@article {829, title = {Coronary artery calcium: associations with brain magnetic resonance imaging abnormalities and cognitive status.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Apr}, pages = {609-15}, abstract = {

OBJECTIVES: To evaluate the association between coronary atherosclerosis and subclinical brain magnetic resonance imaging (MRI) abnormalities and between coronary atherosclerosis and abnormal cognitive function (dementia/mild cognitive impairment).

DESIGN: Cross-sectional.

SETTING: The Cardiovascular Health Study (CHS), an epidemiological study of risk factors for cardiovascular disease in older adults.

PARTICIPANTS: Four hundred nine men and women, mean age 79, recruited from the Pittsburgh center of the CHS.

MEASUREMENTS: Coronary atherosclerosis was defined according to the level of coronary artery calcification (CAC), as measured using electronic beam tomography. Subclinical brain MRI abnormalities included ventricular enlargement, white matter hyperintensities, and number of subcortical brain infarcts. Brain MRI and CAC measurements were performed between 1998 and 2000 at the Pittsburgh center of the CHS. Prevalence of brain MRI abnormalities and abnormal cognitive status were examined across quartiles of the CAC score, before and after controlling for age. Multivariate logistic regression models were used to assess whether CAC level was associated with abnormalities of brain MRI or abnormal cognitive status.

RESULTS: Older adults with high CAC scores were more likely to have more-severe brain MRI abnormalities, including subcortical infarction and high white matter hyperintensities. The associations between CAC and ventricular enlargement showed a similar but not significant trend. The presence of any of the MRI abnormalities attenuated the association between CAC and abnormal cognitive status.

CONCLUSION: Older adults with higher levels of CAC were more likely to have more-severe brain MRI abnormalities and abnormal cognitive status.

}, keywords = {Aged, Brain, Calcinosis, Cognition Disorders, Coronary Artery Disease, Cross-Sectional Studies, Dementia, Female, Humans, Logistic Models, Magnetic Resonance Imaging, Male, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53208.x}, author = {Rosano, Caterina and Naydeck, Barbara and Kuller, Lewis H and Longstreth, William T and Newman, Anne B} } @article {830, title = {Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Apr}, pages = {649-54}, abstract = {

OBJECTIVES: To determine whether severity of subclinical brain magnetic resonance imaging (MRI) abnormalities predicts incident self-reported physical impairment or rate of decline in motor performance.

DESIGN: Longitudinal analysis, average follow-up time: 4.0 years.

SETTING: Cardiovascular Health Study (CHS).

PARTICIPANTS: CHS participants with modified Mini-Mental State Examination (3MS) score of 80 or greater, no self-reported disability, no history of stroke, and at least one assessment of mobility (n=2,450, mean age=74.4).

MEASUREMENTS: Brain MRI abnormalities (ventricular enlargement, white matter hyperintensities, subcortical and basal ganglia small brain infarcts), self-reported physical impairment (difficulty walking half a mile or with one or more activities of daily living), and motor performance (gait speed, timed chair stand).

RESULTS: After adjusting for demographics, cardiovascular risk factors, and diseases, risk of incident self-reported physical impairment was 35\% greater for those with severe ventricular enlargement than for those with minimal ventricular enlargement, 22\% greater for those with moderate white matter hyperintensities than for those with minimal white matter hyperintensities, and 26\% greater for participants with at least one brain infarct than for those with no infarcts. Those with moderate to severe brain abnormalities experienced faster gait speed decline (0.02 m/s per year) than those with no MRI abnormalities (0.01 m/s per year). Further adjustment for incident stroke, incident dementia, and 3MS score did not substantially attenuate hazard ratios for incident self-reported physical impairment or coefficients for decline in gait speed.

CONCLUSION: Subclinical structural brain abnormalities in high-functioning older adults can increase the risk of developing physical disabilities and declining in motor performance.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Brain, Female, Follow-Up Studies, Gait, Humans, Incidence, Magnetic Resonance Imaging, Male, Proportional Hazards Models, Psychomotor Disorders, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53214.x}, author = {Rosano, Caterina and Kuller, Lewis H and Chung, Hyoju and Arnold, Alice M and Longstreth, William T and Newman, Anne B} } @article {866, title = {Quantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults.}, journal = {Neuroepidemiology}, volume = {26}, year = {2006}, month = {2006}, pages = {52-60}, abstract = {

Abnormal gait in high-functioning older adults may indicate underlying subtle structural brain abnormalities. We tested the hypothesis that temporal and spatial parameters of gait, including speed, stride length and double support time, are cross-sectionally associated with white matter hyperintensity, subcortical infarcts or brain atrophy on brain MRI. We examined 321 men and women (mean age = 78.3) participating to the Cardiovascular Health Study who were free of dementia or stroke at the time of the gait assessment. Analyses were set with gait as independent variable and brain MRIs as dependent variables. Gait measures were determined from the footfalls recorded on a 4-meter-long instrumented walking surface, the GaitMat II. Brain MRIs were examined for the presence of white matter hyperintensity (WMG, graded from 0 to 9), brain infarcts (predominantly subcortical) and ventricular enlargement (graded from 0 to 9). Slower gait, shorter stride length and longer double support times were associated with greater prevalence of white matter grade > or =3 (p = 0.02), and at least 1 brain infarct (p = 0.04) independent of age. In multivariate logistic regression models adjusted for demographics and clinical cardiovascular diseases, those with gait speed <1.02 m/s were more likely to have WMG > or =3 and at least 1 brain infarct, compared with those with faster gait - odds ratio (OR): 2.85, 95\% confidence interval (95\% CI): 1.35, 6.02, and OR: 2.09, 95\% CI: 1.04, 4.19. Shorter stride length was also associated with greater probability of having at least 1 brain infarct (gait stride <0.88 vs. >1.10 m: OR: 3.20, 95\% CI: 1.49, 6.88), while longer double support times were associated with a greater probability of having WMG > or =3 (double support time >0.19 vs. <0.14 s: OR: 2.3, 95\% CI: 1.1, 4.7) independent of demographics and clinical cardiovascular diseases. Gait parameters were not significantly associated with ventricular grade. In summary, in this group of high-functioning older adults, poorer gait speed, shorter stride and longer double support time are associated with high white matter disease and subclinical strokes.

}, keywords = {Aged, Brain, Cerebral Infarction, Cerebral Ventricles, Cerebrovascular Disorders, Cohort Studies, Dementia, Female, Gait, Gait Disorders, Neurologic, Humans, Hypertension, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Stroke, United States}, issn = {0251-5350}, doi = {10.1159/000089240}, author = {Rosano, Caterina and Brach, Jennifer and Longstreth, William T and Newman, Anne B} } @article {960, title = {Focal atrophy and cerebrovascular disease increase dementia risk among cognitively normal older adults.}, journal = {J Neuroimaging}, volume = {17}, year = {2007}, month = {2007 Apr}, pages = {148-55}, abstract = {

BACKGROUND AND PURPOSE: This study investigated the association of medial temporal lobe (MTL) atrophy and cerebrovascular disease (white matter hyperintensities [WMH], subclinical infarcts) with the risk of developing Alzheimer{\textquoteright}s disease (AD) among cognitively normal older adults.

METHODS: Risk of developing AD was examined for 155 cognitively normal older adults (77.4 years, 60\% women, 81\% white). The MTL volumes and the presence of WMH and of subclinical infarcts were determined from brain magnetic resonance imaging (MRI) at the beginning of the study. Follow-up cognitive evaluations (average 4.3 years) identified those who developed AD.

RESULTS: The presence of either MTL atrophy or subclinical infarcts was independently and significantly associated with a greater risk to develop AD (OR [95\% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1], respectively). In addition, those participants with both MTL atrophy and at least one brain infarct had a 7-fold increase in the risk of developing AD (OR [95\% CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions.

CONCLUSIONS: In cognitively normal older adults, markers of neurodegeneration (as reflected by MTL atrophy) and of cerebrovascular disease (as reflected by infarcts on MRI) independently contribute to the risk to develop AD.

}, keywords = {Aged, Alzheimer Disease, Analysis of Variance, Atrophy, Cerebrovascular Disorders, Cognition, Female, Humans, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Temporal Lobe, United States}, issn = {1051-2284}, doi = {10.1111/j.1552-6569.2007.00093.x}, author = {Rosano, Caterina and Aizenstein, Howard J and Wu, Minjie and Newman, Anne B and Becker, James T and Lopez, Oscar L and Kuller, Lewis H} } @article {1002, title = {Gait variability is associated with subclinical brain vascular abnormalities in high-functioning older adults.}, journal = {Neuroepidemiology}, volume = {29}, year = {2007}, month = {2007}, pages = {193-200}, abstract = {

BACKGROUND: Gait variability is an index of how much gait parameters, such as step length, change from one step to the next. Gait variability increases with age and in individuals affected by cortical and subcortical neurodegenerative conditions, and it is associated with falls and incident mobility disability. The brain anatomical correlates of gait variability have not been studied in high-functioning community-dwelling older adults.

METHODS: Gait variability and brain MRIs were assessed in a cohort of 331 men and women (mean age = 78.3 years) free from stroke, dementia or Parkinson{\textquoteright}s disease. Gait variability was computed for spatial parameters (step length and step width) and for temporal parameters (stance time). Subclinical brain vascular abnormalities were measured on brain MRIs as infarcts and white matter hyperintensities.

RESULTS: Greater variability of step length was associated with greater prevalence of infarcts, including infarcts in the basal ganglia, and with greater white matter hyperintensities severity, independent of age, gender, cognitive function and cardiovascular disease. Weaker associations were found between the other variability measures and the MRI measures.

CONCLUSION: In this group of older adults free from neurodegenerative diseases, a greater variability of step length was associated with greater burden of subclinical brain vascular abnormalities as defined by MRI.

}, keywords = {Accidental Falls, Activities of Daily Living, Aged, Aged, 80 and over, Basal Ganglia Cerebrovascular Disease, Brain, Cerebral Infarction, Comorbidity, Female, Gait Disorders, Neurologic, Geriatric Assessment, Health Surveys, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mobility Limitation, Neurodegenerative Diseases, Neurologic Examination, Risk Factors, United States}, issn = {1423-0208}, doi = {10.1159/000111582}, author = {Rosano, Caterina and Brach, Jennifer and Studenski, Stephanie and Longstreth, W T and Newman, Anne B} } @article {988, title = {A regions-of-interest volumetric analysis of mobility limitations in community-dwelling older adults.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {62}, year = {2007}, month = {2007 Sep}, pages = {1048-55}, abstract = {

BACKGROUND: In community-dwelling older adults, greater mobility impairment is associated with greater burden of diffuse brain structural abnormalities, such as higher white matter hyperintensities. This study examined the association between gray matter volumes of regions related to motor control, gait, and balance and whether this association is independent of burden of white matter hyperintensities.

METHODS: A random sample of 327 participants of the Cardiovascular Health Study (78.3 +/- 4.1 years old, 57\% women) contributed brain magnetic resonance imaging (MRI) and mobility data. A brain imaging automated method measured gray matter volume in cerebellum, basal ganglia, and prefrontal and parietal cortex in both hemispheres. Gait speed was measured while walking 15 feet at usual pace. Standing balance was assessed by timing tandem stance. Associations between each region{\textquoteright}s volume and gait speed or balance were measured before and after adjustment for demographics, head size, cardiovascular risk factors, and 0-9 grading scores of white matter hyperintensities.

RESULTS: Smaller left cerebellum and left prefrontal regions were associated with slower gait, independently of covariates and of white matter hyperintensities. Smaller right putamen, right posterior superior parietal cortex, and both left and right cerebellum were associated with balance difficulty, independently of covariates and white matter hyperintensities.

CONCLUSIONS: Smaller gray matter volumes in regions crucial for motor control are associated with slower gait and poorer balance, and the association appears to be independent of other diffuse brain abnormalities such as white matter hyperintensities.

}, keywords = {Aged, Aged, 80 and over, Aging, Brain, Female, Gait, Humans, Magnetic Resonance Imaging, Male, Mobility Limitation, Postural Balance}, issn = {1079-5006}, doi = {10.1093/gerona/62.9.1048}, author = {Rosano, Caterina and Aizenstein, Howard J and Studenski, Stephanie and Newman, Anne B} } @article {1054, title = {Anemia is associated with the progression of white matter disease in older adults with high blood pressure: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Oct}, pages = {1867-72}, abstract = {

OBJECTIVES: To investigate whether anemia predicts worsening white matter hyperintensities (WMHs) in older community-dwellers.

DESIGN: Prospective cohort study.

SETTING: Older community-dwellers.

PARTICIPANTS: One thousand eight hundred forty-six Cardiovascular Health Study (CHS) participants (mean age 73.7 +/- 4.4, 41\% male, 15.6\% African American).

MEASUREMENTS: Participants had hemoglobin measured and brain magnetic resonance imaging (MRI) in 1992/93 and a second brain MRI in 1997/98. Anemia was defined according to World Health Organization criteria (hemoglobin <12 g/dL in women and <13 g/dL in men). Worsening WMHs were determined according to standardized side-by-side readings.

RESULTS: After 5 years, WMHs worsened in 517 participants (28\%). Progression was not associated with anemia in the whole sample, in sex or race strata, or in other prespecified subgroups (participants with renal dysfunction or diabetes mellitus), except in participants with high blood pressure (>or=140/90 mmHg). Of the 678 participants with high blood pressure, those with anemia (10.5\%) had a 1.79 times greater risk of WMHs worsening (95\% confidence interval=1.06-2.98; P for interaction between anemia and high blood pressure=.01) independent of demographics, baseline WMHs, cardiovascular risk factors and comorbidities, medications, renal function, inflammation, and incident stroke (logistic regression models). There was no greater risk in participants with anemia with normal blood pressure.

CONCLUSION: Anemia may contribute to worsening of WMHs in older adults with high blood pressure.

}, keywords = {Aged, Anemia, Brain, Cardiovascular Diseases, Disease Progression, Female, Humans, Hypertension, Leukoaraiosis, Magnetic Resonance Imaging, Male}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01950.x}, author = {Inzitari, Marco and Studenski, Stephanie and Rosano, Caterina and Zakai, Neil A and Longstreth, William T and Cushman, Mary and Newman, Anne B} } @article {1049, title = {Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Sep}, pages = {1618-25}, abstract = {

OBJECTIVES: To determine whether, in well-functioning older adults, a lower score on the Digit Symbol Substitution Test (DSST) and slower gait are associated with greater risk of mortality and of developing incident disability independent of other risk factors, including brain structural abnormalities (white matter hyperintensities, brain infarcts, ventricular enlargement) and whether the combination of varying levels of DSST score and gait speed are associated with a greater risk of mortality and disability than low DSST or slow gait alone.

DESIGN: Observational cohort study.

SETTING: Community.

PARTICIPANTS: Three thousand one hundred fifty-six (43\% men, 29\% black, mean age 70.4) participants in the Cardiovascular Health Study (CHS), free from stroke and physical disability and with a modified Mini-Mental State Examination (3MS) score of 80 or higher.

MEASUREMENTS: Total mortality and incident disability (self-report of any difficulty performing one or more of the six activities of daily living) ascertained over a median follow-up time of 8.4 years.

RESULTS: By the end of follow-up, 704 participants had died and 1,096 had incident disability. In Cox proportional hazards models adjusted for age, sex, race, education, cardiovascular disease, and brain magnetic resonance imaging abnormalities, lower DSST score and slower gait remained significantly associated with greater risk of mortality and of incident disability. Mortality rates were higher in those who had both low DSST score (<27 points) and slow gait (speed <1.0 m/s) than in those who had only low DSST score, only slow gait, or neither (rates per 1,000 person years (p-y): 61.2, 42.8, 20.8, and 16.3, respectively). A similar risk gradient was observed for incident disability (82.0, 57.9, 47.9, and 36.0/1,000 p-y, respectively).

CONCLUSION: In well-functioning older adults, low DSST score and slow gait, alone or in combination, could be risk factors for mortality and for developing disability, independent of other risk factors, including measures of brain integrity.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Analysis of Variance, Atrophy, Brain, Brain Diseases, Cause of Death, Cohort Studies, Disability Evaluation, Discrimination Learning, Female, Gait, Humans, Male, Memory, Short-Term, Mobility Limitation, Neuropsychological Tests, Pattern Recognition, Visual, Psychometrics, Psychomotor Performance, Risk Factors}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01856.x}, author = {Rosano, Caterina and Newman, Anne B and Katz, Ronit and Hirsch, Calvin H and Kuller, Lewis H} } @article {1225, title = {The effects of physical activity, education, and body mass index on the aging brain.}, journal = {Hum Brain Mapp}, volume = {32}, year = {2011}, month = {2011 Sep}, pages = {1371-82}, abstract = {

Normal human aging is accompanied by progressive brain tissue loss and cognitive decline; however, several factors are thought to influence brain aging. We applied tensor-based morphometry to high-resolution brain MRI scans to determine whether educational level or physical activity was associated with brain tissue volumes in the elderly, particularly in regions susceptible to age-related atrophy. We mapped the 3D profile of brain volume differences in 226 healthy elderly subjects (130F/96M; 77.9 {\textpm} 3.6 SD years) from the Cardiovascular Health Study-Cognition Study. Statistical maps revealed the 3D profile of brain regions whose volumes were associated with educational level and physical activity (based on leisure-time energy expenditure). After controlling for age, sex, and physical activity, higher educational levels were associated with ~2-3\% greater tissue volumes, on average, in the temporal lobe gray matter. After controlling for age, sex, and education, greater physical activity was associated with ~2-2.5\% greater average tissue volumes in the white matter of the corona radiata extending into the parietal-occipital junction. Body mass index (BMI) was highly correlated with both education and physical activity, so we examined BMI as a contributing factor by including physical activity, education, and BMI in the same model; only BMI effects remained significant. This is one of the largest MRI studies of factors influencing structural brain aging, and BMI may be a key factor explaining the observed relationship between education, physical activity, and brain structure. Independent contributions to brain structure could not be teased apart as all these factors were highly correlated with one another.

}, keywords = {Aged, Aged, 80 and over, Aging, Analysis of Variance, Body Mass Index, Brain, Brain Mapping, Educational Status, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Motor Activity, Neuropsychological Tests, Statistics as Topic}, issn = {1097-0193}, doi = {10.1002/hbm.21113}, author = {Ho, April J and Raji, Cyrus A and Becker, James T and Lopez, Oscar L and Kuller, Lewis H and Hua, Xue and Dinov, Ivo D and Stein, Jason L and Rosano, Caterina and Toga, Arthur W and Thompson, Paul M} } @article {1259, title = {Gait speed and survival in older adults.}, journal = {JAMA}, volume = {305}, year = {2011}, month = {2011 Jan 05}, pages = {50-8}, abstract = {

CONTEXT: Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates.

OBJECTIVE: To evaluate the relationship between gait speed and survival.

DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6\%, women; and 79.8\%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s.

MAIN OUTCOME MEASURES: Survival rates and life expectancy.

RESULTS: There were 17,528 deaths; the overall 5-year survival rate was 84.8\% (confidence interval [CI], 79.6\%-88.8\%) and 10-year survival rate was 59.7\% (95\% CI, 46.5\%-70.6\%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95\% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19\% to 87\% in men and from 35\% to 91\% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization.

CONCLUSION: In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

}, keywords = {Aged, Cohort Studies, Female, Gait, Geriatric Assessment, Humans, Life Expectancy, Male, Survival Analysis, United States}, issn = {1538-3598}, doi = {10.1001/jama.2010.1923}, author = {Studenski, Stephanie and Perera, Subashan and Patel, Kushang and Rosano, Caterina and Faulkner, Kimberly and Inzitari, Marco and Brach, Jennifer and Chandler, Julie and Cawthon, Peggy and Connor, Elizabeth Barrett and Nevitt, Michael and Visser, Marjolein and Kritchevsky, Stephen and Badinelli, Stefania and Harris, Tamara and Newman, Anne B and Cauley, Jane and Ferrucci, Luigi and Guralnik, Jack} } @article {1276, title = {High blood pressure accelerates gait slowing in well-functioning older adults over 18-years of follow-up.}, journal = {J Am Geriatr Soc}, volume = {59}, year = {2011}, month = {2011 Mar}, pages = {390-7}, abstract = {

OBJECTIVES: To examine whether the association between hypertension and decline in gait speed is significant in well-functioning older adults and whether other health-related factors, such as brain, kidney, and heart function, can explain it.

DESIGN: Longitudinal cohort study.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Of 2,733 potential participants with a brain magnetic resonance imaging (MRI) scan, measures of mobility and systolic blood pressure (BP), no self-reported disability in 1992 to 1994 (baseline), and with at least 1 follow-up gait speed measurement through 1997 to 1999, 643 (aged 73.6, 57\% female, 15\% black) who had received a second MRI in 1997 to 1999 and an additional gait speed measure in 2005 to 2006 were included.

MEASUREMENTS: Mixed models with random slopes and intercepts were adjusted for age, race, and sex. Main explanatory factors included white matter hyperintensity progression, baseline cystatin-C, and left cardiac ventricular mass. Incidence of stroke and dementia, BP trajectories, and intake of antihypertensive medications during follow-up were tested as other potential explanatory factors.

RESULTS: Higher systolic BP was associated with faster rate of gait speed decline in this selected group of 643 participants, and results were similar in the parent cohort (N = 2,733). Participants with high BP (n = 293) had a significantly faster rate of gait speed decline than those with baseline BP less than 140/90 mmHg and no history of hypertension (n = 350). Rates were similar for those with history of hypertension who were uncontrolled (n = 110) or controlled (n = 87) at baseline and for those who were newly diagnosed (n = 96) at baseline. Adjustment for explanatory factors or for other covariates (education, prevalent cardiovascular disease, physical activity, vision, mood, cognition, muscle strength, body mass index, osteoporosis) did not change the results.

CONCLUSION: High BP accelerates gait slowing in well-functioning older adults over a long period of time, even for those who control their BP or develop hypertension later in life. Health-related measurements did not explain these associations. Future studies to investigate the mechanisms linking hypertension to slowing gait in older adults are warranted.

}, keywords = {Aged, Antihypertensive Agents, Comorbidity, Female, Follow-Up Studies, Gait, Geriatric Assessment, Humans, Hypertension, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Statistics, Nonparametric}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.03282.x}, author = {Rosano, Caterina and Longstreth, William T and Boudreau, Robert and Taylor, Christopher A and Du, Yan and Kuller, Lewis H and Newman, Anne B} } @article {1367, title = {Markers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer{\textquoteright}s disease.}, journal = {J Alzheimers Dis}, volume = {30}, year = {2012}, month = {2012}, pages = {53-61}, abstract = {

Cholesterol metabolism is believed to play a role in the development of Alzheimer{\textquoteright}s disease (AD). Oxysterol metabolites of cholesterol, 24S-hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have been associated with AD. We investigated whether oxysterols were associated with markers of cerebrovascular disease prior to the onset of cognitive impairment. Oxysterols were quantified in 105 participants (average age: 80 {\textpm} 4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study who remained cognitively normal at blood draw in 2002, had MRI in 1992 and 1998, and annual cognitive assessment for incident AD and mild cognitive impairment made by consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were associated with age, gender, the presence of high grade white matter hyperintensities, and brain infarcts on prior MRI. Participants with higher plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to develop incident cognitive impairment over 8 years of follow-up. Higher levels of 24-OHC suggest increased cholesterol metabolism occurring in the brains of participants with cerebrovascular disease prior to the onset of cognitive impairment. Measurement of oxysterols may provide information about cholesterol metabolism and brain disease over the cognitive impairment process.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Brain, Cerebrovascular Disorders, Cognition Disorders, Cohort Studies, Female, Humans, Hydroxycholesterols, Magnetic Resonance Imaging, Male, Retrospective Studies}, issn = {1875-8908}, doi = {10.3233/JAD-2012-111460}, author = {Hughes, Timothy M and Kuller, Lewis H and Lopez, Oscar L and Becker, James T and Evans, Rhobert W and Sutton-Tyrrell, Kim and Rosano, Caterina} } @article {1334, title = {Slower gait, slower information processing and smaller prefrontal area in older adults.}, journal = {Age Ageing}, volume = {41}, year = {2012}, month = {2012 Jan}, pages = {58-64}, abstract = {

BACKGROUND: Slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and slower gait is explained by lower performance on numerous neuropsychological tests.

HYPOTHESIS: We hypothesise that slower information processing explains this association, while tests of language or memory will not.

METHODS: Data on brain imaging, neuropsychological tests (information processing speed, visuospatial attention, memory, language, mood) and time to walk 15 feet were obtained in 214 adults (73.3 years, 62\% women) free from stroke and dementia. Covariates included central (white matter hyperintensities, vision) and peripheral contributors of gait (vibration sense, muscle strength, arthritis, body mass index), demographics (age, race, gender, education), as well as markers of prevalent vascular diseases (cardiovascular disease, diabetes and ankle arm index).

RESULTS: In linear regression models, smaller PFAv was associated with slower time to walk independent of covariates. This association was no longer significant after adding information processing speed to the model. None of the other neuropsychological tests significantly attenuated this association.

CONCLUSIONS: We conclude that smaller PFAv may contribute to slower gait through slower information processing. Future longitudinal studies are warranted to examine the casual relationship between focal brain atrophy with slowing in information processing and gait.

}, keywords = {Affect, Aged, Aged, 80 and over, Aging, Attention, Body Mass Index, Cross-Sectional Studies, Female, Gait Disorders, Neurologic, Geriatric Assessment, Humans, Male, Memory, Mental Disorders, Mental Processes, Muscle Strength, Neuroimaging, Neuropsychological Tests, Prefrontal Cortex, Prevalence, Walking}, issn = {1468-2834}, doi = {10.1093/ageing/afr113}, author = {Rosano, Caterina and Studenski, Stephanie A and Aizenstein, Howard J and Boudreau, Robert M and Longstreth, William T and Newman, Anne B} } @article {6107, title = {Long-term survival in adults 65 years and older with white matter hyperintensity: association with performance on the digit symbol substitution test.}, journal = {Psychosom Med}, volume = {75}, year = {2013}, month = {2013 Sep}, pages = {624-31}, abstract = {

OBJECTIVE: White matter hyperintensity (WMH) confers increased mortality risk in patients with cardiovascular diseases. However, little is known about differences in survival times among adults 65 years and older who have WMH and live in the community. To characterize the factors that may reduce mortality risk in the presence of WMH, measures of race, sex, apolipoprotein E4, neuroimaging, and cardiometabolic, physiological, and psychosocial characteristics were examined, with a particular focus on information processing as measured by the Digit Symbol Substitution Test (DSST).

METHODS: Cox proportional models were used to estimate mortality risks in a cohort of 3513 adults (74.8 years, 58\% women, 84\% white) with WMH (0-9 points), DSST (0-90 points), risk factor assessment in 1992 to 1994, and data on mortality and incident stroke in 2009 (median follow-up [range] = 14.2 [0.5-18.1] years).

RESULTS: WMH predicted a 48\% greater mortality risk (age-adjusted hazard ratio [HR; 95\% confidence interval {CI}] for WMH >3 points = 1.48 [1.35-1.62]). This association was attenuated after adjustment for DSST (HR [CI] = 1.38 [1.27-1.51]) or lacunar infarcts (HR [CI] = 1.37 [1.25,1.50]) but not after adjustment for other factors. The interaction between DSST and WMH was significant (p = .011). In fully adjusted models stratified by WMH of 3 or higher, participants with DSST greater than or equal to median had a 34\% lower mortality risk among those with WMH of 3 or higher (n = 532/1217) and a 28\% lower mortality risk among those with WMH lower than 3 (n = 1364/2296), compared with participants with DSST less than median (HR [95\% CI] = 0.66 [0.55-0.81] and 0.72 [0.62-0.83], respectively).

CONCLUSIONS: WMH is associated with increased long-term mortality risk in community-dwelling adults 65 years and older. The increased risk is attenuated for those with higher DSST. Assessment of cognitive function with DSST may improve risk stratification of individuals with WMH.

}, keywords = {Aged, Apolipoprotein E4, Biomarkers, Brain, Cardiovascular Diseases, Epidemiologic Methods, Female, Humans, Life Style, Magnetic Resonance Imaging, Male, Neuroimaging, Neuropsychological Tests, Reaction Time, Sex Factors, Stroke, Survivors}, issn = {1534-7796}, doi = {10.1097/PSY.0b013e31829c1df2}, author = {Rosano, Caterina and Chang, Yue-Fang and Kuller, Lewis H and Guralnik, Jack M and Studenski, Stephanie A and Aizenstein, Howard J and Gianaros, Peter J and Lopez, Oscar L and Longstreth, William T and Newman, Anne B} } @article {6692, title = {A variant of sparse partial least squares for variable selection and data exploration.}, journal = {Front Neuroinform}, volume = {8}, year = {2014}, month = {2014}, pages = {18}, abstract = {When data are sparse and/or predictors multicollinear, current implementation of sparse partial least squares (SPLS) does not give estimates for non-selected predictors nor provide a measure of inference. In response, an approach termed "all-possible" SPLS is proposed, which fits a SPLS model for all tuning parameter values across a set grid. Noted is the percentage of time a given predictor is chosen, as well as the average non-zero parameter estimate. Using a "large" number of multicollinear predictors, simulation confirmed variables not associated with the outcome were least likely to be chosen as sparsity increased across the grid of tuning parameters, while the opposite was true for those strongly associated. Lastly, variables with a weak association were chosen more often than those with no association, but less often than those with a strong relationship to the outcome. Similarly, predictors most strongly related to the outcome had the largest average parameter estimate magnitude, followed by those with a weak relationship, followed by those with no relationship. Across two independent studies regarding the relationship between volumetric MRI measures and a cognitive test score, this method confirmed a priori hypotheses about which brain regions would be selected most often and have the largest average parameter estimates. In conclusion, the percentage of time a predictor is chosen is a useful measure for ordering the strength of the relationship between the independent and dependent variables, serving as a form of inference. The average parameter estimates give further insight regarding the direction and strength of association. As a result, all-possible SPLS gives more information than the dichotomous output of traditional SPLS, making it useful when undertaking data exploration and hypothesis generation for a large number of potential predictors.}, issn = {1662-5196}, doi = {10.3389/fninf.2014.00018}, author = {Olson Hunt, Megan J and Weissfeld, Lisa and Boudreau, Robert M and Aizenstein, Howard and Newman, Anne B and Simonsick, Eleanor M and Van Domelen, Dane R and Thomas, Fridtjof and Yaffe, Kristine and Rosano, Caterina} } @article {6596, title = {Multisystem physiologic impairments and changes in gait speed of older adults.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {70}, year = {2015}, month = {2015 Mar}, pages = {319-24}, abstract = {

BACKGROUND: Slowed gait is an important health indicator in older adults but a single identifiable cause is often lacking. We assessed whether a summary index measuring impairments across multiple physiologic systems was associated with slowed gait in older individuals.

METHODS: Data from the Cardiovascular Health Study (n = 3,010) were used to assess associations between baseline physiologic index (measuring vasculature, brain, kidneys, lungs, and glucose metabolism; range 0-10 with 0-2 points/system and lower score indicating higher function) and annual gait speed (m/s) over 6 years. Participants with complete data on the physiologic index and at least two gait speed measures were included. Mean gait speed and 95\% confidence intervals (CI) by category of index were calculated using mixed effects models.

RESULTS: Those with scores of three or higher on the index had significantly slower gait speed at baseline compared to those with scores of 0-2 (7-10: mean speed = 0.83 m/s, 95\% CI: 0.80, 0.84; 0-2: mean speed = 1.01 m/s, 95\% CI: 0.99, 1.03). Those with higher indices also had faster decline in gait speed compared to those with lower scores after adjustment for demographic and health characteristics (7-10: change in speed = -0.020 m/s/year, 95\% CI: -0.024, -0.016; 0-2: change in speed= -0.010 m/s/year, 95\% CI: -0.014, -0.006).

CONCLUSIONS: Greater impairment across five organ systems was associated with slower gait speed and greater declines in gait speed over 6 years. Impairments accumulated over multiple physiologic systems may make older adults more vulnerable to slow gait speed.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Brain, Cardiovascular Physiological Phenomena, Cohort Studies, Female, Gait, Geriatric Assessment, Glucose, Health Status Indicators, Humans, Kidney, Lung, Male, Sensitivity and Specificity, Time Factors}, issn = {1758-535X}, doi = {10.1093/gerona/glu176}, author = {Rosso, Andrea L and Sanders, Jason L and Arnold, Alice M and Boudreau, Robert M and Hirsch, Calvin H and Carlson, Michelle C and Rosano, Caterina and Kritchevsky, Stephen B and Newman, Anne B} } @article {6928, title = {Social Network Size and Cranial Magnetic Resonance Imaging Findings in Older Adults: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {63}, year = {2015}, month = {2015 Nov}, pages = {2430-2}, keywords = {Aged, Brain, Cardiovascular Diseases, Cross-Sectional Studies, Female, Geriatric Assessment, Humans, Magnetic Resonance Imaging, Male, Neuroimaging, Social Participation, Social Support}, issn = {1532-5415}, doi = {10.1111/jgs.13805}, author = {Flatt, Jason D and Rosso, Andrea L and Aizenstein, Howard J and Schulz, Richard and Longstreth, W T and Newman, Anne B and Fowler, Nicole R and Rosano, Caterina} } @article {7131, title = {Digit Symbol Substitution test and future clinical and subclinical disorders of cognition, mobility and mood in older adults.}, journal = {Age Ageing}, volume = {45}, year = {2016}, month = {2016 Sep}, pages = {688-95}, abstract = {

OBJECTIVE: to examine whether psychomotor speed predicts individual and combined disorders in cognition, mobility and mood and if white matter hyperintensities explain these associations.

DESIGN AND SETTING: longitudinal; Cardiovascular Health Study.

SUBJECTS: 5,888 participants (57.6\% women, 15.7\% black, 75.1 (5.5), mean years (SD)).

METHODS: psychomotor speed (Digit Symbol Substitution Test (DSST)) and small vessel disease (white matter hyperintensities (WMH)) were measured in 1992-94. Global cognition (Modified Mini-Mental State (3MS) examination), mobility (gait speed (GS)) and mood (Center for Epidemiologic Studies Depression (CES-D) scale) were measured annually over 5 years and classified as clinical, subclinical or no disorders based on established values (3MS: 80 and 85 points; GS: 0.6 and 1.0 m/s; CES-D: 10 and 5 points). Analyses were adjusted for demographics, baseline status, education, diabetes, hypertension, ankle-arm index.

RESULTS: among those with no disorder in cognition, mobility and mood (N~=~619) in 1992-94, being in the lowest DSST quartile compared to the highest was associated with nearly twice the odds of developing 1+ clinical or subclinical disorders (N~=~413) during follow-up. Associations were stronger for incident clinical disorders in cognition (OR: 8.44, p~<~0.01) or mobility (OR: 9.09, p~<~0.05) than for mood (OR: 1.88, p~<~0.10). Results were similar after adjustment for WMH.

CONCLUSIONS: slower psychomotor speed may serve as a biomarker of risk of clinical disorders of cognition, mobility and mood. While in part attributable to vascular brain disease, other potentially modifiable contributors may be present. Further studying the causes of psychomotor slowing with ageing might provide novel insights into age-related brain disorders.

}, issn = {1468-2834}, doi = {10.1093/ageing/afw116}, author = {Rosano, Caterina and Perera, Subashan and Inzitari, Marco and Newman, Anne B and Longstreth, William T and Studenski, Stephanie} } @article {7161, title = {Gait Speed Predicts Incident Disability: A Pooled Analysis.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {71}, year = {2016}, month = {2016 Jan}, pages = {63-71}, abstract = {

BACKGROUND: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function.

METHODS: We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking {\textonequarter} - {\textonehalf} mile or climbing 10 steps within 3 years.

RESULTS: Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to >= 1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10\% to 1\% in men, and from 15\% to 1\% in women, while mobility difficulty trended from 47\% to 4\% in men and 40\% to 6\% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve.

CONCLUSION: In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Aging, Cohort Studies, Disability Evaluation, Disabled Persons, Female, Gait, Geriatric Assessment, Humans, Independent Living, Male, Mobility Limitation, Predictive Value of Tests, Prognosis, Psychomotor Performance, Risk Assessment, Risk Factors, ROC Curve, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glv126}, author = {Perera, Subashan and Patel, Kushang V and Rosano, Caterina and Rubin, Susan M and Satterfield, Suzanne and Harris, Tamara and Ensrud, Kristine and Orwoll, Eric and Lee, Christine G and Chandler, Julie M and Newman, Anne B and Cauley, Jane A and Guralnik, Jack M and Ferrucci, Luigi and Studenski, Stephanie A} } @article {7132, title = {Neighborhood Socioeconomic Status and Cognitive Function in Late Life.}, journal = {Am J Epidemiol}, volume = {183}, year = {2016}, month = {2016 Jun 15}, pages = {1088-97}, abstract = {

Neighborhood socioeconomic status (NSES) is associated with cognitive function, independently of individual demographic, health, and socioeconomic characteristics. However, research has been largely cross-sectional, and mechanisms of the association are unknown. In 1992-1993, Cardiovascular Health Study participants (n = 3,595; mean age = 74.8 years; 15.7\% black) underwent cognitive testing and magnetic resonance imaging of white matter hyperintensities (WMH), and their addresses were geocoded. NSES was calculated using 1990 US Census data (block groups; 6 measures of wealth, education, and occupation). The Modified Mini-Mental State Examination (3MS) was used to assess general cognition, and the Digit Symbol Substitution Test (DSST) was used to assess speed of processing annually for 6 years. Associations of race-specific NSES tertiles with 3MS, DSST, and WMH were estimated using linear mixed-effects models accounting for geographic clustering, stratified by race, and adjusted for demographic, health, and individual socioeconomic status (education, income, lifetime occupational status) variables. In fully adjusted models, higher NSES was associated with higher 3MS scores in blacks (mean difference between highest and lowest NSES = 2.4 points; P = 0.004) and whites (mean difference = 0.7 points; P = 0.02) at baseline but not with changes in 3MS over time. NSES was marginally associated with DSST and was not associated with WMH. Adjustment for WMH did not attenuate NSES-3MS associations. Associations of NSES with cognition in late adulthood differ by race, are not explained by WMH, and are evident only at baseline.

}, issn = {1476-6256}, doi = {10.1093/aje/kwv337}, author = {Rosso, Andrea L and Flatt, Jason D and Carlson, Michelle C and Lovasi, Gina S and Rosano, Caterina and Brown, Arleen F and Matthews, Karen A and Gianaros, Peter J} } @article {6998, title = {Subclinical Cardiovascular Disease and Death, Dementia, and Coronary Heart Disease in Patients 80+ Years.}, journal = {J Am Coll Cardiol}, volume = {67}, year = {2016}, month = {2016 Mar 8}, pages = {1013-22}, abstract = {

BACKGROUND: The successful prevention and treatment of coronary heart disease (CHD) and stroke has resulted in a substantial increase in longevity, with subsequent growth in the population of older people at risk for dementia.

OBJECTIVES: The authors evaluated the relationship of coronary and other peripheral atherosclerosis to risk of death, dementia, and CHD in the very elderly. Because the extent of vascular disease differs substantially between men and women, sex- and race-specific analyses were included, with a specific focus on women with low coronary artery calcium (CAC) Agatston scores.

METHODS: We evaluated the relationship between measures of subclinical cardiovascular disease (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) and risk of dementia, CHD, and total mortality in 532 participants of the Cardiovascular Health Study-Cognition Study from 1998/1999 (mean age, 80 years) to 2012/2013 (mean age, 93 years).

RESULTS: Thirty-six percent of participants had CAC scores >400. Women and African-Americans had lower CAC scores. Few men had low CAC scores. CAC score and number of coronary calcifications were directly related to age-adjusted total mortality and CHD. The age-specific incidence of dementia was higher than for CHD. Only about 25\% of deaths were caused by CHD and 16\% by dementia. Approximately 64\% of those who died had a prior diagnosis of dementia. White women with low CAC scores had a significantly decreased incidence of dementia.

CONCLUSIONS: In subjects 80+ years of age, there is a greater incidence of dementia than of CHD. CAC, as a marker of atherosclerosis, is a determinant of mortality, and risk of CHD and myocardial infarction. White women with low CAC scores had a significantly decreased risk of dementia. A very important unanswered question, especially in the very elderly, is whether prevention of atherosclerosis and its complications is associated with less Alzheimer disease pathology and dementia. (Cardiovascular Health Study [CHS]; NCT00005133).

}, keywords = {Age Factors, Aged, 80 and over, Cause of Death, Coronary Artery Disease, Dementia, Female, Humans, Incidence, Male, Pennsylvania, Retrospective Studies, Risk Factors, Survival Rate}, issn = {1558-3597}, doi = {10.1016/j.jacc.2015.12.034}, author = {Kuller, Lewis H and Lopez, Oscar L and Mackey, Rachel H and Rosano, Caterina and Edmundowicz, Daniel and Becker, James T and Newman, Anne B} } @article {7544, title = {Late-Life Depressive Symptoms as Partial Mediators in the Associations between Subclinical Cardiovascular Disease with Onset of Mild Cognitive Impairment and Dementia.}, journal = {Am J Geriatr Psychiatry}, year = {2017}, month = {2017 Nov 20}, abstract = {

OBJECTIVE: To study whether depression contributes to the association between subclinical cardiovascular disease (CVD) and dementia, and identify the contribution{\textquoteright}s magnitude.

METHODS: Among participants from the Cardiovascular Health Study Cognition Study who did not have baseline CVD-related events (N = 2,450), causal mediation methodology was implemented to examine whether late-life depressive symptoms, defined as 10-item Center for Epidemiologic Studies-Depression (mCES-D) Scale scores >=8 from 2 to 3 years after baseline, partially mediated the association of baseline subclinical CVD (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) with mild cognitive impairment (MCI)/dementia onset occurring between 5 and 10 years from baseline. The total effect was decomposed into direct and indirect effects (via late-life depressive symptoms), obtained from an accelerated failure time model with weights derived from multivariable logistic regression of late-life depressive symptoms on subclinical CVD. Analyses were adjusted by baseline covariates: age, race, sex, poverty status, marital status, body mass index, smoking status, ApoE4 status, and mCES-D.

RESULTS: Participants contributed 20,994 person-years of follow-up with a median follow-up time of 9.4 years. Subclinical CVD was associated with 12\% faster time to MCI/dementia (time ratio [TR]: 0.88; 95\% CI: 0.83, 0.93). The total effect of subclinical CVD on MCI/dementia onset was decomposed into a direct effect (TR: 0.95, 95\% CI: 0.92, 0.98) and indirect effect (TR: 0.92, 95\% CI: 0.88, 0.97); 64.5\% of the total effect was mediated by late-life depressive symptoms.

CONCLUSIONS: These data suggest late-life depressive symptoms partially mediate the association of subclinical CVD with MCI/dementia onset.

}, issn = {1545-7214}, doi = {10.1016/j.jagp.2017.11.004}, author = {Armstrong, Nicole M and Carlson, Michelle C and Schrack, Jennifer and Xue, Qian-Li and Carnethon, Mercedes R and Rosano, Caterina and Chaves, Paulo H M and Gross, Alden L} } @article {8630, title = {Catechol-O-Methyltransferase Genotype, Frailty, and Gait Speed in a Biracial Cohort of Older Adults.}, journal = {J Am Geriatr Soc}, year = {2020}, month = {2020 Oct 12}, abstract = {

OBJECTIVE: To examine whether the association between dopamine-related genotype and gait speed differs according to frailty status or race.

DESIGN: Cross-sectional population-based study (Cardiovascular Health Study).

SETTING: Multicenter study, four U.S. sites.

PARTICIPANTS: Volunteer community-dwelling adults aged 65 years and older, without evidence of Parkinson{\textquoteright}s disease (N = 3,744; 71 years; 82\% White; 39\% male).

MEASUREMENTS: Gait speed (usual pace; m/s), physical frailty (Fried definition), and genetic polymorphism of catechol-O-methyltransferase (COMT; rs4680), an enzyme regulating tonic brain dopamine levels, were assessed. Interaction of COMT by frailty and by race predicting gait speed were tested, and, if significant, analyses were stratified. Multivariable regression models of COMT predicting gait speed were adjusted for demographics and locomotor risk factors. Sensitivity analyses were repeated, stratified by clinical cutoffs of gait speed (0.6 and 1.0 m/s) instead of frailty status.

RESULTS: The interaction of COMT by frailty and COMT by race were P = .02 and P = .01, respectively. Compared with Met/Met (higher dopaminergic signaling), the Val/Val group (lower dopaminergic signaling) walked marginally more slowly in the full cohort (0.87 vs 0.89 m/s; P = .2). Gait speed differences were significant for frail (n = 220; 0.55 vs 0.63 m/s; P = .03), but not for prefrail (n = 1,691; 0.81 vs 0.81 m/s; P = .9) or nonfrail (n = 1,833; 0.98 vs 0.97 m/s; P = .7); results were similar in fully adjusted models. Among frail, associations were similar for Whites and Blacks, with statistical significance for Whites only. Associations stratified by clinical cutoffs of gait speed were not significant.

CONCLUSION: The association of dopamine-related genotype with gait speed is stronger among adults with frailty compared with those without frailty. The potential effects of dopaminergic signaling on preserving physical function in biracial cohorts of frail adults should be further examined.

}, issn = {1532-5415}, doi = {10.1111/jgs.16842}, author = {Mance, Shannon and Rosso, Andrea and Bis, Joshua and Studenski, Stephanie and Bohnen, Nico and Rosano, Caterina} } @article {9614, title = {Associations of Neurological Biomarkers in Serum with Gait Measures: The Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, year = {2024}, month = {2024 Feb 09}, abstract = {

BACKGROUND: Gait impairment leads to increased mobility decline and may have neurological contributions. This study explores how neurological biomarkers are related to gait in older adults.

METHODS: We studied participants in the Cardiovascular Health Study, a population-based cohort of older Americans, who underwent a serum biomarker assessment from samples collected in 1996-97 for neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and total tau (n=1959, mean age=78.0 years, 60.8\% female). In a subsample (n=380), cross-sectional associations with quantitative gait measures were explored. This subsample was assessed on a mat for gait speed, step length, double support time, step time, step length variability and step time variability. Gait speed was also measured over a 15-ft walkway annually from 1996-97 to 1998-99, for longitudinal analyses. Linear regression models assessed cross-sectional associations of biomarkers with gait measures, while mixed effects models assessed longitudinal gait speed change from baseline to 1998-99.

RESULTS: NfL was significantly associated with annual gait speed decline (standardized β = -0.64 m/s, 95\% CI: [-1.23, -0.06]) after adjustment for demographic and health factors. Among gait mat-assessed phenotypes, NfL was also cross-sectionally associated with gait speed (β = 0.001 m/s [0.0003, 0.002]) but not with other gait measures. None of the remaining biomarkers were significantly related to gait in either longitudinal or cross-sectional analyses.

CONCLUSION: Higher NfL levels were related to greater annual gait speed decline. Gait speed decline may be related to axonal degeneration. The clinical utility of NfL should be explored.

}, issn = {1758-535X}, doi = {10.1093/gerona/glae043}, author = {Nadkarni, Abhijay and Mukamal, Kenneth J and Zhu, Xiaonan and Siscovick, David and Brach, Jennifer S and Jacob, Mini and Seshadri, Sudha and Abe, Temidayo and Rosano, Caterina and Djouss{\'e}, Luc and Rosso, Andrea L} } @article {9915, title = {Joint Pain and Leisure-Time Physical Activity: Cross-Sectional Findings From the Cardiovascular Health Study.}, journal = {Health Sci Rep}, volume = {8}, year = {2025}, month = {2025 Feb}, pages = {e70367}, abstract = {

BACKGROUND: Joint pain is common and limits leisure-time physical activity (LTPA) in older adults. However, some older adults with pain are also physically active. Psychosocial factors that may indicate external engagement (such as social network) and internal drive (such as feeling able to "get going") are emerging as predictors of LTPA and may explain why some older adults with pain are physically active.

METHODS: We investigated the cross-sectional association of psychosocial factors with LTPA (kcal/week) in adults over the age of 64 with pain in their back, hips, knees and/or feet from the Cardiovascular Health Study. Psychosocial factors included: social network score from the Lubben Social Network scale and three questions from the Center of Epidemiologic Studies Depression Scale (CES-D): perceived effort, difficulty getting going, and trouble concentrating. Separate multivariable ordinal regression models estimated the association between these indicators and LTPA, while controlling for demographics and other contributors of LTPA: number of medications, number of pain sites, body mass index, gait speed, digit substitution symbol test, brain white matter hyperintensities, and mood.

RESULTS: Among 902 participants (65\% female, 14\% Non-White) with joint pain and complete data, higher social network score, and no self-reported "difficulty getting going" were associated with higher levels of LTPA, independent of covariates. Associations with perceived effort or trouble concentrating were not statistically significant.

CONCLUSIONS: Our research suggests that some older adults with pain are physically active and psychosocial factors related to external engagement and internal drive might be important targets to support LTPA. Studies should investigate the role of psychosocial states on LTPA among older adults with pain.

IMPACT STATEMENT: We certify that this work is novel.The potential impact of this research on clinical care includes the following: Resiliency factors such as psychosocial factors may be more important targets to promote leisure-time physical activity in older adults with pain than specific pain reduction strategies.

}, issn = {2398-8835}, doi = {10.1002/hsr2.70367}, author = {Witonsky, Kailyn and Zhu, Xiaonan and Rosso, Andrea L and Newman, Anne and Rosano, Caterina} }