- Email: [email protected]
Interrelationships between cognitive and physical impairment
P830
Poster Presentations: P4
Francisco, CA, USA; 2University of Gothenburg, Gothenburg, Sweden; 3 UCSF, San Francisco, CA, USA; 4San Francisco Veteran’s Administration Medical Center, San Francisco, CA, USA; 5University of California San Francisco, San Francisco, CA, USA; 6University of California, San Diego, La Jolla, CA, USA; 7University of California, San Diego, La Jolla, CA, USA. Contact e-mail: [email protected] Background: Our goal was to find the combination of candidate
biomarkers and cognitive endpoints to maximize statistical power and minimize cost of clinical trials of healthy elders at risk for cognitive decline due to Alzheimer’s disease. Methods: 412 cognitively-normal participants were followed over 7 years. Nonlinear methods were used to estimate the longitudinal trajectories of several cognitive outcomes including delayed memory recall, executive function, processing speed, and several cognitive composites by subgroups selected on the basis of biomarkers, including APOE-ε4 allele carriers, CSF biomarkers (Ab42, total tau and phosphorylated tau), and those with small hippocampi. Results: Derived cognitive composites combining ADAS-cog scores with additional delayed memory recall and executive function components captured decline more robustly across biomarker groups than any measure of a single cognitive domain or ADAS-cog alone. Substantial increases in power resulted when including only participants positive for three or more biomarkers in simulations of clinical trials. Conclusions: Clinical trial power may be improved by selecting participants on the basis of amyloid and neurodegeneration biomarkers and carefully tailoring primary cognitive endpoints to reflect the expected decline specific to these individuals.
P4-136
INTERRELATIONSHIPS BETWEEN COGNITIVE AND PHYSICAL IMPAIRMENT
Magdalena I. Tolea1, James E. Galvin1, John C. Morris2, 1NYU Langone Medical Center, New York, NY, USA; 2Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA. Contact e-mail: [email protected] Background: Cognitive and physical impairments are common,
coexisting chronic conditions that have complex, and often bidirectional relationships in which presence of one has the potential to
initiate, synergize, or result from the other. Understanding how the processes that lead to dementia and physical disability interrelate at early stages of dysfunction affords the opportunity for preventative or restorative interventions. We evaluated both crosssectional and longitudinal associations between cognitive and physical function to better understand the directionality of the relationships. Methods: Data from 2 studies of cognitive and functional aging were used: a longitudinal study conducted at the Knight ADRC at Washington University in St. Louis (766 individuals followed up for up to 8 years) and a cross-sectional study conducted at NYU (272 individuals). Both studies enrolled community-dwelling individuals over the age of 50 who underwent cognitive and physical assessments tapping into global (e.g., CDR-SB, MoCA, AD8) and individual cognitive domains (e.g., Naming, Trailmaking) and physical performance (PP) measures (e.g., grip-strength (GS), muscle mass (MM)). Formal diagnoses were available in the longitudinal study, while the cross-sectional studies established impaired vs. non-impaired. Associations were investigated with regression analysis techniques. Results: GS impairment was associated with lower MoCA (B¼-2.0, p¼0.011); when combined with low MM the likelihood of dual cognitive-physical impairment increased. The effect of low GS on global cognition doubled when poor PP was also present (indicator of later stage physical impairment; B¼-3.77, p<0.001). However, while the rate of decline in cognitive (various measures; p<0.001) and physical (slope¼-1.22, p<0.001) performance was sharper in those with baseline cognitive impairment, baseline physical impairment had no significant impact on either cognitive or physical decline. Cross-sectionally, GS impacted MoCA through poor PP (indirect effect¼0.018, p<0.01). When type of dementia was considered, vascular dementia declined faster than controls (slope¼-2.70, p<0.001) or AD (slope¼-2.18, p<0.001). Conclusions: Earlier indicators of physical dysfunction (i.e. low GS) are associated with cognitive impairment with evidence for a dose-response operating in the direction of cognitive-to-physical impairment (although the reverse cannot be ruled out). Targeted interventions to maintain physical functionality and strength in individuals with dementia, particularly vascular dementia may mitigate future decline and disability. P4-137
N-TERMINAL PRO-B TYPE NATRIURETIC PEPTIDE AND MILD COGNITIVE IMPAIRMENT IN THE GENERAL POPULATION: RESULTS OF THE HEINZ NIXDORF RECALL STUDY
Martha Dlugaj1, Kaffer Kara2, Amir-Abbas Mahabadi3, Angela Winkler3, Hagen K€alsch4, Till Neumann5, Nico Dragano6, Susanne Moebus7, KarlHeinz J€ockel7, Raimund Erbel4, Christian Weimar1and on behalf of the Heinz Nixdorf Recall Study Group1Department of Neurology, University Hospital Essen, Essen, Germany; 2St. Josef Hospital, Bochum, Germany; 3 University Hospital Essen, Essen, Germany; 4Clinic of Cardiology, West German Heart and Vascular Centre, University Hospital of Essen, Essen, Germany; 5University Hospital Essen, Essen, Germany; 6University of D€usseldorf, D€usseldorf, Germany; 7Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany. Contact e-mail: [email protected] Background: N-terminal pro-B type natriuretic peptide (NTproBNP) is a marker of cardiac stress and is linked with cardiovascular diseases. Although, an association between cognitive impairment and cardiovascular diseases is well established, little is known about the relationship of NT-proBNP level and cognitive functioning, especially mild cognitive impairment (MCI). Therefore, the aim of the present study was to investigate the cross-sectional association of plasma NT-proBNP
Poster Presentations: P4
Francisco, CA, USA; 2University of Gothenburg, Gothenburg, Sweden; 3 UCSF, San Francisco, CA, USA; 4San Francisco Veteran’s Administration Medical Center, San Francisco, CA, USA; 5University of California San Francisco, San Francisco, CA, USA; 6University of California, San Diego, La Jolla, CA, USA; 7University of California, San Diego, La Jolla, CA, USA. Contact e-mail: [email protected] Background: Our goal was to find the combination of candidate
biomarkers and cognitive endpoints to maximize statistical power and minimize cost of clinical trials of healthy elders at risk for cognitive decline due to Alzheimer’s disease. Methods: 412 cognitively-normal participants were followed over 7 years. Nonlinear methods were used to estimate the longitudinal trajectories of several cognitive outcomes including delayed memory recall, executive function, processing speed, and several cognitive composites by subgroups selected on the basis of biomarkers, including APOE-ε4 allele carriers, CSF biomarkers (Ab42, total tau and phosphorylated tau), and those with small hippocampi. Results: Derived cognitive composites combining ADAS-cog scores with additional delayed memory recall and executive function components captured decline more robustly across biomarker groups than any measure of a single cognitive domain or ADAS-cog alone. Substantial increases in power resulted when including only participants positive for three or more biomarkers in simulations of clinical trials. Conclusions: Clinical trial power may be improved by selecting participants on the basis of amyloid and neurodegeneration biomarkers and carefully tailoring primary cognitive endpoints to reflect the expected decline specific to these individuals.
P4-136
INTERRELATIONSHIPS BETWEEN COGNITIVE AND PHYSICAL IMPAIRMENT
Magdalena I. Tolea1, James E. Galvin1, John C. Morris2, 1NYU Langone Medical Center, New York, NY, USA; 2Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA. Contact e-mail: [email protected] Background: Cognitive and physical impairments are common,
coexisting chronic conditions that have complex, and often bidirectional relationships in which presence of one has the potential to
initiate, synergize, or result from the other. Understanding how the processes that lead to dementia and physical disability interrelate at early stages of dysfunction affords the opportunity for preventative or restorative interventions. We evaluated both crosssectional and longitudinal associations between cognitive and physical function to better understand the directionality of the relationships. Methods: Data from 2 studies of cognitive and functional aging were used: a longitudinal study conducted at the Knight ADRC at Washington University in St. Louis (766 individuals followed up for up to 8 years) and a cross-sectional study conducted at NYU (272 individuals). Both studies enrolled community-dwelling individuals over the age of 50 who underwent cognitive and physical assessments tapping into global (e.g., CDR-SB, MoCA, AD8) and individual cognitive domains (e.g., Naming, Trailmaking) and physical performance (PP) measures (e.g., grip-strength (GS), muscle mass (MM)). Formal diagnoses were available in the longitudinal study, while the cross-sectional studies established impaired vs. non-impaired. Associations were investigated with regression analysis techniques. Results: GS impairment was associated with lower MoCA (B¼-2.0, p¼0.011); when combined with low MM the likelihood of dual cognitive-physical impairment increased. The effect of low GS on global cognition doubled when poor PP was also present (indicator of later stage physical impairment; B¼-3.77, p<0.001). However, while the rate of decline in cognitive (various measures; p<0.001) and physical (slope¼-1.22, p<0.001) performance was sharper in those with baseline cognitive impairment, baseline physical impairment had no significant impact on either cognitive or physical decline. Cross-sectionally, GS impacted MoCA through poor PP (indirect effect¼0.018, p<0.01). When type of dementia was considered, vascular dementia declined faster than controls (slope¼-2.70, p<0.001) or AD (slope¼-2.18, p<0.001). Conclusions: Earlier indicators of physical dysfunction (i.e. low GS) are associated with cognitive impairment with evidence for a dose-response operating in the direction of cognitive-to-physical impairment (although the reverse cannot be ruled out). Targeted interventions to maintain physical functionality and strength in individuals with dementia, particularly vascular dementia may mitigate future decline and disability. P4-137
N-TERMINAL PRO-B TYPE NATRIURETIC PEPTIDE AND MILD COGNITIVE IMPAIRMENT IN THE GENERAL POPULATION: RESULTS OF THE HEINZ NIXDORF RECALL STUDY
Martha Dlugaj1, Kaffer Kara2, Amir-Abbas Mahabadi3, Angela Winkler3, Hagen K€alsch4, Till Neumann5, Nico Dragano6, Susanne Moebus7, KarlHeinz J€ockel7, Raimund Erbel4, Christian Weimar1and on behalf of the Heinz Nixdorf Recall Study Group1Department of Neurology, University Hospital Essen, Essen, Germany; 2St. Josef Hospital, Bochum, Germany; 3 University Hospital Essen, Essen, Germany; 4Clinic of Cardiology, West German Heart and Vascular Centre, University Hospital of Essen, Essen, Germany; 5University Hospital Essen, Essen, Germany; 6University of D€usseldorf, D€usseldorf, Germany; 7Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany. Contact e-mail: [email protected] Background: N-terminal pro-B type natriuretic peptide (NTproBNP) is a marker of cardiac stress and is linked with cardiovascular diseases. Although, an association between cognitive impairment and cardiovascular diseases is well established, little is known about the relationship of NT-proBNP level and cognitive functioning, especially mild cognitive impairment (MCI). Therefore, the aim of the present study was to investigate the cross-sectional association of plasma NT-proBNP