INS NYC 2024 Program

Symposium	Symposia 15 Program Schedule 02/17/2024 10:45 am - 12:10 pm Room: Broadway Ballroom Symposia 15: Risk Factors for Cognitive Decline Among Representative Samples: Baseline Findings from the U.S. POINTER Study Simposium #1 Development and validation of the modified Neuropsychological Test Battery (PmNTB) and associations with cardiovascular and Alzheimer’s disease biomarkers in the U.S. POINTER study Kathryn Papp, Harvard Medical School, Boston, United States Tiia Ngandu, Finnish Institute for Health and Welfare, Helsinki, United States Amber Thro, Wake Forest, Winston Salem, United States Brad Caudle, Wake Forest, Winston Salem, United States Marjorie Howard, Wake Forest, Winston Salem, United States Theresa Harrison, Berkeley, Berkeley, United States Susan Landau, Berkeley, Berkeley, United States Heather Snyder, Alzheimer's Association, Chicago, United States Mark Espeland, Wake Forest, Winston Salem, United States Laura Baker, Wake Forest, Winston Salem, United States Category: Aging Keyword 1: clinical trials Keyword 2: treatment outcome Objective: U.S. POINTER will determine whether lifestyle interventions can protect cognitive health in at-risk older adults. The primary outcome, a modified Neuropsychological Test Battery (PmNTB), was developed to allow for cognitive outcome harmonization with its forerunner, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) and other secondary prevention trials. Here we describe the development of the PmNTB, its validation in the baseline U.S. POINTER sample, and initial associations with cardiovascular and Alzheimer’s disease biomarkers. Participants and Methods: POINTER is a Phase 3, multicenter, randomized 2-year clinical trial of two lifestyle interventions varying in intensity and format, in older adults at increased risk for cognitive decline and dementia. The PmNTB includes performance across 7 cognitive tests and is computed as the mean of three domain-specific composites: Episodic Memory, Processing Speed, and Executive Function. Individual measures contributing to the Episodic Memory Composite include: the Free and Cued Selective Reminding Test, Story Recall, and Visual Paired Associates. The Processing Speed Composite includes Trail Making Test and Digit Symbol Substitution Test. The Executive Function Composite is comprised of Number Span, Word Fluency, Trail Making Test, and Digit Symbol Substitution Test. To assess battery validity, PmNTB was assessed in relation to age and clinical status (Clinical Dementia Rating-CDR). Performance on the PmNTB was also examined in relation to cardiovascular risk (i.e., the Framingham-FHS risk score) and amyloid status (florbetaben PET; cortical summary SUVR>1.08 defines amyloid positive) and entorhinal cortex tau (flortaucipir PET) in a subset of the sample (n=795). PmNTB convergent validity was explored through correlations with established cognitive composites (i.e., FINGER NTB, Preclinical Alzheimer’s Cognitive Composite-PACC-5). Results: 2111 participants have completed the baseline assessment (Mean Age=68.2±5.2 years; 68.8% female, 31.1% from underrepresented groups, mean MMSE=28.9± 1.3). A total of 79.9% of participants have a Global CDR of 0 and 20.1% have a Global CDR of 0.5. After adjusting for education, race/ethnicity, and sex, each year of age was associated with -0.064 z-scores (95%CI=-0.071,-0.056, p<0.001) on the PmNTB. Likewise, a global CDR score of 0.5 (questionable dementia) was associated with worse PmNTB (-0.549 z-scores) compared with a CDR Score of 0 (no dementia) (-0.134 z-scores). The PmNTB was correlated with the FINGER NTB (r=0.858, p<0.001) and the PACC-5 (r=0.876, p<0.001). Worse performance on the PmNTB was associated with greater cerebrovascular risk (FHS risk score; r=-0.251, p<0.001) and greater entorhinal tau (r=-0.12, p<0.001) but not global amyloid (p=0.271). Conclusions: The PmNTB is a valid measure of cognitive functioning, capturing age-related cognitive decrements and tracking with functional status and biomarker risk and exhibits convergent validity with established cognitive outcomes.

Symposium

02/17/2024
10:45 am - 12:10 pm
Room: Broadway Ballroom

Symposia 15: Risk Factors for Cognitive Decline Among Representative Samples: Baseline Findings from the U.S. POINTER Study

Simposium #1

Development and validation of the modified Neuropsychological Test Battery (PmNTB) and associations with cardiovascular and Alzheimer’s disease biomarkers in the U.S. POINTER study

Kathryn Papp, Harvard Medical School, Boston, United States
Tiia Ngandu, Finnish Institute for Health and Welfare, Helsinki, United States
Amber Thro, Wake Forest, Winston Salem, United States
Brad Caudle, Wake Forest, Winston Salem, United States
Marjorie Howard, Wake Forest, Winston Salem, United States
Theresa Harrison, Berkeley, Berkeley, United States
Susan Landau, Berkeley, Berkeley, United States
Heather Snyder, Alzheimer's Association, Chicago, United States
Mark Espeland, Wake Forest, Winston Salem, United States
Laura Baker, Wake Forest, Winston Salem, United States

Category: Aging

Keyword 1: clinical trials
Keyword 2: treatment outcome

Objective:

U.S. POINTER will determine whether lifestyle interventions can protect cognitive health in at-risk older adults. The primary outcome, a modified Neuropsychological Test Battery (PmNTB), was developed to allow for cognitive outcome harmonization with its forerunner, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) and other secondary prevention trials. Here we describe the development of the PmNTB, its validation in the baseline U.S. POINTER sample, and initial associations with cardiovascular and Alzheimer’s disease biomarkers.

Participants and Methods:

POINTER is a Phase 3, multicenter, randomized 2-year clinical trial of two lifestyle interventions varying in intensity and format, in older adults at increased risk for cognitive decline and dementia. The PmNTB includes performance across 7 cognitive tests and is computed as the mean of three domain-specific composites: Episodic Memory, Processing Speed, and Executive Function. Individual measures contributing to the Episodic Memory Composite include: the Free and Cued Selective Reminding Test, Story Recall, and Visual Paired Associates. The Processing Speed Composite includes Trail Making Test and Digit Symbol Substitution Test. The Executive Function Composite is comprised of Number Span, Word Fluency, Trail Making Test, and Digit Symbol Substitution Test. To assess battery validity, PmNTB was assessed in relation to age and clinical status (Clinical Dementia Rating-CDR). Performance on the PmNTB was also examined in relation to cardiovascular risk (i.e., the Framingham-FHS risk score) and amyloid status (florbetaben PET; cortical summary SUVR>1.08 defines amyloid positive) and entorhinal cortex tau (flortaucipir PET) in a subset of the sample (n=795). PmNTB convergent validity was explored through correlations with established cognitive composites (i.e., FINGER NTB, Preclinical Alzheimer’s Cognitive Composite-PACC-5).

Results:

2111 participants have completed the baseline assessment (Mean Age=68.2±5.2 years; 68.8% female, 31.1% from underrepresented groups, mean MMSE=28.9± 1.3). A total of 79.9% of participants have a Global CDR of 0 and 20.1% have a Global CDR of 0.5. After adjusting for education, race/ethnicity, and sex, each year of age was associated with -0.064 z-scores (95%CI=-0.071,-0.056, p<0.001) on the PmNTB. Likewise, a global CDR score of 0.5 (questionable dementia) was associated with worse PmNTB (-0.549 z-scores) compared with a CDR Score of 0 (no dementia) (-0.134 z-scores). The PmNTB was correlated with the FINGER NTB (r=0.858, p<0.001) and the PACC-5 (r=0.876, p<0.001). Worse performance on the PmNTB was associated with greater cerebrovascular risk (FHS risk score; r=-0.251, p<0.001) and greater entorhinal tau (r=-0.12, p<0.001) but not global amyloid (p=0.271).

Conclusions:

The PmNTB is a valid measure of cognitive functioning, capturing age-related cognitive decrements and tracking with functional status and biomarker risk and exhibits convergent validity with established cognitive outcomes.