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1.  Depression, Antidepressants, and Falls Among Community-Dwelling Elderly People: The MOBILIZE Boston Study 
The mechanisms linking falls and depression are still unknown. The aim of the study is to examine the association between depression and antidepressants, with indoor and outdoor falls, and to investigate how antidepressants mediate this relationship.
The study included 763 men and women aged 70 and older with baseline measures for depression and antidepressant use are captured with prospective data on falls from the “Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly” (MOBILIZE) Boston study, which is a population-based longitudinal study (from 2005 to 2009).
Overall, the rate of falls was 26 falls/100 person-years. Seventeen percent of participants had clinically significant depressive symptoms (CSDS), and 12% used antidepressants. CSDS increased the risk of indoor and outdoor falls (incidence rate ratio [IRR] = 1.6, 95% confidence interval [CI] = 1.2–2.3, p < .01; IRR = 1.6, 95% CI = 1.2–2.2, p < .01). Antidepressant use increased the risk of outdoor falls by 70% and partially mediated the association between CSDS and outdoor falls (IRR = 1.7, 95% CI = 1.2–2.5, p < .05). There was no relationship between antidepressant use and indoor falls. Similar results were observed when depression was considered as a continuous variable.
Depression increased the risk of indoor and outdoor falls. Antidepressant use among older adults with CSDS increased the risk of outdoor, but not indoor falls. Clinicians should carefully consider the role of antidepressants among older adults with CSDS and their potential increase for the risk of outdoor falls.
PMCID: PMC3814236  PMID: 23817088
Falls; Depression; Medication.
2.  Stiffness Control of Balance during Dual Task and Prospective Falls in Older Adults: The MOBILIZE Boston Study 
Gait & posture  2013;38(4):757-763.
Outdoor fallers differ from indoor fallers substantially in demographics, lifestyle, health condition and physical function. Biomechanical predictors of outdoor falls have not been well characterized. Current validated measures of postural deficits, which describe only the overall postural behavior, are predictive of indoor falls but not outdoor falls. We hypothesized that a model-based description of postural muscle tone and reflexes, particularly during dual tasking, would predict outdoor falls. We tested whether postural stiffness and damping from an inverted pendulum model were predictive of future indoor and outdoor falls among older adults from the MOBILIZE Boston Study. The center of pressure data during standing were obtained from 717 participants aged 77.9±5.3 years. Participants stood barefoot with eyes open for 30 seconds per trial, in two sets of five standing trials. One set included a serial subtractions task. Postural stiffness and damping values were determined from the postural sway data. After the postural measurements, falls were monitored prospectively using a monthly mail-in calendar over 6-36 months. Associations of postural measures with fall rates were determined using negative binomial regressions. After covariate adjustments, postural stiffness (p=0.02-0.05) and damping (p=0.007-0.1) were associated with lower outdoor falls risk, but not with indoor falls. Results were invariant by direction (anteroposterior versus mediolateral) or by condition (quiet standing versus dual task). Outdoor fall risk may be tied to postural control more so than indoor falls. Dual tasking is likely related to fall risk among older and sicker older adults, but not those relatively healthy.
PMCID: PMC3796021  PMID: 23623606
Postural control; Falls; Dual task; Motor control; Mathematical model
3.  Milk and yogurt consumption are linked with higher bone mineral density but not with hip fracture: the Framingham Offspring Study 
Archives of osteoporosis  2013;8(0):119.
To examine associations of milk, yogurt, cheese, cream, most dairy (total dairy without cream) and fluid dairy (milk+yogurt) with bone density (BMD) at femoral neck (FN), trochanter (TR) and spine, and with incident hip fracture over 12-y follow-up in the Framingham Offspring Study.
3,212 participants completed a food frequency questionnaire (1991–1995 or 1995–1998) and were followed for hip fracture until 2007. 2,506 participants had DXA BMD (1996–2001). Linear regression was used to estimate adjusted mean BMD while Cox-proportional hazards regression was used to estimate adjusted hazard ratios (HR) for hip fracture risk. Final models simultaneously included dairy foods adjusting for each other.
Mean baseline age was 55 (±1.6)y, range: 26–85). Most dairy intake was positively associated with hip and spine BMD. Intake of fluid dairy and milk were related with hip but not spine BMD. Yogurt intake was associated with TR-BMD alone. Cheese and cream intakes were not associated with BMD. In final models, yogurt intake remained positively associated with TR-BMD, while cream tended to be negatively associated with FN-BMD. Yogurt intake showed a weak protective trend for hip fracture [HR(95%CI): ≤4 serv/wk: 0.46 (0.21–1.03) vs. >4 serv/wk: 0.43 (0.06–3.27)]. No other dairy groups showed a significant association (HRs range: 0.53–1.47) with limited power (n, fractures=43).
Milk and yogurt intakes were associated with hip but not spine BMD, while cream may adversely influence BMD. Thus, not all dairy products are equally beneficial for the skeleton. Suggestive fracture results for milk and yogurt intakes need further confirmation.
PMCID: PMC3641848  PMID: 23371478
dairy; milk; yogurt; bone mineral density; hip fracture; dietary intake; bone health
4.  Drug Use and Other Risk Factors Related to Lower Body Mass Index among HIV-Infected Individuals 
Drug and alcohol dependence  2008;95(0):10.1016/j.drugalcdep.2007.12.004.
Malnutrition is associated with morbidity and mortality in HIV infected individuals. Little research has been conducted to identify the roles that clinical, illicit drug use and socioeconomic characteristics play in the nutritional status of HIV-infected patients. This cross-sectional analysis included 562 HIV-infected participants enrolled in the Nutrition for Healthy Living study conducted in Boston, MA and Providence, RI. The relationship between body mass index (BMI) and several covariates (type of drug use, demographic, and clinical characteristics) were examined using linear regression.
Overall, drug users had a lower BMI than non-drug users. The BMI of cocaine users was 1.4 kg/m2 less than that of patients who did not use any drugs, after adjusting for other covariates (p= 0.02). The BMI of participants who were over the age of 55 years was 2.0 kg/m2 less than that of patients under the age of 35, and BMI increased by 0.3 kg/m2 with each 100 cells/mm3 increase in CD4 count. HAART use, adherence to HAART, energy intake, AIDS status, hepatitis B and hepatitis C co-infections, cigarette smoking and depression were not associated with BMI in the final model.
In conclusion, BMI was lower in drug users than non-drug users, and was lowest in cocaine users. BMI was also directly associated with CD4 count and inversely related to age more than 55 years old. HIV infected cocaine users may be at higher risk of developing malnutrition, suggesting the need for anticipatory nutritional support.
PMCID: PMC3837518  PMID: 18243579
drug users; cocaine users; BMI; HIV; CD4 count
5.  The Long-Term Effect of Delirium on the Cognitive Trajectory of Persons with Dementia 
Archives of internal medicine  2012;172(17):1324-1331.
Delirium is characterized by acute cognitive impairment. We examined the effect of delirium on long-term cognitive trajectory in older adults with Alzheimer's disease (AD).
Prospectively collected longitudinal data from a nested cohort of hospitalized patients with AD (n=263) in the Massachusetts Alzheimer's Disease Research Center Patient Registry during 1991–2006 (median follow-up: 3.2 years). Cognitive function was measured using the Information-Memory-Concentration (IMC) section of the Blessed Dementia Rating Scale. Delirium was identified using a validated chart review method. The pace of cognitive deterioration was contrasted using random effect regression models.
Over half of the sample of patients with AD developed delirium during hospitalization (56%). The pace of cognitive deterioration prior to hospitalization did not differ between patients who developed delirium (1.4 IMC points/year, 95% confidence interval, CI,0.7,2.1) and those who did not (0.8 IMC points/year, 95% CI: 0.3,1.3) (P=0.24). In the year following hospitalization, patients who had developed delirium experienced greater cognitive deterioration (3.1 IMC points/year, 95% CI: 2.1,4.1) relative to patients who did not develop delirium (1.4 IMC points/year, 95% CI: 0.2,2.6) after adjusting for confounders. The ratio of these changes suggests that following delirium, cognitive deterioration proceeds at 2.2 times the rate in patients without delirium in the year after hospitalization. The delirium group maintained a more rapid pace of cognitive deterioration throughout the 5-year period following hospitalization. Sensitivity analyses excluding rehospitalized patients and matching on baseline cognitive function and baseline pace of cognitive deterioration produced essentially identical results. The acceleration due to delirium was independent of dementia severity, comorbidity, and demographic characteristics.
Delirium is highly prevalent among persons with AD who are hospitalized and associated with an increased pace of cognitive deterioration which is maintained for up to 5 years. Strategies to prevent delirium may offer a promising avenue to explore for ameliorating cognitive deterioration in AD.
PMCID: PMC3740440  PMID: 23403619
6.  Cognitive Trajectories after Postoperative Delirium 
Delirium is common after cardiac surgery and may be associated with long-term changes in cognitive function. We examined postoperative delirium and the cognitive trajectory during the first year after cardiac surgery.
We enrolled 225 patients 60 years of age or older who were planning to undergo coronary-artery bypass grafting or valve replacement. Patients were assessed preoperatively, daily during hospitalization beginning on postoperative day 2, and at 1, 6, and 12 months after surgery. Cognitive function was assessed with the use of the Mini–Mental State Examination (MMSE; score range, 0 to 30, with lower scores indicating poorer performance). Delirium was diagnosed with the use of the Confusion Assessment Method. We examined performance on the MMSE in the first year after surgery, controlling for demographic characteristics, coexisting conditions, hospital, and surgery type.
The 103 participants (46%) in whom delirium developed postoperatively had lower pre-operative mean MMSE scores than those in whom delirium did not develop (25.8 vs. 26.9, P<0.001). In adjusted models, those with delirium had a larger drop in cognitive function (as measured by the MMSE score) 2 days after surgery than did those without delirium (7.7 points vs. 2.1, P<0.001) and had significantly lower postoperative cognitive function than those without delirium, both at 1 month (mean MMSE score, 24.1 vs. 27.4; P<0.001) and at 1 year (25.2 vs. 27.2, P<0.001) after surgery. With adjustment for baseline differences, the between-group difference in mean MMSE scores was significant 30 days after surgery (P<0.001) but not at 6 or 12 months (P = 0.056 for both). A higher percentage of patients with delirium than those without delirium had not returned to their preoperative baseline level at 6 months (40% vs. 24%, P = 0.01), but the difference was not significant at 12 months (31% vs. 20%, P = 0.055).
Delirium is associated with a significant decline in cognitive ability during the first year after cardiac surgery, with a trajectory characterized by an initial decline and prolonged impairment. (Funded by the Harvard Older Americans Independence Center and others.)
PMCID: PMC3433229  PMID: 22762316
7.  The Non-linear Relationship between Gait Speed and Falls: The MOBILIZE Boston Study 
Although several studies suggest that slow gait speed is a predictor of falls, it may also be a protective mechanism to prevent falls. Further, fast walking may precipitate falls. Therefore, we examined the relationship between gait speed and falls risk.
Longitudinal analysis of the association between gait speed and subsequent falls and analysis of gait speed decline as a predictor of future falls
Population-based cohort study
763 community-dwelling elders underwent baseline assessments and were followed for falls. Of these, 600 completed an 18-month follow-up assessment to determine change in gait speed and were followed for subsequent falls.
Gait speed was measured during a 4-meter walk, falls data were collected from monthly post-card calendars, and covariates were collected from in-home and clinic visits.
There was a U-shaped relation between gait speed and falls with faster (≥1.3 m/s, incident rate ratio (IRR) = 2.12, 95% CI = 1.48 – 3.04) and slower speeds (<0.6 m/sec, IRR = 1.60, CI = 1.06 – 2.42) at highest risk compared to normal gait speeds (≥1.0 and < 1.3 m/sec). In adjusted analyses, slower gait speeds were associated with an increased risk ratio for indoor falls (for <0.6 m/sec, IRR = 2.17, CI = 1.33 – 3.55 and for ≥0.6 and <1.0 m/sec, IRR = 1.45, CI = 1.08 – 1.94). Faster gait speed was associated with an increased risk ratio for outdoor falls (IRR = 2.11, CI = 1.40 – 3.16). A gait speed decline of >0.15 m/sec/year predicted an increased risk for all falls (IRR = 1.86, CI = 1.15 – 3.01).
There is a non-linear relation between gait speed and falls with a greater risk of outdoor falls in faster walkers and greater risk of indoor falls in slow walkers.
PMCID: PMC3141220  PMID: 21649615
9.  Hypertension, Orthostatic Hypotension, and the Risk of Falls in a Community-Dwelling Elderly Population: The Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston Study 
To investigate the relationships between uncontrolled and controlled hypertension, orthostatic hypotension (OH), and falls in participants of the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston Study (N = 722, mean age 78.1).
Prospective population-based study.
Seven hundred twenty-two adults aged 70 and older living within a 5-mile radius of the study headquarters at Hebrew Rehabilitation Center in Boston.
Blood pressure (BP) was measured at baseline in the supine position and after 1 and 3 minutes of standing. Systolic OH (SOH) and diastolic OH at 1 and 3 minutes were defined as a 20-mmHg decline in systolic BP and a 10-mmHg decline in diastolic BP upon standing. Hypertension was defined as BP of 140/90 mmHg or greater or receiving antihypertensive medications (controlled if BP < 140/90 mmHg and uncontrolled if ≥140/90 mmHg). Falls data were prospectively collected using monthly calendars. Fallers were defined as those with at least two falls within 1 year of follow-up.
OH was highest in participants with uncontrolled hypertension; SOH at 1 minute was 19% in participants with uncontrolled hypertension, 5% in those with controlled hypertension, and 2% in those without hypertension (P≤.001)). Participants with SOH at 1 minute and uncontrolled hypertension were at greater risk of falls (hazard ratio = 2.5, 95% confidence interval = 1.3–5.0) than those with uncontrolled hypertension without OH. OH by itself was not associated with falls.
Older adults with uncontrolled hypertension and SOH at 1 minute are at greater risk for falling within 1 year. Hypertension control, with or without OH, is not associated with greater risk of falls in older community-dwelling adults.
PMCID: PMC3306056  PMID: 21391928
hypertension; orthostatic hypotension; falls; elderly
10.  Hypertension, white matter hyperintensities and concurrent impairments in mobility, cognition and mood: The Cardiovascular Health Study 
Circulation  2011;123(8):858-865.
Our objective was to investigate the association between hypertension and concurrent impairments in mobility, cognition and mood; the role of brain white matter hyperintensities in mediating this association; and the impact of these impairments on disability and mortality in elderly hypertensive individuals.
Methods and Results
Blood pressure, gait speed, digit symbol substitution test, and the Center for Epidemiologic Studies Depression Scale were measured yearly (1992-1999) on 4700 participants in the Cardiovascular Health Study (age: 74.7, 58% women, 17% African Americans, 68% hypertension, 3600 had brain MRI in 1992-93, survival data 1992-2005). Using latent profile analysis at baseline, we found that 498 (11%) subjects had concurrent impairments and 3086 (66%) were intact on all three measures. Between 1992 and 1999, 651 (21%) became impaired in all three domains. Hypertensive individuals were more likely to be impaired at baseline (Odds ratio 1.23, 95% CI (1.04-1.42), p=0.01) and become impaired during the follow-up (Hazard Ratio (HR)= 1.3, 95% Confidence Interval (CI): 1.02 to 1.66, p=0.037). Greater degree of white matter hyperintensities was associated with impairments in the 3 domains (p=0.007) and mediated the association with hypertension (p=0.19 for hypertension after adjusting for white matter hyperintensities in the model, 21% HR change). Impairments in the three domains increased subsequent disability with hypertension (p<0.0001). Hypertension mortality also was increased in those impaired (compared to unimpaired hypertensive individuals HR=1.10, 95% CI (1.04-1.17), p=0.004).
Hypertension increases the risk of concurrent impairments in mobility, cognition and mood, which increases disability and mortality. This association is partly mediated by microvascular brain injury.
PMCID: PMC3081662  PMID: 21321150
Hypertension; disability; white matter hyperintensities
11.  Markers of Atherosclerosis and Inflammation and Mortality in Patients with HIV Infection 
Atherosclerosis  2010;214(2):468-473.
HIV-infected patients are at increased risk for cardiovascular disease, which may be mediated in part by inflammation. Surrogate marker studies suggest an increased prevalence of vascular abnormalities in HIV infection. We examined the association of all-cause mortality in HIV-infected patients with carotid artery intima-media thickness (cIMT) and high-sensitivity C-reactive protein (hsCRP).
Design and Methods
Baseline risk factors, cIMT and hsCRP were prospectively measured in 327 HIV-infected participants. Follow-up time with median of 3.1 years was calculated from baseline to death or censored dated 7/31/07. Cox Proportional Hazards models were used to study risk factors associated with mortality.
Thirty eight (11.6 %) of participants have died since study enrollment. CIMT was significantly higher in those who died and decedents were significantly more likely to have cIMT above the 75th percentile. Those who died had higher hsCRP than those alive and more had hsCRP values above 3 mg/L. CD4 count was lower and log10 viral load was higher in decedents, but antiretroviral regimens were similar in both groups. CIMT and hsCRP levels were significantly associated with mortality (HR=2.74, 95% CI 1.26 to 5.97, p=0.01; HR=2.38, 95% CI 1.15 to 4.9, p=0.02).
Our study demonstrated a strong association of carotid IMT and hsCRP with all-cause death in this HIV-infected population despite being similar with respect to exposure to antiretroviral medications. Together these surrogate markers may be indices of chronic inflammation and unfavorable outcomes in HIV-positive patients.
PMCID: PMC3034311  PMID: 21130995
12.  Dietary Protein Intake and Subsequent Falls in Older Men and Women: The Framingham Study 
Poor nutritional status is often present among older adults who experience a fall. However, dietary intake and weight loss are often overlooked as potential factors. The objective of this study was to test the association between dietary protein intake and risk of subsequent falls in a population-based cohort of elderly men and women.
Dietary intake and clinic data from 807 men and women (ages 67–93 years) from the Framingham Original Cohort Study were analyzed. Protein intake (total, animal and plant) was assessed as a continuous variable and by tertile of intake. Falls were reported by participants using a validated questionnaire at two time points. Weight was ascertained at each examination to examine the effect of weight loss over follow-up.
Higher dietary protein intakes were associated with a reduced odds of falling, although of borderline statistical significance (OR=0.80, 95% CI: 0.60–1.07) and were not associated with the rate of falls over follow-up (RR=0.93, 95%CI: 0.73–1.19). Tertile analyses tended towards a protective association, but most did not achieve statistical significance; there was no dose-response. For those who lost ≥ 5% of their baseline weight, higher intakes of total, animal and plant protein showed a significantly lower rate of subsequent falls.
This work highlights the importance of adequate protein intake as a potentially modifiable risk factor for fall prevention in older adults. Further exploration of the interaction of protein intake and weight loss as related to falls is needed.
PMCID: PMC3136106  PMID: 21365169
protein intake; falls; dietary protein; animal protein; elderly; cohort study
13.  Indoor and Outdoor Falls in Older Adults are Different: The MOBILIZE Boston Study 
To identify risk factors for indoor and outdoor falls.
Prospective cohort study.
MOBILIZE Boston, a study of falls etiology among community-dwelling older individuals.
765 women and men, mainly of age 70 years and older, from randomly sampled households in the Boston MA area.
Baseline data were collected by questionnaire and comprehensive clinic examination. During follow-up participants recorded falls on daily calendars. A telephone interview queried the location and circumstances of each fall.
598 indoor and 524 outdoor falls were reported over a median follow-up of 21.7 months. Risk factors for indoor falls included older age, being female, and various indicators of poor health. Risk factors for outdoor falls included younger age, being male, and being relatively physically active and healthy. For instance, the age- and gender-adjusted rate ratio (and 95% confidence interval) for having much difficulty or inability to perform activities of daily living relative to no difficulty was 2.57 (1.69–3.90) for indoor falls, but 0.27 (0.13–0.56) for outdoor falls. The rate ratio for gait speed of <0.68 m/sec relative to a speed of >1.33 m/sec was 1.48 (0.81–2.68) for indoor falls, but 0.27 (0.15–0.50) for outdoor falls.
Risk factors for indoor and outdoor falls differ. Combining these falls, as is done in many studies, masks important information. Prevention recommendations for non-institutionalized older people should be more effective if targeted differently for frail, inactive older people at high risk for indoor falls and relatively active, healthy people at high risk for outdoor falls.
PMCID: PMC2975756  PMID: 20831726
falls; risk factors; elders; aging research; population-based; epidemiology; aged; cohort studies
14.  Poor Adherence to Medications May Be Associated with Falls 
Poor medication adherence is associated with negative health outcomes. We investigated whether poor medication adherence increases the rate of falls as part of Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston (MOBILIZE Boston), a prospective, community-based cohort recruited for the purpose of studying novel risk factors for falls.
A total of 246 men and 408 women (mean age, 78 years) were followed for the occurrence of falls (median follow-up, 1.8 years). Adherence was assessed by the Morisky scale based on the following four questions: whether an individual ever forgets, is careless at times, stops taking medications when feels better, or stops taking medications when feels worse. Low adherence was defined as a “yes” answer to one or more questions. High adherence was defined as a “no” answer to every question.
Forty-eight percent of subjects were classified as having low medication adherence. The rate of falls in the low adherence group was 1.1 falls/person-year (95% confidence interval [CI]: 1.0–1.3) compared with 0.7 falls/person-year (95% CI: 0.6–0.8) in the high adherence group. After adjusting for age, sex, race/ethnicity, education, alcohol use, cognitive measures, functional status, depression, and number of medications, low medication adherence was associated with a 50% increased rate of falls compared with high medication adherence (rate ratio = 1.5, 95% CI: 1.2–1.9; p < .001).
Low medication adherence may be associated with an increased rate of falls among older adults. Future studies should confirm this association and explore whether interventions to improve medication adherence might decrease the frequency of falls and other serious health-related outcomes.
PMCID: PMC2854886  PMID: 20231214
Falls; Community; Medication adherence

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