- Email: [email protected]
Distinct rates of cognitive decline associated with normal aging
Poster Presentations: P3
mediated the relationship between social functioning and ADLS. Thus, decreasing social limitations and improving cognition may be appropriate targets of intervention for future studies aiming to improve ADLS in older adults. Social activities recruiting EF may be especially beneficial. P3-210
CONSCIOUS MONITORING OF ERRORS INFLUENCES SUBJECTIVE COGNITIVE DECLINE IN HEALTHY OLDER ADULTS
Rachel F. Buckley1,2, Robert Hester1, 1University of Melbourne, Melbourne, Australia; 2The Florey Institutes of Neurosciences and Mental Health, Melbourne, Australia. Contact e-mail: [email protected] Background: A critical element of human cognition is the capacity to adjust one’s behaviour subsequent to an error. Normal ageing has been associated with a progressive deterioration in conscious error awareness. This study examined whether gradual accumulation of undetected errors would relate to greater subjective concerns of cognitive decline. Methods: Thirty cognitively-normal (CN) adults (Mage¼71.1 years, range¼60-86 years) were administered a nonverbal memory measure (the CANTAB Paired Associates Learning paradigm), and a motor Go/No-go response inhibition task where participants make errors of which they were both aware and unaware. Participants filled out an SCD questionnaire (the Everyday Cognition battery), and the Geriatric Depression Scale. Results: Poorer error awareness was significantly related to greater SCD in the executive function domain (b¼-0.45, p¼.03), after taking into account age, depression, education level and non-verbal memory function. Poorer error awareness showed a trend with greater SCD in the memory domain, but did not pass the significance threshold (b¼-0.33, p¼.09). Error awareness was not related to age, education level, memory function, or depression, suggesting that variability in error awareness was not confounded by these factors. Conclusions: Mounting evidence supports the notion that SCD is a risk factor for Alzheimer’s disease (AD) in CN older adults. In particular, the literature has implicated subjective concerns in both the memory and executive function domains. The current study suggests that increasing concern of executive dysfunction is associated with decreasing error awareness in cognitively normal individuals. It is possible that accumulating, and unaccounted for, selfmade errors contribute to larger-scale executive functioning failures, which lead to executive function-specific SCD. Concerns of memory function only exhibited a trend relationship with error awareness, perhaps due to the small sample size (n ¼ 30). Error awareness is linked to neural activity in the anterior cingulate cortex; a part the default mode network which becomes dysfunctional early in AD. Our finding supports the notion that SCD in the executive domain are related to objective changes in cognitive processing. Executive function-related SCD has been previously related to b-amyloid burden, the role of b-amyloid burden should be investigated in the relationship between error awareness and SCD.
P3-211
DIFFERENTIAL RISK OF INCIDENT ALZHEIMER’S DISEASE DEMENTIA IN STABLE VERSUS UNSTABLE PATTERNS OF SUBJECTIVE COGNITIVE DECLINE
Michael Wagner1, Steffen Wolfsgruber2, Luca Kleineidam3, Alexander Koppara2, Steffi G. Riedel-Heller4, Wolfgang Maier1,3, Martin Scherer5, Frank Jessen1,6, 1German Center for Neurodegenerative Diseases, Bonn, Germany; 2DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany; 3University of Bonn, Bonn, Germany; 4Leipzig
P713
University, Leipzig, Germany; 5Hamburg University Medical School, Hamburg, Germany; 6University of Cologne, Cologne, Germany. Contact e-mail: [email protected] Background: Cognitively normal elderly with Subjective Cognitive
Decline (SCD) have an increased risk to develop dementia, as suggested by many studies with a single cross-sectional measurement of SCD. However, because Alzheimer’s disease (AD) is a constantly progressing disease, and because the reliability of a single measurement of SCD may be limited, longitudinal assessment of SCD may contribute further information with regard to AD dementia risk. We hypothesized that individuals who repeatedly report SCD should have a higher risk of AD, as compared to those with an unstable pattern of SCD reports. Methods: We analyzed the data of 1990 participants from the General Practitioner-based, longitudinal AgeCoDe Study. Patients (mean age at baseline¼79.5 years) were personally interviewed both at baseline and at first follow-up 18 months later, and were cognitively normal at baseline (mean MMSE¼27.9). They were asked “Do you feel like your memory is becoming worse?” Possible answers were “no” (no SCD), “yes” (SCD without concerns), “yes that worries me” (SCD with concerns). Participants were classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n¼613), (b) inconsistent SCD (with SCD reported only at baseline, or only at follow-up 1, n¼637), (c) consistent SCD without worries (n¼610) or consistent SCD with worries (n¼110). Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status and depression estimated the risk of incident AD over up to 6 years for each group. Results: As compared to CO, inconsistent SCD had no significant risk increase for AD dementia (HR 1.42, 95% CI 0.896–2.25). In contrast, the AD dementia risk was doubled in consistent SCD without worries (HR 2.03, 95% CI 1.30-3.15, p < 0.002), and even higher in consistent SCD with worries (HR 3.72, 95% CI 2.10–6.50, p < 0.001). These results could be replicated with similar hazard ratios when using follow-up 1 to follow-up 2 response patterns for group definition. Conclusions: These findings suggest that longitudinal stability vs. instability is an important modifying factor of the association between SCD and AD dementia risk. This has implications both for clinical practice and research on SCD samples.
P3-212
DISTINCT RATES OF COGNITIVE DECLINE ASSOCIATED WITH NORMAL AGING
David Bergeron, Marie-Pierre Fortin, Michele Houde, Stephane Poulin, Louis Verret, Remi W. Bouchard, Robert Laforce, Jr., Clinique Interdisciplinaire de memoire du CHU de Quebec, Quebec, QC, Canada. Contact e-mail: [email protected] Background: The subtle interface between normal and pathological
aging has been a field of intense research lately. While much emphasis has been put on the characterization of mild cognitive impairment and patterns of cognitive decline within various dementing disorders, classic signature and biological underpinnings of cognitive changes associated with normal aging are still poorly understood. This holds great importance in deciphering the secret of successful aging and better distinguishing normal from diseased states. We sought to evaluate the decline in memory, visuospatial, executive and language functions associated with normal aging. Methods: As part of the validation of the ‘D epistage Cognitif de Quebec’ (DCQ), a novel cognitive screening test for atypical/complex dementias, 180 normal individuals from 51 to 88 years-old (mean 67) were tested. The DCQ is made of 5 distinct sections,
P714
Poster Presentations: P3
namely Memory, Visuospatial, Executive, Language and Behaviour. We cross-sectionally analyzed the scores within these domains as a function of age and generated ‘cognitive curves’ to estimate which domain shows the most significant age-related decline. Results: Among the five indices, executive functions were the most affected by aging (-0.71%/year), followed by memory (-0.44%/year) and visuospatial skills (0.33%). Language abilities were globally preserved in the different age groups (-0.26%/ year). Within the executive domain the Stroop Color-Word Test (-2.1%/year) was the most affected by aging followed by Verbal fluency (-1.2%/year). Of note, 82% of the 70- individuals succeeded at the Stroop (naming correctly 14 colors in 15 seconds), compared to only 42% of 70+ individuals. Conclusions: These results suggest that aging primarily affects executive functions such as interference inhibition and processing speed. Decline in cognitive screening tests over time due to failure in executive tests should therefore be interpreted with caution, as this may merely reflect normal aging.
(p<.0001 vs. RN5, p¼.20 vs. IFU). Age-related annual decline was 0.18 in RN5, 0.24 in IFU (p¼.34 vs. RN5), and 0.28 in DO (p¼.054 vs. RN5, p¼.52 vs. IFU). Similarly, Logical Memory I intercept was 21.8 in RN5, 19.5 in IFU (p<.0001 vs. RN5), and 19.4 in DO (p<.0001 vs. RN5, p¼.92 vs. IFU). Annual decline was 0.13 in RN5, 0.20 in DO (p¼0.25 vs. RN5), and 0.30 in IFU (p¼.02 vs. RN5, p¼.19 vs. DO). Conclusions: Overall episodic memory performance is relatively stable over time in nondemented older adults. The more striking differences are in the intercepts which may reflect many years of change. The robust normal group has the best mean performance and the slowest rate of decline. Subgroups of persons with insufficient follow up or who drop out could be on the trajectory to dementia, so these two groups had lower intercepts and had more rapid decline.
Figure 1. Estimated pFCSRT+IR Free Recall and Logical Memory I scores over years of age for the 5-year robust normal (RN5) group, the drop out (DO) group and the insufficient follow up (IFU) group.
P3-214
P3-213
ESTIMATING EPISODIC MEMORY WITHINSUBJECT DECLINE AMONG NONDEMENTED OLDER ADULTS: RESULTS FROM THE EINSTEIN AGING STUDY (EAS)
Wenzhu Mowrey1, Ellen Grober1, Molly E. Zimmerman1, Mindy J. Katz1, Charles B. Hall1, Martin J. Sliwinski2, Richard B. Lipton1, 1Albert Einstein College of Medicine, Bronx, NY, USA; 2Pennsylvania State University, University Park, PA, USA. Contact e-mail: [email protected] Background: We aimed to estimate within-subject age-related decline in episodic memory among nondemented older adults. Methods: The picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR; range: 048) and the Logical Memory I subtest of the Wechsler Memory Scale–Revised (range: 050) were administered annually to adults initially aged 7090. This study included 1827 subjects who were free of dementia at baseline and had follow up data up to 5 years. Persons developing incident dementia within 5 years (n¼93) were excluded. Final follow up status was used to define the following three subgroups: Robust normal (RN5; n¼438) included subjects who had remained dementia free for 5 years; Drop out group (DO; n¼789) included subjects who withdrew from the study or died within 5 years; Insufficient follow up group (IFU; n¼507) included subjects who were followed up <5 years and were still being actively followed. Linear mixed models with random intercept and random slope were used to estimate mean memory performance at age 80, i.e. intercepts, and age slopes. Results: The pFCSRT+IR free recall intercept was estimated to be 30.9 in RN5, 28.9 in IFU (p<.0001 vs. RN5), 28.4 in DO
LONGITUDINAL RELATIONS AMONG WALKING ACTIVITY, GAIT SPEED, AND COGNITIVE FUNCTIONING OVER A 10-YEAR PERIOD: FINDINGS FROM THE HEALTH, AGING, AND BODY COMPOSITION STUDY
John R. Best1,2, Teresa Liu-Ambrose1,2, Robert M. Boudreau3, Hilsa N. Ayonayon4, Suzanne Satterfield5, Eleanor M. Simonsick6, Stephanie Studenski6, Kristine Yaffe7, Anne B. Newman3, Caterina Rosano3, 1Djavad Mowafaghian Centre for Brain Health, Vancouver, BC, Canada; 2University of British Columbia, Vancouver, BC, Canada; 3University of Pittsburgh, Pittsburgh, PA, USA; 4University of California San Francisco, San Francisco, CA, USA; 5University of Tennessee Health Science Centre, Memphis, TN, USA; 6National Institutes of Health, Baltimore, MD, USA; 7University of California, San Francisco, San Francisco, CA, USA. Contact e-mail: [email protected] Background: Previous studies have linked both physical activity and functional mobility to future changes in cognition among older adults. However, few studies have assessed all three constructs longitudinally in order to determine their interrelations over time and whether physical activity and functional mobility have independent associations with cognition. This study examined self-reported time spent walking, gait speed, and general cognition as measured by the Modified Mini Mental State Test (3MS) over a ten-year period. Methods: 2527 older adults (mean age ¼ 73.5 years at year 1) with complete data at year 1 from the Health ABC study, a biracial cohort were included. Self-reported time spent walking (mins/week), 3MS, and gait speed over a 20-meter walk were assessed at several time points from year 1 to 10. Joint longitudinal models were constructed using Mplus 7.3 and maximum likelihood estimation with robust standard errors. Covariates included clinical site, age, education, race, BMI, sex, smoking and drinking status, and prevalent diabetes, cerebrovascular and cardiovascular disease. Results: A covariate-adjusted latent growth curve model examined the longitudinal relationships among walking
mediated the relationship between social functioning and ADLS. Thus, decreasing social limitations and improving cognition may be appropriate targets of intervention for future studies aiming to improve ADLS in older adults. Social activities recruiting EF may be especially beneficial. P3-210
CONSCIOUS MONITORING OF ERRORS INFLUENCES SUBJECTIVE COGNITIVE DECLINE IN HEALTHY OLDER ADULTS
Rachel F. Buckley1,2, Robert Hester1, 1University of Melbourne, Melbourne, Australia; 2The Florey Institutes of Neurosciences and Mental Health, Melbourne, Australia. Contact e-mail: [email protected] Background: A critical element of human cognition is the capacity to adjust one’s behaviour subsequent to an error. Normal ageing has been associated with a progressive deterioration in conscious error awareness. This study examined whether gradual accumulation of undetected errors would relate to greater subjective concerns of cognitive decline. Methods: Thirty cognitively-normal (CN) adults (Mage¼71.1 years, range¼60-86 years) were administered a nonverbal memory measure (the CANTAB Paired Associates Learning paradigm), and a motor Go/No-go response inhibition task where participants make errors of which they were both aware and unaware. Participants filled out an SCD questionnaire (the Everyday Cognition battery), and the Geriatric Depression Scale. Results: Poorer error awareness was significantly related to greater SCD in the executive function domain (b¼-0.45, p¼.03), after taking into account age, depression, education level and non-verbal memory function. Poorer error awareness showed a trend with greater SCD in the memory domain, but did not pass the significance threshold (b¼-0.33, p¼.09). Error awareness was not related to age, education level, memory function, or depression, suggesting that variability in error awareness was not confounded by these factors. Conclusions: Mounting evidence supports the notion that SCD is a risk factor for Alzheimer’s disease (AD) in CN older adults. In particular, the literature has implicated subjective concerns in both the memory and executive function domains. The current study suggests that increasing concern of executive dysfunction is associated with decreasing error awareness in cognitively normal individuals. It is possible that accumulating, and unaccounted for, selfmade errors contribute to larger-scale executive functioning failures, which lead to executive function-specific SCD. Concerns of memory function only exhibited a trend relationship with error awareness, perhaps due to the small sample size (n ¼ 30). Error awareness is linked to neural activity in the anterior cingulate cortex; a part the default mode network which becomes dysfunctional early in AD. Our finding supports the notion that SCD in the executive domain are related to objective changes in cognitive processing. Executive function-related SCD has been previously related to b-amyloid burden, the role of b-amyloid burden should be investigated in the relationship between error awareness and SCD.
P3-211
DIFFERENTIAL RISK OF INCIDENT ALZHEIMER’S DISEASE DEMENTIA IN STABLE VERSUS UNSTABLE PATTERNS OF SUBJECTIVE COGNITIVE DECLINE
Michael Wagner1, Steffen Wolfsgruber2, Luca Kleineidam3, Alexander Koppara2, Steffi G. Riedel-Heller4, Wolfgang Maier1,3, Martin Scherer5, Frank Jessen1,6, 1German Center for Neurodegenerative Diseases, Bonn, Germany; 2DZNE, German Center for Neurodegenerative Diseases, Bonn, Germany; 3University of Bonn, Bonn, Germany; 4Leipzig
P713
University, Leipzig, Germany; 5Hamburg University Medical School, Hamburg, Germany; 6University of Cologne, Cologne, Germany. Contact e-mail: [email protected] Background: Cognitively normal elderly with Subjective Cognitive
Decline (SCD) have an increased risk to develop dementia, as suggested by many studies with a single cross-sectional measurement of SCD. However, because Alzheimer’s disease (AD) is a constantly progressing disease, and because the reliability of a single measurement of SCD may be limited, longitudinal assessment of SCD may contribute further information with regard to AD dementia risk. We hypothesized that individuals who repeatedly report SCD should have a higher risk of AD, as compared to those with an unstable pattern of SCD reports. Methods: We analyzed the data of 1990 participants from the General Practitioner-based, longitudinal AgeCoDe Study. Patients (mean age at baseline¼79.5 years) were personally interviewed both at baseline and at first follow-up 18 months later, and were cognitively normal at baseline (mean MMSE¼27.9). They were asked “Do you feel like your memory is becoming worse?” Possible answers were “no” (no SCD), “yes” (SCD without concerns), “yes that worries me” (SCD with concerns). Participants were classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n¼613), (b) inconsistent SCD (with SCD reported only at baseline, or only at follow-up 1, n¼637), (c) consistent SCD without worries (n¼610) or consistent SCD with worries (n¼110). Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status and depression estimated the risk of incident AD over up to 6 years for each group. Results: As compared to CO, inconsistent SCD had no significant risk increase for AD dementia (HR 1.42, 95% CI 0.896–2.25). In contrast, the AD dementia risk was doubled in consistent SCD without worries (HR 2.03, 95% CI 1.30-3.15, p < 0.002), and even higher in consistent SCD with worries (HR 3.72, 95% CI 2.10–6.50, p < 0.001). These results could be replicated with similar hazard ratios when using follow-up 1 to follow-up 2 response patterns for group definition. Conclusions: These findings suggest that longitudinal stability vs. instability is an important modifying factor of the association between SCD and AD dementia risk. This has implications both for clinical practice and research on SCD samples.
P3-212
DISTINCT RATES OF COGNITIVE DECLINE ASSOCIATED WITH NORMAL AGING
David Bergeron, Marie-Pierre Fortin, Michele Houde, Stephane Poulin, Louis Verret, Remi W. Bouchard, Robert Laforce, Jr., Clinique Interdisciplinaire de memoire du CHU de Quebec, Quebec, QC, Canada. Contact e-mail: [email protected] Background: The subtle interface between normal and pathological
aging has been a field of intense research lately. While much emphasis has been put on the characterization of mild cognitive impairment and patterns of cognitive decline within various dementing disorders, classic signature and biological underpinnings of cognitive changes associated with normal aging are still poorly understood. This holds great importance in deciphering the secret of successful aging and better distinguishing normal from diseased states. We sought to evaluate the decline in memory, visuospatial, executive and language functions associated with normal aging. Methods: As part of the validation of the ‘D epistage Cognitif de Quebec’ (DCQ), a novel cognitive screening test for atypical/complex dementias, 180 normal individuals from 51 to 88 years-old (mean 67) were tested. The DCQ is made of 5 distinct sections,
P714
Poster Presentations: P3
namely Memory, Visuospatial, Executive, Language and Behaviour. We cross-sectionally analyzed the scores within these domains as a function of age and generated ‘cognitive curves’ to estimate which domain shows the most significant age-related decline. Results: Among the five indices, executive functions were the most affected by aging (-0.71%/year), followed by memory (-0.44%/year) and visuospatial skills (0.33%). Language abilities were globally preserved in the different age groups (-0.26%/ year). Within the executive domain the Stroop Color-Word Test (-2.1%/year) was the most affected by aging followed by Verbal fluency (-1.2%/year). Of note, 82% of the 70- individuals succeeded at the Stroop (naming correctly 14 colors in 15 seconds), compared to only 42% of 70+ individuals. Conclusions: These results suggest that aging primarily affects executive functions such as interference inhibition and processing speed. Decline in cognitive screening tests over time due to failure in executive tests should therefore be interpreted with caution, as this may merely reflect normal aging.
(p<.0001 vs. RN5, p¼.20 vs. IFU). Age-related annual decline was 0.18 in RN5, 0.24 in IFU (p¼.34 vs. RN5), and 0.28 in DO (p¼.054 vs. RN5, p¼.52 vs. IFU). Similarly, Logical Memory I intercept was 21.8 in RN5, 19.5 in IFU (p<.0001 vs. RN5), and 19.4 in DO (p<.0001 vs. RN5, p¼.92 vs. IFU). Annual decline was 0.13 in RN5, 0.20 in DO (p¼0.25 vs. RN5), and 0.30 in IFU (p¼.02 vs. RN5, p¼.19 vs. DO). Conclusions: Overall episodic memory performance is relatively stable over time in nondemented older adults. The more striking differences are in the intercepts which may reflect many years of change. The robust normal group has the best mean performance and the slowest rate of decline. Subgroups of persons with insufficient follow up or who drop out could be on the trajectory to dementia, so these two groups had lower intercepts and had more rapid decline.
Figure 1. Estimated pFCSRT+IR Free Recall and Logical Memory I scores over years of age for the 5-year robust normal (RN5) group, the drop out (DO) group and the insufficient follow up (IFU) group.
P3-214
P3-213
ESTIMATING EPISODIC MEMORY WITHINSUBJECT DECLINE AMONG NONDEMENTED OLDER ADULTS: RESULTS FROM THE EINSTEIN AGING STUDY (EAS)
Wenzhu Mowrey1, Ellen Grober1, Molly E. Zimmerman1, Mindy J. Katz1, Charles B. Hall1, Martin J. Sliwinski2, Richard B. Lipton1, 1Albert Einstein College of Medicine, Bronx, NY, USA; 2Pennsylvania State University, University Park, PA, USA. Contact e-mail: [email protected] Background: We aimed to estimate within-subject age-related decline in episodic memory among nondemented older adults. Methods: The picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR; range: 048) and the Logical Memory I subtest of the Wechsler Memory Scale–Revised (range: 050) were administered annually to adults initially aged 7090. This study included 1827 subjects who were free of dementia at baseline and had follow up data up to 5 years. Persons developing incident dementia within 5 years (n¼93) were excluded. Final follow up status was used to define the following three subgroups: Robust normal (RN5; n¼438) included subjects who had remained dementia free for 5 years; Drop out group (DO; n¼789) included subjects who withdrew from the study or died within 5 years; Insufficient follow up group (IFU; n¼507) included subjects who were followed up <5 years and were still being actively followed. Linear mixed models with random intercept and random slope were used to estimate mean memory performance at age 80, i.e. intercepts, and age slopes. Results: The pFCSRT+IR free recall intercept was estimated to be 30.9 in RN5, 28.9 in IFU (p<.0001 vs. RN5), 28.4 in DO
LONGITUDINAL RELATIONS AMONG WALKING ACTIVITY, GAIT SPEED, AND COGNITIVE FUNCTIONING OVER A 10-YEAR PERIOD: FINDINGS FROM THE HEALTH, AGING, AND BODY COMPOSITION STUDY
John R. Best1,2, Teresa Liu-Ambrose1,2, Robert M. Boudreau3, Hilsa N. Ayonayon4, Suzanne Satterfield5, Eleanor M. Simonsick6, Stephanie Studenski6, Kristine Yaffe7, Anne B. Newman3, Caterina Rosano3, 1Djavad Mowafaghian Centre for Brain Health, Vancouver, BC, Canada; 2University of British Columbia, Vancouver, BC, Canada; 3University of Pittsburgh, Pittsburgh, PA, USA; 4University of California San Francisco, San Francisco, CA, USA; 5University of Tennessee Health Science Centre, Memphis, TN, USA; 6National Institutes of Health, Baltimore, MD, USA; 7University of California, San Francisco, San Francisco, CA, USA. Contact e-mail: [email protected] Background: Previous studies have linked both physical activity and functional mobility to future changes in cognition among older adults. However, few studies have assessed all three constructs longitudinally in order to determine their interrelations over time and whether physical activity and functional mobility have independent associations with cognition. This study examined self-reported time spent walking, gait speed, and general cognition as measured by the Modified Mini Mental State Test (3MS) over a ten-year period. Methods: 2527 older adults (mean age ¼ 73.5 years at year 1) with complete data at year 1 from the Health ABC study, a biracial cohort were included. Self-reported time spent walking (mins/week), 3MS, and gait speed over a 20-meter walk were assessed at several time points from year 1 to 10. Joint longitudinal models were constructed using Mplus 7.3 and maximum likelihood estimation with robust standard errors. Covariates included clinical site, age, education, race, BMI, sex, smoking and drinking status, and prevalent diabetes, cerebrovascular and cardiovascular disease. Results: A covariate-adjusted latent growth curve model examined the longitudinal relationships among walking