Brain levels of high-energy phosphate metabolites and executive function in geriatric depression.

OBJECTIVES: Depression in late life has been associated with difficulties in cognitive processing, particularly in the domains of executive function, processing speed and memory, and increases the risk of developing dementia suggesting a neurodegenerative phenotype. Mitochondrial dysfunction is frequently an early event in neurodegenerative illnesses and may be operative in patients with late life depression. Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the quantification of bioenergetic molecules produced by mitochondria. METHODS: Ten patients with late life depression and eight normal elderly controls were studied with Stroop color and interference tests, which are widely used measures of processing speed and executive function, respectively, followed by (31P) MRS 3-dimensional chemical-shift imaging measuring levels of adenosine triphosphate, phosphocreatine, inorganic phosphate, and pH over the whole brain. RESULTS: In all subjects, gray matter phosphocreatine was positively associated with Stroop interference. Levels of white matter adenosine triphosphate were associated with Stroop interference in subjects with late life depression but not normal elderly. There was also a complementary association between white matter inorganic phosphate and Stroop interference in late life depression patients. CONCLUSIONS: These findings suggest two independent sources of executive function dependence on bioenergetic state in the aging brain. The dependence of executive function performance in subjects with late life depression on ATP in white matter may be associated with mitochondrial impairment and is consistent with predictions of the vascular depression hypothesis. Further research with wider neuropsychological testing targeting bioenergetic markers could help clarify the scope of these effects. Copyright © 2016 John Wiley & Sons, Ltd.

Decreased functional connectivity is associated with increased levels of Cerebral Spinal Fluid soluble-PDGFRß, a marker of blood brain barrier breakdown, in older adults.

Resting-state functional connectivity (FC) is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. For instance, studies in pre-clinical AD subjects have shown increases of cerebral spinal fluid soluble platelet-derived growth factor receptor-ß (CSF sPDGFRß, a marker of BBB breakdown) but have not demonstrated if this vascular impairment affects neuronal dysfunction. It's possible that increased levels of sPDGFRß in the CSF may correlate with impaired FC in metabolically demanding brain regions (i.e. Default Mode Network, DMN). Our study aimed to investigate the relationship between these two markers in older individuals that were cognitively normal and had cognitive impairment. Eighty-nine older adults without dementia from the University of Southern California were selected from a larger cohort. Region of interest (ROI) to ROI analyses were conducted using DMN seed regions. Linear regression models measured significant associations between BOLD FC strength among seed-target regions and sPDGFRß values, while covarying for age and sex. Comparison of a composite ROI created by averaging FC values between seed and all target regions among cognitively normal and impaired individuals was also examined. Using CSF sPDGFRß as a biomarker of BBB breakdown, we report that increased breakdown correlated with decreased functional connectivity in DMN areas, specifically the PCC while the hippocampus exhibited an interaction effect using CDR score. We conclude that BBB breakdown as measured by CSF sPDGFRß affects neural networks resulting in decreased functional connections that leads to cognitive dysfunction.

Medicare's Annual Wellness Visit and diagnoses of dementias and cognitive impairment.

Introduction: Early detection of Alzheimer's disease and related dementias allows clinicians and patients to prepare for future needs and identify treatment options. Medicare's Annual Wellness Visit (AWV) requires detection of cognitive impairment and may increase dementia diagnosis. We estimated the relationship between AWV receipt and incident dementia. Methods: Using a retrospective cohort of Medicare Fee-For-Service (FFS) beneficiaries enrolled for at least 3 years from 2009 to 2016 and two-stage least squares, we quantified the relationship between AWV and incident diagnosis of cognitive impairment/dementia, and by race/ethnicity. The county-level change in percent of beneficiaries receiving AWVs was used as an instrumental variable to account for unobserved factors associated with individuals' AWV receipt and diagnosis. Sample included 3,333,617 beneficiaries ages 67 years and older, without dementia at the beginning of the study. Results: Beneficiaries included 2,713,573 White, 251,958 Black, 196,845 Hispanic, 95,719 Asian, 11,727 American Indian/Alaska Native, and 63,795 of other race/ethnicity. Using ordinary least squares, dementia incidence was -0.79 percentage points (95% CI -0.81 to -0.76) lower for persons receiving an AWV compared to no AWV. Using instrumental variables reversed the direction of the effect: AWV receipt increased dementia diagnoses by 0.47 percentage points (95% CI 0.14 to 0.80), 15% over baseline. AWVs increased diagnoses 2.0 percentage points (95% CI 0.05 to 3.94) among Blacks, 0.40 percentage points (95% CI 0.05 to 0.75) among Whites, but est were imprecise for Hispanics and Asians. Discussion: Increasing AWV take-up and supporting physicians' performance of cognitive assessment may further improve dementia detection in the population and among groups at higher risk of undiagnosed dementia.