Papers by David A Merrill
Alzheimer's & Dementia, 2015
P1⁄40.00153). According to the cognitive impairment level, a moderate positive correlation was ob... more P1⁄40.00153). According to the cognitive impairment level, a moderate positive correlation was observed in the MCI level (FAST stage: 2-3) (r1⁄40.310, t1⁄42.62, P1⁄40.0109), but no correlation was noted in the dementia level ( FAST stage 4) (r1⁄4-0.0771, t1⁄4-0.604, P1⁄40.548). Conclusions: Since the results of this study indicated that the Z score tends to increase with the FAST stage, the degree of atrophy of the medial temporal region is considered to increase with the severity of Alzheimer’s disease. While the Z score increased with the FAST stage in the MCI group, no correlation was observed between the FAST stage and Z score in the Alzheimer’s disease group. Therefore, the VSRAD was suggested to be useful as an index for the follow-up of patients with MCI.
Alzheimer's & dementia : the journal of the Alzheimer's Association, Jan 6, 2017
The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium... more The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with apolipoprotein E (APOE), has received attention more recently as a promising gene in Alzheimer's disease (AD) risk. TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. In this study, we examined the effects of TOMM40 using high-resolution magnetic resonance imaging in 65 healthy, older subjects with and without the APOE ε4 AD-risk variant. Examining individual subregions within the MTL, we found a significant relationship between increasing poly-T lengths of the TOMM40 variant and thickness of the entorhinal cortex only in subjects who did not carry the APOE ε4 allele. Our data provide support for TOMM40 variant repeat length as an important contributor to AD-like MTL pathology in the absence of APOE ε4.
Alzheimer's & Dementia, 2015
The American Journal of Geriatric Psychiatry, 2013
The American Journal of Geriatric Psychiatry, 2013
Recent epidemiological and clinical-trials evidence points to mental health benefits from various... more Recent epidemiological and clinical-trials evidence points to mental health benefits from various lifestyle habits and alternative therapies. For example, cardiovascular conditioning is associated with a delay in age-related cognitive decline, and physical conditioning improves mood and cognition. This panel will highlight recent findings demonstrating cognitive and mood benefits of lifestyle behaviors and alternative treatments involving physical exercise, management of vascular risk factors, memory training, and stress management and the underlying neural mechanisms for these interactions. Discussions will include the extent of these effects throughout the lifespan from a large-scale sampling of U.S. households; the neurobiology of treatment response to mind-body interventions in chronic stress and mood disorders in late life; and prefrontal cortex mediation of aerobic fitness and executive function. Gary Small, MD, UCLA, will describe relationships between nutrition and exercise and responses to meta-memory questions shown to correlate with plaque and tangle brain PET scan measures. David Merrill, MD, PhD will discuss benefits of exercise and management of vascular risk factors on cognition; Linda Ercoli PhD will present the results of the community-based memory training, Helen Lavretsky, MD, UCLA, will present results showing that daily meditation improves mood, cognition, neural activation (fMRI and FDG-PET). The relationship between these brain changes and improvements in aspects of mood, resilience, and cognition will also be discussed. Dr Charles Reynolds will serve as a Discussant.
Abou-Saleh/Principles and Practice of Geriatric Psychiatry, 2010
The American Journal of Geriatric Psychiatry, 2015
The American Journal of Geriatric Psychiatry, 2014
This is a case filed against an insurance agent and against an insurance company for selling seve... more This is a case filed against an insurance agent and against an insurance company for selling several insurance policies and annuities to a 79 year old widow, including some which would not start paying out for many years (e.g., when she would be in her 90's). An appointed guardian brought the lawsuit several years later after the woman was diagnosed with dementia, in an attempt to recover the monies paid for the policies, plus substantial sums claimed for punitive damages and for RICO conspiracy claims. The case alleges that the agent should have known she was cognitively impaired and that the insurance company targeted elderly infirmed people to buy policies. Issues include capacity to make financial decisions and questions of influence and elder manipulation, recognition of possible early cognitive impairment (in this person who subsequently was diagnosed with a dementia), as well as questions of ageism, and the expectations, rights, and limitations of aged individuals, and of those who deal with them. The presenters will take the roles of the judge, the two opposing attorneys, and the expert psychiatric witnesses for each side.
Alzheimer's & Dementia, 2010
Background: Whether perceived changes in memory parallel changes in brain pathology is uncertain.... more Background: Whether perceived changes in memory parallel changes in brain pathology is uncertain. Positron emission tomography (PET) scans using 2-(1- {6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) can measure levels of amyloid plaques and tau neurofibrillary tangles in vivo. Here we investigate whether degree of self-reported memory impairment is associated with FDDNP-PET binding levels in persons without dementia.
Background: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer's dis... more Background: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer's disease (AD). In assessing physical activity, caloric expenditure is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual. Objective: To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons. Methods: All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older. We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain. Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent.
![Research paper thumbnail of In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging](https://attachments.academia-assets.com/51877854/thumbnails/1.jpg)
Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cogniti... more Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropa-thology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropa-thology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE. traumatic brain injury | chronic traumatic encephalopathy | [F-18]FDDNP PET | tau imaging | concussions
Nerve growth factor (NGF) is produced in the hippocampus throughout life and is retrogradely traf... more Nerve growth factor (NGF) is produced in the hippocampus throughout life and is retrogradely trafficked to septal cholinergic neurons, providing a potential mechanism for modulating cholinergic inputs and, thereby, hippocampal plasticity. To explore NGF modulation of hippocampal plasticity and function, NGF levels were augmented or blocked in intact adult rats, and subsequent in vivo effects on cholinergic neurons, hippocampal long-term potentiation (LTP), and learning were examined. NGF augmentation significantly enhanced cholinergic neuronal markers and facilitated induction of hippocampal LTP. Blockade of endogenous NGF significantly reduced hippocampal LTP and impaired retention of spatial memory. These findings reveal an essential role for NGF in regulating biological mechanisms related to plasticity and memory in the intact adult brain.
The overall goal of this chapter is to review the nature of neuroimaging methods and their applic... more The overall goal of this chapter is to review the nature of neuroimaging methods and their application in geropsychiatry. The content includes selected information about methodology, research fi ndings, and clinical applications. The order of considering these topics has been designed to support the overall goal. Presented in sequence are some basic concepts about imaging in general, the fundamentals of the major neuroimaging modalities, results of important research studies on aging and the major geropsychiatric disorders, clinical use of the key techniques, and some emerging methods and directions.
Background Prior research indicates that workplace wellness programmes (WWPs) are generally assoc... more Background Prior research indicates that workplace wellness programmes (WWPs) are generally associated with lowered healthcare costs and improved employee health. Despite the importance of mental well-being in workplace productivity and attendance, few WWP studies have focused on improvements in psychological well-being. Aims To examine the effects of the Bruin Health Improvement Program (BHIP), a 3-month exercise and nutrition WWP, on seven domains of health: physical and mental health, stress, energy level, social satisfaction, self-efficacy and quality of life. Methods Using data from BHIP completers, we conducted multiple one-way multivariate analyses of variance and follow-up univariate t-tests to examine changes in physical and mental health, stress, energy level, social satisfaction, self-efficacy and quality of life. Effect sizes were also calculated post hoc to determine the magnitude of each effect. Results Results for the 281 participants reveal significant improvements across all seven domains (P < 0.001). Effect sizes ranged from 0.19 to 0.67. Conclusions This study is unique in revealing the effects of a WWP on multiple domains of psychological well-being. Given rising healthcare costs associated with mental health, targeting mental health through WWP may be an effective strategy for reducing indirect healthcare costs associated with absenteeism and presenteeism.
Hippocampal volumetrics provides valuable information related to the accurate diagnosis of Alzhei... more Hippocampal volumetrics provides valuable information related to the accurate diagnosis of Alzheimer's disease.
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Papers by David A Merrill