Andrea L. Rosso

The Urban Built Environment and Mobility in Older Adults: A Comprehensive Review

Mobility restrictions in older adults are common and increase the likelihood of negative health outcomes and premature mortality. The effect of built environment on mobility in older populations, among whom environmental effects may be strongest, is the focus of a growing body of the literature. We reviewed recent research (1990–2010) that examined associations of objective measures of the built environment with mobility and disability in adults aged 60 years or older. Seventeen empirical articles were identified. The existing literature suggests that mobility is associated with higher street connectivity leading to shorter pedestrian distances, street and traffic conditions such as safety measures, and proximity to destinations such as retail establishments, parks, and green spaces. Existing research is limited by differences in exposure and outcome assessments and use of cross-sectional study designs. This research could lead to policy interventions that allow older adults to live more healthy and active lives in their communities.

Aging, the Central Nervous System, and Mobility

BACKGROUND Mobility limitations are common and hazardous in community-dwelling older adults but are largely understudied, particularly regarding the role of the central nervous system (CNS). This has limited development of clearly defined pathophysiology, clinical terminology, and effective treatments. Understanding how changes in the CNS contribute to mobility limitations has the potential to inform future intervention studies. METHODS A conference series was launched at the 2012 conference of the Gerontological Society of America in collaboration with the National Institute on Aging and the University of Pittsburgh. The overarching goal of the conference series is to facilitate the translation of research results into interventions that improve mobility for older adults. RESULTS Evidence from basic, clinical, and epidemiological studies supports the CNS as an important contributor to mobility limitations in older adults without overt neurologic disease. Three main goals for future work that emerged were as follows: (a) develop models of mobility limitations in older adults that differentiate aging from disease-related processes and that fully integrate CNS with musculoskeletal contributors; (b) quantify the contribution of the CNS to mobility loss in older adults in the absence of overt neurologic diseases; (c) promote cross-disciplinary collaboration to generate new ideas and address current methodological issues and barriers, including real-world mobility measures and life-course approaches. CONCLUSIONS In addition to greater cross-disciplinary research, there is a need for new approaches to training clinicians and investigators, which integrate concepts and methodologies from individual disciplines, focus on emerging methodologies, and prepare investigators to assess complex, multisystem associations.

Obesity and Migraine: The Effect of Age, Gender and Adipose Tissue Distribution

(Headache 2010;50:52‐62)

Mobility, Disability, and Social Engagement in Older Adults

Objective: To examine cross sectional associations between mobility with or without disability and social engagement in a community-based sample of older adults. Methods: Social engagement of participants (n = 676) was outside the home (participation in organizations and use of senior centers) and in home (talking by phone and use of Internet). Logistic or proportional odds models evaluated the association between social engagement and position in the disablement process (no mobility limitations, mobility limitations/no disability, and mobility limitations/disability). Results: Low mobility was associated with lower level of social engagement of all forms (Odds ratio (OR) = 0.59, confidence intervals (CI): 0.41-0.85 for organizations; OR = 0.67, CI: 0.42-1.06 for senior center; OR = 0.47, CI: 0.32-0.70 for phone; OR = 0.38, CI: 0.23-0.65 for Internet). For social engagement outside the home, odds of engagement were further reduced for individuals with disability. Discussion: Low mobility is associated with low social engagement even in the absence of disability; associations with disability differed by type of social engagement.

Episodic migraine and obesity and the influence of age, race, and sex

Objective: To evaluate the episodic migraine (EM)-obesity association and the influence of age, race, and sex on this relationship. Methods: We examined the EM-obesity association and the influence of age, race, and sex in 3,862 adult participants of both black and white race interviewed in the National Comorbidity Survey Replication. EM diagnostic criteria were based on the International Classification of Headache Disorders. Body mass index was classified as underweight (<18.5 kg/m2), normal (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), or obese (≥30 kg/m2). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for EM were estimated using logistic regression. Models were stratified by age (<50/≥50 years), race (white/black), and sex (male/female). Results: A total of 188 participants fulfilled criteria for EM. In all participants, the adjusted odds of EM were 81% greater in individuals who were obese compared with those of normal weight (OR 1.81; 95% CI: 1.27–2.57; p = 0.001), with a significant trend of increasing odds of EM with increasing obesity status from normal weight to overweight to obese (p = 0.001). In addition, stratified analyses demonstrated that the odds of EM were greater in obese as compared with normal-weight individuals who were 1) younger than 50 years of age (OR 1.86; 95% CI: 1.20–2.89; p for trend = 0.008), 2) white (OR 2.06; 95% CI: 1.41–3.01; p for trend ≤0.001), or 3) female (OR 1.95; 95% CI: 1.38–2.76; p for trend ≤0.001). Conclusion: The odds of EM are increased in those with obesity, with the strongest relationships among those younger than 50 years, white individuals, and women.

Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer's disease

Synaptic loss underlies the memory deficit of Alzheimers disease (AD). The molecular mechanism is elusive; however, excitatory synapses organized by the postsynaptic density (PSD) have been used as targets for AD treatment. To identify pathological entities at the synapse in AD, synaptic proteins were screened by quantitative proteomic profiling. The critical proteins were then selected for immunoblot analysis. The glutamate receptors N-methyl-d-aspartate (NMDA) receptor 1 and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor 2 (GluR2) were substantially lost; specifically, the loss of GluR2 was up to 40% at PSD in AD. Shank proteins, the organizers of these glutamate receptors at excitatory synapses, were dramatically altered in AD. The level of Shank2 was increased, whereas the protein level of Shank3 was decreased. Further, the Shank3 protein was modified by ubiquitin, indicating that abnormal activity of the ubiquitin-proteasome system may lead to Shank3 degradation in AD. Our findings suggest that disruption of glutamate receptors at the Shank-postsynaptic platform could contribute to destruction of the PSD which underlies the synaptic dysfunction and loss in AD.

Post-traumatic stress disorder, drug abuse and migraine: new findings from the National Comorbidity Survey Replication (NCS-R).

Background: Post-traumatic stress disorder (PTSD) has been shown to be associated with migraine and drug abuse. Methods: This was an analysis of data from the National Comorbidity Survey Replication (NCS-R) to evaluate the association of PTSD in those with episodic migraine (EM) and chronic daily headache (CDH). Results: Our sample consisted of 5,692 participants. Lifetime and 12-month prevalence rates of PTSD were increased in those with EM and CDH. After adjustments, the lifetime odds ratio (OR) of PTSD was greater in those with EM (OR 3.07 confidence interval [CI]: 2.12, 4.46) compared to those without headache; was greater in men than women with EM (men: OR 6.86; CI: 3.11, 15.11; women: OR 2.77; CI: 1.83, 4.21); and was comparable or greater than the association between migraine with depression or anxiety. The lifetime OR of PTSD was also increased in CDH sufferers. The OR of illicit drug abuse was not increased in those with EM or CDH unless co-occurring with PTSD or depression. Conclusion: The lifetime and 12-month OR of PTSD is increased in those with migraine or CDH, and is greater in men than women with migraine. The lifetime and 12-month OR of illicit drug abuse is not increased in those with migraine or CDH unless co-occurring with PTSD or depression.

Geriatric Syndromes and Incident Disability in Older Women: Results from the Women's Health Initiative Observational Study

To determine how the number of geriatric syndromes is associated with incident disability in community‐based populations of older adults.

Transactive Response DNA-Binding Protein 43 Burden in Familial Alzheimer Disease and Down Syndrome

OBJECTIVE To assess the transactive response DNA-binding protein 43 (TDP-43) burden in familial forms of Alzheimer disease (FAD) and Down syndrome (DS) to determine whether TDP-43 inclusions are also present. DESIGN Using standard immunohistochemical techniques, we examined brain tissue samples from 42 subjects with FAD and 14 with DS. RESULTS We found pathological TDP-43 aggregates in 14.0% of participants (6 of 42 and 2 of 14 participants with FAD and DS, respectively). In both FAD and DS, TDP-43 immunoreactivity did not colocalize with neurofibrillary tangles. Occasionally participants with FAD or DS had TDP-43-positive neuropil threads or dots. Overall, the amygdala was most commonly affected, followed by the hippocampus, with no TDP-43 pathology in neocortical regions. A similar distribution of TDP-43 inclusions is seen in sporadic Alzheimer disease, but it differs from that seen in amyotrophic lateral sclerosis and frontotemporal dementia. CONCLUSIONS Transactive response DNA-binding protein 43 pathology occurs in FAD and DS, similar to that observed in sporadic Alzheimer disease. Thus, pathological TDP-43 may contribute the cognitive impairments in familial and sporadic forms of Alzheimer disease.

Progranulin (PGRN) expression in ALS: An immunohistochemical study

Mutations in the gene progranulin (PGRN) were recently identified as the cause of some forms of frontotemporal dementia with ubiquitin-positive intraneuronal inclusion pathology (FTLD-U). The DNA-binding protein, TDP-43, was determined to be a component of these ubiquitinated inclusions in FTLD-U and amyotrophic lateral sclerosis (ALS) with dementia (ALS-D). These findings raise many interesting questions as to the shared pathology and possible common pathologic process between ALS and FTLD-U. This study examines the immunoexpression of PGRN in ALS patients using immunohistochemical analysis of post-mortem tissue. Available brain and spinal cord sections of eight ALS patients, including one case with severe dementia, and eighteen control-aged brains were stained with anti-PGRN antibodies. We found increased staining for PGRN in motor tracts with vacuolar degeneration and glial cells in ALS sample spinal cord and brainstem sections compared to controls. Variable upper motor neuron staining and reactive glia were seen in ALS motor cortex samples. Frontal lobe and hippocampal sections showed no consistent differences from control tissues with the exception of the ALS-dementia case, which showed PGRN immunoexpression in non-motor cortical areas. These results describe a pattern of increased PGRN expression in areas of active degeneration in ALS. The meaning of this association is unclear, but may indicate a potential role for PGRN in the variable expression of motor and cognitive deficits in the ALS-FTD spectrum.