnosed with DLB.” Dr. Ballard also discussed antiproteosomal treatments as a future direction for the treatment of DLB.

Dr. Morris Freedman (University of Toronto) provided the audience with a video-packed presentation on frontotemporal dementia and Dr. Sandra Black (University of Toronto) reviewed the state of the art pertaining to neuroimaging in Alzheimer’s disease. Michelle Tremblay (University of Ottawa) helped the audience conceptualize issues around capacity, emphasizing the importance of the two key components: “understanding and appreciating.” Dr. Malcolm Man-Son-Hing, also from the University of Ottawa, reviewed the sensitive issue of driving and dementia. According to Dr. Man-Son-Hing, decision making about driving involves balancing safety and quality of life.

Dr. Gustavo Roman (University of Texas) delivered a presentation on “The Shifting Limits between Vascular Dementia (CVD) and Alzheimer’s Disease.” Dr. Roman described the importance of CVD in the expression of dementia in patients with AD pathology. He stressed the importance of treating vascular risk factors in the possible prevention of dementia onset and its progression.

The audience of the third CCD was treated to very stimulating debates on two hot clinical topics. Drs. Nathan Herrmann (University of Toronto) and Dr. Ira Katz debated in favour of the resolution “Treatment of Behaviour in Dementia with Atypical Neuroleptics: Benefits Outweigh Risks” while Drs. Jiska Cohen-Mansfield (George Washington University) and Clive Ballard debated against the resolution. Despite excellent arguments on the efficacy and relative safety of these agents from Drs. Herrmann and Katz, it was Drs. Cohen-Mansfield and Ballard who seemed to change most of the opinions in the audience through their claims that behavioural interventions have not been sufficiently utilized and the concerns they raised about the safety of atypical neuroleptics in older adults. However, both sides agreed that there are cases where safety is of a major concern, and a role for atypical neuroleptics cannot be disputed.

Dr. Howard Chertkow (McGill University), who was in favour, and Dr. Ron Petersen (Mayo Clinic College of Medicine), who was opposed, debated the resolution: “Cholinesterase Inhibitors Should Be Used to Treat Mild Cognitive Impairment.” Through a number of case presentations, Dr. Chertkow managed to change many of the opinions in the audience, suggesting that evidence-based medicine and clinical medicine are not always one and the same.

The third CCD wrapped up with an opportunity for the audience to demonstrate the knowledge they gained from the conference through clinicopathological vignettes presented by Drs. Howard Feldman and Ian MacKenzie from the University of British Columbia.

While still savouring the success of the third CCD, the organizing committee is already working hard on the program for the fourth CCD, to be held in Vancouver, British Columbia from October 18-20, 2007. We look forward to seeing you there!

The Third CCD gratefully acknowledges unrestricted educational grants from Janssen-Otho Inc., Lundbeck Canada, Novartis Canada, and Pfizer Canada.

No competing financial interests declared.