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The field of neuromodulation has progressed significantly over the past two decades. It is evident that application of electrical (via tDCS, transcranial direct current stimulation) or magnetic (via rTMS, repetitive transcranial magnetic stimulation) brain stimulation over the skull surface can effect change in brain function, which appears sufficiently robust to have a therapeutic effect. Sometimes the neuromodulation is best coupled with other forms of training or rehabilitation for best efficacy. What are the most promising approaches? What conditions appear to benefit? What are the situations/diseases/ disease states where neuromodulation is sufficiently well-proven now (or may be so in the future) that clinicians should start to consider its use in their psychogeriatric practice? We will review studies showing that tDCS can have a therapeutic effect in dementia, stroke, depression, and a range of other psychiatric conditions. Recent work is showing that with tDCS one can achieve improvement in picture naming, executive function, and memory in Alzheimer Disease and Frontotemporal dementia (Howard Chertkow presentation, Baycrest Health Sciences, Toronto). In stroke rehabilitation, rTMS treatment has been shown to aid in motor and language recovery (Alex Thiel, McGill University). There is now sufficient evidence that tDCS and Magnetic Seizure therapy are beneficial in depression, that these can now become part of the therapeutic armamentarium in selected cases (Jeff Daskalakis, University of Toronto). A range of other neuropsychiatric conditions can also be considered for neuromodulation therapy with rTMS (Daniel Blumberger, University of Toronto, CAMH).By attending this symposium, a physician or health care professional will become familiar with the latest research into neuromodulation and its role in current therapy of neurological and psychiatric diseases.

It is not clear how best to coordinate, facilitate, and catalyze dementia research at the national level of most countries. Literature search on CCNA and qualitative review of website of CCNA, newsletters, and grant renewals in Canada. The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government in 2014 through the Canadian Institutes for Health Research (CIHR). Two five-year funding cycles have occurred following peer review, and a third cycle (Phase 3) has just begun. Twenty national teams were established, with research topics focussing on national research strengths, spanning from basic to clinical science to health resource systems. Teams have facilitated greater interaction. Responding to the needs of researchers within the CCNA teams, a unique sample of 1,173 deeply phenotyped patients with various forms of dementia was accrued and studied over eight years (COMPASS-ND). In the second phase of funding (2019-2024), a national dementia prevention research program (CAN-THUMBS UP) was set up. In a short time, this prevention program became a member of the World Wide FINGERS prevention consortium. Cross-cutting programs were established to support the enterprise, focussing on KT, Training, and Sex and Gender in Dementia. A unique group integrated persons with lived experience into the national research program (EPLED, Engagement of People with Lived Experience of Dementia). An emphasis was placed on developing knowledge and capacity and procedures for investigating dementia in the Canadian Indigenous communities, where it is higher than other populations. Objective measures have demonstrated increased synergy and productivity among Canadian dementia researchers since establishment of CCNA, along with leveraging of new grants equal to the CIHR funding. More than 600 journal articles have resulted from CCNA work, with higher impact than corresponding non-CCNA work. The network has had demonstrable impact on policy-makers and been a conduit towards greater impact of the research community nationally and internationally. Enhancement of synergy and networking have contributed to the considerable success of CCNA by all measures. CCNA is evidence that an organized \"centrally-organized\" approach to dementia research can catalyze important progress nationally and yield significant and measurable results.

Recent work (Jack et al, 2024) proposes an AD diagnostic framework which moves biomarkers to the centre, proposing that short of biomarker access, clinicians should simply refer to patients as having \"dementia\" or \"MCI\" without further differentiation. Such a move would have a significant negative impact on all patients and physicians lacking access to diagnostic biomarkers, ignores their clinical acumen, and negates the considerable progress in clinical neurology over the past generation. A review of the literature on clinical diagnosis was supplemented by database review of convenience sample of 52 subjects with clinical probable AD and known amyloid status (csf or PET), as well as 145 subjects from the Canadian COMPASS-ND dataset with known amyloid status (csf). A proposal is made to continue diagnostic algorithms promoting distinction of dementia patients into those with and without motor features. A proposal is further made to refer to clinical \"AD phenotype\" dementia patients without motor features as having \"Alzheimer Syndrome\". A further level of diagnosis would consist of distinguishing Alzheimer Syndrome patients into those with and without presence of amyloid. This can be accomplished with about 80% accuracy using clinical guidelines such as CAPS (A Clinical beta Amyloid Positivity prediction Score; Lahiri et al, 2024) utilizing presence of neuropsychiatric features, rapidity of cognitive decline, and presence of white matter disease. Greater accuracy than this would require use of amyloid biomarkers. Changes in terminology are now necessary to acknowledge the language proposed by the academic community which has easy access to biomarkers, without disempowering clinicians (most of them) who lack easy access to the biomarkers. Good (but not excellent) level of specifying likelihood of amyloid being present, can likely be achieved with more accessible clinical markers. This approach should be pursued and replicated among diverse populations of patients around the world.

Background It is not clear how best to coordinate, facilitate, and catalyze dementia research at the national level of most countries. Method Literature search on CCNA and qualitative review of website of CCNA, newsletters, and grant renewals in Canada. Result The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government in 2014 through the Canadian Institutes for Health Research (CIHR). Two five‐year funding cycles have occurred following peer review, and a third cycle (Phase 3) has just begun. Twenty national teams were established, with research topics focussing on national research strengths, spanning from basic to clinical science to health resource systems. Teams have facilitated greater interaction. Responding to the needs of researchers within the CCNA teams, a unique sample of 1,173 deeply phenotyped patients with various forms of dementia was accrued and studied over eight years (COMPASS‐ND). In the second phase of funding (2019–2024), a national dementia prevention research program (CAN‐THUMBS UP) was set up. In a short time, this prevention program became a member of the World Wide FINGERS prevention consortium. Cross‐cutting programs were established to support the enterprise, focussing on KT, Training, and Sex and Gender in Dementia. A unique group integrated persons with lived experience into the national research program (EPLED, Engagement of People with Lived Experience of Dementia). An emphasis was placed on developing knowledge and capacity and procedures for investigating dementia in the Canadian Indigenous communities, where it is higher than other populations. Objective measures have demonstrated increased synergy and productivity among Canadian dementia researchers since establishment of CCNA, along with leveraging of new grants equal to the CIHR funding. More than 600 journal articles have resulted from CCNA work, with higher impact than corresponding non‐CCNA work. The network has had demonstrable impact on policy‐makers and been a conduit towards greater impact of the research community nationally and internationally. Conclusion Enhancement of synergy and networking have contributed to the considerable success of CCNA by all measures. CCNA is evidence that an organized “centrally‐organized” approach to dementia research can catalyze important progress nationally and yield significant and measurable results.

Background Recent work (Jack et al, 2024) proposes an AD diagnostic framework which moves biomarkers to the centre, proposing that short of biomarker access, clinicians should simply refer to patients as having “dementia” or “MCI” without further differentiation. Such a move would have a significant negative impact on all patients and physicians lacking access to diagnostic biomarkers, ignores their clinical acumen, and negates the considerable progress in clinical neurology over the past generation. Method A review of the literature on clinical diagnosis was supplemented by database review of convenience sample of 52 subjects with clinical probable AD and known amyloid status (csf or PET), as well as 145 subjects from the Canadian COMPASS‐ND dataset with known amyloid status (csf). Result A proposal is made to continue diagnostic algorithms promoting distinction of dementia patients into those with and without motor features. A proposal is further made to refer to clinical “AD phenotype” dementia patients without motor features as having “Alzheimer Syndrome”. A further level of diagnosis would consist of distinguishing Alzheimer Syndrome patients into those with and without presence of amyloid. This can be accomplished with about 80% accuracy using clinical guidelines such as CAPS (A Clinical beta Amyloid Positivity prediction Score; Lahiri et al, 2024) utilizing presence of neuropsychiatric features, rapidity of cognitive decline, and presence of white matter disease. Greater accuracy than this would require use of amyloid biomarkers. Conclusion Changes in terminology are now necessary to acknowledge the language proposed by the academic community which has easy access to biomarkers, without disempowering clinicians (most of them) who lack easy access to the biomarkers. Good (but not excellent) level of specifying likelihood of amyloid being present, can likely be achieved with more accessible clinical markers. This approach should be pursued and replicated among diverse populations of patients around the world.

Involvement of caregivers in dementia research is an admirable goal. Involvement of caregivers in care planning for patients and people living with dementia, is essential to good medicine. However, it is important to assess and realistically consider areas where researchers and caregivers, and physicians and caregivers, may disagree. Several kinds of such disagreement and formulating an approach to these will be discussed. Three examples: Involvement of patients in Alzheimer Disease clinical trials. The researcher must be realistic but optimistic in the possible benefits of clinical trials. At the same time, expectations must be managed. It would be naive to consider that caregivers and people with lived experience participate for purely altruistic reasons. Therefore, when a clinical trial fails to produce obvious benefits (the patient may be in a placebo group, or the drug may have limited efficacy), the caregiver often considers withdrawing from the study. How should a researcher approach such a situation? Is there a way for caregivers and patients to be given autonomy, and yet carry clinical trials to the necessary completion? A second example involves prognostication. particularly when (as in Canada) medical assistance in death is now available for dementia patients. Who determines the narrative to be presented to the patient? If the caregiver wishes for greater pessimism or optimism on the part of the physician, is it ethical to diverge from the “scientific” information to accomodate prognostication to the preference of the caregiver? A third complex area is communication. Some caregivers are now requesting that the word “dementia” not be used, because it brings with it stigma. Other families maintain that the new terminology (such as “major neurocognitive disorder”) is mere obfuscation a lacks the clarity needed for communication. Should the language and terminology used be determined by caregivers? Should this be an area of discussion at the beginning of any medical interaction? We will discuss these and other scenarios where the complexity of the relationship between caregiver and physician/researcher are notable, and suggest approaches and processes to address these.

Evaluating the cognitive status of individuals who are visually impaired is limited by the design of the test that is used. This article presents data on the sensitivity and specificity of the version of the Montreal Cognitive Assessment for people who are visually impaired. The original validation data were reanalyzed, excluding the five visual items. The results indicated that the specificity was excellent, while sensitivity was reduced; however, the recommended proportionally adjusted cutoff values showed better sensitivity.

Anomia is common in Primary Progressive Aphasia (PPA), and there is considerable evidence that semantic problems (as opposed to impaired access to output word phonology) exist in many PPA individuals irrespective of their strict subtype, including a loss of representations from semantic memory, which is typical for people with the semantic variant of PPA. In this manuscript we present a straightforward novel clinical algorithm that quantifies this degree of semantic storage impairment. We sought to produce an algorithm by employing tasks that would measure key elements of semantic storage loss: a) whether an unrecalled name could be retrieved with cues; b) if performance for items was consistent across tasks; and c) the degree to which a participant's performance was related to general severity of cognitive impairment rather than semantic loss. More specifically, these tasks were given to 28 individuals with PPA (12 participants had a clinical diagnosis of atypical Alzheimer's Disease with the logopenic variant of PPA; the remaining 16 participants received a clinical diagnosis of Frontotemporal dementia (11 were classified as the non-fluent variant of PPA and five were the semantic variant of PPA). Scores from these tasks produced a single omnibus semantic memory storage loss score (SSL score) for each person that ranged from 0.0 to 1.0, with scores closer to 0 more indicative of semantic storage loss. Indeed, supporting the hypothesis that our scores measure the degree of semantic storage loss, we found participants with the semantic variant of PPA had the lowest scores, and SSL scores could predict the degree of hypometabolism in the anterior temporal lobe; even when only people with the logopenic variant of PPA were examined. Thus, these scores show promise quantitating the degree of a person's semantic representation loss.

Total tau (t-tau) and phosphorylated tau (p-tau) are abnormally elevated in the brain and cerebrospinal fluid of individuals with Alzheimer's disease (AD). Tau is also present in the salivary gland tissue and saliva, and salivary measures might produce an accurate, accessible, and inexpensive biomarker. Using unstimulated saliva and Western blot analysis, we quantified the p-tau/t-tau ratio at different phosphorylation sites. We found that for one phosphorylation site, S396, p-tau/t-tau ratio was significantly elevated in patients with AD compared with normal elderly control subjects. The elevation in saliva, however, did not correlate with cerebrospinal fluid tau or with brain measures such as hippocampal volume. There is significant elevation of p-tau/t-tau ratio for the S396 phosphorylation site. Large variation in the AD salivary tau levels, however, limits the utility of this test as a clinical biomarker.

Évaluation complète d’une étude de cohorte canadienne portant sur la démence et la neuro-dégénérescence. Contexte : L’évaluation globale de la neuro-dégénérescence et de la démence (COMPASS-ND), étude de cohorte du Consortium canadien en neuro-dégénérescence associée au vieillissement (CCNV), représente une initiative nationale visant à promouvoir la recherche portant sur la démence et à soutenir les programmes de recherche des équipes du CCNV. Totalisant 2310 sujets recrutés partout au pays, cette cohorte longitudinale regroupe des individus fortement « phénotypés » qui présentent diverses formes de démence et de pertes de mémoire légères. En plus de sujets âgés dont les fonctions cognitives sont intactes, ces 2310 sujets ont permis de valider les hypothèses formulées par les équipes du CCNV. Méthodes : Nous avons utilisé de nombreux documents pour décrire cette étude : le protocole de la COMPASS-ND ; la demande initiale de subvention ; le cinquième rapport d’étape semi-annuel du CCNV soumis aux Instituts de recherche en santé du Canada (IRSC) en décembre 2017 ; ainsi que d’autres documents produits à la suite de modifications consécutives à la mise en œuvre de ce projet. Résultats : L’étude de cohorte COMPASS-ND du CCNV inclut des participants de partout au Canada dont les divers états cognitifs sont associés à des maladies neurodégénératives ou au risque d’en souffrir. Ils feront l’objet d’un large éventail d’examens expérimentaux, cliniques, génétiques et d’imagerie afin d’aborder de manière spécifique les causes, le diagnostic, le traitement et la prévention de ces états cognitifs chez les personnes âgées. Les données obtenues à la suite d’évaluations cliniques et cognitives, ainsi que celles issues d’échantillons biologiques, d’imagerie cérébrale, de tests génétiques et de dons de cerveaux, seront utilisées pour tester les hypothèses générées par les équipes de recherche du CCNV et d’autres chercheurs canadiens. Cette étude constitue donc à ce jour l’étude canadienne la plus complète et la plus ambitieuse au sujet de la démence. La présentation des données initiales ayant eu lieu en 2018, la cohorte devrait atteindre sa taille maximale d’ici à 2020.Conclusion : La disponibilité des données de l’étude COMPASS-ND stimulera considérablement la recherche sur la démence au Canada au cours des prochaines années.