The associations between serum brain-derived neurotrophic factor, potential confounders, and cognitive decline: A longitudinal study

Brain-derived neurotrophic factor (BDNF) plays a role in the maintenance and function of neurons. Although persons with Alzheimer's disease have lower cortical levels of BDNF, evidence regarding the association between circulating BDNF and cognitive function is conflicting. We sought to determine the correlates of BDNF level and whether BDNF level was prospectively associated with cognitive decline in healthy older adults. We measured serum BDNF near baseline in 912 individuals. Cognitive status was assessed repeatedly with the modified Mini-Mental Status Examination and the Digit Symbol Substitution test over the next 10 years. We evaluated the association between BDNF and cognitive decline with longitudinal models. We also assessed the association between BDNF level and demographics, comorbidities and health behaviors. We found an association between serum BDNF and several characteristics that are also associated with dementia (race and depression), suggesting that future studies should control for these potential confounders. We did not find evidence of a longitudinal association between serum BDNF and subsequent cognitive test trajectories in older adults, although we did identify a potential trend toward a cross-sectional association. Our results suggest that serum BDNF may have limited utility as a biomarker of prospective cognitive decline

Monitoring the early signs of cognitive decline in elderly by computer games: an MRI study

BACKGROUND: It is anticipated that current and future preventive therapies will likely be more effective in the early stages of dementia, when everyday functioning is not affected. Accordingly the early identification of people at risk is particularly important. In most cases, when subjects visit an expert and are examined using neuropsychological tests, the disease has already been developed. Contrary to this cognitive games are played by healthy, well functioning elderly people, subjects who should be monitored for early signs. Further advantages of cognitive games are their accessibility and their cost-effectiveness. PURPOSE: The aim of the investigation was to show that computer games can help to identify those who are at risk. In order to validate games analysis was completed which measured the correlations between results of the 'Find the Pairs' memory game and the volumes of the temporal brain regions previously found to be good predictors of later cognitive decline. PARTICIPANTS AND METHODS: 34 healthy elderly subjects were enrolled in the study. The volume of the cerebral structures was measured by MRI. Cortical reconstruction and volumetric segmentation were performed by Freesurfer. RESULTS: There was a correlation between the number of attempts and the time required to complete the memory game and the volume of the entorhinal cortex, the temporal pole, and the hippocampus. There was also a correlation between the results of the Paired Associates Learning (PAL) test and the memory game. CONCLUSIONS: The results gathered support the initial hypothesis that healthy elderly subjects achieving lower scores in the memory game have increased level of atrophy in the temporal brain structures and showed a decreased performance in the PAL test. Based on these results it can be concluded that memory games may be useful in early screening for cognitive decline

Development and validation of risk index for cognitive decline using blood-derived markers

ObjectiveWe sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers.MethodsThe index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma β-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index.ResultsThe risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: -0.46, -0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: -0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: -0.85, -0.54). Using the secondary index, which included β-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: -0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: -0.72, -0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: -1.14, -0.51).ConclusionsA risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary

Targeted versus tailored multimedia patient engagement to enhance depression recognition and treatment in primary care: randomized controlled trial protocol for the AMEP2 study

Abstract Background Depression in primary care is common, yet this costly and disabling condition remains underdiagnosed and undertreated. Persisting gaps in the primary care of depression are due in part to patients’ reluctance to bring depressive symptoms to the attention of their primary care clinician and, when depression is diagnosed, to accept initial treatment for the condition. Both targeted and tailored communication strategies offer promise for fomenting discussion and reducing barriers to appropriate initial treatment of depression. Methods/design The Activating Messages to Enhance Primary Care Practice (AMEP2) Study is a stratified randomized controlled trial comparing two computerized multimedia patient interventions --- one targeted (to patient gender and income level) and one tailored (to level of depressive symptoms, visit agenda, treatment preferences, depression causal attributions, communication self-efficacy and stigma)--- and an attention control. AMEP2 consists of two linked sub-studies, one focusing on patients with significant depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] scores ≥ 5), the other on patients with few or no depressive symptoms (PHQ-9 < 5). The first sub-study examined effectiveness of the interventions; key outcomes included delivery of components of initial depression care (antidepressant prescription or mental health referral). The second sub-study tracked potential hazards (clinical distraction and overtreatment). A telephone interview screening procedure assessed patients for eligibility and oversampled patients with significant depressive symptoms. Sampled, consenting patients used computers to answer survey questions, be randomized, and view assigned interventions just before scheduled primary care office visits. Patient surveys were also collected immediately post-visit and 12 weeks later. Physicians completed brief reporting forms after each patient’s index visit. Additional data were obtained from medical record abstraction and visit audio recordings. Of 6,191 patients assessed, 867 were randomized and included in analysis, with 559 in the first sub-study and 308 in the second. Discussion Based on formative research, we developed two novel multimedia programs for encouraging patients to discuss depressive symptoms with their primary care clinicians. Our computer-based enrollment and randomization procedures ensured that randomization was fully concealed and data missingness minimized. Analyses will focus on the interventions’ potential benefits among depressed persons, and the potential hazards among the non-depressed. Trial registration ClinicialTrials.gov Identifier: http://NCT0114410