Publications by authors named "Sarah Banks"

99 Publications

Story Memory Impairment Rates and Association with Hippocampal Volumes in a Memory Clinic Population.

J Int Neuropsychol Soc 2021 Jun 30:1-9. Epub 2021 Jun 30.

Department of Neuropsychology, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.

Objective: Story memory tasks are among the most commonly used memory tests; however, research suggests they may be less sensitive to memory decline and have a weaker association with hippocampal volumes than list learning tasks. To examine its utility, we compared story memory to other memory tests on impairment rates and association with hippocampal volumes.

Method: Archival records from 1617 older adults (Mage = 74.41, range = 65-93) who completed the Wechsler Memory Scale - 4th edition (WMS-IV) Logical Memory (LM), Hopkins Verbal Learning Test - Revised (HVLT-R), and Brief Visuospatial Memory Test - Revised (BVMT-R) as part of a clinical neuropsychological evaluation were reviewed. Scores >1.5 SD below age-adjusted means were considered impaired, and frequency distributions were used to examine impairment rates. A subset of participants (n = 179) had magnetic resonance imaging (MRI) data that underwent image quality assessment. Partial correlations and linear regression analyses, accounting for age, education, and total intracranial volume (TIV), examined associations between memory raw scores and hippocampal volumes.

Results: For delayed recall, nearly half of the sample was impaired on HVLT-R (48.8%) and BVMT-R (46.1%), whereas a little more than a third was impaired on LM (35.7%). Better performance on all three measures was related to larger hippocampal volumes (r's =. 26-.43, p's < .001). Individually adding memory scores to regression models predicting hippocampal volumes improved the model fit for all measures.

Conclusions: Despite findings suggesting that story memory is less sensitive to memory dysfunction, it was not differentially associated with hippocampal volumes compared to other memory measures. Results support assessing memory using different formats and modalities in older adults.
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http://dx.doi.org/10.1017/S1355617721000850DOI Listing
June 2021

A survey of smartphone and interactive video technology use by participants in Alzheimer's disease research: Implications for remote cognitive assessment.

Alzheimers Dement (Amst) 2021 19;13(1):e12188. Epub 2021 May 19.

Department of Neurosciences University of California San Diego La Jolla California USA.

Introduction: Participants from a longitudinal cohort study were surveyed to evaluate the practical feasibility of remote cognitive assessment.

Methods: All active participants/informants at the University of California San Diego Alzheimer's Disease Research Center were invited to complete a nine-question survey assessing technology access/use and willingness to do cognitive testing remotely.

Results: Three hundred sixty-nine of 450 potential participants/informants (82%) completed the survey. Overall, internet access (88%), device ownership (77%), and willingness to do cognitive testing remotely (72%) were high. Device access was higher among those with normal cognition (85%) or cognitive impairment (85%) than those with dementia (52%), as was willingness to do remote cognitive testing (84%, 74%, 39%, respectively). Latinos were less likely than non-Latinos to have internet or device access but were comparable in willingness to do remote testing.

Discussion: Remote cognitive assessment using interactive video technology is a practicable option for nondemented participants in longitudinal studies; however, additional resources will be required to ensure representative participation of Latinos.
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http://dx.doi.org/10.1002/dad2.12188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132053PMC
May 2021

National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome.

Neurology 2021 05 15;96(18):848-863. Epub 2021 Mar 15.

From the Boston University CTE Center (D.I.K.), Department of Neurology, Boston University School of Medicine, Boston; Brain Injury Program (D.I.K.), Encompass Health Braintree Rehabilitation Hospital, Braintree, MA; University of Washington Memory & Brain Wellness Clinic (C.B.), Department of Neurology, University of Washington School of Medicine, Seattle; Department of Neurology (D.W.D., C.H.A.), Mayo Clinic, Scottsdale, AZ; Boston University CTE Center (J.M., M.L.A.), Boston University Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine; Boston University CTE Center (M.L.M.), Boston University School of Medicine, MA; Departments of Neurology (L.J.B.), Ophthalmology, and Population Health, New York University Grossman School of Medicine; Departments of Neurosciences and Psychiatry University of California San Diego (S.J.B.), La Jolla; Departments of Neurology and Psychiatry (W.B.B.), New York University Grossman School of Medicine; Center for Neuroscience and Regenerative Medicine (D.L.B.), Uniformed Services University of the Health Sciences, Department of Neurology, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; Boston University CTE Center (R.C.C.), Boston University Alzheimer's Disease Center, Departments of Neurology and Neurosurgery, Boston University School of Medicine, MA; Departments of Rehabilitation Medicine and Neurology (K.D.-O.C.), Icahn School of Medicine, Mount Sinai, New York; Department of Neurology (Y.E.G.), Barrow Neurological Institute, Phoenix, AZ; Rancho Los Amigos National Rehabilitation Center (B.D.J.), Downey, CA; Department of Neurology (B.D.J.), Keck School of Medicine of USC. Los Angeles, CA; Departments of Psychiatry and Neurology (T.W.M.), Indiana University School of Medicine, Indianapolis; Veterans Affairs Northwest Mental Illness (E.R.P.), Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA; Department of Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle; Mayo Clinic Alzheimer's Disease Research Center (R.C.P.), Mayo Clinic, Rochester, MN; Department of Psychiatry and Psychology (J.V.W.), Mayo Clinic, Scottsdale, AZ; Department of Physical Medicine and Rehabilitation (R.D.Z.), Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston; Faculty of Psychology and Neuroscience (É.M.F.), Maastricht University, the Netherlands, Department of Psychiatry, University of Cambridge, United Kingdom; National Institute of Neurological Disorders and Stroke (D.J.B.), National Institutes of Health; National Institute of Neurological Disorders and Stroke (W.J.K.), Bethesda, MD; Boston University CTE Center (Y.T.), Boston University Alzheimer's Disease Center, Boston University School of Medicine, Department of Biostatistics, Boston University School of Public Health; Boston University CTE Center (A.C.M.), Boston University Alzheimer's Disease Center, Departments of Neurology and Pathology & Laboratory Medicine, Boston University School of Medicine; VA Boston Healthcare System (A.C.M.), US Department of Veteran Affairs, MA; Psychiatry Neuroimaging Laboratory (M.E.S.), Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Chambers-Grundy Center for Transformative Neuroscience (J.L.C.), Department of Brain Health, University of Nevada School of Integrated Health Sciences; Cleveland Clinic Lou Ruvo Center for Brain Health (J.L.C.), Las Vegas, NV; Banner Alzheimer's Institute (E.M.R.), Arizona State University; Department of Psychiatry (E.M.R.), University of Arizona, Phoenix, AZ; and Boston University CTE Center (R.A.S.), Boston University Alzheimer's Disease Center, Departments of Neurology, Neurosurgery, and Anatomy & Neurobiology, Boston University School of Medicine, MA.

Objective: To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE).

Methods: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298).

Results: Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features.

Conclusions: New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.
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http://dx.doi.org/10.1212/WNL.0000000000011850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166432PMC
May 2021

Elevated Inflammatory Markers and Arterial Stiffening Exacerbate Tau but Not Amyloid Pathology in Older Adults with Mild Cognitive Impairment.

J Alzheimers Dis 2021 ;80(4):1451-1463

Research Services, VA San Diego Healthcare System, San Diego, CA, USA.

Background: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer's disease (AD), although their interactive effects have yet to be fully examined.

Objective: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI).

Methods: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1-42 (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified.

Results: Multiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ42 (B = -1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s < 0.05).

Conclusion: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults.
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http://dx.doi.org/10.3233/JAD-201382DOI Listing
January 2021

Sleep and Tau Pathology in Vietnam War Veterans with Preclinical and Prodromal Alzheimer's Disease.

J Alzheimers Dis Rep 2021 Jan 20;5(1):41-48. Epub 2021 Jan 20.

Department of Neuroscience, University of California, San Diego, La Jolla, CA, USA.

Background: The increasing prevalence of Alzheimer's disease (AD) and lack of effective medications has led to a need to identify modifiable risk factors as targets for interventions.

Objective: In this cross-sectional study, we sought to determine whether worse sleep quality is associated with increased pathological tau, and whether this relationship is affected by amyloid pathology.

Methods: 66 male participants underwent Florbetapir (AV45) positron emission tomography (PET) and Flortaucipir (FTP) PET and completed the Pittsburgh Sleep Quality Index questionnaire (PSQI) as part of the Department of Defense Alzheimer's Disease Neuroimaging Initiative, a multicenter study collecting data from Vietnam War veterans, some of whom have a history of post-traumatic stress disorder, or non-penetrating traumatic brain injury. AV45 PET was used to determine the presence of significant amyloid pathology. We used regression models to determine the effects of amyloid pathology and PSQI on tau deposition in brain regions associated with Braak stages.

Results: Among the 66 participants, 14 individuals were amyloid positive (21%) and 52 were amyloid negative (79%). In regions associated with Braak stages III-IV, there was a significant interaction of amyloid status on PSQI (β= 0.04,  = 0.003) with higher PSQI correlating with higher FTP SUVr in amyloid-positive individuals only (β= 0.031,  = 0.005).

Conclusion: Our study found that an AD profile of tau deposition was associated with an interaction between self-reported sleep quality and amyloid pathology such that worse self-reported sleep was related to higher tau in regions usually associated with AD progression, but only in individuals with high cerebral amyloid deposition.
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http://dx.doi.org/10.3233/ADR-200245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903001PMC
January 2021

Sex differences for phenotype in pathologically defined dementia with Lewy bodies.

J Neurol Neurosurg Psychiatry 2021 Jul 9;92(7):745-750. Epub 2021 Feb 9.

Neurosciences, University of California San Diego, La Jolla, California, USA.

Introduction: Sex differences in dementia with Lewy bodies (DLB) have been reported in clinically defined cohorts; however, clinical diagnostic accuracy in DLB is suboptimal and phenotypic differences have not been assessed in pathologically confirmed participants.

Methods: Core DLB features were compared across 55 women and 156 men with pathologically defined DLB in the National Alzheimer's Coordinating Center. These analyses were repeated for 55 women and 55 men matched for age, education and tau burden.

Results: In the total sample, women died older, had fewer years of education, had higher tau burden but were less likely to be diagnosed with dementia and clinical DLB. In the matched sample, visual hallucinations continued to be less common in women, and fewer women met clinical DLB criteria.

Discussion: Sex impacts clinical manifestations of underlying pathologies in DLB. Despite similar underlying Lewy body pathology, women are less likely to manifest core DLB features and may be clinically underdiagnosed.
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http://dx.doi.org/10.1136/jnnp-2020-325668DOI Listing
July 2021

Sex Moderates the Relationship That Number of Professional Fights Has With Cognition and Brain Volumes.

Front Neurol 2020 29;11:574458. Epub 2020 Oct 29.

Departments of Neurosciences and Psychiatry, University of California, San Diego, San Diego, CA, United States.

Incidence of concussions and report of symptoms are greater among women across sports. While structural brain changes and cognitive declines are associated with repetitive head impact (RHI), the role of sex is not well-understood. This study aimed to determine if there is a moderating effect of sex on the relationship the number of professional fights has with cognitive functioning and regional brain volumes in a cohort of boxers, mixed martial artists, and martial artists. A total of 55 women were matched with 55 men based on age, years of education, ethnicity, and fighting style. Cognition was assessed the CNS Vital Signs computerized cognitive battery and supplemental measures. Structural brain scans, demographic data, and number of professional fights (NoPF) were also considered. The matched pairs were compared analysis of covariance, accounting for total brain volume. Within-subject moderation models were utilized to assess the moderating effect of sex on the relationship between NoPF and brain volumes and cognitive performance. Men were observed to have poorer performance on measures of psychomotor speed when compared to women. On a series of analyses assessing the role of sex as a moderator of the relationship between NoPF and regional brain volumes/cognitive performance, a significant moderation effect was observed across multiple measures of cognitive functioning, such that men had poorer performance. Differences in numerous regional brain volumes were also observed, such that the relationship between NoPF and brain volumes was steeper among men. Sex was observed to be an important moderator in the relationship between NoPF, aspects of cognitive functioning, and volumes of numerous brain regions, suggesting that sex differences in neuroanatomic and cognitive response to RHI deserve further attention.
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http://dx.doi.org/10.3389/fneur.2020.574458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673387PMC
October 2020

Enriching the design of Alzheimer's disease clinical trials: Application of the polygenic hazard score and composite outcome measures.

Alzheimers Dement (N Y) 2020 13;6(1):e12071. Epub 2020 Sep 13.

University of California San Diego San Diego California USA.

Introduction: Selecting individuals at high risk of Alzheimer's disease (AD) dementia and using the most sensitive outcome measures are important aspects of trial design.

Methods: We divided participants from Alzheimer's Disease Neuroimaging Initiative at the 50th percentile of the predicted absolute risk of the polygenic hazard score (PHS). Outcome measures were the Alzheimer's Disease Assessment Schedule-Cognitive Subscale (ADAS-Cog), ADNI-Mem, Clinical Dementia Rating-Sum of Boxes (CDR SB), and Cognitive Function Composite 2 (CFC2). In addition to modeling, we use a power analysis compare numbers needed with each technique.

Results: Data from 188 cognitively normal and 319 mild cognitively impaired (MCI) participants were analyzed. Using the ADAS-Cog to estimate sample sizes, without stratification over 24 months, would require 930 participants with MCI, while using the CFC2 and restricting participants to those in the upper 50th percentile would require only 284 participants.

Discussion: Combining stratification by PHS and selection of a sensitive combined outcome measure in a cohort of patients with MCI can allow trial design that is more efficient, potentially less burdensome on participants, and more cost effective.
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http://dx.doi.org/10.1002/trc2.12071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507583PMC
September 2020

Is Increased Sleep Responsible for Reductions in Myocardial Infarction During the COVID-19 Pandemic?

Am J Cardiol 2020 09 20;131:128-130. Epub 2020 Jun 20.

Pulmonary Critical Care Section, Veterans Affairs (VA) San Diego Healthcare System, La Jolla, California; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, California. Electronic address:

The COVID-19 pandemic caused by the highly contagious SARS-CoV-2 virus has had devastating consequences across the globe. However, multiple clinics and hospitals have experienced a decrease in rates of acute myocardial infarction and corresponding cardiac catheterization lab activations, raising the question: Has the risk of myocardial infarction decreased during COVID? Sleep deprivation is known to be an independent risk factor for myocardial infarction, and sleep has been importantly impacted during the pandemic, possibly due to the changes in work-home life leading to a lack of structure. We conducted a social media-based survey to assess potential mechanisms underlying the observed improvement in risk of myocardial infarction. We used validated questionnaires to assess sleep patterns, tobacco consumption and other important health outcomes to test the hypothesis that increases in sleep duration may be occurring which have a beneficial impact on health. We found that the COVID-19 pandemic led to shifts in day/night rhythm, with subjects waking up 105 minutes later during the pandemic (p <0.0001). Subjects also reported going to sleep 41 minutes later during the pandemic (p <0.0001). These shifts led to longer duration of sleep during the COVID-19 pandemic. Before the pandemic, subjects reported sleeping 6.8 hours per night, which rose to 7.5 hours during the pandemic, a 44 minute or 11% increase (p <0.0001). We acknowledge the major negative health impact of the global pandemic but would advocate for using this crisis to improve the work and sleep habits of the general population, which may lead to overall health benefits for our society.
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http://dx.doi.org/10.1016/j.amjcard.2020.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305870PMC
September 2020

Sex-dependent autosomal effects on clinical progression of Alzheimer's disease.

Brain 2020 07;143(7):2272-2280

Department of Radiology, University of California, San Diego, USA.

Sex differences in the manifestations of Alzheimer's disease are under intense investigation. Despite the emerging importance of polygenic predictions for Alzheimer's disease, sex-dependent polygenic effects have not been demonstrated. Here, using a sex crossover analysis, we show that sex-dependent autosomal genetic effects on Alzheimer's disease can be revealed by characterizing disease progress via the hazard function. We first performed sex-stratified genome-wide associations, and then applied derived sex-dependent weights to two independent cohorts. Relative to sex-mismatched scores, sex-matched polygenic hazard scores showed significantly stronger associations with age-at-disease-onset, clinical progression, amyloid deposition, neurofibrillary tangles, and composite neuropathological scores, independent of apolipoprotein E. Models without using hazard weights, i.e. polygenic risk scores, showed lower predictive power than polygenic hazard scores with no evidence for sex differences. Our results indicate that revealing sex-dependent genetic architecture requires the consideration of temporal processes of Alzheimer's disease. This has strong implications not only for the genetic underpinning of Alzheimer's disease but also for how we estimate sex-dependent polygenic effects for clinical use.
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http://dx.doi.org/10.1093/brain/awaa164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364740PMC
July 2020

Sex differences in Alzheimer's-related Tau biomarkers and a mediating effect of testosterone.

Biol Sex Differ 2020 06 19;11(1):33. Epub 2020 Jun 19.

Department of Neuroscience, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.

Women show greater pathological Tau biomarkers than men along the Alzheimer's disease (AD) continuum, particularly among apolipoprotein ε-E4 (APOE4) carriers; however, the reason for this sex difference in unknown. Sex differences often indicate an underlying role of sex hormones. We examined whether testosterone levels might influence this sex difference and the modifying role of APOE4 status. Analyses included 172 participants (25 cognitively normal, 97 mild cognitive impairment, 50 AD participants) from the Alzheimer's Disease Neuroimaging Initiative (34% female, 54% APOE4 carriers, aged 55-90). We examined the separate and interactive effects of plasma testosterone levels and APOE4 on cerebrospinal fluid phosphorylated-tau181 (p-Tau) levels in the overall sample and the sex difference in p-Tau levels before and after adjusting for testosterone. A significant APOE4-by-testosterone interaction revealed that lower testosterone levels related to higher p-Tau levels among APOE4 carriers regardless of sex. As expected, women had higher p-Tau levels than men among APOE4 carriers only, yet this difference was eliminated upon adjustment for testosterone. Results suggest that testosterone is protective against p-Tau particularly among APOE4 carriers. The lower testosterone levels that typically characterize women may predispose them to pathological Tau, particularly among female APOE4 carriers.
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http://dx.doi.org/10.1186/s13293-020-00310-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304096PMC
June 2020

COVID-19-associated acute disseminated encephalomyelitis (ADEM).

J Neurol 2020 Oct 30;267(10):2799-2802. Epub 2020 May 30.

The Hospital of Central Connecticut, Hartford Healthcare, 100 Grand St., New Britain, CT, 06052, USA.

A 51-year-old woman with COVID-19 infection developed coma and an impaired oculocephalic response to one side. MRI of the brain demonstrated acute multifocal demyelinating lesions, and CSF testing did not identify a direct cerebral infection. High-dose steroids followed by a course of IVIG was administered, and the patient regained consciousness over the course of several weeks. As more patients reach the weeks after initial infection with COVID-19, acute disseminated encephalomyelitis should be considered a potentially treatable cause of profound encephalopathy or multifocal neurological deficits.
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http://dx.doi.org/10.1007/s00415-020-09951-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260459PMC
October 2020

Women can bear a bigger burden: ante- and post-mortem evidence for reserve in the face of tau.

Brain Commun 2020 14;2(1):fcaa025. Epub 2020 Apr 14.

Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA.

In this study, we aimed to assess whether women are able to withstand more tau before exhibiting verbal memory impairment. Using data from 121 amyloid-β-positive Alzheimer's Disease Neuroimaging Initiative participants, we fit a linear model with Rey Auditory Verbal Learning Test score as the response variable and tau-PET standard uptake value ratio as the predictor and took the residuals as an estimate of verbal memory reserve for each subject. Women demonstrated higher reserve (i.e. residuals), whether the Learning ( = 2.78, =0.006) or Delay ( = 2.14, =0.03) score from the Rey Auditory Verbal Learning Test was used as a measure of verbal memory ability. To validate these findings, we examined 662 National Alzheimer's Coordinating Center participants with a C2/C3 score (Consortium to Establish a Registry for Alzheimer's Disease) at autopsy. We stratified our National Alzheimer's Coordinating Center sample into Braak 1/2, Braak 3/4 and Braak 5/6 subgroups. Within each subgroup, we compared Logical Memory scores between men and women. Men had worse verbal memory scores within the Braak 1/2 (Logical Memory Immediate: = -5.960 ± 1.517, <0.001, Logical Memory Delay: = -5.703 ± 1.677, =0.002) and Braak 3/4 (Logical Memory Immediate: = -2.900 ± 0.938, =0.002, Logical Memory Delay: = -2.672 ± 0.955, =0.006) subgroups. There were no sex differences in Logical Memory performance within the Braak 5/6 subgroup (Logical Memory Immediate: = -0.314 ± 0.328, =0.34, Logical Memory Delay: = -0.195 ± 0.287, =0.50). Taken together, our results point to a sex-related verbal memory reserve.
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http://dx.doi.org/10.1093/braincomms/fcaa025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166251PMC
April 2020

Impact of pre-departure preparation on the health and wellbeing of Australian gap year travellers.

Travel Med Infect Dis 2020 Sep - Oct;37:101682. Epub 2020 Apr 20.

Travel Medicine Alliance Clinics, Brisbane, Australia.

Background: Medical problems are prevalent among young travellers. A quasi-experimental study was conducted to investigate the impact of country-specific pre-departure preparation in the occurrence of medical and psychological problems among Australian gap year.

Methods: Participants were recruited during two periods, 2013-14 and 2017-18 from an organisation that specialises in gap year placements. Based on results of our previous study of the 2013-14 cohort, improvements in the pre-departure preparation were introduced. Demographic, placement, and pre-departure preparation characteristics as well as psychological stressors, coping mechanisms, and medical problems were collected and compared between the two cohorts.

Results: Demographic and placement characteristics were similar between the two cohorts. There was a significant increase in the proportion of travellers that read the briefing material (from 80% to 100%; p-value<0.001), carried a first aid kit (from 26% to 62%; p-value<0.001), and accessed information on how to deal with common health problems (from 46% to 61%; p-value = 0.047). All psychological stressors decreased, except for feeling home sick that remained high (72%). Medical problems remained prevalent; half of the gap year travellers sought medical attention, yet there was a significant reduction in sunburn (from 59% to 37%; p-value = 0.040), diarrhoea/food poisoning (from 44% to 21%; p-value = 0.015), weight change (from 41% to 16%; p-value = 0.006), and skin infections (from 38% to 9%; p-value<0.001).

Conclusions: Gap year travellers are exposed to a wide range of health risks and experience higher proportion of medical problems than standard tourists. A comprehensive country-specific pre-departure preparation had a positive impact on the gap year travellers' wellbeing.
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http://dx.doi.org/10.1016/j.tmaid.2020.101682DOI Listing
April 2020

New Insights Into the APOE ε4-Soccer Heading Interaction: Handle With Care.

JAMA Neurol 2020 04;77(4):417-418

Boston University Alzheimer's Disease and Chronic Traumatic Encephalopathy Center, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamaneurol.2019.4451DOI Listing
April 2020

Cognitively normal women with Alzheimer's disease proteinopathy show relative preservation of memory but not of hippocampal volume.

Alzheimers Res Ther 2019 12 26;11(1):109. Epub 2019 Dec 26.

Clinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, PO Box 188, 221, Lund, Sweden.

Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes.

Methods: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer's disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes.

Results: Amyloid-positive (Aβ/P-tau+) CN women (women with preclinical AD) showed memory equivalent to amyloid-negative (Aβ/P-tau-) CN women. In contrast, Aβ/P-tau+ CN men (men with preclinical AD) showed poorer memory than Aβ/P-tau- CN men. Symptomatic groups showed no sex differences in effect of AD proteinopathy on memory. There was no interactive effect of sex, diagnosis, and Aβ/P-tau on other measures of cognition or on hippocampal volume.

Conclusions: CN women show relatively preserved verbal memory, but not general cognitive reserve or preserved hippocampal volume in the presence of Aβ/P-tau+. Results have implications for diagnosing AD in women, and for clinical trials.
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http://dx.doi.org/10.1186/s13195-019-0565-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933621PMC
December 2019

Longitudinal change in regional brain volumes with exposure to repetitive head impacts.

Neurology 2020 01 23;94(3):e232-e240. Epub 2019 Dec 23.

From the Cleveland Clinic (C.B., V.R.M.), Las Vegas; University of Nevada (G.S.), Las Vegas; Sahlgrenska Academy (H.Z., K.B.), University of Gothenburg, Sweden; University of California (S.B.), San Diego; and Cleveland Clinic (L.B., J.B.L.), OH.

Objective: This study tests the hypothesis that certain MRI-based regional brain volumes will show reductions over time in a cohort exposed to repetitive head impacts (RHI).

Methods: Participants were drawn from the Professional Fighters Brain Health Study, a longitudinal observational study of professional fighters and controls. Participants underwent annual 3T brain MRI, computerized cognitive testing, and blood sampling for determination of neurofilament light (NfL) and tau levels. Yearly change in regional brain volume was calculated for several predetermined cortical and subcortical brain volumes and the relationship with NfL and tau levels determined.

Results: A total of 204 participants who had at least 2 assessments were included in the analyses. Compared to controls, the active boxers had an average yearly rate of decline in volumes of the left thalamus (102.3 mm/y [ = 0.0004], mid anterior corpus callosum (10.2 mm/y [ = 0.018]), and central corpus callosum (16.5 mm/y [ = <0.0001]). Retired boxers showed the most significant volumetric declines compared to controls in left (32.1 mm/y [ = 0.002]) and right (30.6 mm/y [ = 0.008]) amygdala and right hippocampus (33.5 mm/y [ = 0.01]). Higher baseline NfL levels were associated with greater volumetric decline in left hippocampus and mid anterior corpus callosum.

Conclusion: Volumetric loss in different brain regions may reflect different pathologic processes at different times among individuals exposed to RHI.
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http://dx.doi.org/10.1212/WNL.0000000000008817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108810PMC
January 2020

The Relationship Between Fighting Style, Cognition, and Regional Brain Volume in Professional Combatants: A Preliminary Examination Using Brief Neurocognitive Measures.

J Head Trauma Rehabil 2020 May/Jun;35(3):E280-E287

Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nevada (Mr Stephen and Drs Bernick and Bennett); Department of Environmental and Occupational Health, School of Public Health, University of Nevada Las Vegas (Dr Shan); and University of California San Diego, La Jolla (Dr Banks).

Objective: Repetitive head impacts (RHIs) in combat sports are associated with cognitive decline and brain volume reduction. While fighting style differences between boxers, mixed martial artists (MMAs), and martial artists (MAs) have resulted in a broader spectrum of injury, the effects of RHIs on MAs relative to other fighters have not yet been explored. This study aimed to determine a differential effect of fighting style on cognition and brain.

Setting: A large outpatient medical center specializing in neurological care.

Participants, Design, And Main Measures: In total, 40 MAs, 188 boxers, and 279 MMAs were compared on baseline measures of subcortical regional brain volumes, after controlling for total brain volumes, and cognitive performance.

Results: Significant differences between MAs, MMAs, and boxers were observed in subcortical brain structure volumes and cognitive measures. MMAs and MAs consistently had larger volumes and higher scores than boxers. Fighting style significantly moderated the relationship between the number of professional fights and the volumes of various subcortical brain structures and performance on a measure of processing speed at baseline.

Conclusions: Differences in RHIs across fighting styles may be of clinical significance. Exploring changes over time within the MA, boxer, and MMA cohorts may provide insight into longer-term discrepancies in subcortical regional brain volumes and cognitive functioning across fighting styles.
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http://dx.doi.org/10.1097/HTR.0000000000000540DOI Listing
December 2019

Sex Differences in Cognitive Changes in De Novo Parkinson's Disease.

J Int Neuropsychol Soc 2020 02 11;26(2):241-249. Epub 2019 Dec 11.

Lou Ruvo Center for Brain Health, Cleveland Clinic, Las Vegas, NV, USA.

Objective: To evaluate the sex differences in cognitive course over 4 years in Parkinson's disease (PD) patients with and without mild cognitive impairment (MCI) compared to controls.

Methods: Four-year longitudinal cognitive scores of 257 cognitively intact PD, 167 PD-MCI, and 140 controls from the Parkinson's Progression Markers Initiative were included. Longitudinal scores of men and women, and PD with and without MCI were compared.

Results: Women had better verbal memory, men had better visuospatial function. There was no interaction between sex, diagnostic group, and/or time (4-year follow-up period).

Conclusions: Sex differences in cognitive course in de novo PD are similar to healthy aging. Cognitive decline rates in PD with and without MCI are similar for the first 4 years of PD.
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http://dx.doi.org/10.1017/S1355617719001085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282562PMC
February 2020

Associations Between Microstructure, Amyloid, and Cognition in Amnestic Mild Cognitive Impairment and Dementia.

J Alzheimers Dis 2020 ;73(1):347-357

Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.

Background: Although amyloid-β (Aβ) and microstructural brain changes are both effective biomarkers of Alzheimer's disease, their independent or synergistic effects on cognitive decline are unclear.

Objective: To examine associations of Aβ and brain microstructure with cognitive decline in amnestic mild cognitive impairment and dementia.

Methods: Restriction spectrum imaging, cerebrospinal fluid Aβ, and longitudinal cognitive data were collected on 23 healthy controls and 13 individuals with mild cognitive impairment or mild to moderate Alzheimer's disease. Neurite density (ND) and isotropic free water diffusion (IF) were computed in fiber tracts and cortical regions of interest. We examined associations of Aβ with regional and whole-brain microstructure, and assessed whether microstructure mediates effects of Aβ on cognitive decline.

Results: Lower ND in limbic and association fibers and higher medial temporal lobe IF predicted baseline impairment and longitudinal decline across multiple cognitive domains. ND and IF predicted cognitive outcomes after adjustment for Aβ or whole-brain microstructure. Correlations between microstructure and cognition were present for both amyloid-positive and amyloid-negative individuals. Aβ correlated with whole-brain, rather than regional, ND and IF.

Conclusion: Aβ correlates with widespread microstructural brain changes, whereas regional microstructure correlates with cognitive decline. Microstructural abnormalities predict cognitive decline regardless of amyloid, and may inform about neural injury leading to cognitive decline beyond that attributable to amyloid.
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http://dx.doi.org/10.3233/JAD-190871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266036PMC
April 2021

Sex-specific composite scales for longitudinal studies of incipient Alzheimer's disease.

Alzheimers Dement (N Y) 2019 3;5:508-514. Epub 2019 Oct 3.

Department of Family Medicine and Public Health, UCSD, La Jolla, CA.

Introduction: The impact of Alzheimer's disease (AD) on cognitive decline differs by sex. Composite scores are useful as singular outcomes in clinical trials, yet to date these have not been developed to measure sex-specific change.

Method: We derived optimal composites from component scales available in the AD Neuroimaging Initiative (ADNI) database among cognitively normal and mild cognitively impaired subjects who are cerebrospinal fluid amyloid-β positive for early AD. Maximally sensitive composites were constructed separately for men and women using standard formulas. We compared the statistical power of the composites with the ADNI Prodromal Alzheimer's Cognitive Composite.

Results: Among 9 cognitive measures and clinical dementia rating sum of boxes, the optimal sex-specific composites included 5 measures, including the clinical dementia rating and 4 distinct cognitive measures. The sex-specific composites consistently outperformed sex-agnostic composites and the ADNI Prodromal Alzheimer's Cognitive Composite.

Discussion: Sex-specific composite scales may improve the power of longitudinal studies of early AD and clinical trials.
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http://dx.doi.org/10.1016/j.trci.2019.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804506PMC
October 2019

Comparing the Boston Naming Test With the Neuropsychological Assessment Battery-Naming Subtest in a Neurodegenerative Disease Clinic Population.

Assessment 2021 Jul 13;28(5):1256-1266. Epub 2019 Sep 13.

Cleveland Clinic, Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.

The Boston Naming Test-Second edition (BNT-2) and the Neuropsychological Assessment Battery-Naming (NAB-N) subtest are two commonly used confrontation naming tests used to evaluate word-finding ability in individuals suspected of neurodegenerative disease. The BNT-2 and NAB-N are designed to measure the same construct; however, observations in practice suggest these two tests provide divergent estimates of naming ability. This study sought to systematically investigate the level of agreement between performance on the BNT-2 and NAB-N. Records from 105 consecutive referrals seen for neuropsychological evaluation as part of routine care in an outpatient memory disorders clinic were reviewed. Discrepancy scores, concordance correlation coefficients, and root mean squared differences were calculated between demographically adjusted -scores on the BNT-2 and NAB-N. Results indicated that estimates of word finding ability generated by the BNT-2 and NAB-N have a strong linear relationship but systematically generate scores that are inconsistent. Despite similar task demands, the BNT-2 and NAB-N provide different information about naming ability and further research is needed to understand these differences and inform clinicians on interpreting the naming estimates provided by each test.
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http://dx.doi.org/10.1177/1073191119872253DOI Listing
July 2021

Association of Cavum Septum Pellucidum and Cavum Vergae With Cognition, Mood, and Brain Volumes in Professional Fighters.

JAMA Neurol 2020 01;77(1):35-42

Imaging Institute, Cleveland Clinic, Cleveland, Ohio.

Importance: Many studies have investigated the imaging findings showing sequelae of repetitive head trauma, with mixed results.

Objective: To determine whether fighters (boxers and mixed martial arts fighters) with cavum septum pellucidum (CSP) and cavum vergae (CV) have reduced volumes in various brain structures or worse clinical outcomes on cognitive and mood testing.

Design, Setting, And Participants: This cohort study assessed participants from the Professional Fighters Brain Health Study. Data were collected from April 14, 2011, to January 17, 2018, and were analyzed from September 1, 2018, to May 23, 2019. This study involved a referred sample of 476 active and retired professional fighters. Eligible participants were at least 18 years of age and had at least a fourth-grade reading level. Healthy age-matched controls with no history of trauma were also enrolled.

Exposures: Presence of CSP, CV, and their total (additive) length (CSPV length).

Main Outcomes And Measures: Information regarding depression, impulsivity, and sleepiness among study participants was obtained using the Patient Health Questionnaire depression scale, Barrett Impulsiveness Scale, and the Epworth Sleepiness Scale. Cognition was assessed using raw scores from CNS Vital Signs. Volumes of various brain structures were measured via magnetic resonance imaging.

Results: A total of 476 fighters (440 men, 36 women; mean [SD] age, 30.0 [8.2] years [range, 18-72 years]) and 63 control participants (57 men, 6 women; mean [SD] age, 30.8 [9.6] years [range, 18-58 years]) were enrolled in the study. Compared with fighters without CV, fighters with CV had significantly lower mean psychomotor speed (estimated difference, -11.3; 95% CI, -17.4 to -5.2; P = .004) and lower mean volumes in the supratentorium (estimated difference, -31 191 mm3; 95% CI, -61 903 to -479 mm3; P = .05) and other structures. Longer CSPV length was associated with lower processing speed (slope, -0.39; 95% CI, -0.49 to -0.28; P < .001), psychomotor speed (slope, -0.43; 95% CI, -0.53 to -0.32; P < .001), and lower brain volumes in the supratentorium (slope, -1072 mm3 for every 1-mm increase in CSPV length; 95% CI, -1655 to -489 mm3; P < .001) and other structures.

Conclusions And Relevance: This study suggests that the presence of CSP and CV is associated with lower regional brain volumes and cognitive performance in a cohort exposed to repetitive head trauma.
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http://dx.doi.org/10.1001/jamaneurol.2019.2861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735412PMC
January 2020

Sex Moderates Amyloid and Apolipoprotein ε4 Effects on Default Mode Network Connectivity at Rest.

Front Neurol 2019 20;10:900. Epub 2019 Aug 20.

Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States.

Women are more likely to have Alzheimer's disease (AD) and decline more rapidly once diagnosed despite greater verbal memory early in the disease compared to men-an advantage that has been termed "memory reserve." Resting state functional MRI (fMRI) investigations demonstrate interactions between sex and AD risk factors in default mode network (DMN) connectivity, a network of brain regions showing progressive dysfunction in AD. Separate work suggests connectivity of left prefrontal cortex (PFC) may correlate with more general cognitive reserve in healthy aging. It is unknown whether left prefrontal functional connectivity with anterior and posterior default mode network (aDMN, pDMN) might differ by sex in AD. This study employed group independent component analysis (ICA) to analyze resting state fMRI data from 158 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with baseline diagnoses of normal cognition or early mild cognitive impairment (eMCI). pDMN and aDMN were defined on a subject-specific basis; prefrontal areas were selected from the Brodmann atlas (BA 6, 44, 8, and 9). Moderation regression analyses examined whether sex and amyloid PET positivity (A+/-) moderated effects of apolipoprotein ε4 ( ε) on connectivity between left PFC, aDMN, and pDMN; and between aDMN and pDMN. Significant analyses were followed up with partial correlations assessing relationship of connectivity to verbal memory on the Rey Auditory Verbal Learning Test (RAVLT), and with preliminary analyses within NC and eMCI groups separately. Results showed no sex moderation of effects of A+ and ε on left prefrontal/DMN connectivity in the full sample. However, sex significantly moderated impact of A+ and ε on connectivity between aDMN and pDMN ( < 0.01). Women with an allele (ε4+) and A+ showed greater aDMN/pDMN connectivity than their ε4- counterparts. No significant results were observed in men. Subgroup analyses suggested the aDMN/pDMN finding was true for those with NC, not eMCI. Partial correlations controlling for age and education showed increased aDMN/pDMN connectivity related to better verbal learning in women ( < 0.01) and not men ( = 0.18). In women at risk for AD or in early symptomatic stages who also have evidence of amyloid burden, stronger aDMN/pDMN connectivity may support verbal learning.
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http://dx.doi.org/10.3389/fneur.2019.00900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710397PMC
August 2019

Training in improvisation techniques helps reduce caregiver burden and depression: Innovative Practice.

Dementia (London) 2021 Jan 13;20(1):364-372. Epub 2019 Aug 13.

Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, USA.

This study measured outcomes of a novel pilot program designed to teach improvisation skills to caregivers of family members with dementia. Fifteen caregivers completed questionnaires measuring changes in their perception of burden (Zarit Burden Interview), depression (Beck Depression Inventory), their cared-for person's neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire), and experiences related to caregiving. Caregivers' depressive symptoms and sense of burden significantly decreased after completing the six-week program. Caregivers reported that their loved ones' neuropsychiatric symptoms increased during the course of the intervention, though associated distress did not also increase. The Improv for Care program shows promise as an intervention for caregivers to improve stress, mood, and coping skills.
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http://dx.doi.org/10.1177/1471301219869122DOI Listing
January 2021

Understanding white matter structural connectivity differences between cognitively impaired and nonimpaired active professional fighters.

Hum Brain Mapp 2019 12 12;40(17):5108-5122. Epub 2019 Aug 12.

Lou Ruvo Center for Brain Health, Cleveland Clinic Foundation, Las Vegas, Nevada.

Long-term traumatic brain injury due to repeated head impacts (RHI) has been shown to be a risk factor for neurodegenerative disorders, characterized by a loss in cognitive performance. Establishing the correlation between changes in the white matter (WM) structural connectivity measures and neuropsychological test scores might help to identify the neural correlates of the scores that are used in daily clinical setting to investigate deficits due to repeated head blows. Hence, in this study, we utilized high angular diffusion MRI (dMRI) of 69 cognitively impaired and 70 nonimpaired active professional fighters from the Professional Fighters Brain Health Study, and constructed structural connectomes to understand: (a) whether there is a difference in the topological WM organization between cognitively impaired and nonimpaired active professional fighters, and (b) whether graph-theoretical measures exhibit correlations with neuropsychological scores in these groups. A dMRI derived structural connectome was constructed for every participant using brain regions defined in AAL atlas as nodes, and the product of fiber number and average fractional anisotropy of the tracts connecting the nodes as edges. Our study identified a topological WM reorganization due to RHI in fighters prone to cognitive decline that was correlated with neuropsychological scores. Furthermore, graph-theoretical measures were correlated differentially with neuropsychological scores between groups. We also found differentiated WM connectivity involving regions of hippocampus, precuneus, and insula within our cohort of cognitively impaired fighters suggesting that there is a discernible WM topological reorganization in fighters prone to cognitive decline.
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http://dx.doi.org/10.1002/hbm.24761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865667PMC
December 2019

Awareness of Psychiatric Symptoms in a Mixed Clinical Sample of Older Adults.

J Geriatr Psychiatry Neurol 2020 05 11;33(3):124-134. Epub 2019 Aug 11.

Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.

Objective: This study examined the neuropsychological correlates and impact on caregiver distress of reduced awareness of mood symptoms in patients with suspected neurodegenerative disease.

Method: Records from a clinical sample of older adults were examined (N = 940).

Results: More than one-third of patient and caregiver ratings of mood symptoms did not agree (comparing patient and caregiver self-report measures); 27.9% of patients were unaware of depression (UoD) and 16.6% of patients were unaware of anxiety (UoA). The UoD group exhibited poorer verbal memory and executive abilities and the UoA group exhibited poorer verbal memory than those with preserved awareness. Unawareness was not associated with caregiver distress.

Conclusions: These findings highlight the importance of capturing informant report in clinical practice with older adults suspected of cognitive impairment. Unawareness of mood symptoms was related to memory dysfunction and-to a lesser extent-to executive abilities and may have implications for addressing patient and caregiver needs for disorders affecting these cognitive systems.
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http://dx.doi.org/10.1177/0891988719868311DOI Listing
May 2020

Tau and atrophy: domain-specific relationships with cognition.

Alzheimers Res Ther 2019 07 27;11(1):65. Epub 2019 Jul 27.

Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.

Background: Late-onset Alzheimer's disease (AD) is characterized by primary memory impairment, which then progresses towards severe deficits across cognitive domains. Here, we report how performance in cognitive domains relates to patterns of tau deposition and cortical thickness.

Methods: We analyzed data from 131 amyloid-β positive participants (55 cognitively normal, 46 mild cognitive impairment, 30 AD) of the Alzheimer's Disease Neuroimaging Initiative who underwent magnetic resonance imaging (MRI), flortaucipir (FTP) positron emission tomography, and neuropsychological testing. Surface-based vertex-wise and region-of-interest analyses were conducted between FTP and cognitive test scores, and between cortical thickness and cognitive test scores.

Results: FTP and thickness were differentially related to cognitive performance in several domains. FTP-cognition associations were more widespread than thickness-cognition associations. Further, FTP-cognition patterns reflected cortical systems that underlie different aspects of cognition.

Conclusions: Our findings indicate that AD-related decline in domain-specific cognitive performance reflects underlying progression of tau and atrophy into associated brain circuits. They also suggest that tau-PET may have better sensitivity to this decline than MRI-derived measures of cortical thickness.
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http://dx.doi.org/10.1186/s13195-019-0518-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661099PMC
July 2019

Performing Sparse Regularization and Dimension Reduction Simultaneously in Multimodal Data Fusion.

Front Neurosci 2019 3;13:642. Epub 2019 Jul 3.

Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States.

Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities. In CCA-based data fusion, principal component analysis (PCA) is frequently applied as a preprocessing step to reduce data dimension followed by CCA on dimension-reduced data. PCA, however, does not differentiate between informative voxels from non-informative voxels in the dimension reduction step. Sparse PCA (sPCA) extends traditional PCA by adding sparse regularization that assigns zero weights to non-informative voxels. In this study, sPCA is incorporated into CCA-based fusion analysis and applied on neuroimaging data. A cross-validation method is developed and validated to optimize the parameters in sPCA. Different simulations are carried out to evaluate the improvement by introducing sparsity constraint to PCA. Four fusion methods including sPCA+CCA, PCA+CCA, parallel ICA and sparse CCA were applied on structural and functional magnetic resonance imaging data of mild cognitive impairment subjects and normal controls. Our results indicate that sPCA significantly can reduce the impact of non-informative voxels and lead to improved statistical power in uncovering disease-related patterns by a fusion analysis.
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http://dx.doi.org/10.3389/fnins.2019.00642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618346PMC
July 2019

Gender Disparity in Referral for Definitive Care of Malignant Pleural Effusions.

J Surg Res 2019 12 17;244:409-416. Epub 2019 Jul 17.

Department of Thoracic Surgery, University of Michigan, Ann Arbor, Michigan. Electronic address:

Background: Gender disparities exist in cancer care. Malignant pleural effusions (MPEs) carry a poor prognosis and are managed by different physicians. This study sought to evaluate referral patterns and gender differences for definitive treatment and outcomes of MPE patients.

Materials And Methods: Patients diagnosed with MPE from 1999 to 2015 at a quaternary care hospital were retrospectively reviewed to obtain patient history, referral to thoracic surgery for definitive management, and outcomes. Analysis was performed using chi-squared/Fisher's exact test, logistic regression models, and multivariate analysis.

Results: 224/686 patients (32.7%) were referred to thoracic surgery. No survival difference existed between referral and nonreferral groups or referred patients who received or did not receive pleurodesis. 405 patients (59.0%) were women. Women were statistically significantly less likely to be referred than men (27.9% versus 39.5%, P = 0.0014). This disparity persisted when comorbidities were controlled for (P = 0.0004) and when gynecologic cancers (e.g., uterine, ovarian, but not including breast; 55 female patients) were excluded from analysis (28.9% versus 39.5%, P = 0.0049). Women had statistically significantly more thoracenteses (3.34 versus 2.19, P < 0.0001) and improved survival compared with males (median survival = 136 d versus 54; P = 0.0004).

Conclusions: Gender disparity exists in referral patterns for definitive management of MPE; women are less likely to be referred than men. Women have longer survival and a greater number of thoracenteses performed, despite a lower referral rate for definitive care. Further research is needed to understand the differences in referral rates and outcomes between men and women.
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http://dx.doi.org/10.1016/j.jss.2019.06.068DOI Listing
December 2019
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