Motor slowing and cognitive slowing are more prevalent as we age. Importantly, the presence of both in an older person increases their risk of having dementia by ten times. Currently, there are no clinically meaningful predictors of progression to dementia in people with mild cognitive impairment (MCI). The main hypothesis is that subtle variations in gait while performing a simple cognitive task is a reliable, easy to perform, and feasible methodology to detect those older adults at higher risk of progression to dementia and also, at higher risk of further mobility decline and falls.

Rationale. The Canadian population is aging. According to recent estimates, the proportion of the population aged 65 and older will increase rapidly from 13% in 2005 to 25% by 2031. This increase in proportion is accompanied by a considerable amount of disability and subsequent dependency which has major effects on both the quality of life of older adults and their caregivers, and on the Canadian health care system. An important goal of geriatric medicine is to reduce the gap between life expectancy and disability-free life expectancy by reducing disability and dependency in the later years of life. A substantial portion of this disability stems from two major geriatric syndromes: cognitive impairment and mobility limitation. The ultimate manifestations of these syndromes are dementia and falls. Interestingly, these manifestations often coexist in elderly people: falling is a common geriatric syndrome affecting about a third of older adults each year, and dementia affects about a third of Canadians aged 80 and over. Together, dementia and falls are responsible for much of the discomfort, disability, and health care utilization in older adults and each will become more prevalent as older Canadians are expected to number approximately $9 million by 2031. The combined direct cost of dementia and falls for the Canadian Health System is over $4.9 billion per year.

Establishing reliable and easy to obtain predictors to accurately identify MCI patients at highest risk of progressing to dementia is essential first, to determine who will benefit from additional and/or invasive testing and second, to implement preventative strategies, including cognitive training, physical exercises, and aggressive vascular risk factors correction to delay progression. Even a modest one-year delay in dementia incidence could save Canada $109 billion over 30 years.

This longitudinal cohort study started in 2007 and is aiming to assess 600 older persons (60 y/o to 85 y/o) at risk of development cognitive impairment and dementia, during a 25 year of follow-up, since we expanded the study to recruit more participants, which was approved by our Institutional Research Board. The follow-up period was selected in order to cover the potential progression to dementia of at least two-third of the participants. From 2007 to 2023, for the first five years of follow up, assessments were conducted at baseline and every 6 months; since 2023, this was changed by which assessments are being conducted every 12-months along with performing a virtual assessment of outcomes only, every 6-months. After the visit at 60 months, participants will then be followed once a year for 20 years. The six months period between assessments during the first 5 years was selected since it is the minimum time required for detecting significant changes between assessments in cognitive measurements and for avoiding testing learning effects. If changes are not noted within the first five years, then the annual follow-up period will provide sufficient time periods to detect significant changes in cognition, gait, and balance measures.

Blood test for genotyping (ApoE4 carrier) is being performed only at baseline assessments. Cognitive, gait and balance assessments are being performed in all 12-month follow-up visits. From 2010 to 2021, 3Tesla Magnetic Resonance Imaging (structural and functional -resting state-) and MRI spectroscopy are being performed at four different time points: at baseline, month 18 and month 36, and month 60, following the Canadian Dementia Imaging protocol (http://www.cdip-pcid.ca.). Since 2021, the 18-month MRI timepoint changed to be performed at 12-month visit to align MRI timepoints with blood draw, which allows analysis of MRI and biomarker comparisons over time. For the 20-month Follow-Up period, MRI was performed at Year-2, Year-5 and Year-7 until 2018. Since 2018, the 20-Year Follow-Up MRI timepoints changed to Year-3, Year-5, Year-7 and Year-10. Blood and brain imaging were added after the second wave of the study, in 2010.

General Inclusion Criteria:

• Absence of Dementia (DSM IV-TR or DSM V criteria)
• Aged 60-85 years
• Able to walk independently 10 meters without any gait aid (for example: walker, cane);

Exclusion Criteria:

• Unable to understand English;
• Parkinsonism or any neurological disorder with residual motor deficit (e.g.: stroke, epilepsy);
• Musculoskeletal disorder detected by clinical examination which affects gait performance;
• Active osteoarthritis affecting the lower limbs at clinical evaluation
• Use of psychotropics which can affect motor performance (e.g. neuroleptics and benzodiazepines)
• Severe Depression (score > 12/15 on the Geriatric Depression Scale).

Participants 60 years or older are being recruited from the community, our Geriatrics and Memory Clinics at University of Western Ontario affiliated hospitals, from advertisements placed in local (London, ON) newspapers, and referrals from family physicians or community partners. Participants are being followed-up for up to 25 years after baseline measurements (twice annual or annual follow-up visits).