Overview of the VLS: Longitudinal and Epidemiological Research on Aging

1. Overview of the VLS:Longitudinal and Epidemiological Research on Aging Roger A. Dixon Stuart W.S. MacDonald Principal Investigator

2. Acknowledgements • Funded in part by Grant R13AG030995-01A1 from the National Institute on Aging • The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

3. VLS Support and Funding Recent Funding NIH R37 AG008235-20 (PI: Dixon) AHS-FOMD: (PIs: Westaway, Dixon, Jhamandas) NIH R03 AG024082 (PI: Small) Canada Research Chairs (PI: Dixon) STINT (Sweden; PIs: Nilsson, Dixon ACNAlberta Cognitive Neuroscience

4. Acknowledging VLS Collaborators VLS Co-founders*/Executive PI: Roger A. Dixon (University of Alberta)* Christopher Hertzog (Georgia Tech)* David Hultsch (University of Victoria)* Stuart MacDonald (University of Victoria) VLS Co-investigators and Consultants Lars Bäckman (Karolinska Institute) Richard Camicioli (University of Alberta) Cindy de Frias (University of Texas) Jack McArdle (Univ. of Southern California) Lars-Göran Nilsson (Stockholm University) Brent Small (University of South Florida) Esther Strauss (University of Victoria) Åke Wahlin (Stockholm University)

5. Toward Capturing Elements of the Dynamics of Human Aging Large-Scale Longitudinal Studies (LSLS) Examples of existing LSLS, all of which have some of the necessary features Australian Longitudinal Study of Ageing Berlin Aging Study (BASE) Betula Project (Umeå) Seattle Longitudinal Study Victoria Longitudinal Study

6. Large-Scale Longitudinal Studies:Contributions to Memory Aging LSLS Research Designs May Include Indicators of: Time: Change in Levels and Variability of Performance Observation: Gains, Losses, Maintenance Interpretation: Level, Resilience, Adaptation, Compensation, Leading-Lagging Inputs: From Bio, Psycho, Social, Environmental Levels Output: Multiple Indicators of Cognitive Health/Disease Crossing: Interactions Within/Across Levels Over Time Risk Factors: Precursors to Loss Protection Factors: Promoting Maintenance or Managed Loss Existing LSLS share logic, methods, and purview

7. A VLS PlatformTracking Normal, Clinical, Healthy Transitions in Human Aging Brief Background VLS Overall Research Headquarters: University of Alberta VLS Satellite Research Lab: University of Victoria Begun in the late 1980s (and continuing > 20 years) Continuous Funding from U.S. National Institutes of Health Brief (Original) Rationale Recruit successive cohorts of healthy adults (ages 55-85 years) and follow them longitudinally as they develop various aging-related conditions, including neurodegenerative diseases. Conduct research on patterns, profiles, and precursors of Healthy/Successful Aging, Normal Aging, Mild Cognitive Impairment, Dementia Other emergent biological/health conditions Recent: BioAge, CVD, CerebroVD, T2D, Health Burden, Obesity, Genetic/Epigenetic Markers

8. VLS Research Design Design: “Longitudinal Sequential” Three Main Cohorts (Samples): Initiated in VLS S1: 1980s; VLS S2: 1990s; VLS S3: 2000s Detail: Cohorts initially 55-85 years old and healthy Detail: Initial n per cohort = 500-600 Plus control groups VLS N > 2000 Detail: 3/4-year intervals between “waves” Detail: 12-14 hours of testing and data per wave

9. VLS Research Blueprint:Main Longitudinal Samples VLS Sample 1 [Wave 7 (18 years) completed, now aged 73-103 years] VLS Sample 2 [Wave 5 (12 years) completed, now aged 67-97 years] VLS Sample 3 [Wave 3 (6 years) underway, now aged 61-91 years] 1987-88 Wave 1 2001-03 Wave 1 1993-94 Wave 1 1990-91 Wave 2 2004-06 Wave 2 1996-97 Wave 2 2008-09 Wave 3 1999-00 Wave 3 1993-94 Wave 3 2011-12 Wave 4 2003-04 Wave 4 1996-97 Wave 4 2006-07 Wave 5 1999-00 Wave 5 2014-15 Wave 5 2002-03 Wave 6 2017-18 Wave 6 2009-10 Wave 6 2005-06 Wave 7 2012-13 Wave 7 2020-21 Wave 7

10. The VLS “Sequential” Longitudinal Design VLS Sample 1 (b. 1902-1932) W1 W2 W3 W4 W5 W6 W7 VLS Sample 2 (b. 1909-1939) W1 W2 W3 W4 W5 W6 W7 VLS Sample 3 (b. 1916-1946) W1 W2 W3 W4 W5 W6 1980s 1990s 2000s 2010s Historical Time

11. Microscope on One Longitudinal Sample of the VLS Design VLS Sample X(55-85 years) VLS Sample X(58-88 years) VLS Sample X(61-91 years) CSL Data Wave 1 3-year Data Wave 2 6-year Data Wave 3 3 years 3 years 3 years Attrition:Three waves of data(6 years) Attrition:Two wavesof data(3 years) Attrition:One waveof data Morbidity Morbidity Mobility Mobility Morbidity Mobility Impairment Impairment Impairment

12. Sketch of VLS ProtocolHighlights of VLS BatteryThemes (1) Cognitive and Neurocognitive Performance and Status (2) Health and Medications (3) Biomarkers, Fitness, Genetics, and “BioAge” (4) Background, Life History, Affect, Activities, and Experience

13. Sketch of VLS Protocol Constructs and Associated Indicators 1. Cognitive and Neurocognitive Performance and Status Memory Episodic (story recall, word list recall * 2) Semantic (fact recall, vocabulary) Working (sentence construction, listening span, computation span) Neurocognitive Speed and Inconsistency Semantic (semantic verification task, lexical decision task) Perceptual (identical pictures, number comparison, digit symbol) Reaction Time (simple RT, 2-4-8 choice RT) Memory Compensation and Metacognition Executive Functions Inhibition (Stroop), Updating (various WM tasks), Shifting (Color Trails) General Cognition (MMSE) Reasoning Letter series and letter sets

14. 2. Health and Medications Comprehensive Health Inventory Conditions, Risk Factors, Frailty Medications Self-report Linkage consent Functional, Instrumental, and Subjective Health Health relative to others and perfect ADLs and IADLs Change in daily activity patterns Sketch of VLS Protocol Constructs and Associated Indicators

15. 3. Biomarkers, Fitness, Genetics, and “BioAge” Physiological Function Anthropometric (height, weight, BMI, head circumference) Pulmonary (peak expiratory flow) Balance and Gait (timed walk, turn 360) Muscle strength (grip test) Sensory Function Audition Vision Smell Genetics and Epigenetics Sketch of VLS Protocol Constructs and Associated Indicators

16. 4. Background, Life History, Affect, Activities, and Experience Demographic, Personal Background, Family History Personal Data Sheet (PDS) Affect and Psychosocial Personality (NEO) Depression (CES-D) Well-being (Bradburn affect balance scale) Life Experience and Lifestyle Activities (Physical, Social, Cognitive) Activity Lifestyle Questionnaire (VLS-ALQ) Sketch of VLS Protocol Constructs and Associated Indicators

17. Activity Lifestyle Questionnaire VLS-ALQ consists of 64 items and six subscales representing 3 domains of everyday cognition, physical activity, and social activity The six activity subscales are identified as follows: Physical activity (e.g., jogging, walking); 4 items Self-maintenance (e.g., preparing a meal, shopping); 6 items Social activity (e.g., attending concerts, visiting friends); 7 items Hobbies/Home Maintenance (e.g., using the computer, playing an instrument); 12 items Passive Information Processing (e.g., reading the paper, watching a documentary); 8 items Novel Information Processing (e.g., completing income tax forms, playing bridge); 27 items

18. Activity Lifestyle Questionnaire Items measured on a 9-point scale

19. VLS Contributions to the Activity-Cognition Hypothesis Hultsch et al (1999) Examined hypothesis that maintaining intellectual engagement through participation in everyday activities buffers against cognitive decline N = 250 participants tested 3 times over 6 years Used SEM/latent change approach to examine associations between changes in lifestyle variables and cognitive functioning Psychology and Aging, 14, 245-263

20. VLS Contributions to the Activity-Cognition Hypothesis Changes in intellectually-engaging activities (Novel CH) were systematically linked to cognitive change Findings imply that remaining cognitively active buffers against decline OR that high-ability individuals lead intellectually-active lives until cognitive declines limit their participation

21. VLS Contributions to Activity-Cognition Hypothesis Bielak (2009) Summarized key unanswered questions in the “use it or lose it” literature How does activity engagement impact cognition, and which domains benefit most Optimal methods for assessing activity engagement Directionality of cognition-activity association Moderators of relationship Activity with largest impact on cognition

22. VLS Contributions to the Activity-Cognition Hypothesis Small et al (2010) -- Changes in Lifestyle Activities as Moderators of Age-Related Declines in Cognitive Abilities examined whether multivariate changes in physical, social, or cognitive lifestyle activities were related to cognitive change N = 952 participants tested up to 5 times spanning 12 years Psychological Science (under review)

23. VLS Contributions to the Activity-Cognition Hypothesis Applied latent change score models to examine associations between change in activities and cognition limitations in cognitivelifestyle activities were linked to subsequent declines in processing speed, episodic memory, and semantic memory results also indicated that poorer cognitive functioning was linked to subsequent decrements in activity participation (particularly social activities)

24. www.ualberta.ca/~vlslab