Dementia affects over half a million Canadians, with Alzheimer’s disease (AD) accounting for 60-80
percent of the cases (1,2). The disease mainly affects cognitive functioning and is often
progressive (meaning it worsens over time), which leaves the affected individuals highly
debilitated. Currently, in most progressive dementias, including AD, there is no cure or treatment
to slow or stop the progression (2). As the aging population grows, dementia poses a rising
challenge in our healthcare system. It is projected that the healthcare cost associated with
dementia will increase to $16.6 billion by 2031 (3). This crisis calls for a need to expand on
research for novel approaches to diagnose and treat dementia.
The Translational Biomarkers in Aging and Dementia (TRIAD) cohort was established in 2017 to conduct leading studies on AD and other types of dementias. The cohort is composed of patients from the MCSA and the general public. Currently, over 1000 people are enrolled in the TRIAD cohort and around 500 of them are participating in a study. The specific study measurements for subjects depend on the project, but the subjects generally undergo baseline and yearly follow-up appointments that include the following
The MCSA was established in 1985 as a multi-disciplinary academic unit dedicated to gerontological research and postgraduate teaching on the mechanisms of aging as well as prevention of age-associated disorders. It has achieved international recognition for its integrative work on the neurodegeneration of the aging central nervous system and neurodegenerative diseases. The Centre’s scientists are renowned for their contributions in the fields of Alzheimer’s and Parkinson’s diseases and other cognitive disorders. The MCSA team is composed of neurologists, undergrad and grad students, post-doctoral fellows, administrative staff, research nurses and research assistants.
Crossroads is a new annex to the MCSA that opened on April of 2018. Clinical aspects of the research projects, including biosample collections, neuropsychological assessments and clinical assessments are conducted at this location. The research assistants at Crossroads assist in participant recruitment and scheduling of appointments for all measures of the study.
|Mini Mental State Examination (MMSE)||Clinical Dementia Rating (CDR)|
|Montreal Cognitive Assessment (MoCA)||NPI questionnaire|
|Rey Auditory Verbal Learning Test (RAVLT)||Geriatric depression scale (GDS)|
|Aggie Figure test||Beck Depression Inventory II|
|Face-Name association test||Geriatric anxiety inventory (GAI)|
|Brief Visuospatial Memory Test (BVMT)||Apathy inventory|
|Logical memory||Hachinski ischemic scale|
|Emotional Memory Test||Subjective questionnaire|
|Digit span (WAIS-III; forward and backward)||Epworth sleep questionnaire|
|Boston naming||Sleep duration questionnaire|
|Semantic verbal fluency||MBI-C|
|IQ (WASI-II; matrix reasoning, vocabulary)||Functional activity questionnaire|
|Digit symbol (WAIS-III)||eCOG|
|Stroop test (D-KEFS)||Exercise questionnaire (GPAQ)|
|Trail making||Nutrition assessment|
|BORB – object decision test||Generalized anxiety disorder questionnaire (GAD7)|
|BORB – line orientation||Social support questionnaire|
|Pyramids and Palm trees test|
|For English speakers: sentences in English (UCSF), for French speakers: repetition du Montréal-Toulouse|
|Rey Osterrieth Complex Figure test (copy)|
|Oral description of the picnic scene picture (Western Aphasia Battery)|
The TRIAD cohort consists of study participants belonging to distinct populations, including cognitively unimpaired, mild cognitive impairment, Alzheimer’s disease, as well as atypical dementia. Each of these populations has a fundamental role in our investigation of biomarkers of aging and dementia in the human brain. Since all of our studies involve positron emission tomography (PET) and magnetic resonance imaging (MRI), we exclude individuals who are unable to undergo these procedures from our cohort. In addition, we are unable to include individuals who have any uncontrolled systemic or neurological diseases and people who are unable to give consent.
The cognitively healthy population consists of participants who do not exhibit any cognitive symptoms. These individuals do not meet the criteria for mild cognitive impairment or any form of dementia, nor any psychiatric disorder. The TRIAD cohort recruits both young (between 20 and 45 years of age) and elderly (between 55 and 85 years of age) subjects into the cognitively healthy group. The aim of this population is (1) to serve as a control group for comparison purposes in our studies of aging and dementia biomarkers and (2) study the pre-symptomatic phase of Alzheimer’s disease.
The mild cognitive impairment (MCI) population includes participants who exhibit cognitive symptoms, which include memory loss as well as problems with thinking, judgment, and language, but who do not meet the criteria for dementia. Cognitive symptoms in MCI are more significant than normal age-related changes in cognition, but typically are not sufficient to affect daily activities. The cognitive impairment should not be explained by any other disease or condition, nor by the use of certain medications. MCI diagnosis is determined through neuropsychological evaluation, MRI and PET scans and is confirmed during the weekly clinical meeting. Subtypes of MCI exist, including amnesic mild cognitive impairment (aMCI), in which episodic memory in particular is impaired. The aim of this population is to study biomarkers in an intermediate stage of dementia as a diagnosis of MCI is associated with a higher likelihood of progression to dementia.
The Alzheimer’s disease (AD) population consists of individuals who have been diagnosed with Alzheimer’s disease by a clinician. Alzheimer’s disease patients present with a progressive decline in memory and other cognitive functions which significantly impacts daily activities, which is typically accompanied by behavioral or neuropsychiatric symptoms. AD diagnosis is determined by a clinician and involves neuropsychological testing as well as brain imaging tests. Aside from typical Alzheimer’s disease, the AD population may include individuals who have been diagnosed with variant forms of Alzheimer’s disease, including early onset Alzheimer’s disease (EOAD), posterior cortical atrophy (PCA), and primary progressive aphasia (PPA). The early onset Alzheimer’s disease subgroup includes individuals who develop Alzheimer’s disease symptoms before the age of 65, and is in many cases explained by genetic risk factors (i.e. familial Alzheimer’s disease). Individuals with PCA show marked degeneration of cerebral cortex in the posterior region of the brain, and symptoms particularly affect visual function. Individuals with PPA primarily have a significant impairment in language. This subgroup includes individuals who are diagnosed with the logopenic variant of PPA, which is associated with slower speech and difficulties with word retrieval. The AD population, including its various subgroups, is crucial in investigating how various biomarkers present in different types of AD and dementia, as well as how they interact in different stages of the disease.
The atypical dementia population includes individuals who do not meet the criteria for Alzheimer’s disease and instead present with conditions including frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and vascular dementia (vD). Diagnosis of these disorders is determined by the clinician who refers us the patients. Individuals with FTD, sometimes referred to as Pick’s disease, FTD is associated with deterioration in behavior, personality, and language, as well as disturbances in motor functions in some cases. In particular, the most common form of FTD, behavioral variant of frontotemporal dementia (bvFTD), is characterized by significant alterations in behavioral, judgment, and empathy, as well as by symptoms such as apathy, impulsivity, and lack of restraint based on social norms. PSP, sometimes referred to as Steele–Richardson–Olszewski syndrome, is a condition which primarily affects balance and eye movements, as well as sleep. CBD is characterized by a significant impairment in motor functioning. vD describes individuals whose cognitive symptoms are caused by impaired blood flow to the brain, typically due to a stroke. Patients with vD typically experience cognitive decline in a step-like manner, as opposed to gradually as in typical Alzheimer’s disease. The aim of the atypical dementia population is primarily to examine the differences in the presentation of biomarkers in these various forms of dementia, which helps to improve the differentiation and diagnosis of these disorders.