Browsing by Subject "Neuropsychology"
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Item A comparison of techniques for deriving clustering and switching scores from verbal fluency word lists(Frontiers Media, 2022-09-14) Bushnell, Justin; Svaldi, Diana; Ayers, Matthew R.; Gao, Sujuan; Unverzagt, Frederick; Del Gaizo, John; Wadley, Virginia G.; Kennedy, Richard; Goñi, Joaquín; Clark, David Glenn; Neurology, School of MedicineObjective: To compare techniques for computing clustering and switching scores in terms of agreement, correlation, and empirical value as predictors of incident cognitive impairment (ICI). Methods: We transcribed animal and letter F fluency recordings on 640 cases of ICI and matched controls from a national epidemiological study, amending each transcription with word timings. We then calculated clustering and switching scores, as well as scores indexing speed of responses, using techniques described in the literature. We evaluated agreement among the techniques with Cohen's κ and calculated correlations among the scores. After fitting a base model with raw scores, repetitions, and intrusions, we fit a series of Bayesian logistic regression models adding either clustering and switching scores or speed scores, comparing the models in terms of several metrics. We partitioned the ICI cases into acute and progressive cases and repeated the regression analysis for each group. Results: For animal fluency, we found that models with speed scores derived using the slope difference algorithm achieved the best values of the Watanabe-Akaike Information Criterion (WAIC), but with good net reclassification improvement (NRI) only for the progressive group (8.2%). For letter fluency, different models excelled for prediction of acute and progressive cases. For acute cases, NRI was best for speed scores derived from a network model (3.4%), while for progressive cases, the best model used clustering and switching scores derived from the same network model (5.1%). Combining variables from the best animal and letter F models led to marginal improvements in model fit and NRI only for the all-cases and acute-cases analyses. Conclusion: Speed scores improve a base model for predicting progressive cognitive impairment from animal fluency. Letter fluency scores may provide complementary information.Item Assessing and validating reliable change across ADNI protocols(Taylor & Francis, 2022) Hammers, Dustin B.; Kostadinova, Ralitsa; Unverzagt, Frederick W.; Apostolova, Liana G.; Alzheimer’s Disease Neuroimaging Initiative; Neurology, School of MedicineObjective: Reliable change methods can aid in determining whether changes in cognitive performance over time are meaningful. The current study sought to develop and cross-validate 12-month standardized regression-based (SRB) equations for the neuropsychological measures commonly administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI) longitudinal study. Method: Prediction algorithms were developed using baseline score, retest interval, the presence/absence of a 6-month evaluation, age, education, sex, and ethnicity in two different samples (n = 192 each) of robustly cognitively intact community-dwelling older adults from ADNI - matched for demographic and testing factors. The developed formulae for each sample were then applied to one of the samples to determine goodness-of-fit and appropriateness of combining samples for a single set of SRB equations. Results: Minimal differences were seen between Observed 12-month and Predicted 12-month scores on most neuropsychological tests from ADNI, and when compared across samples the resultant Predicted 12-month scores were highly correlated. As a result, samples were combined and SRB prediction equations were successfully developed for each of the measures. Conclusions: Establishing cross-validation for these SRB prediction equations provides initial support of their use to detect meaningful change in the ADNI sample, and provides the basis for future research with clinical samples to evaluate potential clinical utility. While some caution should be considered for measuring true cognitive change over time - particularly in clinical samples - when using these prediction equations given the relatively lower coefficients of stability observed, use of these SRBs reflects an improvement over current practice in ADNI.Item Associating Persistent Self-Reported Cognitive Decline with Neurocognitive Decline in Older Breast Cancer Survivors Using Machine Learning: The Thinking and Living with Cancer Study(Elsevier, 2022) Van Dyk, Kathleen; Ahn, Jaeil; Zhou, Xingtao; Zhai, Wanting; Ahles, Tim A.; Bethea, Traci N.; Carroll, Judith E.; Cohen, Harvey Jay; Dilawari, Asma A.; Graham, Deena; Jacobsen, Paul B.; Jim, Heather; McDonald, Brenna C.; Nakamura, Zev M.; Patel, Sunita K.; Rentscher, Kelly E.; Saykin, Andrew J.; Small, Brent J.; Mandelblatt, Jeanne S.; Root, James C.; Radiology and Imaging Sciences, School of MedicineIntroduction: Many cancer survivors report cognitive problems following diagnosis and treatment. However, the clinical significance of patient-reported cognitive symptoms early in survivorship can be unclear. We used a machine learning approach to determine the association of persistent self-reported cognitive symptoms two years after diagnosis and neurocognitive test performance in a prospective cohort of older breast cancer survivors. Materials and methods: We enrolled breast cancer survivors with non-metastatic disease (n = 435) and age- and education-matched non-cancer controls (n = 441) between August 2010 and December 2017 and followed until January 2020; we excluded women with neurological disease and all women passed a cognitive screen at enrollment. Women completed the FACT-Cog Perceived Cognitive Impairment (PCI) scale and neurocognitive tests of attention, processing speed, executive function, learning, memory and visuospatial ability, and timed activities of daily living assessments at enrollment (pre-systemic treatment) and annually to 24 months, for a total of 59 individual neurocognitive measures. We defined persistent self-reported cognitive decline as clinically meaningful decline (3.7+ points) on the PCI scale from enrollment to twelve months with persistence to 24 months. Analysis used four machine learning models based on data for change scores (baseline to twelve months) on the 59 neurocognitive measures and measures of depression, anxiety, and fatigue to determine a set of variables that distinguished the 24-month persistent cognitive decline group from non-cancer controls or from survivors without decline. Results: The sample of survivors and controls ranged in age from were ages 60-89. Thirty-three percent of survivors had self-reported cognitive decline at twelve months and two-thirds continued to have persistent decline to 24 months (n = 60). Least Absolute Shrinkage and Selection Operator (LASSO) models distinguished survivors with persistent self-reported declines from controls (AUC = 0.736) and survivors without decline (n = 147; AUC = 0.744). The variables that separated groups were predominantly neurocognitive test performance change scores, including declines in list learning, verbal fluency, and attention measures. Discussion: Machine learning may be useful to further our understanding of cancer-related cognitive decline. Our results suggest that persistent self-reported cognitive problems among older women with breast cancer are associated with a constellation of mild neurocognitive changes warranting clinical attention.Item Characterization of Behavioral Profiles for Inbred P and NP and Congenic P.NP and NP.P Rats(2012-08-27) Jensen, Meredith; Grahame, Nicholas J.; Stewart, Robert; Czachowski, Cristine; Roman, ErikaAlcoholism inheritance rates have been estimated as high as 60% in a human population. Many significant features of alcohol dependence have been replicated in rodent animal models of alcoholism, however not in totality. These animal models include inbred preferring (iP) and nonpreferring (iNP) rat types. Congenic rats have been engineered from the iP and iNP strains whereby a P congenic rat has in its genome a well-chosen chromosomal portion taken from an NP rat (P.NP) and, reciprocally, an NP congenic rat has acquired the analogous DNA from a P rat (NP.P). In this case, a quantitative trait locus (QTL) from chromosome 4 is the donor genetic material for the congenic rats. It is of great interest to further study this chromosome 4 QTL because it has been found to control a significant portion of ethanol consumption behavior in iP and iNP rats. This study aimed to behaviorally profile the iP, iNP and reciprocal congenic rats. As a result of the behavioral profiling of these genetically related groups, some conclusions could be made regarding which behaviors appear to be controlled by the chromosome 4 donor DNA.This study primarily utilized the Multivariate Concentric Square Field apparatus (MCSF) to characterize behavioral profiles for the inbred and congenic rats. The Open field (OF) and Elevated plus maze (EPM) supported this effort. The MCSF is valuable in that it allows for the animals to interact within an environment that has ethological value. The 12 different zones that make up the field are characterized by some functional quality in terms of type and duration of behavior performed, etc. The behavioral data is aggregated and finally represented in terms of five functional categories, the elements of the behavioral profile: general activity, exploratory activity, risk assessment, risk taking, and shelter seeking. The study hypotheses were shaped by prior research suggesting that iPs should display lower general activity and risk taking strategy than iNPs in the MCSF. Inbred Ps should be more active in the OF and spend more time in the center of the EPM. Generally, it is expected that the iP QTL confer behavioral phenotypes to the iNP strain that deviate toward a "P" behavioral phenotype and reciprocally, the iNP QTL confer behavioral phenotypes to the iP strain that deviate toward an "NP" behavioral phenotype. The results showed that iP rats performed more risk assessment and risk taking behavior and less shelter seeking and anxiety-like behavior than iNP rats. It followed that P.NP congenic rats significantly downgraded their risk assessment and risk taking behavior when compared to iP rats. This decrease can be attributed to the chromosome 4 QTL donated from the iNP breed. All together this study concludes that risk assessment and risk taking behavior in the iP rats is controlled by the same DNA region that, in part, determines voluntary intake of ethanol consumption. Further fine mapping of the QTL region should help in discovering if the same DNA sequences that influence ethanol intake also significantly influence risk behavior.Item The Feasibility of Telephone-Administered Cognitive Testing in Individuals 1 and 2 Years after Inpatient Rehabilitation for Traumatic Brain Injury(Mary Ann Liebert, 2018-05-15) Dams-O'Connor, Kristen; Sy, Karla Therese L.; Landau, Alexandra; Bodien, Yelena; Dikmen, Sureyya; Felix, Elizabeth R.; Giacino, Joseph T.; Gibbons, Laura; Hammond, Flora M.; Hart, Tessa; Johnson-Greene, Doug; Lengenfelder, Jeannie; Lequerica, Anthony; Newman, Jody; Novack, Thomas; O'Neil-Pirozzi, Therese M.; Whiteneck, Gale; Physical Medicine and Rehabilitation, School of MedicineTraumatic brain injury (TBI) often results in cognitive impairment, and trajectories of cognitive functioning can vary tremendously over time across survivors. Traditional approaches to measuring cognitive performance require face-to-face administration of a battery of objective neuropsychological tests, which can be time- and labor-intensive. There are numerous clinical and research contexts in which in-person testing is undesirable or unfeasible, including clinical monitoring of older adults or individuals with disability for whom travel is challenging, and epidemiological studies of geographically dispersed participants. A telephone-based method for measuring cognition could conserve resources and improve efficiency. The objective of this study is to examine the feasibility and usefulness of the Brief Test of Adult Cognition by Telephone (BTACT) among individuals who are 1 and 2 years post-moderate-to-severe TBI. A total of 463 individuals participated in the study at Year 1 post-injury, and 386 participated at Year 2. The sample was mostly male (73%) and white (59%), with an average age of (mean ± standard deviation) 47.9 ± 20.9 years, and 73% experienced a duration of post-traumatic amnesia (PTA) greater than 7 days. A majority of participants were able to complete the BTACT subtests (61-69% and 56-64% for Years 1 and 2 respectively); score imputation for those unable to complete a test due to severity of cognitive impairment yields complete data for 74-79% of the sample. BTACT subtests showed expected changes between Years 1-2, and summary scores demonstrated expected associations with injury severity, employment status, and cognitive status as measured by the Functional Independence Measure. Results indicate it is feasible, efficient, and useful to measure cognition over the telephone among individuals with moderate-severe TBI.Item Investigating the Role of Hypothalamic Tumor Involvement in Sleep and Cognitive Outcomes Among Children Treated for Craniopharyngioma(Oxford Academic, 2016-07) Jacola, Lisa M.; Conklin, Heather M.; Scoggins, Matthew A.; Ashford, Jason M.; Merchant, Thomas E.; Mandrell, Belinda N.; Ogg, Robert J.; Curtis, Elizabeth; Wise, Merrill S.; Indelicato, Daniel J.; Crabtree, Valerie M.; Medicine, School of MedicineObjective: Despite excellent survival prognosis, children treated for craniopharyngioma experience significant morbidity. We examined the role of hypothalamic involvement (HI) in excessive daytime sleepiness (EDS) and attention regulation in children enrolled on a Phase II trial of limited surgery and proton therapy. Methods: Participants completed a sleep evaluation (N = 62) and a continuous performance test (CPT) during functional magnetic resonance imaging (fMRI; n = 29) prior to proton therapy. Results: EDS was identified in 76% of the patients and was significantly related to increased HI extent (p = .04). There was no relationship between CPT performance during fMRI and HI or EDS. Visual examination of group composite fMRI images revealed greater spatial extent of activation in frontal cortical regions in patients with EDS, consistent with a compensatory activation hypothesis. Conclusion: Routine screening for sleep problems during therapy is indicated for children with craniopharyngioma, to optimize the timing of interventions and reduce long-term morbidity.Item Mayo Normative Studies: Amyloid and Neurodegeneration Negative Normative Data for the Auditory Verbal Learning Test and Sex-Specific Sensitivity to Mild Cognitive Impairment/Dementia(IOS Press, 2024) Stricker, Nikki H.; Christianson, Teresa J.; Pudumjee, Shehroo B.; Polsinelli, Angelina J.; Lundt, Emily S.; Frank, Ryan D.; Kremers, Walter K.; Machulda, Mary M.; Fields, Julie A.; Jack, Clifford R., Jr.; Knopman, David S.; Graff-Radford, Jonathan; Vemuri, Prashanthi; Mielke, Michelle M.; Petersen, Ronald C.; Neurology, School of MedicineBackground: Conventional normative samples include individuals with undetected Alzheimer's disease neuropathology, lowering test sensitivity for cognitive impairment. Objective: We developed Mayo Normative Studies (MNS) norms limited to individuals without elevated amyloid or neurodegeneration (A-N-) for Rey's Auditory Verbal Learning Test (AVLT). We compared these MNS A-N- norms in female, male, and total samples to conventional MNS norms with varying levels of demographic adjustments. Methods: The A-N- sample included 1,059 Mayo Clinic Study of Aging cognitively unimpaired (CU) participants living in Olmsted County, MN, who are predominantly non-Hispanic White. Using a regression-based approach correcting for age, sex, and education, we derived fully-adjusted T-score formulas for AVLT variables. We validated these A-N- norms in two independent samples of CU (n = 261) and mild cognitive impairment (MCI)/dementia participants (n = 392) > 55 years of age. Results: Variability associated with age decreased by almost half in the A-N- norm sample relative to the conventional norm sample. Fully-adjusted MNS A-N- norms showed approximately 7- 9% higher sensitivity to MCI/dementia compared to fully-adjusted MNS conventional norms for trials 1- 5 total and sum of trials. Among women, sensitivity to MCI/dementia increased with each normative data refinement. In contrast, age-adjusted conventional MNS norms showed greatest sensitivity to MCI/dementia in men. Conclusions: A-N- norms show some benefits over conventional normative approaches to MCI/dementia sensitivity, especially for women. We recommend using these MNS A-N- norms alongside MNS conventional norms. Future work is needed to determine if normative samples that are not well characterized clinically show greater benefit from biomarker-refined approaches.Item Neurocognition after motor vehicle collision and adverse post-traumatic neuropsychiatric sequelae within 8 weeks: Initial findings from the AURORA study(Elsevier, 2022) Germine, Laura T.; Joormann, Jutta; Passell, Eliza; Rutter, Lauren A.; Scheuer, Luke; Martini, Paolo; Hwang, Irving; Lee, Sue; Sampson, Nancy; Barch, Deanna M.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Stevens, Jennifer S.; Zeng, Donglin; Linnstaedt, Sarah D.; Jovanovic, Tanja; Clifford, Gari D.; Neylan, Thomas C.; Rauch, Scott L.; Lewandowski, Christopher; Hendry, Phyllis L.; Sheikh, Sophia; Storrow, Alan B.; Musey, Paul I.; Jones, Christopher W.; Punches, Brittney E.; McGrath, Meghan E.; Pascual, Jose L.; Mohiuddin, Kamran; Pearson, Claire; Peak, David A.; Domeier, Robert M.; Bruce, Steven E.; Rathlev, Niels K.; Sanchez, Leon D.; Pietrzak, Robert H.; Pizzagalli, Diego A.; Harte, Steven E.; Elliott, James M.; Koenen, Karesten C.; Ressler, Kerry J.; McLean, Samuel A.; Kessler, Ronald C.; Emergency Medicine, School of MedicineBackground: Previous work has indicated that differences in neurocognitive functioning may predict the development of adverse post-traumatic neuropsychiatric sequelae (APNS). Such differences may be vulnerability factors or simply correlates of APNS-related symptoms. Longitudinal studies that measure neurocognitive functioning at the time of trauma are needed to determine whether such differences precede the development of APNS. Methods: Here, we present findings from a subsample of 666 ambulatory patients from the AURORA (Advancing Understanding of RecOvery afteR trumA) study. All patients presented to EDs after a motor vehicle collision (MVC). We examined associations of neurocognitive test performance shortly after MVC with peritraumatic symptoms in the ED and APNS (depression, post-traumatic stress, post-concussive symptoms, and pain) 2 weeks and 8 weeks later. Neurocognitive tests assessed processing speed, attention, verbal reasoning, memory, and social perception. Results: Distress in the ED was associated with poorer processing speed and short-term memory. Poorer short-term memory was also associated with depression at 2 weeks post-MVC, even after controlling for peritraumatic distress. Finally, higher vocabulary scores were associated with pain 2 weeks post-MVC. Limitations: Self-selection biases among those who present to the ED and enroll in the study limit generalizability. Also, it is not clear whether observed neurocognitive differences predate MVC exposure or arise in the immediate aftermath of MVC exposure. Conclusions: Our results suggest that processing speed and short-term memory may be useful predictors of trauma-related characteristics and the development of some APNS, making such measures clinically-relevant for identifying at-risk individuals.Item Peri-adolescent Alcohol Consumption Enhances the Reinforcing and Stimulatory Properties of Ethanol within the Adult Mesolimbic Dopamine System in Alcohol Preferring P Rats(2012-08-07) Toalston, Jamie E.; Murphy, James M.; Neal-Beliveau, Bethany S.; Bell, Richard L.; Kinzig, Kimberly P.Research in the alcohol preferring (P) rat has indicated that peri-adolescent alcohol (EtOH) consumption enhances the acquisition of oral operant EtOH self-administration, inhibits the extinction of responding for EtOH, augments EtOH-seeking behaviors, and increases relative reward value of EtOH during adulthood. Experiment 1 was conducted to determine if these adult effects of peri-adolescent EtOH intake could be observed using an Intracranial Self-Administration (ICSA) model. It was hypothesized that an increased sensitivity to the rewarding actions of EtOH would be manifested in peri-adolescent-EtOH-exposed subjects compared to naive subjects when the opportunity to self-administer EtOH to the posterior ventral tegmental area (pVTA) is available in adulthood. The pVTA is a primary site for EtOH’s reinforcing and rewarding properties in the mesolimbic dopamine (DA) system. Experiment 2 was a dose-response examination of the effects of EtOH administered to the pVTA on downstream DA efflux in the nucleus accumbens shell (AcbSh) via a joint Microinjection-Microdialysis (MicroMicro) procedure. Male P rats were given 24-h free-choice exposure to 15% volume/volume EtOH from postnatal day (PD) 30 to PD 60, or remained experimentally naive, with ad lib food and water. By the end of the periadolescent exposure period, average consumption was 7.3 g/kg/day of EtOH. After PD 75, periadolescent-EtOH-exposed and naïve rats were either implanted with an injector guide cannula aimed at the right pVTA for ICSA (Experiment 1), or two cannulae, one aimed at the right pVTA (injector) and one at the ipsilateral AcbSh (microdialysis) for MicroMicro (Experiment 2). Following one week of recovery from surgery, ICSA subjects were placed in standard two-lever (active and inactive) operant chambers. Test sessions were 60 min in duration and occurred every other day for a total of 7 sessions. Rats were randomly assigned to one of 5 groups (n=4-9/group) that self-infused (FR1 schedule) either aCSF (vehicle, 0 mg%), 50, 75, 100, or 150 mg% EtOH during 4 sessions, aCSF only for sessions 5 and 6 (extinction), and the initial concentration again for session 7 (reinstatement). MicroMicro subjects received six days of recovery from surgery, probe implantation the day before testing, and then continuous microdialysis for DA with 15 min microdialysis samples collected before, during, and then two hrs after 10-min pulse microinjection of either aCSF (vehicle, 0 mg%), 50, 75, 100, or 150 mg% EtOH. Neither EtOH-exposed nor naive groups of P rats self-infused the aCSF or 50 mg% EtOH concentration. While the naive group did not self-infuse the 75 or 100 mg% EtOH concentrations, the peri-adolescent EtOH-exposed group of P rats did readily discriminate the active lever from the inactive lever at these concentrations. Both groups self-infused the 150 mg% EtOH concentration. Pulse microinjections of EtOH during the MicroMicro procedure revealed that 75 and 100 mg% concentrations of EtOH increased downstream DA in the AcbSh of EtOH-exposed, but not naïve, subjects. 150 mg% EtOH increased downstream DA in both adolescent treatment groups. Overall, the results indicate that consumption of EtOH by P rats during peri-adolescence increases the reinforcing properties of EtOH in the pVTA in adulthood. The results also indicate that there were differential effects of peri-adolescent EtOH exposure on DA efflux in the AcbSh. This provides evidence that peri-adolescent EtOH-exposure produces long-lasting alterations in neural circuitry involved in EtOH-reinforcement, during adulthood.Item Recognition memory and divergent cognitive profiles in prodromal genetic frontotemporal dementia(Elsevier, 2021) Barker, Megan S.; Manoochehri, Masood; Rizer, Sandra J.; Appleby, Brian S.; Brushaber, Danielle; Dev, Sheena I.; Devick, Katrina L.; Dickerson, Bradford C.; Fields, Julie A.; Foroud, Tatiana M.; Forsberg, Leah K.; Galasko, Douglas R.; Ghoshal, Nupur; Graff-Radford, Neill R.; Grossman, Murray; Heuer, Hilary W.; Hsiung, Ging-Yuek; Kornak, John; Litvan, Irene; Mackenzie, Ian R.; Mendez, Mario F.; Pascual, Belen; Rankin, Katherine P.; Rascovsky, Katya; Staffaroni, Adam M.; Tartaglia, Maria Carmela; Weintraub, Sandra; Wong, Bonnie; Boeve, Bradley F.; Boxer, Adam L.; Rosen, Howard J.; Goldman, Jill; Huey, Edward D.; Cosentino, Stephanie; ALLFTD consortium; Medical and Molecular Genetics, School of MedicineAlthough executive dysfunction is the characteristic cognitive marker of behavioral variant frontotemporal dementia (bvFTD), episodic memory deficits are relatively common, and may be present even during the prodromal disease phase. In a cohort of mutation carriers with mild behavioral and/or cognitive symptoms consistent with prodromal bvFTD, we aimed to investigate patterns of performance on an abbreviated list learning task, with a particular focus on recognition memory. We further aimed to characterize the cognitive prodromes associated with the three major genetic causes of frontotemporal dementia, as emerging evidence suggests there may be subtle differences in cognitive profiles among carriers of different genetic mutations. Participants included 57 carriers of a pathogenic mutation in microtubule-associated protein tau (MAPT, N = 23), or progranulin (GRN, N = 15), or a or a hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72, N = 19), with mild cognitive and/or behavioral symptoms consistent with prodromal bvFTD. Familial non-carriers were included as controls (N = 143). All participants completed a comprehensive neuropsychological examination, including an abbreviated list learning test assessing episodic memory recall and recognition. MAPT mutation carriers performed worse than non-carriers in terms of list recall, and had difficulty discriminating targets from distractors on the recognition memory task, primarily due to the endorsement of distractors as targets. MAPT mutation carriers also showed nonverbal episodic memory and semantic memory dysfunction (object naming). GRN mutation carriers were variable in performance and overall the most dysexecutive. Slowed psychomotor speed was evident in C9orf72 repeat expansion carriers. Identifying the earliest cognitive indicators of bvFTD is of critical clinical and research importance. List learning may be a sensitive cognitive marker for incipient dementia in MAPT and potentially a subset of GRN carriers. Our results highlight that distinct cognitive profiles may be evident in carriers of the three disease-causing genes during the prodromal disease stage.