Objectives: Loneliness is a modifiable risk factor for depression and dementia in older age. Validated interventions are needed to mitigate the impact of loneliness in older adults. Some evidence suggests that mindfulness meditation may reduce stress, improve mood and cognitive function, and may also impact loneliness per se. Many meditation apps offer an accessible way to meditate at home. However, robust research is needed to assess the benefits of meditation using this technology for older adults. Muse is a meditation app that analyzes brain signals during meditation and provides users with real-time neurofeedback on their level offocus.

Methods: We conducted a pilot, randomized controlled trial to establish the acceptability and feasibility of a remote, mindfulness intervention using Muse in older adults, and to obtain preliminary data on its impact on mood and cognition. Twenty-six adults reporting feeling lonely were enrolled and randomized to an 8-week Muse- based meditation (MM) or a brain- training active control (BT) program. The MM group completed meditation sessions with real- time neurofeedback and guided meditation sessions using Muse. The BT group completed cognitively challenging games on the commercially available Peak app and listened to podcasts. The groups were matched on the amount of interactions with study staff and total program duration. Outcome measures included standardized self-report scales of loneliness, stress, depression, well-being, quality of life, sleep disturbance, resilience, and mindfulness. Staff blinded to program assignment administered cognitive tasks of episodic memory, working memory, and sustained attention, as well as a breath counting task. Assessments were taken at Pre, Mid, and Post intervention, and after a 2-month and 4-month (4M) follow-upperiod.

Results: Participants found both programs engaging and the remote assessments were feasible. The MM group showed a greater improvement in depressive symptoms, and psychological andphysical QOL, compared to the BT group, at Post and at 4M.

Conclusions: A Muse-based mindfulness program is an acceptable and accessible intervention for older adults. A large-scale randomized trial is warranted to evaluate the efficacy of this intervention in this group.

Objectives: Patients with dementia (PWD) benefit from interdisciplinary care. Depression is a well-known risk factor for the progression of neurocognitive impairment and dementia; other psychiatric disorders (i.e. anxiety, post-traumatic stress disorder, bipolar disorder, psychotic disorders) also may confer an increased risk for dementia. PWD may also present with behaviours and psychological symptoms that overlap with psychiatric disorders. Our aim is threefold: (1) Review the current literature on managing psychiatric comorbidities in PWD. (2) Present an illustrative case series of PWD with psychiatric comorbidities. (3) Introduce a model of care on our Behavioural Neurology Unit (BNU) for treating PWD with psychiatric comorbidities.

Methods: Our BNU is a 20-bed quaternary inpatient unit for difficult-to-treat behaviours related to dementia. Psychiatric consultation is readily available to clinicians and often times for PWD with psychiatric comorbidities. We review best practices in managing these patients. We present a case series of PWD with psychiatric comorbidities predating their diagnosis of dementia who have significant behavioural and psychological symptoms and have failed other settings.

Results: Current guidelines for PWD do not discuss the management of psychiatric and neurologic comorbidities in detail. Among 26 cases, we highlight the judicious use of anticonvulsants, lithium, clozapine, and nabilone in PWD. We also demonstrate the importance of interdisciplinary care with primary care, neurology, psychiatry, and allied health support.

Conclusions: Dementia care is challenging and requires individualized attention and interdisciplinary collaboration. These challenges are augmented when dealing with psychiatric comorbidities. We advocate for increased attention and creative solutions to address these complex cases.

Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.

The terms “cortical” and “subcortical” dementia are controversial; however, the clinical distinction between them is real. For example, although Alzheimer's and Parkinson's disease (prototypical of cortical and subcortical dementia, respectively) share clinical features, they differ in the presence of aphasia, apraxia, and agnosia in Alzheimer's disease but not in Parkinson's dementia. We review our studies aimed at clarifying the mechanisms underlying the differences between these neurological disorders. Experimental paradigms adopted from animal models were used to study the functional anatomy and neuropsychological characteristics of Alzheimer's and Parkinson's disease. The tasks administered include delayed alternation (DA) and delayed response (DR), which are sensitive to frontal system damage, and tactile discrimination learning (TOL) and reversal (TRL) paradigms sensitive to parietal system damage. Alzheimer's patients were significantly impaired on all tasks whereas Parkinsonians with dementia were impaired only on DR and TRL. Consideration of neuroanatomical and neuropsychological mechanisms involved in DA, DR, TOL, and TRL appears to have sharpened the distinction between Alzheimer's and Parkinson's dementia. Dementia in Alzheimer's disease may involve dorsolateral frontal, orbitofrontal and parietal systems. In contrast, dementia in Parkinson's disease may involve prominent dorsolateral frontal system damage.

Retrograde amnesia was assessed in demented and non-demented Parkinson’s patients using a test of remote memory spanning the years from 1920-1979. Results indicated that the demented patients 1) scored significantly below normal controls and 2) had equal impairment for all time periods. This pattern was like that seen in other dementing illnesses (i.e., Huntington’s and Alzheimer’s diseases), but different from that in amnesic disorders, such as Korsakoff s syndrome. The data, therefore, suggest qualitative differences in pattern of remote memory loss between the dementias and amnesic syndromes.

99mTc-HM-PAO single photon emission computed tomography (SPECT) was used to image 30 patients referred for the assessment of dementia. SPECT images revealed various patterns of regional cerebral perfusion (rCBF) in the subgroups of patients with the clinical diagnoses of Alzheimer's disease (AD, n = 14), Pick's disease (n = 1), and multi-infarct dementia (n = 7). In three patients, SPECT clarified the clinical differential diagnostic possibilities. Using a relative rCBF quantification technique, the relationship between specific cognitive impairments and rCBF in the AD patients was determined. There was a significant correlation between language impairment and left hemisphere hypoperfusion, whereas, apraxia correlated with hypoperfusion in the left parietal region. Thus, HMPAO SPECT is useful as an aid in the differential diagnosis of dementia and the technique of relative rCBF quantification with SPECT may contribute to the understanding of the clinico-anatomical relations of cognitive deficits in dementia.

The value of CT as a routine screening procedure in the investigation of cognitive impairment is being increasingly challenged. To address this issue, we reviewed the records of 175 patients with intellectual deficits admitted to a Behavioural Neurology Unit over a two-year period. In the vast majority of cases, ie. 82%, the CT served essentially to confirm the clinical impression and added no new diagnostic information that impacted the management of the presenting problem. In 15% of cases the CT scan was helpful for diagnosis, especially in the differentiation between Alzheimer's disease and multi-infarct dementia.

Objective: To replicate a previous finding that the trajectory of the Neuropsychiatric Inventory (NPI) shifts in the sixth year of behavioural variant frontotemporal dementia (bvFTD). We evaluated longitudinal tracking with both the Frontal Behavioural Inventory (FBI) and NPI, comparing bvFTD against other dementias.Methods: Chart reviews over two to five years for patients with bvFTD (n=30), primary progressive aphasia (PPA, n=13) and Alzheimer’s disease (AD, n=118) at an urban Canadian tertiary clinic specializing in dementia. Linear regressions of the longitudinal data tested predictors of annualized rates of change (ROC) in NPI and FBI total and subscales for apathy and disinhibition among dementia groups. Results: The mode of the overall sample for the most advanced duration of illness observed was 5 years, with the median at 7 years. We did not find a crescendo-decrescendo pattern in scores although, for bvFTD and AD, high initial scores correlated with ensuing downward ROCs on the NPI and FBI. Educational level showed an influence on disinhibition ROCs. The FBI was no more revealing than the NPI for apathy and disinhibition scores in these dementias. Conclusions: A cognitive reserve effect on behavioural disturbance was supported but it may take longer than our 4 years of observing the clinical sample to record inflection points in the behavioural and psychiatric symptoms seen in bvFTD. The current data only imply that both apathy and disinhibition will diminish over the course of dementia.

The magnitude of the problems faced by an aging Canadian society has been clearly identified. Perhaps the single most important problem is the increasing incidence of dementia. Alzheimer's disease (AD) accounts for 50-60% of the dementias in later life within a spectrum of other contributing dementias. Regulatory approval has been given to Acetylcholinesterase inhibitors for the symptomatic treatment of mild to moderate AD, and conditional approval to memantine for the symptoms of moderate to severe AD. There has been no regulatory approval for the treatment of the degenerative dementias beyond AD. The very rapid progress in the past decade in biotechnology and in the molecular biology of the dementias is supporting a new generation of innovative treatment strategies that will more directly target the underlying disease pathogenic mechanisms. Such treatments will foreseeably include immunotherapies, anti-aggregants that may prevent misfolding and deposition of proteins, and neuroregenerative interventions. These Guidelines follow the 2nd Canadian Conference on the Development of Antidementia Therapies, held in 2004, which covered a range of design, methodological and ethical issues facing clinical researchers and regulatory authorities. They are intended to provide a common point of reference and guidance in Canada for therapeutic development of the dementias.

Frontotemporal dementia (FTD) is one of three neurobehavioural syndromes produced by frontotemporal lobar degeneration. Despite the importance of FTD as a cause of dementia, especially in younger age groups, and a rationale for therapies targeting serotonergic and dopaminergic systems, there have been no large scale treatment trials in FTD. Moreover, there is no consensus on standards to facilitate comparison across therapeutic trials. This paper reviews the literature on therapeutic trials in FTD and outlines general recommendations for standards related to the development of future treatment studies in this disorder. Drugs tested in FTD include trazodone, galantamine, idazoxan, lithium plus fluoxetine, lithium plus paroxetine, SSRIs, l-deprenyl, moclobemide, methylphenidate, piracetam, rivastigmine, donepezil, olanzapine, risperidone, amantadine, guanfacine, allopurinol, and bromocriptine. Improvement has been reported in FTD for all drugs except piracetam, guanfacine and galantamine, although there was improvement on galantamine in primary progressive aphasia. Whereas improvement has been reported for paroxetine and other SSRIs, as well as idazoxan and methylphenidate, paroxetine and idazoxan have also been reported to cause a decline in function, and a marginally significant decline has been reported for methylphenidate. In addition, patients with Pick's disease, which is part of the spectrum of frontotemporal lobar degeneration, showed improvement on calcium EDTA. Six studies are double-blind placebo-controlled trials: two reports of cases using idazoxan and group trials using trazodone, paroxetine, galantamine and methylphenidate. It is recommended that experts in FTD arrive at a consensus to define standards for all clinical trials in FTD. These should include standards for diagnostic criteria, tests of severity, experimental design, and outcome measures.