Publications by authors named "John L Woodard"

78 Publications

Five-Year Change in Body Mass Index Predicts Conversion to Mild Cognitive Impairment or Dementia Only in APOE ɛ4 Allele Carriers.

J Alzheimers Dis 2021 ;81(1):189-199

Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.

Background: Body mass index (BMI) has been identified as an important modifiable lifestyle risk factor for dementia, but less is known about how BMI might interact with Apolipoprotein E ɛ4 (APOE ɛ4) carrier status to predict conversion to mild cognitive impairment (MCI) and dementia.

Objective: The aim of this study was to investigate the interaction between APOE ɛ4 status and baseline (bBMI) and five-year BMI change (ΔBMI) on conversion to MCI or dementia in initially cognitively healthy older adults.

Methods: The associations between bBMI, ΔBMI, APOE ɛ4 status, and conversion to MCI or dementia were investigated among 1,289 cognitively healthy elders from the National Alzheimer's Coordinating Center (NACC) database.

Results: After five years, significantly more carriers (30.6%) converted to MCI or dementia than noncarriers (17.6%), p < 0.001, OR = 2.06. Neither bBMI (OR = 0.99, 95%CI = 0.96-1.02) nor the bBMI by APOE interaction (OR = 1.02, 95%CI = 0.96-1.08) predicted conversion. Although ΔBMI also did not significantly predict conversion (OR = 0.90, 95%CI = 0.78-1.04), the interaction between ΔBMI and carrier status was significant (OR = 0.72, 95%CI = 0.53-0.98). For carriers only, each one-unit decline in BMI over five years was associated with a 27%increase in the odds of conversion (OR = 0.73, 95%CI = 0.57-0.94).

Conclusion: A decline in BMI over five years, but not bBMI, was strongly associated with conversion to MCI or dementia only for APOE ɛ4 carriers. Interventions and behaviors aimed at maintaining body mass may be important for long term cognitive health in older adults at genetic risk for AD.
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http://dx.doi.org/10.3233/JAD-201360DOI Listing
January 2021

Forward-focused coping predicts better mental health outcomes in mid- to late-life during the COVID-19 pandemic.

Aging Ment Health 2021 Mar 18:1-9. Epub 2021 Mar 18.

Department of Kinesiology, University of Maryland, College Park, MD, USA.

Psychosocial stressors associated with the COVID-19 pandemic may increase the risk of depression and anxiety in the general population. Individuals approaching or within older adulthood may be especially vulnerable to these psychosocial stressors and their impact on mental health outcomes. Consequently, there is an urgent need to identify protective factors for older adults. The purpose of the present study was to determine the relative contribution of coping flexibility (CF) and two distinct coping strategies, forward-focused and trauma-focused, on negative affect in persons 50 years of age and older during the COVID-19 pandemic. Data were collected using an online survey, including questions about demographic information, coping, depression, and anxiety. Participants aged 50 and over were included in our analyses of depression ( = 800) and anxiety ( = 638). Both higher CF and higher forward-focused coping predicted lower depression and lower anxiety. In contrast, higher trauma-focused coping predicted slightly higher depressive symptoms but was not a significant predictor of anxiety. Our findings suggest that higher forward-focused coping may serve as a protective factor in older adults during the pandemic and, therefore, may be an effective treatment target for mental health interventions.
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http://dx.doi.org/10.1080/13607863.2021.1897523DOI Listing
March 2021

Spouse-Appraised Memory Functioning Predicts Memory Decline Better Than Subjective Memory Complaints in Community Dwelling Older Adults at Genetic Risk for Alzheimer's Disease.

Front Psychiatry 2021 22;12:633102. Epub 2021 Feb 22.

Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.

Alzheimer's disease (AD) begins with subtle memory decline, years before dementia onset. The presence of subjective memory complaints (SMC) has been proposed as a marker of preclinical AD. However, recent evidence has demonstrated early and progressive loss of awareness of memory difficulties in non-demented older adults harboring AD pathology. We investigated the respective contributions of SMC and spouse-appraised memory functioning (SAM) to predict memory decline in a large cohort of community dwelling older adults. The Wisconsin Longitudinal Study collected cognitive data from a community-based cohort of 3,583 participants in both 2005 and 2011. The participant and the participant's spouse were each asked to rate the participant's memory functioning using a Likert scale. We predicted change in objective episodic memory with models including baseline SMC, baseline SAM, or both SMC and SAM. We also evaluated an awareness index (SMC minus SAM). We then tested the interaction between Apolipoprotein E (APOE ε4) carrier status and SMC/SAM to evaluate whether the effects were driven by individuals at-risk for AD pathology. In separate models, SMC (-0.081 ± 0.036, = 0.025) and SAM (-0.084 ± 0.278, = 0.003) were both associated with memory decline over ~6 years. However, the AI was not significantly associated with memory decline (0.031 ± 0.024, = 0.19). When both predictors were included in the same model, SAM (-0.074 ± 0.03, = 0.0092) was associated with memory decline, while SMC was not significant (-0.061 ± 0.04, = 0.99). The association between SAM and memory decline was stronger in the APOE ε4 carriers than in the non-carriers (APOE-by-SAM interaction: = 6.07; = 0.002), and follow up analyses revealed that SAM was particularly predictive of decline only for APOE ε4 carriers. The association between SMC and memory decline was independent of APOE ε4 carrier status (APOE-by-SMC interaction: = 2.29; = 0.13). Spouse-appraised memory functioning was more predictive of memory decline than SMC or an awareness index, particularly in APOE ε4 carriers, who are at increased risk for AD pathology.
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http://dx.doi.org/10.3389/fpsyt.2021.633102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937915PMC
February 2021

The Mental Health Benefits of Physical Activity in Older Adults Survive the COVID-19 Pandemic.

Am J Geriatr Psychiatry 2020 10 30;28(10):1046-1057. Epub 2020 Jun 30.

Department of Kinesiology, University of Maryland (DDC, NAA-N, LSJ, GSP, JW, JCS), College Park, MD; Program in Neuroscience and Cognitive Science, University of Maryland (DDC, LSJ, JCS), College Park, MD. Electronic address:

Objective: To determine the relationship between the amount and intensity of physical activity performed by older adults in North America (United States and Canada) and their depression and anxiety symptoms while currently under social distancing guidelines (SDG) for the COVID-19 pandemic.

Design: Descriptive cross-sectional study.

Setting: Online survey conducted between April 9 and April 30, 2020, during the COVD-19 pandemic.

Participants: About 1,046 older adults over the age of 50 who live in North America.

Measurements: Participants were asked about their basic demographic information, current health status, and the impact of the current SDG on their subjective state of mental health. Participants completed the Physical Activity Scale for the Elderly, to determine the amount and intensity of physical activity performed, as well as both the Geriatric Depression Scale and Geriatric Anxiety Scale, to ascertain the extent of their depression and anxiety-like symptoms.

Results: Ninety-seven percent of participants indicated that they adhered to current SDG "Most of the time" or "Strictly." Participants who performed greater levels of physical activity experienced lower levels of depression-like symptoms when age, sex, and education were accounted for; however, no relationship between physical activity and anxiety-like symptoms was found. A hierarchical regression analysis that incorporated the intensity of physical activity performed (light, moderate, and vigorous) in the model indicated that greater light and strenuous activity, but not moderate, predicted lower depression-like symptoms.

Conclusions: These results suggest that performing even light physical activity during the COVID-19 pandemic may help alleviate some of the negative mental health impacts that older adults may be experiencing while isolated and adhering to SDG during the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.jagp.2020.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831892PMC
October 2020

Defining a Centiloid scale threshold predicting long-term progression to dementia in patients attending the memory clinic: an [F] flutemetamol amyloid PET study.

Eur J Nucl Med Mol Imaging 2021 01 29;48(1):302-310. Epub 2020 Jun 29.

Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.

Purpose: To evaluate cerebral amyloid-β(Aβ) pathology in older adults with cognitive complaints, visual assessment of PET images is approved as the routine method for image interpretation. In research studies however, Aβ-PET semi-quantitative measures are associated with greater risk of progression to dementia; but until recently, these measures lacked standardization. Therefore, the Centiloid scale, providing standardized Aβ-PET semi-quantitation, was recently validated. We aimed to determine the predictive values of visual assessments and Centiloids in non-demented patients, using long-term progression to dementia as our standard of truth.

Methods: One hundred sixty non-demented participants (age, 54-86) were enrolled in a monocentric [F] flutemetamol Aβ-PET study. Flutemetamol images were interpreted visually following the manufacturers recommendations. SUVr values were converted to the Centiloid scale using the GAAIN guidelines. Ninety-eight persons were followed until dementia diagnosis or were clinically stable for a median of 6 years (min = 4.0; max = 8.0). Twenty-five patients with short follow-up (median = 2.0 years; min = 0.8; max = 3.9) and 37 patients with no follow-up were excluded. We computed ROC curves predicting subsequent dementia using baseline PET data and calculated negative (NPV) and positive (PPV) predictive values.

Results: In the 98 participants with long follow-up, Centiloid = 26 provided the highest overall predictive value = 87% (NPV = 85%, PPV = 88%). Visual assessment corresponded to Centiloid = 40, which predicted dementia with an overall predictive value = 86% (NPV = 81%, PPV = 92%). Inclusion of the 25 patients who only had a 2-year follow-up decreased the PPV = 67% (NPV = 88%), reflecting the many positive cases that did not progress to dementia after short follow-ups.

Conclusion: A Centiloid threshold = 26 optimally predicts progression to dementia 6 years after PET. Visual assessment provides similar predictive value, with higher specificity and lower sensitivity.

Trial Registration: Eudra-CT number: 2011-001756-12.
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http://dx.doi.org/10.1007/s00259-020-04942-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835306PMC
January 2021

Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers.

J Int Neuropsychol Soc 2020 08 5;26(7):733-738. Epub 2020 Mar 5.

Schey Center for Cognitive Neuroimaging, Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH44195, USA.

Objective: The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI.

Methods: Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65-85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted to z-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes.

Results: At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1-5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1-5 scores were significant predictors of MCI conversion.

Conclusions: Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.
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http://dx.doi.org/10.1017/S1355617720000181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423643PMC
August 2020

Cardiovascular health and cognitive functioning among centenarians: a comparison between the Tokyo and Georgia centenarian studies.

Int Psychogeriatr 2019 04 21;31(4):455-465. Epub 2019 Feb 21.

Keio University,Tokyo,Japan.

ABSTRACTObjectives:Centenarians have survived into very late life, but whether they reach very old age in good health remains unclear. The purpose of this study was to compare the cardiovascular health status and cognitive functioning of centenarians in the United States with centenarians in Japan.

Design, Setting, And Participants: This cross-national design compared centenarians from the United States and Japan. The sample of U.S. centenarians was recruited from the Georgia Centenarian Study and included 287 centenarians. The sample of Japanese centenarians was recruited from the Tokyo Centenarian Study and included 304 centenarians.

Measurements: Cognitive functioning was assessed with a mental status questionnaire, and cardiovascular disease by a health history assessment, blood pressure, and selected blood parameters.

Results: The results suggest that Tokyo centenarians had lower disease experiences and BMI values, when compared to Georgia centenarians, but blood pressure was higher among Japanese centenarians. Lower levels of hemoglobin in Japanese centenarians and higher levels of C-reactive protein in Georgia were also found. The positive association of hypertension and albumin levels with cognitive functioning and the negative association of stroke occurrence with cognitive functioning were replicated in both countries. Differential effects were obtained for heart problems, BMI, and C-reactive protein (with positive effects for Tokyo centenarians, except for C-reactive protein).

Conclusion: For extremely old individuals, some markers of cardiovascular disease are replicable across countries, whereas differential effects for cardiovascular health also need to be considered in cardiovascular health.
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http://dx.doi.org/10.1017/S1041610218001813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483832PMC
April 2019

Duration of Fame and Extent of Semantic Knowledge of Famous Names in Cognitively Intact Older Adults.

Arch Clin Neuropsychol 2019 Nov;34(8):1382-1391

Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.

Objective: The greater resilience of older memories relative to recent memories has primarily been demonstrated in clinical groups, but this phenomenon has been less extensively examined in cognitively intact older adults. Additionally, most studies of person-identity have only examined recognition or familiarity of a famous face or name, and there has been less systematic study of access to more specific person-identity semantic knowledge. The current study examined the effect of both memory age and extent of semantic knowledge on famous name recognition and retrieval of person-identity biographical information in healthy older adults.

Method: We examined recognition accuracy and response time of famous names at three time epochs (recent fame, transitory fame and enduring fame) in cognitively intact older adults. We also compared access to semantic knowledge that differed on the degree of specificity of biographical information: categorical, associative, and attribute knowledge.

Results: As predicted, participants recognized transitory famous names more quickly and accurately than recent famous names. Additionally, participants recognized enduring famous names more accurately than transitory famous names and recent names. We also found that categorical semantic knowledge was accessed more quickly and accurately than semantic knowledge for associative and attribute information.

Conclusions: These findings provide data on the cognitive structure and retrieval of person-identity knowledge and memory age in older cognitively intact individuals.
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http://dx.doi.org/10.1093/arclin/acy109DOI Listing
November 2019

The fear of Alzheimer's disease: mediating effects of anxiety on subjective memory complaints.

Aging Ment Health 2020 02 9;24(2):308-314. Epub 2018 Nov 9.

Department of Psychology, Rosalind Franklin University of Medicine and Science, Chicago, IL, USA.

To determine if the fear of developing Alzheimer's disease (FDAD) construct, in combination with similar psychoemotional factors, could help elucidate the nature of older adults' subjective memory complaints (SMCs) and subsequent objective memory performance. One hundred ninety-three healthy older adults (aged 65-93) were administered clinician and self-report measures of depression, worry, anxiety, illness attitudes, and memory, and each rated their concern with developing AD. Self-reported FDAD was not associated with objective memory performance ( > .05). FDAD, trait anxiety, general anxiety, and general and illness-related worry were independently associated with subjective memory report ( < .05). The relationship between FDAD and subjective memory report was mediated by measures of general trait and state anxiety, but not general worry or illness-specific worry. FDAD was not associated with objective memory functioning, suggesting AD concerns were not reflective of memory pathology. The mediating effect of anxiety on the relationship between FDAD and subjective memory report suggests that assessment of anxiety, beyond AD fear, may help identify older adults at risk for developing negative perceptions of memory and related distress.
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http://dx.doi.org/10.1080/13607863.2018.1534081DOI Listing
February 2020

Convergent Synthesis of the NS5B Inhibitor GSK8175 Enabled by Transition Metal Catalysis.

J Org Chem 2019 04 29;84(8):4680-4694. Epub 2018 Oct 29.

API Chemistry , GlaxoSmithKline , King of Prussia , Pennsylvania 19406 , United States.

A convergent eight-stage synthesis of the boron-containing NS5B inhibitor GSK8175 is described. The previous route involves 13 steps in a completely linear sequence, with an overall 10% yield. Key issues include a multiday SAr arylation of a secondary sulfonamide using HMPA as solvent, multiple functional group interconversions after all of the carbon atoms are installed (including a Sandmeyer halogenation), use of carcinogenic chloromethyl methyl ether to install a protecting group late in the synthesis, and an unreliable Pd-catalyzed Miyaura borylation as the penultimate step. We have devised an orthogonal approach using a Chan-Lam coupling between a halogenated aryl pinacol boronate ester and an aryl methanesulfonamide. This reaction is performed using a cationic Cu(I) precatalyst, which can be easily generated in situ using KPF as a halide abstractor. High-throughput screening revealed a new Pd catalyst system to effect the penultimate borylation chemistry using simple monodentate phosphine ligands, with PCyPh identified as optimal. Reaction progress analysis of this borylation indicated likely mass-transfer rate limitations under standard conditions using KOAc as the base. We have devised a KCO/pivalic acid system as an alternative, which dramatically outperforms the standard conditions. This new synthesis proceeds in eight stages with a 20% overall yield.
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http://dx.doi.org/10.1021/acs.joc.8b02269DOI Listing
April 2019

Physical, sensory, and cognitive functioning among centenarians: a comparison between the Tokyo and Georgia centenarian studies.

Qual Life Res 2018 Nov 26;27(11):3037-3046. Epub 2018 Jul 26.

School of Medicine, Keio University, 2 Chome-15-45 Mita, Minato-ku, Tokyo, 108-8345, Japan.

Purpose: The purpose of this study was to compare centenarians in the United States and Japan on sensory, cognitive, and physical functioning and to evaluate a model that tests the interrelationship between physical function, cognition, and sensory impairment in these two unique samples of the oldest old.

Methods: The sample of U. S. centenarians included 245 centenarians, the sample of Japanese centenarians included 304 centenarians. Sensory impairment was assessed by general assessments of vision and hearing, and physical function was assessed with six physical activities of daily living (i.e., eating, grooming, dressing, transporting, bathing, and walking).

Results: The results suggest that centenarians from the Georgia study showed higher levels of functioning in all domains when compared to the Tokyo sample. A structural equation model yielded stronger associations between cognitive and sensory function with physical function for the Tokyo sample.

Conclusions: Functional differences may be due, in part, to different care patterns for the oldest old in the United States when compared to Japan.
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http://dx.doi.org/10.1007/s11136-018-1943-zDOI Listing
November 2018

Differential 5-year brain atrophy rates in cognitively declining and stable APOE-ε4 elders.

Neuropsychology 2018 Sep 18;32(6):647-653. Epub 2018 Jun 18.

Schey Center for Cognitive Neuroimaging, Cleveland Clinic.

Objective: The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for late-onset Alzheimer's disease. Many ε4 carriers, however, never develop Alzheimer's disease. The purpose of this study is to characterize the variability in phenotypic expression of the ε4 allele, as measured by the longitudinal trajectory of cognitive test scores and MRI brain volumes, in cognitively intact elders.

Method: Healthy older adults, ages 65-85, participated in a 5-year longitudinal study that included structural MRI and cognitive testing administered at baseline and at 1.5 and 5 years postenrollment. Participants included 22 ε4 noncarriers, 15 ε4 carriers who experienced a decline in cognition over the 5-year interval, and 11 ε4 carriers who remained cognitively stable.

Results: No baseline cognitive or volumetric group differences were observed. Compared to noncarriers, declining ε4 carriers had significantly greater rates of atrophy in left (p = .001, Cohen's d = .691) and right (p = .003, d = .622) cortical gray matter, left (p = .003, d = .625) and right (p = .020, d = .492) hippocampi, and greater expansion of the right inferior lateral ventricle (p < .001, d = .751) over 5 years.

Conclusions: This study illustrates the variability in phenotypic expression of the ε4 allele related to neurodegeneration. Specifically, only those individuals who exhibited longitudinal declines in cognitive function experienced concomitant changes in brain volume. Future research is needed to better understand the biological and lifestyle factors that may influence the expression of the ε4 allele. (PsycINFO Database Record
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http://dx.doi.org/10.1037/neu0000444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126943PMC
September 2018

The recency ratio as predictor of early MCI.

Int Psychogeriatr 2018 12 18;30(12):1883-1888. Epub 2018 Apr 18.

Geriatric Research Education and Clinical Center,Wm. S. Middleton Veterans Hospital,Madison,Wisconsin,USA.

ABSTRACTObjectives:Individuals with Alzheimer's disease (AD) present poor immediate primacy recall accompanied by intact or exaggerated recency, which then tends to decline after a delay. Bruno et al. (Journal of Clinical and Experimental Neuropsychology, Vol. 38, 2016, pp. 967-973) have shown that higher ratio scores between immediate and delayed recency (i.e. the recency ratio; Rr) are associated with cognitive decline in high-functioning older individuals. We tested whether Rr predicted conversion to early mild cognitive impairment (early MCI) from a cognitively healthy baseline.

Design: Data were analyzed longitudinally with binomial regression. Baseline scores were used to predict conversion to early MCI after approximately nine years.

Setting: Data were collected at the Wisconsin Registry of Alzheimer's Prevention, in Madison, Wisconsin.

Participants: For the study, 427 individuals were included in the analysis; all participants were 50 years of age or older and cognitively intact at baseline, and were native English speakers.

Measurements: Memory data were collected using the Rey's Auditory Verbal Learning Test, and the early MCI diagnosis was obtained via consensus conference.

Results: Our results showed that higher Rr scores are correlated with greater risk of later early MCI diagnosis, and this association is independent of total recall performance.

Conclusions: Rr is an emerging cognitive marker of cognitive decline.
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http://dx.doi.org/10.1017/S1041610218000467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193873PMC
December 2018

Synthesis and antiproliferative activity of derivatives of the phyllanthusmin class of arylnaphthalene lignan lactones.

Bioorg Med Chem 2018 05 23;26(9):2354-2364. Epub 2018 Mar 23.

Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States. Electronic address:

A series of arylnaphthalene lignan lactones based on the structure of the phyllanthusmins, a class of potent natural products possessing diphyllin as the aglycone, has been synthesized and screened for activity against multiple cancer cell lines. SAR exploration was performed on both the carbohydrate and lactone moieties of this structural class. These studies have revealed the importance of functionalization of the carbohydrate hydroxy groups with both acetylated and methylated analogues showing increased potency relative to those with unsubstituted sugar moieties. In addition, the requirement for the presence and position of the C-ring lactone has been demonstrated through reduction and selective re-oxidation of the lactone ring. The most potent compound in this study displayed an IC value of 18 nM in an HT-29 assay with several others ranging from 50 to 200 nM. In an effort to elucidate their potential mechanism(s) of action, the DNA topoisomerase IIa inhibitory activity of the most potent compounds was examined based on previous reports of structurally similar compounds, but does not appear to contribute significantly to their antiproliferative effects.
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http://dx.doi.org/10.1016/j.bmc.2018.03.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962029PMC
May 2018

Guillain-BarrÉ syndrome subtype diagnosis: A prospective multicentric European study.

Muscle Nerve 2018 Jan 5. Epub 2018 Jan 5.

Centre de référence des maladies Neuromusculaires et la SLA. Hôpital de la Timone, Marseille, France.

Introduction: There is uncertainty as to whether the Guillain-Barré syndrome (GBS) subtypes, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), can be diagnosed electrophysiologically.

Methods: We prospectively included 58 GBS patients. Electrodiagnostic testing (EDX) was performed at means of 5 and 33 days after disease onset. Two traditional and one recent criteria sets were used to classify studies as demyelinating or axonal. Results were correlated with anti-ganglioside antibodies and reversible conduction failure (RCF).

Results: No classification shifts were observed, but more patients were classified as axonal with recent criteria. RCF and anti-ganglioside antibodies were present in both subtypes, more frequently in the axonal subtype.

Discussion: Serial EDX has no effect on GBS subtype proportions. The absence of exclusive correlation with RCF and anti-ganglioside antibodies may challenge the concept of demyelinating and axonal GBS subtypes based upon electrophysiological criteria. Frequent RCF indicates that nodal/paranodal alterations may represent the main pathophysiology. Muscle Nerve, 2018.
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http://dx.doi.org/10.1002/mus.26056DOI Listing
January 2018

A quarter century of advances in the statistical analysis of longitudinal neuropsychological data.

Authors:
John L Woodard

Neuropsychology 2017 11 22;31(8):1020-1035. Epub 2017 Jun 22.

Wayne State University.

Objective: Over the last 25 years, there has been an unprecedented increase in federal funding for large-scale longitudinal studies, many of which collect neuropsychological or neuroimaging outcome measures. These studies have collected data from thousands of study participants across multiple waves of data collection over many years. With the increased availability of longitudinal data, data sharing policies have become more liberal, thereby offering significant opportunities for interested researchers to carry out their own longitudinal research with these data. At the same time, these opportunities have stimulated new conceptualizations of longitudinal change and have led to the development of novel approaches toward analysis of longitudinal data. My aim is to review these new conceptualizations and novel data analytic approaches.

Method: In this article, I describe the state of the field a quarter century ago with respect to available longitudinal studies, and I trace the growth of federally funded longitudinal studies over the last 25 years by describing 18 of these projects, many of which are still collecting data. In the second part of this article, I describe changes in the methods used to analyze longitudinal data, transitioning from the paired t test and repeated measures ANOVA to latent change scores, linear mixed effects modeling, and latent growth curve models. Changes in the approach to management of missing data are also discussed.

Conclusions: Future studies should abandon traditional longitudinal analytic methods in favor of contemporary approaches given their increased power, greater accuracy, and widespread availability. (PsycINFO Database Record
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http://dx.doi.org/10.1037/neu0000386DOI Listing
November 2017

Motor timing intraindividual variability in amnestic mild cognitive impairment and cognitively intact elders at genetic risk for Alzheimer's disease.

J Clin Exp Neuropsychol 2017 Nov 4;39(9):866-875. Epub 2017 Jan 4.

f Neurological Institute , Cleveland Clinic , Cleveland , OH , USA.

Introduction: Intraindividual variability (IIV) in motor performance has been shown to predict future cognitive decline. The apolipoprotein E-epsilon 4 (APOE-ε4) allele is also a well-established risk factor for memory decline. Here, we present novel findings examining the influence of the APOE-ε4 allele on the performance of asymptomatic healthy elders in comparison to individuals with amnestic MCI (aMCI) on a fine motor synchronization, paced finger-tapping task (PFTT).

Method: Two Alzheimer's disease (AD) risk groups, individuals with aMCI (n = 24) and cognitively intact APOE-ε4 carriers (n = 41), and a control group consisting of cognitively intact APOE-ε4 noncarriers (n = 65) completed the Rey Auditory Verbal Learning Test and the PFTT, which requires index finger tapping in synchrony with a visual stimulus (interstimulus interval = 333 ms).

Results: Motor timing IIV, as reflected by the standard deviation of the intertap interval (ITI), was greater in the aMCI group than in the two groups of cognitively intact elders; in contrast, all three groups had statistically equivalent mean ITI. No significant IIV differences were observed between the asymptomatic APOE-ε4 carriers and noncarriers. Poorer episodic memory performance was associated with greater IIV, particularly in the aMCI group.

Conclusions: Results suggest that increased IIV on a fine motor synchronization task is apparent in aMCI. This IIV measure was not sensitive in discriminating older asymptomatic individuals at genetic risk for AD from those without such a genetic risk. In contrast, episodic memory performance, a well-established predictor of cognitive decline in preclinical AD, was able to distinguish between the two cognitively intact groups based on genetic risk.
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http://dx.doi.org/10.1080/13803395.2016.1273321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916765PMC
November 2017

Diffusion Tensor Imaging Predictors of Episodic Memory Decline in Healthy Elders at Genetic Risk for Alzheimer's Disease.

J Int Neuropsychol Soc 2016 11;22(10):1005-1015

6Neurological Institute,Cleveland Clinic,Cleveland,Ohio.

Objectives: White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer's disease (AD).

Methods: Fifty-one cognitively intact elders (52% with family history (FH) of dementia and 33% possessing an Apolipoprotein E ε4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up. DTI scanning, conducted at study entry, examined fractional anisotropy and mean, radial and axial diffusion within three MTL WM tracts: uncinate fasciculus (UNC), cingulate-hippocampal (CHG), and fornix-stria terminalis (FxS). Correlations were performed between residualized change scores computed from RAVLT trials 1-5, immediate recall, and delayed recall scores and baseline DTI measures; MTL gray matter (GM) and WM volumes; demographics; and AD genetic and metabolic risk factors.

Results: Higher MTL mean and axial diffusivity at baseline significantly predicted 3-year changes in EM, whereas baseline MTL GM and WM volumes, FH, and metabolic risk factors did not. Both ε4 status and DTI correlated with change in immediate recall.

Conclusions: Longitudinal EM changes in cognitively intact, healthy elders can be predicted by disruption of the MTL WM microstructure. These results are derived from a sample with a disproportionately higher genetic risk for AD, suggesting that the observed WM disruption in MTL pathways may be related to early neuropathological changes associated with the preclinical stage of AD. (JINS, 2016, 22, 1005-1015).
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http://dx.doi.org/10.1017/S1355617716000904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916766PMC
November 2016

Prediction of Free and Cued Selective Reminding Test Performance Using Volumetric and Amyloid-Based Biomarkers of Alzheimer's Disease.

J Int Neuropsychol Soc 2016 11;22(10):991-1004

1Institute of Neuroscience,Université Catholique de Louvain,Brussels,Belgium.

Objectives: Relatively few studies have investigated relationships between performance on clinical memory measures and indexes of underlying neuropathology related to Alzheimer's disease (AD). This study investigated predictive relationships between Free and Cued Selective Reminding Test (FCSRT) cue efficiency (CE) and free-recall (FR) measures and brain amyloid levels, hippocampal volume (HV), and regional cortical thickness.

Methods: Thirty-one older controls without memory complaints and 60 patients presenting memory complaints underwent the FCSRT, amyloid imaging using [F18]-flutemetamol positron emission tomography, and surface-based morphometry (SBM) using brain magnetic resonance imaging. Three groups were considered: patients with high (Aβ+P) and low (Aβ- P) amyloid load and controls with low amyloid load (Aβ- C).

Results: Aβ+P showed lower CE than both Aβ- groups, but the Aβ- groups did not differ significantly. In contrast, FR discriminated all groups. SBM analyses revealed that CE indexes were correlated with the cortical thickness of a wider set of left-lateralized temporal and parietal regions than FR. Regression analyses demonstrated that amyloid load and left HV independently predicted FCSRT scores. Moreover, CE indexes were predicted by the cortical thickness of some regions involved in early AD, such as the entorhinal cortex.

Conclusions: Compared to FR measures, CE indexes appear to be more specific for differentiating persons on the basis of amyloid load. Both CE and FR performance were predicted independently by brain amyloid load and reduced left HV. However, CE performance was also predicted by the cortical thickness of regions known to be atrophic early in AD. (JINS, 2016, 22, 991-1004).
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http://dx.doi.org/10.1017/S1355617716000813DOI Listing
November 2016

Five-Year Longitudinal Brain Volume Change in Healthy Elders at Genetic Risk for Alzheimer's Disease.

J Alzheimers Dis 2017 ;55(4):1363-1377

Schey Center for Cognitive Neuroimaging, Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.

Neuropathological changes associated with Alzheimer's disease (AD) precede symptom onset by more than a decade. Possession of an apolipoprotein E (APOE) ɛ4 allele is the strongest genetic risk factor for late onset AD. Cross-sectional studies of cognitively intact elders have noted smaller hippocampal/medial temporal volumes in ɛ4 carriers (ɛ4+) compared to ɛ4 non-carriers (ɛ4-). Few studies, however, have examined long-term, longitudinal, anatomical brain changes comparing healthy ɛ4+ and ɛ4- individuals. The current five-year study examined global and regional volumes of cortical and subcortical grey and white matter and ventricular size in 42 ɛ4+ and 30 ɛ4- individuals. Cognitively intact participants, ages 65-85 at study entry, underwent repeat anatomical MRI scans on three occasions: baseline, 1.5, and 4.75 years. Results indicated no between-group volumetric differences at baseline. Over the follow-up interval, the ɛ4+ group experienced a greater rate of volume loss in total grey matter, bilateral hippocampi, right hippocampal subfields, bilateral lingual gyri, bilateral parahippocampal gyri, and right lateral orbitofrontal cortex compared to the ɛ4- group. Greater loss in grey matter volumes in ɛ4+ participants were accompanied by greater increases in lateral, third, and fourth ventricular volumes. Rate of change in white matter volumes did not differentiate the groups. The current results indicate that longitudinal measurements of brain atrophy can serve as a sensitive biomarker for identifying neuropathological changes in persons at genetic risk for AD and potentially, for assessing the efficacy of treatments designed to slow or prevent disease progression during the preclinical stage of AD.
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http://dx.doi.org/10.3233/JAD-160504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924681PMC
February 2018

Does cognitive self-consciousness link older adults' cognitive functioning to obsessive-compulsive symptoms?

Behav Res Ther 2016 10 31;85:23-32. Epub 2016 Jul 31.

Department of Psychology, Wayne State University, USA.

To elucidate how obsessional symptoms might develop or intensify in late-life, we tested a risk model. We posited that cognitive self-consciousness (CSC), a tendency to be aware of and monitor thinking, would increase reactivity to aging-related cognitive changes and mediate the relationship between cognitive functioning and obsessive-compulsive disorder (OCD) symptoms. Older adults (Mage = 76.7 years) completed the Dementia Rating Scale-2 (DRS-2), a CSC measure, and an OCD symptom measure up to four times over 18 months. A model that included DRS-2 age and education adjusted total score as the indicator of cognitive functioning fit the data well, and CSC score change mediated the relationship between initial cognitive functioning and changes in OCD symptoms. In tests of a model that included DRS-2 Initiation/Perseveration (I/P) and Conceptualization subscale scores, the model again fit the data well. Conceptualization scores, but not I/P scores, were related to later OCD symptoms, and change in CSC scores again mediated the relationship. Lower scores on initial cognitive functioning measures predicted increases in CSC scores over time, which in turn predicted increases in OCD symptoms over the 18 months of the study. Implications for understanding late-life obsessional problems are discussed.
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http://dx.doi.org/10.1016/j.brat.2016.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026964PMC
October 2016

Brain pathologies in extreme old age.

Neurobiol Aging 2016 Jan 19;37:1-11. Epub 2015 Oct 19.

Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA. Electronic address:

With an emphasis on evolving concepts in the field, we evaluated neuropathologic data from very old research volunteers whose brain autopsies were performed at the University of Kentucky Alzheimer's Disease Center, incorporating data from the Georgia Centenarian Study (n = 49 cases included), Nun Study (n = 17), and University of Kentucky Alzheimer's Disease Center (n = 11) cohorts. Average age of death was 102.0 (range: 98-107) years overall. Alzheimer's disease pathology was not universal (62% with "moderate" or "frequent" neuritic amyloid plaque densities), whereas frontotemporal lobar degeneration was absent. By contrast, some hippocampal neurofibrillary tangles (including primary age-related tauopathy) were observed in every case. Lewy body pathology was seen in 16.9% of subjects and hippocampal sclerosis of aging in 20.8%. We describe anatomic distributions of pigment-laden macrophages, expanded Virchow-Robin spaces, and arteriolosclerosis among Georgia Centenarians. Moderate or severe arteriolosclerosis pathology, throughout the brain, was associated with both hippocampal sclerosis of aging pathology and an ABCC9 gene variant. These results provide fresh insights into the complex cerebral multimorbidity, and a novel genetic risk factor, at the far end of the human aging spectrum.
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http://dx.doi.org/10.1016/j.neurobiolaging.2015.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688098PMC
January 2016

Interactive effects of physical activity and APOE-ε4 on white matter tract diffusivity in healthy elders.

Neuroimage 2016 05 8;131:102-12. Epub 2015 Aug 8.

Schey Center for Cognitive Neuroimaging, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave/U10, Cleveland, OH 44195, USA. Electronic address:

Older adult apolipoprotein-E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer's disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts.
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http://dx.doi.org/10.1016/j.neuroimage.2015.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746115PMC
May 2016

Trichormamides C and D, antiproliferative cyclic lipopeptides from the cultured freshwater cyanobacterium cf. Oscillatoria sp. UIC 10045.

Bioorg Med Chem 2015 Jul 1;23(13):3153-62. Epub 2015 May 1.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60612, United States. Electronic address:

Extract from the cultured freshwater cf. Oscillatoria sp. UIC 10045 showed antiproliferative activity against HT-29 cell line. Bioassay-guided fractionation led to the isolation of two new cyclic lipopeptides, named trichormamides C (1) and D (2). The planar structures were determined by combined analyses of HRESIMS, Q-TOF ESIMS/MS, and 1D and 2D NMR spectra. The absolute configurations of the amino acid residues were assigned by advanced Marfey's analysis after partial and complete acid hydrolysis. Trichormamides C (1) is a cyclic undecapeptide and D (2) is a cyclic dodecapeptide, both containing a lipophilic β-aminodecanoic acid residue. Trichormamide C (1) displayed antiproliferative activities against HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 1.7 and 1.0μM, respectively, as well as anti-Mycobacterium tuberculosis activity with MIC value of 23.8μg/mL (17.3μM). Trichormamide D (2) was found to be less potent against both HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 11.5 and 11.7μM, respectively.
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http://dx.doi.org/10.1016/j.bmc.2015.04.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469202PMC
July 2015

Genetic risk for Alzheimer's disease alters the five-year trajectory of semantic memory activation in cognitively intact elders.

Neuroimage 2015 May 14;111:136-46. Epub 2015 Feb 14.

Department of Neurology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer's disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE ε4 carriers (N=24) and non-carriers (N=21). All participants, ages 65-85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57 months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE ε4 carriers and non-carriers. The APOE ε4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the onset of cognitive symptoms and increased structural brain pathology. Our fMRI results could not be attributed to changes in task performance, group differences in cerebral perfusion, or regional cortical atrophy.
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http://dx.doi.org/10.1016/j.neuroimage.2015.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387085PMC
May 2015

Octogenarian and centenarian performance on the Fuld Object Memory Evaluation.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2015 16;22(4):438-51. Epub 2014 Dec 16.

a Department of Psychology , Wayne State University , Detroit , MI , USA.

The Fuld Object Memory Evaluation (FOME) has considerable utility for cognitive assessment in older adults, but there are few normative data, particularly for the oldest old. In this study, 80 octogenarians and 244 centenarians from the Georgia Centenarian Study completed the FOME. Total and trial-to-trial performance on the storage, retrieval, repeated retrieval, and ineffective reminder indices were assessed. Additional data stratified by age group, education, and cognitive impairment are provided in the Supplemental data. Octogenarians performed significantly better than centenarians on all FOME measures. Neither age group benefitted from additional learning trials beyond Trial 3 for storage and Trial 2 for retention and retrieval. Ineffective reminders showed no change across learning trials for octogenarians, while centenarians improved only between Trials 1 and 2. This minimal improvement past Trial 2 indicates that older adults might benefit from a truncated version of the test that does not include trials three through five, with the added benefit of reducing testing burden in this population.
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http://dx.doi.org/10.1080/13825585.2014.968085DOI Listing
January 2016

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses.

J Neurotrauma 2015 Jul 6;32(14):1031-45. Epub 2015 Mar 6.

1 Department of Biomedical Engineering, Wayne State University , Detroit, Michigan.

Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting.
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http://dx.doi.org/10.1089/neu.2014.3610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504339PMC
July 2015

Trichormamides A and B with Antiproliferative Activity from the Cultured Freshwater Cyanobacterium Trichormus sp. UIC 10339.

J Nat Prod 2014 Aug 4;77(8):1871-80. Epub 2014 Aug 4.

†Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, Illinois 60612, United States.

Two new cyclic lipopeptides, trichormamides A (1) and B (2), were isolated from the cultured freshwater cyanobacterium Trichormus sp. UIC 10339. The strain was obtained from a sample collected in Raven Lake in Northern Wisconsin. The planar structures of trichormamides A (1) and B (2) were determined using a combination of spectroscopic analyses including HRESIMS and 1D and 2D NMR experiments. The absolute configurations of the amino acid residues were assigned by the advanced Marfey's method after acid hydrolysis. Trichormamide A (1) is a cyclic undecapeptide containing two D-amino acid residues (D-Tyr and D-Leu) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) is a cyclic dodecapeptide characterized by the presence of four nonstandard α-amino acid residues (homoserine, N-methylisoleucine, and two 3-hydroxyleucines) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) was cytotoxic against MDA-MB-435 and HT-29 cancer cell lines with IC50 values of 0.8 and 1.5 μM, respectively.
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http://dx.doi.org/10.1021/np5003548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143178PMC
August 2014

Assessing Older Adults' Obsessive-Compulsive Disorder Symptoms: Psychometric Characteristics of the Obsessive Compulsive Inventory-Revised.

J Obsessive Compuls Relat Disord 2014 Apr;3(2):124-131

Eastern Illinois University.

The lack of Obsessive-Compulsive disorder (OCD) symptom measures validated for use with older adults has hindered research and treatment development for the age group. We evaluated the Obsessive-Compulsive Inventory-Revised (OCI-R; Foa et al., 2002) with participants aged 65 and older ( = 180) to determine if the measure was an effective tool for evaluating obsessional symptoms. Participants completed the OCI-R and a comprehensive assessment battery up to four times over approximately 18 months. Results supported the well-replicated latent structure of the OCI-R (i.e., Washing, Checking, Ordering, Obsessing, Hoarding, and Neutralizing.). OCI-R total score was robustly associated with OCD symptoms assessed 18 months later by clinical interview, while scores on self-report measures of worry, general anxiety, and depression were not. Results indicate the OCI-R is an effective OCD symptom measure for older adults, although replication with additional older adult samples is needed.
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http://dx.doi.org/10.1016/j.jocrd.2014.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059555PMC
April 2014

Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease.

Front Aging Neurosci 2014 23;6:61. Epub 2014 Apr 23.

Cleveland Clinic, Schey Center for Cognitive Neuroimaging, Neurological Institute Cleveland, OH, USA.

We examined the impact of physical activity (PA) on longitudinal change in hippocampal volume in cognitively intact older adults at varying genetic risk for the sporadic form of Alzheimer's disease (AD). Hippocampal volume was measured from structural magnetic resonance imaging (MRI) scans administered at baseline and at an 18-month follow-up in 97 healthy, cognitively intact older adults. Participants were classified as High or Low PA based on a self-report questionnaire of frequency and intensity of exercise. Risk status was defined by the presence or absence of the apolipoprotein E-epsilon 4 (APOE-ε4) allele. Four subgroups were studied: Low Risk/High PA (n = 24), Low Risk/Low PA (n = 34), High Risk/High PA (n = 22), and High Risk/Low PA (n = 17). Over the 18 month follow-up interval, hippocampal volume decreased by 3% in the High Risk/Low PA group, but remained stable in the three remaining groups. No main effects or interactions between genetic risk and PA were observed in control brain regions, including the caudate, amygdala, thalamus, pre-central gyrus, caudal middle frontal gyrus, cortical white matter (WM), and total gray matter (GM). These findings suggest that PA may help to preserve hippocampal volume in individuals at increased genetic risk for AD. The protective effects of PA on hippocampal atrophy were not observed in individuals at low risk for AD. These data suggest that individuals at genetic risk for AD should be targeted for increased levels of PA as a means of reducing atrophy in a brain region critical for the formation of episodic memories.
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http://dx.doi.org/10.3389/fnagi.2014.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005962PMC
May 2014