Lisa D. Ravdin - US grants

The long term objective of this study is to determine whether a genetic susceptibility factor for Alzheimer's disease (apolipoprotein xi4; APOE Xi4), predisposes head trauma victims to subsequent development of neurodegenerative disorders. The specific aim is to assess the relationship between possession of the APOE xi4 allele and recovery from acute head trauma. Separate lines of research have shown that both APOE- xi4 and a history of head trauma are associated with increased risk for development of Alzheimer's disease (AD). Further, evidence suggests that the risk attributable to APOE xi4 is greater in head trauma victims. Virtually every investigator who has speculated that head trauma is a risk factor for AD has cited the occurrence of dementia pugilstica, or chronic traumatic brain injury (cTBI), in boxers to support their theory. cTBI represents the extreme clinical endpoint of cumulative sports-related neurologic deficits, which manifests as progressive disturbances in motor, behavior, and cognitive functioning. Preliminary findings suggest APOE xi4 is also a risk factor for development of chronic traumatic brain injury in boxers. Boxers are an ideal model for the study of head trauma in that baseline assessment is obtainable and trauma can be quantified. The proposed study is a prospective cohort investigation of recovery from acute head injury in professional boxers. Boxers will complete a baseline neuropsychological battery and APOE genotyping. Post-bout changes in cognitive functioning will be assessed at one day, one week and one month following active competition. Genotype-specific recovery (i.e., presence or absence of the xi4 allele) will be measured in terms of return to baseline on neuropsychological testing. Potential applications of this research include advancing our understanding of genetic risk factors for the brain's response to trauma and development of neurodegenerative disorders as well as objectifying safety standards in high risk sports.

This MPI R01 combines the expertise of the Departments of Psychiatry, Neurology, and Internal Medicine at Weill Cornell Medicine to address MCI (mild cognitive impairment) and early stage AD/ADRD in patients with comorbid chronic pain and depression. We propose to test whether Problem Adaptation Therapy for Pain (PATH-Pain), a novel primary-care based psychosocial intervention designed to reduce stress in MCI and early stage AD/ADRD patients with comorbid depression and pain, has better cognitive, affective, and functional outcomes than Attention Control Usual Care. PATH-Pain is an easy-to-administer psychosocial intervention designed to improve emotion regulation and reduce stress in older adults with MCI or early stage AD/ADRD, chronic pain, and depression. To reduce stress, PATH-Pain aims to: a) reduce negative emotions associated with pain and pain-related disability; b) reduce negative emotions that interfere with pain treatment (e.g., hopelessness, helplessness); c) increase positive emotions and increase engagement in pleasurable activities; d) help patients identify addressable problems in their lives and try to find the best possible solution to these problems; e) reduce interpersonal tension between patients and family members, caregivers, and friends; and f) shift attention during experiences of pain to reduce pain intensity. To achieve these aims, PATH-Pain employs emotion regulation, problem solving, and behavioral activation techniques. In our preliminary study, PATH-Pain participants showed high acceptability and treatment satisfaction with the intervention. Based on our power analysis, we will randomize 100 older adults (60 years and older) with MCI or early stage dementia (probable or possible Alzheimer?s Disease), comorbid depression, and chronic pain to 8 weekly in-office sessions and 6 monthly phone (3 individual and 3 group) sessions of PATH-Pain vs. Attention Control Usual Care in 4 primary care sites. The Attention Control Usual Care arm consists of Usual Care, a pamphlet on pain and depression, and a structured interview of the same duration as each PATH-Pain session. The structured interview aims to control for attention and time, and will consist of general questions regarding health habits and other non-medical topics unrelated to cognitive impairment, pain, and depression. The investigators have shown evidence of feasibility of recruitment, retention, and assessment procedures for the proposed study. Assessments will be performed at baseline, and weeks 5 (no cognitive outcomes), 9, 24 (no cognitive outcomes), 36, and 52 by research assistants unaware of the study hypotheses and the participants? randomization status. PATH-Pain will be administered by certified mental health workers and the Attention-Control sessions will be administered by a non-clinician team member experienced in structured interviews.