Parkinson's Disease and Diabetes Mellitus: Individual and Combined Effects on Motor, Cognitive, and Psychosocial Functions.

BACKGROUND/OBJECTIVE: Understanding the effects of multimorbidity on motor and cognitive function is important for tailoring therapies. Individuals with diabetes mellitus (DM) have a greater risk of developing Parkinson's disease (PD). This study investigated if individuals with comorbid PD and DM experienced poorer functional ability compared to individuals with only PD or DM. METHODS: A cross-sectional analysis of 424 individuals: healthy older adults (HOA), n = 170; PD without DM (PD-only), n = 162; DM without PD (DM-only), n = 56; and comorbid PD and DM (PD+DM), n = 36. Motor, motor-cognitive, cognitive, and psychosocial functions and PD motor symptoms were compared among groups using a two-way analyses of covariance with PD and DM as factors. RESULTS: The PD-only and DM-only participants exhibited slower gait, worse balance, reduced strength, and less endurance. Motor-cognitive function was impaired in individuals with PD but not DM. DM-only participants exhibited impaired inhibition. Individuals with comorbid PD+DM had worse PD motor symptoms and exhibited impaired attention compared to the PD-only group. CONCLUSIONS: Having PD or DM was independently associated with poorer physical and mental quality of life, depression, and greater risk for loss of function. Both PD and DM have independent adverse effects on motor function. Comorbid PD+DM further impairs attention compared to the effect of PD-only, suggesting the importance of therapies focusing on attention. Understanding the functional ability levels for motor and cognitive domains will enhance the clinical care for PD, DM, and PD+DM.

The Utility of Cerebrovascular Reactivity MRI in Brain Rehabilitation: A Mechanistic Perspective.

Cerebrovascular control and its integration with other physiological systems play a key role in the effective maintenance of homeostasis in brain functioning. Maintenance, restoration, and promotion of such a balance are one of the paramount goals of brain rehabilitation and intervention programs. Cerebrovascular reactivity (CVR), an index of cerebrovascular reserve, plays an important role in chemo-regulation of cerebral blood flow. Improved vascular reactivity and cerebral blood flow are important factors in brain rehabilitation to facilitate desired cognitive and functional outcomes. It is widely accepted that CVR is impaired in aging, hypertension, and cerebrovascular diseases and possibly in neurodegenerative syndromes. However, a multitude of physiological factors influence CVR, and thus a comprehensive understanding of underlying mechanisms are needed. We are currently underinformed on which rehabilitation method will improve CVR, and how this information can inform on a patient's prognosis and diagnosis. Implementation of targeted rehabilitation regimes would be the first step to elucidate whether such regimes can modulate CVR and in the process may assist in improving our understanding for the underlying vascular pathophysiology. As such, the high spatial resolution along with whole brain coverage offered by MRI has opened the door to exciting recent developments in CVR MRI. Yet, several challenges currently preclude its potential as an effective diagnostic and prognostic tool in treatment planning and guidance. Understanding these knowledge gaps will ultimately facilitate a deeper understanding for cerebrovascular physiology and its role in brain function and rehabilitation. Based on the lessons learned from our group's past and ongoing neurorehabilitation studies, we present a systematic review of physiological mechanisms that lead to impaired CVR in aging and disease, and how CVR imaging and its further development in the context of brain rehabilitation can add value to the clinical settings.

Association between anti-inflammatory interleukin-10 and executive function in African American women at risk for Alzheimer's disease.

INTRODUCTION: African-Americans (AAs) are 64% more likely to be diagnosed with AD than non-Hispanic Whites. AAs with elevated AD biomarkers exhibit greater neurodegeneration in AD signature regions compared to non-Hispanic Whites with elevated AD biomarkers. This pilot trial examined whether normal or elevated plasma levels of interleukin (IL)-10 are associated with changes in executive function and short-term memory in AA women at risk for developing AD due to parental history. METHOD: Observational study comparing groups with elevated and normal plasma IL-10 levels. Study included 31 AA women (age=58.9±8 years) with parental history of AD. Measures included inflammatory blood biomarkers, executive function and visuospatial short-term memory tests. Multivariate linear regression with adjustment for comorbidities, and Bonferroni corrections for multiple comparisons were used to compare groups. Effect sizes (Cohen's d) were generated. Using endpoints with moderate-large effects between groups, Pearson correlations determined associations between biomarker levels and cognitive performance. RESULTS: The elevated IL-10 group performed worse on the Trail-Making Test proportional score ((B-A)/A) (effect size (d =-0.87 (-1.6, -.1)). Moderate effects with large confident intervals were noted in inhibition, set-switching, and body position spatial memory. Significant differences between groups in levels of other inflammatory markers were noted, including IL-7 (p=0.002) and interferon γ (p=0.02). IL-7 remained significant after Bonferroni correction. Correlation matrices revealed moderate-large, significant correlations (yet with wide confidence intervals) between levels of IL-10 and IL-9 with BPST total correct trials, and between interferon γ and delayed recall. CONCLUSIONS: Interleukins may incite inflammation, leading to impaired aspects of executive function and short-term memory in this sample of African American women at risk for developing AD. This research provides effect sizes that will be used to power future research that will further investigate the relationship between inflammation, AD biomarkers, and cognitive function in an understudied population.

Aging in the Brain: New Roles of Epigenetics in Cognitive Decline.

Gene expression in the aging brain depends on transcription signals generated by senescent physiology, interacting with genetic and epigenetic programs. In turn, environmental factors influence epigenetic mechanisms, such that an epigenetic-environmental link may contribute to the accumulation of cellular damage, susceptibility or resilience to stressors, and variability in the trajectory of age-related cognitive decline. Epigenetic mechanisms, DNA methylation and histone modifications, alter chromatin structure and the accessibility of DNA. Furthermore, small non-coding RNA, termed microRNA (miRNA) bind to messenger RNA (mRNA) to regulate translation. In this review, we examine key questions concerning epigenetic mechanisms in regulating the expression of genes associated with brain aging and age-related cognitive decline. In addition, we highlight the interaction of epigenetics with senescent physiology and environmental factors in regulating transcription.