APOE Genotype Modifies the Association of Fusiform Gyrus Cerebral Metabolic Rate of Oxygen Consumption and Object Naming Performance.

BACKGROUND: The apolipoprotein E (APOE) ɛ4 allele confers risk for age and Alzheimer's disease related cognitive decline but the mechanistic link remains poorly understood. Blood oxygenation level dependent (BOLD) response in the fusiform gyrus (FG) during object naming appears greater among APOEɛ4 carriers even in the face of equivalent cognitive performance, suggesting neural compensation. However, BOLD is susceptible to known age and APOE-related vascular changes that could confound its interpretation. OBJECTIVE: To address this limitation, we used calibrated fMRI during an object naming task and a hypercapnic challenge to obtain a more direct measure of neural function - percent change cerebral metabolic rate of oxygen consumption (%ΔCMRO2). METHODS: Participants were 45 older adults without dementia (28 ɛ4-, 17 ɛ4+) between the ages of 65 and 85. We examined APOE-related differences in %ΔCMRO2 in the FG during object naming and the extent to which APOE modified associations between FG %ΔCMRO2 and object naming accuracy. Exploratory analyses also tested the hypothesis that %ΔCMRO2 is less susceptible to vascular compromise than are measures of %ΔCBF and %ΔBOLD. RESULTS: We observed a modifying role of APOE on associations between FG %ΔCMRO2 and cognition, with ɛ4 carriers (but not non-carriers) demonstrating a positive association between right FG %ΔCMRO2 and object naming accuracy. CONCLUSION: Results suggest that the relationship between neural function and cognition is altered among older adult APOEɛ4 carriers prior to the onset of dementia, implicating CMRO2 response as a potential mechanism to support cognition in APOE-related AD risk.

The Independent Walking for Brain Health Intervention for Older Adults: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Extensive research suggests that physical activity (PA) is important for brain and cognitive health and may help to delay or prevent Alzheimer's disease and related dementias. Most PA interventions designed to improve brain health in older adults have been conducted in laboratory, gym, or group settings that require extensive resources and travel to the study site or group sessions. Research is needed to develop novel interventions that leverage mobile health (mHealth) technologies to help older adults increase their engagement in PA in free-living environments, reducing participant burden and increasing generalizability of research findings. Moreover, promoting engagement in moderate-to-vigorous PA (MVPA) may be most beneficial to brain health; thus, using mHealth to help older adults increase time spent in MVPA in free-living environments may help to offset the burden of Alzheimer's disease and related dementias and improve quality of life in older age. OBJECTIVE: We developed a novel PA intervention that leverages mHealth to help older adults achieve more minutes of MVPA independently. This pilot study was a 12-week randomized controlled trial to investigate the feasibility of providing just-in-time (JIT) feedback about PA intensity during free-living exercise sessions to help older adults meet current PA recommendations (150 minutes per week of MVPA). METHODS: Participants were eligible if they were cognitively healthy English speakers aged between 65 and 80 years without major cardiovascular, neurologic, or mental health conditions; could ambulate independently; and undergo magnetic resonance imaging. Enrollment occurred from October 2017 to March 2020. Participants randomized to the PA condition received an individualized exercise prescription and an mHealth device that provided heart rate-based JIT feedback on PA intensity, allowing them to adjust their behavior in real time to maintain MVPA during exercise sessions. Participants assigned to the healthy aging education condition received a reading prescription consisting of healthy aging topics and completed weekly quizzes based on the materials. RESULTS: In total, 44 participants were randomized to the intervention. A follow-up manuscript will describe the results of the intervention as well as discuss screening, recruitment, adverse events, and participants' opinions regarding their participation in the intervention. CONCLUSIONS: The long-term goal of this intervention is to better understand how MVPA affects brain and cognitive health in the real world and extend laboratory findings to everyday life. This pilot randomized controlled trial was conducted to determine the feasibility of using JIT heart rate zone feedback to help older adults independently increase time spent in MVPA while collecting data on the plausible mechanisms of change (frontal and medial temporal cerebral blood flow and cardiorespiratory fitness) that may affect cognition (memory and executive function) to help refine a planned stage 2 behavioral trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03058146; https://clinicaltrials.gov/ct2/show/NCT03058146. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42980.

Distal neuropathic pain in HIV is associated with functional connectivity patterns in default mode and salience networks.

HIV-associated distal neuropathic pain (DNP) is one of the most prevalent, disabling, and treatment-resistant complications of HIV, but its biological underpinnings are incompletely understood. While data specific to mechanisms underlying HIV DNP are scarce, functional neuroimaging of chronic pain more broadly implicates the role of altered resting-state functional connectivity within and between salience network (SN) and default mode network (DMN) regions. However, it remains unclear the extent to which HIV DNP is associated with similar alterations in connectivity. The current study aimed to bridge this gap in the literature through examination of resting-state functional connectivity patterns within SN and DMN regions among people with HIV (PWH) with and without DNP. Resting state functional magnetic resonance imaging (rs-fMRI) scans were completed among 62 PWH with HIV-associated peripheral neuropathy, of whom 27 reported current DNP and 35 did not. Using subgrouping group iterative multiple estimation, we compared connectivity patterns in those with current DNP to those without. We observed weaker connectivity between the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) and stronger connectivity between the anterior cingulate cortex (ACC) and thalamus among those reporting DNP. Overall, these findings implicate altered within DMN (i.e., MPFC-PCC) and within SN (i.e., ACC-thalamus) connectivity as potential manifestations of adaptation to pain from neuropathy and/or mechanisms underlying the development/maintenance of DNP. Findings are discussed in the context of differential brain response to pain (i.e., mind wandering, pain aversion, pain facilitation/inhibition) and therapeutic implications.