Background and objectives

There is increasing interest in characterizing the earliest phases of Parkinson disease (PD). However, few studies have investigated prediagnostic trajectories of cognition and function. Our objective was to describe prediagnostic cognitive and functional trajectories in PD in older women and men.

Methods

We studied 9,595 women and 5,795 men from 2 prospective cohort studies of community-dwelling elders followed up to 20 years. In individuals without prevalent PD, we estimated the associations of incident PD diagnosis with rates of change in cognition and function before and after diagnosis compared with healthy older adults using multivariate mixed-effects models.

Results

Over follow-up, 297 individuals developed incident PD. Interactions between the terms in our model and sex were statistically significant for the 3 outcomes (p < 0.001 for all), so we stratified results by sex. Compared with older men without PD, men who developed PD exhibited faster decline in global cognition (0.04 SD more annual change, p < 0.001), executive function (0.05 SD more annual change, p < 0.001), and functional status (0.06 SD more annual change, p < 0.001) in the prediagnostic period. Women who developed PD compared with women without PD displayed faster decline in executive function (0.02 SD more annual change, p = 0.006) and functional status in the prediagnostic period (0.07 SD more annual change, p < 0.001).

Discussion

Individuals with incident PD exhibit cognitive and functional decline during the prediagnostic phase that exceeds rates associated with normal aging. Better understanding heterogeneity in prodromal PD is essential to enable earlier diagnosis and identify impactful nonmotor symptoms in all subgroups.

BACKGROUND: Life-space mobility captures the daily, enacted mobility of older adults. We determined cross-sectional associations between life-space mobility and cognitive impairment (CI) among community-dwelling women in the 9th and 10th decades of life. METHODS: A total of 1375 (mean age 88 years; 88% White) community-dwelling women enrolled in a prospective cohort of older women. Life-space score was calculated with range 0 (daily restriction to ones bedroom) to 120 (daily trips leaving town without assistance) and categorized (0-20, 21-40, 41-60, 61-80, 81-120). The primary outcome was adjudicated CI defined as mild cognitive impairment or dementia; scores on a 6-test cognitive battery were secondary outcomes. RESULTS: Compared to women with life-space scores of 81-120 and after adjustment for demographics and depressive symptoms, the odds of CI was 1.4-fold (OR 1.36, 95% CI 0.91-2.03) higher for women with life-space scores of 61-80, twofold (OR 1.98, 95% CI 1.33-2.94) higher for women with life-space scores of 41-60, 2.6-fold (OR 2.62, 95% CI 1.71-4.01) higher for women with life-space scores of 21-40, and 2.7-fold (OR 2.71, 95% CI 1.27-5.79) higher for women with life-space scores of 0-20. The association of life-space scores with adjudicated CI was primarily due to higher odds of dementia; the odds of dementia versus normal cognition was eightfold (OR 8.63, 95% CI 3.20-23.26) higher among women with life-space scores of 0-20 compared to women with life-space scores of 81-120. Lower life-space scores were associated in a graded manner with lower mean scores on tests of delayed recall (California Verbal Learning Test-II delayed recall) and language and executive function (phonemic fluency, category fluency, and Trails B). Life-space score was not associated with scores on tests of attention and working memory (forward and backward digit span). CONCLUSIONS: Lower life-space mobility is associated in a graded manner with CI among community-dwelling White women in the 9th and 10th decades of life.

Aging is associated with an increase in circulating inflammatory factors. One, the cytokine stromal cell-derived factor 1 (SDF-1 or CXCL12), is critical to stem cell mobilization, migration, and homing as well as to bone marrow stem cell (BMSC), osteoblast, and osteoclast function. SDF-1 has pleiotropic roles in bone formation and BMSC differentiation into osteoblasts/osteocytes, and in osteoprogenitor cell survival. The objective of this study was to examine the association of plasma SDF-1 in participants in the cardiovascular health study (CHS) with bone mineral density (BMD), body composition, and incident hip fractures. In 1536 CHS participants, SDF-1 plasma levels were significantly associated with increasing age (p < 0.01) and male gender (p = 0.04), but not with race (p = 0.63). In multivariable-adjusted models, higher SDF-1 levels were associated with lower total hip BMD (p = 0.02). However, there was no significant association of SDF-1 with hip fractures (p = 0.53). In summary, circulating plasma levels of SDF-1 are associated with increasing age and independently associated with lower total hip BMD in both men and women. These findings suggest that SDF-1 levels are linked to bone homeostasis.

Background

Variations in thyroid function within the laboratory reference range have been associated with a number of clinical outcomes. However, quality of life, mood, and cognitive function have not been extensively studied, and it is not clear whether mild variations in thyroid function have major effects on these neurocognitive outcomes.

Methods

Data were analyzed from the Osteoporotic Fractures in Men (MrOS) Study, a cohort of community-dwelling men aged 65 years and older in the United States. A total of 539 participants who were not taking thyroid medications and had age-adjusted TSH levels within the reference range underwent detailed testing of quality of life, mood, and cognitive function at baseline. The same quality of life, mood, and cognitive outcomes were measured again in 193 of the men after a mean follow-up of 6 years. Outcomes were analyzed using thyrotropin (TSH) and free thyroxine (FT4) levels as continuous independent variables, adjusting for relevant covariates.

Results

At baseline, there were no associations between TSH or FT4 levels and measures of quality of life, mood, or cognition in the 539 euthyroid men. Baseline thyroid function did not predict changes in these outcomes over a mean of 6 years in the 193 men in the longitudinal analysis.

Conclusions

Variations in thyroid function within the age-adjusted laboratory reference range are not associated with variations in quality of life, mood, or cognitive function in community-dwelling older men.

Background

Results of prospective studies examining the association between cystatin C and incident cognitive impairment have been inconsistent. We tested the hypothesis that there is a U-shaped association in older women between cystatin C and risk of incident cognitive impairment 10 years later.

Methods

We conducted a longitudinal analysis of a prospective cohort of 1,332 community-dwelling elderly women without dementia at baseline who had baseline cystatin C and serum creatinine measurements and completed an extended cognitive battery of neuropsychological tests with determination of cognitive status 10 years later. Incident cognitive impairment was defined as either new onset of adjudicated diagnosis of mild cognitive impairment or dementia.

Results

Incident mild cognitive impairment or dementia was identified among 140 (26.0%) women in quartile 1 (Q1), 122 (22.6%) in Q2, 121 (22.5%) in Q3, and 156 (28.9%) in Q4 of cystatin C. In the fully adjusted model, compared to women in Q2-Q3 of cystatin C, adjusted odds ratios (95% CI) for incident cognitive impairment were 1.31 (0.98-1.75) for Q1, and 1.25 (0.94-1.66) for Q4 Compared to women in Q2-Q3 of estimated glomerular filtration rate (eGFRCysC), adjusted odds ratios (95% CI) for incident cognitive impairment after 10 years of follow-up were 1.18 (0.88-1.58) for Q4 (eGFRCysC 76.1-109.4mL/min/1.73 m(2)) and 1.26 (0.94-1.67) for Q1 (eGFRCysC 21.8-55.5mL/min/1.73 m(2)).

Conclusions

These results support a U-shaped association between cystatin C concentration and risk of cognitive impairment or dementia 10 years later, but the association is not independent of potential confounding factors.

BACKGROUND: Stressful life events, such as loss of a partner, loss of a pet or financial problems, are more common with increasing age and may impact the experience of pain. The aim of the current study is to determine the cross-sectional and prospective association between stressful life events and low back pain reporting in the Osteoporotic Fracture in Men Study, a cohort of older men aged ≥65 years. METHODS: At a study visit (March 2005-May 2006), 5149 men reported whether they had experienced a stressful life event or low back pain in the prior 12 months. Following that visit, data on low back pain patients were gathered through triannual questionnaires every 4 months for 1 year. Multivariable logistic regression analyses estimated the association of stressful life events with recent past low back pain or future low back pain. RESULTS: N = 2930, (57%) men reported at least one stressful life event. The presence of a stressful life event was associated with greater odds of any low back pain (OR = 1.42 [1.26-1.59]) and activity-limiting low back pain (OR = 1.74 [1.50-2.01]) in the same period and of any low back pain (OR = 1.56 [1.39-1.74]) and frequent low back pain (OR = 1.80 [1.55-2.08]) in the following year. CONCLUSION: In this cohort of men, the presence of stressful life events increased the likelihood of reporting past and future low back pain. SIGNIFICANCE: Stressful life events such as accident or illness to a partner are common in later life and may impact the experience of pain. We present cross-sectional and prospective data highlighting a consistent association between stressful life events and low back pain in older men. Further, there is evidence to suggest that this relationship is upregulated by an individuals living situation. This information may be used to strengthen a biopsychosocial perspective of an individuals pain experience.

To characterize fracture circumstances by age at time of fracture among community-dwelling older men, we analyzed incident clinical fractures in the Osteoporotic Fractures in Men study. Participants were contacted every 4 mo to identify fractures confirmed by radiographic reports. Fractures were classified as fall- or non-fall-related and further categorized by degree of trauma: minimal (fall from ≤ standing height), moderate (fall on stairs, steps or curb), or severe (fall from > standing height) for fall-related fractures; and minimal (eg, coughing), moderate (eg, collisions with objects during normal activity without falling), or severe (eg, motor vehicle accident) for non-fall-related fractures. Of 2351 clinical fractures in 1424 men during an average follow-up of 9.9 yr, 12.7% occurred at age <75 yr, 15.7% at age 75-79 yr, 26.1% at age 80-84 yr, and 45.5% at age ≥85 yr. A total of 1891 fractures (80.4% of all fractures) were the result of a fall. The proportion of fall-related fractures steadily rose with increasing age at time of fracture, ranging from 65.8% in men <75 yr rising to 84.7% in men ≥85 yr (p < .001). Most fall-related fractures (76.4%) were due to minimal trauma; the proportion of all fractures due to a fall with minimal trauma steadily rose with increasing age (p < .001). In contrast, approximately half of non-fall-related fractures (53.5%) were due to severe trauma. The proportion of all fractures due to severe trauma (whether fall-related or not) declined with advancing age (p < .001). In conclusion, the most frequently occurring fracture circumstance in older men was a fall from ≤standing height. This circumstance was increasingly common with advancing age occurring in 7 of every 10 fractures in men ≥85 yr, while a fracture (fall-related or not) due to severe trauma was less common with advancing age. Findings have implications for development of fracture prevention strategies in older men.

Introduction

Hyperkyphosis commonly affects older people but is not widely acknowledged as a clinically actionable problem, especially in men. There are several techniques to quantify kyphosis including the blocks and Cobb angle measurements. This study includes both kyphosis measures to investigate whether older men with accentuated kyphosis may be at increased mortality risk.

Methods

Men aged ≥65 years (N = 5994) were recruited to participate in the MrOS prospective cohort study from 2000 to 2002 (baseline). Our primary cohort included 2931 enrollees (mean age 79.3 years; SD 5.2) who underwent blocks-measured kyphosis from 2006 to 2009. Our secondary cohort included 2351 participants who underwent radiographic Cobb angle measurements at baseline. Cox proportional hazards analyses were used to determine association between kyphosis and all-cause mortality while adjusting for prevalent radiographic vertebral fractures, bone mineral density, incident fractures, gait speed, timed chair stands, self-reported health, alcohol use, medical co-morbidities, and physical activity.

Results

During a mean follow-up of 8.3 (SD 3.2) years, 1393 participants died in the primary cohort. In this group, compared to men with 0-1 block kyphosis, increasing blocks-measured kyphosis was associated with increased mortality (HR: 1.26-1.53, p trend <0.001). With addition of prevalent vertebral fracture to adjusted models, the association remained significant in participants with severe kyphosis (3+ blocks-measured). Similarly, with addition of chair stand performance the association remained significant for 4+ blocks kyphosis. Walking speed did not attenuate the association of kyphosis and mortality. In the secondary cohort, there were no significant associations between radiographic Cobb angle kyphosis and mortality.

Conclusions

Increasing blocks-measured kyphosis was associated with a greater risk of mortality in older men, indicating that hyperkyphosis identified on physical exam should be considered a clinically significant finding that may warrant further evaluation and treatment.

Aims

Features of central sensitization (CS) are present in almost all chronic pain conditions, including painful urinary conditions and back pain. Recently CS was proposed as a mechanism of nonpainful lower urinary tract symptoms (LUTS). Using musculoskeletal pain as an indicator of CS, we investigated whether the prevalence of musculoskeletal pain is greater among community-dwelling men with moderate or severe LUTS compared to those with mild LUTS.

Methods

We conducted a cross-sectional study of 5966 men ≥65 years who attended the Osteoporotic Fractures in Men Study baseline visit. LUTS were assessed with the American Urological Association Symptom Index (AUA-SI) and categorized as none/mild (0-7), moderate (8-19), or severe (≥20). Self-reported back, neck, hip, or knee pain within the 12 months before baseline was categorized as any pain and multilocation pain. We tested our hypothesis using odds ratios (OR) and 95% confidence intervals (CI) estimated from multivariable logistic regression models.

Results

The adjusted odds of any pain were higher among men with moderate (OR 1.49, 95% CI: 1.29-1.72) and severe LUTS (OR 1.76, 95% CI: 1.28-2.40) compared to those with no/mild LUTS. The adjusted odds of pain at ≥ 2 locations were 69% higher among men with moderate (OR 1.69, 95% CI: 1.45-196) and more than double among men with severe LUTS (OR 2.24, 95% CI: 1.62-3.10) compared to men with no/mild LUTS.

Conclusions

Musculoskeletal pain, especially at multiple locations, is associated with greater LUTS severity among older men. CS may represent a novel shared mechanism of pain and LUTS.

CONTEXT: Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) may adversely affect bone by inducing oxidative stress. Whether this translates into increased fracture risk in older adults is uncertain. OBJECTIVE: Determine the associations of plasma TMAO with hip fracture and bone mineral density (BMD) in older adults. DESIGN AND SETTING: Cox hazard models and linear regression stratified by sex examined the associations of TMAO with hip fracture and BMD in the longitudinal cohort of the Cardiovascular Health Study. PARTICIPANTS: 5019 U.S. adults aged ≥65 years. EXPOSURE: Plasma TMAO. MAIN OUTCOME MEASURES: Incident hip fractures; total hip BMD dual x-ray absorptiometry in a subset (n = 1400). RESULTS: Six hundred sixty-six incident hip fractures occurred during up to 26 years of follow-up (67,574 person-years). After multivariable adjustment, TMAO was not significantly associated with hip fracture (women: hazard ratio (HR) [95% confidence interval (CI)] of 1.00[0.92,1.09] per TMAO doubling; men: 1.12[0.95,1.33]). TMAO was also not associated with total hip BMD (women: BMD difference [95% CI] of 0.42 g/cm2*100 [-0.34,1.17] per TMAO doubling; men: 0.19[-1.04,1.42]). In exploratory analyses, we found an interaction between body mass index (BMI) and the association of TMAO with hip fracture (P < 0.01). Higher TMAO was significantly associated with risk of hip fracture in adults with overweight or obesity (BMI ≥ 25) (HR [95% CI]:1.17[1.05,1.31]), but not normal or underweight. CONCLUSIONS: Among older US men and women, TMAO was not significantly associated with risk of hip fracture or BMD overall. Exploratory analyses suggested a significant association between higher TMAO and hip fracture when BMI was elevated, which merits further study.