Search

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p-tau) accumulation. The clinical features associated with CTE pathology are unclear. In brain donors with autopsy-confirmed CTE, we investigated the association of CTE p-tau pathology density and location with cognitive, functional, and neuropsychiatric symptoms. Methods: In 364 brain donors with autopsy confirmed CTE, semi-quantitative p-tau severity (range: 0–3) was assessed in 10 cortical and subcortical regions. We summed ratings across regions to form a p-tau severity global composite (range: 0–30). Informants completed standardized scales of cognition (Cognitive Difficulties Scale, CDS; BRIEF-A Metacognition Index, MI), activities of daily living (Functional Activities Questionnaire), neurobehavioral dysregulation (BRIEF-A Behavioral Regulation Index, BRI; Barratt Impulsiveness Scale, BIS-11), aggression (Brown-Goodwin Aggression Scale), depression (Geriatric Depression Scale-15, GDS-15), and apathy (Apathy Evaluation Scale, AES). Ordinary least squares regression models examined associations between global and regional p-tau severity (separate models for each region) with each clinical scale, adjusting for age at death, racial identity, education level, and history of hypertension, obstructive sleep apnea, and substance use treatment. Ridge regression models that incorporated p-tau severity across all regions in the same model assessed which regions showed independent effects. Results: The sample was predominantly American football players (333; 91.2%); 140 (38.5%) had low CTE and 224 (61.5%) had high CTE. Global p-tau severity was associated with higher (i.e., worse) scores on the cognitive and functional scales: MI (β standardized = 0.02, 95%CI = 0.01–0.04), CDS (β standardized = 0.02, 95%CI = 0.01–0.04), and FAQ (β standardized = 0.03, 95%CI = 0.01–0.04). After false-discovery rate correction, p-tau severity in the frontal, inferior parietal, and superior temporal cortex, and the amygdala was associated with higher CDS (β sstandardized = 0.17–0.29, ps < 0.01) and FAQ (β sstandardized = 0.21–0.26, ps < 0.01); frontal and inferior parietal cortex was associated with higher MI (β sstandardized = 0.21–0.29, ps < 0.05); frontal cortex was associated with higher BRI (β standardized = 0.21, p < 0.01). Regions with effects independent of other regions included frontal cortex (CDS, MI, FAQ, BRI), inferior parietal cortex (CDS) and amygdala (FAQ). P-tau explained 13–49% of variance in cognitive and functional scales and 6–14% of variance in neuropsychiatric scales. Conclusion: Accumulation of p-tau aggregates, especially in the frontal cortex, are associated with cognitive, functional, and certain neurobehavioral symptoms in CTE. [ABSTRACT FROM AUTHOR]

Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer’s disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD = 69, non-AD = 54) from the Boston University Alzheimer’s disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195–205, 212–221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC = 89.8), p-tau231 (AUC = 83.4), and p-tau205 (AUC = 81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR < 1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217 = 15.29, ORp-tau205 = 5.05 and ORp-tau231 = 3.86) and Braak staging (ORp-tau217 = 14.29, ORp-tau205 = 5.27 and ORp-tau231 = 4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease. [ABSTRACT FROM AUTHOR]

Introduction: Previous Alzheimer's disease and related dementias (AD/ADRD) research studies have illustrated the significance of studying alterations in white matter (WM). Fewer studies have examined how WM integrity, measured with diffusion tensor imaging (DTI), is associated with volume of gray matter (GM) regions and measures of cognitive function in aged participants spanning the dementia continuum. Methods: Magnetic resonance imaging and cognitive data were collected from 241 Boston University Alzheimer's Disease Research Center participants who spanned from cognitively normal controls to amnestic mild cognitive impairment to having dementia. Primary DTI tracts of interest were the cingulum ventral (CV) and cingulum dorsal (CD) pathways. GM regions of interest (ROIs) were in the medial temporal lobe (MTL), prefrontal cortex, and retrosplenial cortex. Analyses of covariance models were used to assess differences in WM integrity across groups (control, amnestic mild cognitive impairment, and dementia). Multiple linear regression models were used to assess associations between WM integrity and GM volume, and with measures of memory and executive function. Results: Differences in WM integrity were shown in both cingulum pathways in participants across the dementia continuum. Associations between WM integrity of both cingulum pathways and volume of selected GM ROIs were widespread. Functionally significant associations were found between WM of the CV pathway and memory, independent of MTL GM volume. Discussion: Differences in WM integrity of the cingulum bundle and surrounding GM ROI are likely related to the progression of AD/ADRD. Such differences should continue to be studied, particularly in association with memory performance. [ABSTRACT FROM AUTHOR]

Exposure to repetitive head impacts (RHI) has been associated with long-term disturbances in cognition, mood, and neurobehavioral dysregulation, and reflected in neuroimaging. Distinct patterns of changes in quantitative features of the brain electrical activity (quantitative electroencephalogram [qEEG]) have been demonstrated to be sensitive to brain changes seen in neurodegenerative disorders and in traumatic brain injuries (TBI). While these qEEG biomarkers are highly sensitive at time of injury, the long-term effects of exposure to RHI on brain electrical activity are relatively unexplored. Ten minutes of eyes closed resting EEG data were collected from a frontal and frontotemporal electrode montage (BrainScope Food and Drug Administration–cleared EEG acquisition device), as well as assessments of neuropsychiatric function and age of first exposure (AFE) to American football. A machine learning methodology was used to derive a qEEG-based algorithm to discriminate former National Football League (NFL) players (n = 87, 55.40 ± 7.98 years old) from same-age men without history of RHI (n = 68, 54.94 ± 7.63 years old), and a second algorithm to discriminate former players with AFE <12 years (n = 33) from AFE ≥12 years (n = 54). The algorithm separating NFL retirees from controls had a specificity = 80%, a sensitivity = 60%, and an area under curve (AUC) = 0.75. Within the NFL population, the algorithm separating AFE <12 from AFE ≥12 resulted in a sensitivity = 76%, a specificity = 52%, and an AUC = 0.72. The presence of a profile of EEG abnormalities in the NFL retirees and in those with younger AFE includes features associated with neurodegeneration and the disruption of neuronal transmission between regions. These results support the long-term consequences of RHI and the potential of EEG as a biomarker of persistent changes in brain function. [ABSTRACT FROM AUTHOR]

Purpose: Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer's disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players. Methods: Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs). Results: Four brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions. Conclusions: Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed. [ABSTRACT FROM AUTHOR]

Background: Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players. Methods: One hundred seventy male former football players (n=111 professional, n=59 college; 45–74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests. Results: Most football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent. Conclusions: In this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain. [ABSTRACT FROM AUTHOR]

Background: Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players. Methods: One hundred seventy male former football players (n=111 professional, n=59 college; 45–74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests. Results: Most football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent. Conclusions: In this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain. [ABSTRACT FROM AUTHOR]

Former American football players are at risk for chronic traumatic encephalopathy (CTE) which may have parkinsonism as a clinical feature. Former football players were prospectively assessed for parkinsonism. 120 former professional football players, 58 former college football players, and 60 same-age asymptomatic men without repetitive head impacts, 45–74 years, were studied using the MDS-UPDRS to assess for parkinsonism, and the Timed Up and Go (TUG). Traumatic encephalopathy syndrome (TES), the clinical syndrome of CTE, was adjudicated and includes parkinsonism diagnosis. Fisher's Exact Test compared groups on parkinsonism due to small cell sizes; analysis of covariance or linear regressions controlling for age and body mass index were used otherwise. Twenty-two (12.4%) football players (13.3% professional, 10.3% college) met parkinsonism criteria compared with two (3.3%) in the unexposed group. Parkinsonism was higher in professional (p = 0.037) but not college players (p = 0.16). There were no differences on the MDS-UPDRS Part III total scores. Scores on the individual MDS-UPDRS items were low. TUG times were longer in former professional but not college players compared with unexposed men (13.09 versus 11.35 s, p < 0.01). There were no associations between years of football, age of first exposure, position or level of play on motor outcomes. TES status was not associated with motor outcomes. Parkinsonism rates in this sample of football players was low and highest in the professional football players. The association between football and parkinsonism is inconclusive and depends on factors related to sample selection, comparison groups, and exposure characteristics. • Parkinsonism/motor finding prevalence did not differ in former American football players compared to asymptomatic unexposed men. • Former players did have slowness on the Timed Up and Go (TUG) compared to the asymptomatic unexposed men. • TUG times were slower in former football players with TES-CTE probable compared to those with no TES and TES-CTE possible. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy, cannot currently be diagnosed during life. Atrophy patterns on magnetic resonance imaging could be an effective in vivo biomarker of CTE, but have not been characterized. Mechanisms of neurodegeneration in CTE are unknown. Here, we characterized macrostructural magnetic resonance imaging features of brain donors with autopsy-confirmed CTE. The association between hyperphosphorylated tau (p-tau) and atrophy on magnetic resonance imaging was examined. Methods: Magnetic resonance imaging scans were obtained by medical record requests for 55 deceased symptomatic men with autopsy-confirmed CTE and 31 men (n = 11 deceased) with normal cognition at the time of the scan, all >60 years Three neuroradiologists visually rated regional atrophy and microvascular disease (0 [none]–4 [severe]), microbleeds, and cavum septum pellucidum presence. Neuropathologists rated tau severity and atrophy at autopsy using semi-quantitative scales. Results: Compared to unimpaired males, donors with CTE (45/55=stage III/IV) had greater atrophy of the orbital-frontal (mean diff.=1.29), dorsolateral frontal (mean diff.=1.31), superior frontal (mean diff.=1.05), anterior temporal (mean diff.=1.57), and medial temporal lobes (mean diff.=1.60), and larger lateral (mean diff.=1.72) and third (mean diff.=0.80) ventricles, controlling for age at scan (ps<0.05). There were no effects for posterior atrophy or microvascular disease. Donors with CTE had increased odds of a cavum septum pellucidum (OR = 6.7, p < 0.05). Among donors with CTE, greater tau severity across 14 regions corresponded to greater atrophy on magnetic resonance imaging (beta = 0.68, p < 0.01). Conclusions: These findings support frontal-temporal atrophy as a magnetic resonance imaging finding of CTE and show p-tau accumulation is associated with atrophy in CTE. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine and validate clinical research diagnostic criteria (i.e., traumatic encephalopathy syndrome [TES]); examine repetitive head impact exposure, genetic, and other risk factors; and provide shared resources of anonymized data and biological samples to the research community. In this paper, we provide a detailed overview of the rationale, design, and methods for the DIAGNOSE CTE Research Project. Methods: The targeted sample and sample size was 240 male participants, ages 45–74, including 120 former professional football players, 60 former collegiate football players, and 60 asymptomatic participants without a history of head trauma or participation in organized contact sports. Participants were evaluated at one of four U.S. sites and underwent the following baseline procedures: neurological and neuropsychological examinations; tau and amyloid positron emission tomography; magnetic resonance imaging and spectroscopy; lumbar puncture; blood and saliva collection; and standardized self-report measures of neuropsychiatric, cognitive, and daily functioning. Study partners completed similar informant-report measures. Follow-up evaluations were intended to be in-person and at 3 years post-baseline. Multidisciplinary diagnostic consensus conferences are held, and the reliability and validity of TES diagnostic criteria are examined. Results: Participant enrollment and all baseline evaluations were completed in February 2020. Three-year follow-up evaluations began in October 2019. However, in-person evaluation ceased with the COVID-19 pandemic, and resumed as remote, 4-year follow-up evaluations (including telephone-, online-, and videoconference-based cognitive, neuropsychiatric, and neurologic examinations, as well as in-home blood draw) in February 2021. Conclusions: Findings from the DIAGNOSE CTE Research Project should facilitate detection and diagnosis of CTE during life, and thereby accelerate research on risk factors, mechanisms, epidemiology, treatment, and prevention of CTE. Trial registration: NCT02798185 [ABSTRACT FROM AUTHOR]

Probable rapid eye movement (REM) sleep behavior disorder (pRBD) is a synucleinopathy-associated parasomnia in which loss of REM sleep muscle atonia results in motor behavior during REM sleep, including dream enactment. Traumatic brain injury is independently associated with increased risk of pRBD and Lewy body disease, and both pRBD and Lewy body disease are often observed in chronic traumatic encephalopathy (CTE). However, the frequency and pathological substrate of pRBD in CTE have not been formally studied and remain unknown. Of the total sample of 247 men, age at death of 63.1 ± 18.8 years (mean ± SD), 80 [32%] were determined by informant report to have symptoms of pRBD. These participants had played more years of contact sports (18.3 ± 11.4) than those without pRBD (15.1 ± 6.5; P = 0.02) and had an increased frequency of Lewy body disease (26/80 [33%] vs 28/167 [17%], P = 0.005). Of the 80 participants with pRBD, 54 [68%] did not have Lewy body disease; these participants were more likely to have neurofibrillary tangles and pretangles in the dorsal and median raphe (41 of 49 [84%] non-LBD participants with pRBD symptoms vs 90 of 136 [66%] non-LBD participants without pRBD symptoms, P = 0.02), brainstem nuclei with sleep regulatory function. Binary logistic regression modeling in the total study sample showed that pRBD in CTE was associated with dorsal and median raphe nuclei neurofibrillary tangles (OR = 3.96, 95% CI [1.43, 10.96], P = 0.008), Lewy body pathology (OR = 2.36, 95% CI [1.18, 4.72], P = 0.02), and years of contact sports participation (OR = 1.04, 95% CI [1.00, 1.08], P = 0.04). Overall, pRBD in CTE is associated with increased years of contact sports participation and may be attributable to Lewy body and brainstem tau pathologies. [ABSTRACT FROM AUTHOR]

Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive head impacts (RHI) that has been neuropathologically diagnosed in American football players and other contact sport athletes. In 2013, McKee and colleagues proposed a staging scheme for characterizing the severity of the hyperphosphorylated tau (p-tau) pathology, the McKee CTE staging scheme. The staging scheme defined four pathological stages of CTE, stages I(mild)–IV(severe), based on the density and regional deposition of p-tau. The objective of this study was to test the utility of the McKee CTE staging scheme, and provide a detailed examination of the regional distribution of p-tau in CTE. We examined the relationship between the McKee CTE staging scheme and semi-quantitative and quantitative assessments of regional p-tau pathology, age at death, dementia, and years of American football play among 366 male brain donors neuropathologically diagnosed with CTE (mean age 61.86, SD 18.90). Spearman's rho correlations showed that higher CTE stage was associated with higher scores on all semi-quantitative and quantitative assessments of p-tau severity and density (p's < 0.001). The severity and distribution of CTE p-tau followed an age-dependent progression: older age was associated with increased odds for having a higher CTE stage (p < 0.001). CTE stage was independently associated with increased odds for dementia (p < 0.001). K-medoids cluster analysis of the semi-quantitative scales of p-tau across 14 regions identified 5 clusters of p-tau that conformed to increasing CTE stage (stage IV had 2 slightly different clusters), age at death, dementia, and years of American football play. There was a predilection for p-tau pathology in five regions: dorsolateral frontal cortex (DLF), superior temporal cortex, entorhinal cortex, amygdala, and locus coeruleus (LC), with CTE in the youngest brain donors and lowest CTE stage restricted to DLF and LC. These findings support the usefulness of the McKee CTE staging scheme and demonstrate the regional distribution of p-tau in CTE. [ABSTRACT FROM AUTHOR]

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impacts (RHI), such as those received in contact/collision sports, blast injury in military veterans, and domestic violence. Currently, CTE can only be diagnosed following death. Although the clinical features of former boxers have been described for almost a century, and there is increasing evidence of long-term cognitive and neuropsychiatric impairments in living former American football players, the specific clinical presentation associated with underlying CTE neuropathology remains unclear. These features include diverse and nonspecific changes in cognition, mood, behavior, and motor functioning. Currently, there are no validated and widely accepted clinical diagnostic criteria. Proposed criteria are primarily based on retrospective telephonic interviews with the next of kin of individuals who were diagnosed with CTE postmortem. Prospective studies involving individuals presumably at high risk for CTE are underway; these will hopefully clarify the clinical features and course of CTE, allow the diagnostic criteria to be refined, and lead to the development and validation of in vivo biomarkers. This article reviews what is currently known about the clinical presentation of CTE and describes the evolution of this knowledge from early case reports of "punch drunk" boxers through larger case series of neuropathologically confirmed CTE. This article concludes with a discussion of gaps in research and future directions to address these areas. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been associated with a history of repetitive head impacts. The neuropathological diagnosis is based on a specific pattern of tau deposition with minimal amyloid-beta deposition that differs from other disorders, including Alzheimer's disease. The feasibility of detecting tau and amyloid deposition in the brains of living persons at risk for CTE has not been well studied.Methods: We used flortaucipir positron-emission tomography (PET) and florbetapir PET to measure deposition of tau and amyloid-beta, respectively, in the brains of former National Football League (NFL) players with cognitive and neuropsychiatric symptoms and in asymptomatic men with no history of traumatic brain injury. Automated image-analysis algorithms were used to compare the regional tau standardized uptake value ratio (SUVR, the ratio of radioactivity in a cerebral region to that in the cerebellum as a reference) between the two groups and to explore the associations of SUVR with symptom severity and with years of football play in the former-player group.Results: A total of 26 former players and 31 controls were included in the analysis. The mean flortaucipir SUVR was higher among former players than among controls in three regions of the brain: bilateral superior frontal (1.09 vs. 0.98; adjusted mean difference, 0.13; 95% confidence interval [CI], 0.06 to 0.20; P<0.001), bilateral medial temporal (1.23 vs. 1.12; adjusted mean difference, 0.13; 95% CI, 0.05 to 0.21; P<0.001), and left parietal (1.12 vs. 1.01; adjusted mean difference, 0.12; 95% CI, 0.05 to 0.20; P = 0.002). In exploratory analyses, the correlation coefficients in these three regions between the SUVRs and years of play were 0.58 (95% CI, 0.25 to 0.79), 0.45 (95% CI, 0.07 to 0.71), and 0.50 (95% CI, 0.14 to 0.74), respectively. There was no association between tau deposition and scores on cognitive and neuropsychiatric tests. Only one former player had levels of amyloid-beta deposition similar to those in persons with Alzheimer's disease.Conclusions: A group of living former NFL players with cognitive and neuropsychiatric symptoms had higher tau levels measured by PET than controls in brain regions that are affected by CTE and did not have elevated amyloid-beta levels. Further studies are needed to determine whether elevated CTE-associated tau can be detected in individual persons. (Funded by Avid Radiopharmaceuticals and others.). [ABSTRACT FROM AUTHOR]

Objective Neuropsychological test performance can provide insight into functional abilities in patients with dementia, particularly in the absence of an informant. The relationship between neuropsychological measures and instrumental activities of daily living (IADLs) is unclear due to hetereogeneity in cognitive domains assessed and neuropsychological tests administered. Practical and ecologically valid performance-based measures of IADLs are also limited. The Neuropsychological Assessment Battery (NAB) is uniquely positioned to provide a dual-purpose assessment of cognitive and IADL function, as it includes Daily Living tests that simulate real-world functional tasks. We examined the utility of select NAB tests in predicting informant-reported IADLs in mild cognitive impairment and dementia. Methods The sample of 327 participants included 128 normal controls, 97 individuals with mild cognitive impairment, and 102 individuals with Alzheimer’s disease dementia from the Boston University Alzheimer’s Disease Center research registry. Informants completed the Lawton Brody Instrumental Activities of Daily Living Scale, and study participants were administered selected NAB tests that were complementary to the existing protocol. Results ROC curves showed strongest prediction of IADL (AUC > 0.90) for memory measures (List Learning delayed recall and Daily Living Memory delayed recall) and Daily Living Driving Scenes. At a predetermined level of specificity (95%), List Learning delayed recall (71%) and Daily Living Memory delayed recall (88%) were the most sensitive. The Daily Living Memory and Driving Scenes tests strongly predicted IADL status, and the other Daily Living tests contributed unique variance. Conclusions NAB memory measures and Daily Living Tests may have clinical utility in detecting informant-rated functional impairment in dementia. [ABSTRACT FROM AUTHOR]

Majority of dementia research is conducted in non-Hispanic White participants despite a greater prevalence of dementia in other racial groups. To obtain a better understanding of biomarker presentation of Alzheimer's disease (AD) in the non-Hispanic White population, this study exclusively examined AD biomarker abnormalities in 85 Black and/or African American participants within the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants were classified by the ADNI into 3 clinical groups: cognitively normal, mild cognitive impairment, or dementia. Data examined included demographics, apolipoprotein E (APOE) ε4, cerebrospinal fluid (CSF) Aβ 1-42 , CSF total tau (t-tau), CSF phosphorylated tau (p-tau), 3T magnetic resonance imaging (MRI), and measures of cognition and function. Analyses of variance and covariance showed lower cortical thickness in 5 of 7 selected MRI regions, lower hippocampal volume, greater volume of white matter hyperintensities, lower measures of cognition and function, lower measures of CSF Aβ 1 -42 , and greater measures of CSF t-tau and p-tau between clinical groups. Our findings confirmed greater AD biomarker abnormalities between clinical groups in this sample. [ABSTRACT FROM AUTHOR]

Background: White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been postulated to be a core feature of Alzheimer's disease. Clinicopathological studies are needed to elucidate and confirm this possibility.Objective: This study examined: 1) the association between antemortem WMH and autopsy-confirmed Alzheimer's disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH, and ADNP.Methods: The sample included 82 participants from the National Alzheimer's Coordinating Center's Data Sets who had quantitated volume of WMH from antemortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy.Results: 60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p = 0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p = 0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts, and lacunes (ps < 0.04). ADNP+ participants were more likely to have moderate-severe arteriolosclerosis and cerebral amyloid angiopathy compared to ADNP-participants (ps < 0.04).Conclusions: This study found a direct association between total volume of WMH and increased odds for having ADNP. In patients with Alzheimer's disease, FLAIR MRI WMH may be able to provide key insight into disease severity and progression. The association between WMH and ADNP may be explained by underlying cerebrovascular disease. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of age of first exposure to tackle football on chronic traumatic encephalopathy (CTE) pathological severity and age of neurobehavioral symptom onset in tackle football players with neuropathologically confirmed CTE.Methods: The sample included 246 tackle football players who donated their brains for neuropathological examination. Two hundred eleven were diagnosed with CTE (126 of 211 were without comorbid neurodegenerative diseases), and 35 were without CTE. Informant interviews ascertained age of first exposure and age of cognitive and behavioral/mood symptom onset.Results: Analyses accounted for decade and duration of play. Age of exposure was not associated with CTE pathological severity, or Alzheimer's disease or Lewy body pathology. In the 211 participants with CTE, every 1 year younger participants began to play tackle football predicted earlier reported cognitive symptom onset by 2.44 years (p < 0.0001) and behavioral/mood symptoms by 2.50 years (p < 0.0001). Age of exposure before 12 predicted earlier cognitive (p < 0.0001) and behavioral/mood (p < 0.0001) symptom onset by 13.39 and 13.28 years, respectively. In participants with dementia, younger age of exposure corresponded to earlier functional impairment onset. Similar effects were observed in the 126 CTE-only participants. Effect sizes were comparable in participants without CTE.Interpretation: In this sample of deceased tackle football players, younger age of exposure to tackle football was not associated with CTE pathological severity, but predicted earlier neurobehavioral symptom onset. Youth exposure to tackle football may reduce resiliency to late-life neuropathology. These findings may not generalize to the broader tackle football population, and informant-report may have affected the accuracy of the estimated effects. Ann Neurol 2018;83:886-901. [ABSTRACT FROM AUTHOR]

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder involving cognitive, motor, and psychiatrically-relevant symptoms resulting from repetitive head impacts. Psychiatric phenotypes of CTE, including depression and suicidality, present particular challenges for CTE research, given that the diagnosis requires postmortem neuropathological examination. The pathognomonic lesion of CTE is the perivascular accumulation of hyperphosphorylated tau (ptau) protein at the depths of cortical sulci. These lesions are found in the earliest disease stages, and with advancing pathological severity, ptau deposition occurs in widespread brain regions in a four-stage scheme of severity. We review the psychiatric phenotypes of individuals neuropathologically diagnosed with CTE, and suggest that earlier CTE stages hold particular interest for psychiatric CTE research. In the early CTE stages, there is ptau pathology in frontal cortex and axonal loss in the frontal white matter, followed by progressive ptau neurofibrillary degeneration in the amygdala and hippocampus. Neuropathological changes in the frontal and medial temporal lobes may underlie psychiatric phenotypes. Additional insight into the association between CTE pathology and psychiatric sequelae may come from advancements in in vivo methods of CTE detection. Further epidemiological, clinical, and postmortem studies are needed to validate the nature of psychiatric sequelae in CTE. [ABSTRACT FROM AUTHOR]

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI). Currently, CTE can only be diagnosed after death by postmortem, as validated in vivo biomarkers of CTE do not yet exist. Proton magnetic resonance spectroscopy (MRS) measures brain tissue metabolism in vivo and could facilitate a "probable CTE" diagnosis during life. Here, we propose MRS as one potential biomarker for CTE through a review of CTE neuropathology, and the extant literature that has examined the acute and long-term effects of RHI exposure on brain chemistry. There is preliminary empirical support for MRS in the detection of later-life neurological impairment associated with RHI exposure, but further ante-and postmortem research is needed before MRS can be considered a diagnostic biomarker for CTE. [ABSTRACT FROM AUTHOR]

Objective: Former National Football League (NFL) players’ working knowledge of concussion has not yet been evaluated, despite this population being a major clinical research target due to the association between repetitive head impacts (RHI) and long-term clinical impairments. This study examined former NFL players’ understanding of the current concussion definition, and the association between number of concussions with clinical function. Methods: 95 former NFL players (mean age = 55.29; mean NFL year = 8.10) self-reported number of concussions before being provided with a concussion definition and after being read a modern definition of concussion. Subjects reported number of concussions with loss of consciousness (LOC). Principal Component Analysis of a battery of tests generated behaviour/mood, psychomotor speed/executive function, and verbal and visual memory factor scores. Results: Post-definition number of concussions (median = 50) was five times the pre-definition (median = 10;p< 0.001). Greater pre- (p= 0.019) and post-definition concussions (p= 0.036) correlated with worse behaviour/mood scores, after controlling for years of football played, with specific effects for depressive symptoms and impulsivity. LOC did not account for variance beyond number of concussions. Conclusions: Practitioners and clinical researchers should provide a definition of concussion in the assessment of concussion history in former football players to facilitate accuracy and standardization. [ABSTRACT FROM PUBLISHER]

Traumatic brain injury (TBI) is thought to be a risk factor for dementia, including dementia due to Alzheimer's disease (AD). However, the influence of TBI history on the neuropsychological course of AD is unknown and, more broadly, the effect of TBI history on age-related cognitive change is poorly understood. We examined the relationship between history of TBI with loss of consciousness (LOC) history and cognitive change in participants with normal cognition and probable AD, stratified by APOEɛ4 allele status. The sample included 706 participants (432 with normal cognition; 274 probable AD) from the National Alzheimer's Coordinating Center (NACC) dataset that completed the Uniform Data Set evaluation between 2005 and 2014. Normal and probable AD participants with a history of TBI were matched to an equal number of demographically and clinically similar participants without a TBI history. In this dataset, TBI with LOC was defined as brain trauma with brief or extended unconsciousness. For the normal and probable AD cohorts, there was an average of 3.2±1.9 and 1.8±1.1 years of follow-up, respectively. 30.8% of the normal cohort were APOEɛ4 carriers, whereas 70.8% of probable AD participants were carriers. Mixed effects regressions showed TBI with LOC history did not affect rates of cognitive change in APOEɛ4 carriers and non-carriers. Findings from this study suggest that TBI with LOC may not alter the course of cognitive function in older adults with and without probable AD. Future studies that better characterize TBI (e.g., severity, number of TBIs, history of subconconcussive exposure) are needed to clarify the association between TBI and long-term neurocognitive outcomes. [ABSTRACT FROM AUTHOR]

The relationship between late-life body mass index (BMI) and Alzheimer's disease (AD) is poorly understood due to the lack of research in samples with autopsy-confirmed AD neuropathology (ADNP). The role of cerebrovascular disease (CVD) in the interplay between late-life BMI and ADNP is unclear. We conducted a retrospective longitudinal investigation and used joint modeling of linear mixed effects to investigate causal relationships among repeated antemortem BMI measurements, CVD (quantified neuropathologically), and ADNP in an autopsy sample of subjects across the AD clinical continuum. The sample included 1,421 subjects from the National Alzheimer's Coordinating Center's Uniform Data Set and Neuropathology Data Set with diagnoses of normal cognition (NC; n = 234), mild cognitive impairment (MCI; n = 201), or AD dementia (n = 986). ADNP was defined as moderate to frequent neuritic plaques and Braak stageIII-VI. Ischemic Injury Scale (IIS) operationalized CVD. Joint modeling examined relationships among BMI, IIS, and ADNP in the overall sample and stratified by initial visit Clinical Dementia Rating score. Subject-specific random intercept for BMI was the predictor for ADNP due to minimal BMI change (p = 0.3028). Analyses controlling for demographic variables and APOE ɛ4 showed lower late-life BMI predicted increased odds of ADNP in the overall sample (p < 0.001), and in subjects with CDR of 0 (p = 0.0021) and 0.5 (p = 0.0012), but not ≥1.0 (p = 0.2012). Although higher IIS predicted greater odds of ADNP (p < 0.0001), BMI did not predict IIS (p = 0.2814). The current findings confirm lower late-life BMI confers increased odds for ADNP. Lower late-life BMI may be a preclinical indicator of underlying ADNP. [ABSTRACT FROM AUTHOR]

Professional American football players incur thousands of repetitive head impacts (RHIs) throughout their lifetime. The long-term consequences of RHI are not well characterized, but may include olfactory dysfunction. RHI has been associated with changes to brain regions involved in olfaction, and olfactory impairment is common after traumatic brain injury. Olfactory dysfunction is a frequent early sequelae of neurodegenerative diseases (e.g., Alzheimer's disease), and RHI is associated with the neurodegenerative disease, chronic traumatic encephalopathy (CTE). We examined olfaction, and its association with clinical measures, in former National Football League (NFL) players. Ninety-five former NFL players (ages 40-69) and 28 same-age controls completed a neuropsychological and neuropsychiatric evaluation as part of a National Institutes of Health-funded study. The Brief Smell Identification Test (B-SIT) assessed olfaction. Principal component analysis generated a four-factor structure of the clinical measures: behavioral/mood, psychomotor speed/executive function, and verbal and visual memory. Former NFL players had worse B-SIT scores relative to controls ( p = 0.0096). A B-SIT cutoff of 11 had the greatest accuracy (c-statistic = 0.61) and specificity (79%) for discriminating former NFL players from controls. In the former NFL players, lower B-SIT scores correlated with greater behavioral/mood impairment ( p = 0.0254) and worse psychomotor speed/executive functioning ( p = 0.0464) after controlling for age and education. Former NFL players exhibited lower olfactory test scores relative to controls, and poorer olfactory test performance was associated with worse neuropsychological and neuropsychiatric functioning. Future work that uses more-comprehensive tests of olfaction and structural and functioning neuroimaging may improve understanding on the association between RHI and olfaction. [ABSTRACT FROM AUTHOR]

The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment ( p < 0.0001), self-reported executive dysfunction ( p < 0.0001), depression ( p < 0.0001), apathy ( p = 0.0161), and behavioral dysregulation ( p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics. [ABSTRACT FROM AUTHOR]

Aging is associated with performance reductions in executive function and episodic memory, although there is substantial individual variability in cognition among older adults. One factor that may be positively associated with cognition in aging is physical activity. To date, few studies have objectively assessed physical activity in young and older adults, and examined whether physical activity is differentially associated with cognition in aging. Young (n=29, age 18–31 years) and older adults (n=31, ages 55–82 years) completed standardized neuropsychological testing to assess executive function and episodic memory capacities. An experimental face-name relational memory task was administered to augment assessment of episodic memory. Physical activity (total step count and step rate) was objectively assessed using an accelerometer, and hierarchical regressions were used to evaluate relationships between cognition and physical activity. Older adults performed more poorly on tasks of executive function and episodic memory. Physical activity was positively associated with a composite measure of visual episodic memory and face-name memory accuracy in older adults. Physical activity associations with cognition were independent of sedentary behavior, which was negatively correlated with memory performance. Physical activity was not associated with cognitive performance in younger adults. Physical activity is positively associated with episodic memory performance in aging. The relationship appears to be strongest for face-name relational memory and visual episodic memory, likely attributable to the fact that these tasks make strong demands on the hippocampus. The results suggest that physical activity relates to cognition in older, but not younger adults. (JINS, 2015, 21, 780–790) [ABSTRACT FROM AUTHOR]

Cognitive impairment in heart failure (HF) is believed to in part stem from structural brain alterations, including shrinkage of subcortical regions. Fortunately, neurocognitive dysfunction in HF can be mitigated by physical activity (PA), though mechanisms for this phenomenon are unclear. PA is protective against age-related cognitive decline that may involve improved structural integrity to brain regions sensitive to aging (e.g., subcortical structures). Yet, no study has examined the benefits of PA on the brain in HF and we sought to do so and clarify related cognitive implications. Fifty older adults with HF completed a neuropsychological battery and wore an accelerometer for 7 days. All participants underwent brain MRI. This study targeted subcortical brain volume given subcortical alterations are often observed in HF and the sensitivity of PA to subcortical structures in other patient populations. Participants averaged 4348.49 (SD=2092.08) steps per day and greater daily steps predicted better attention/executive function, episodic memory, and language abilities, p’s<.05. Medical and demographically adjusted regression analyses revealed higher daily steps per day predicted greater subcortical volume, with specific effects for the thalamus and ventral diencephalon, p’s<.05. Greater subcortical volume was associated with better attention/executive function, p<.05. Higher daily PA was associated with increased subcortical brain volume and better cognition in older adults with HF. Longitudinal work is needed to clarify whether daily PA can attenuate brain atrophy in HF to reduce accelerated cognitive decline in this population. (JINS, 2015, 21, 851–860) [ABSTRACT FROM AUTHOR]

Obesity-associated cognitive impairments may be partially reversible through bariatric surgery. Depression, a prevalent comorbidity in bariatric surgery candidates, is linked with cognitive impairment and poorer surgical outcomes in other populations. No study has examined the effects of pre-operative depression on cognitive changes in bariatric surgery patients. Sixty-seven bariatric surgery patients completed a computerized cognitive test battery prior to surgery and 12 months post-operatively. The structured clinical interview for the DSM-IV Axis I disorders assessed major depressive disorder (MDD). Pre-surgery history of MDD was found in 47.8% of patients, but was not associated with greater baseline cognitive impairments. Repeated measures revealed improved cognitive abilities 12 months after surgery. Pre-surgery history of MDD did not influence post-operative cognitive function. Pre-operative history of MDD did not limit post-operative cognitive improvements. Larger studies with extended follow-ups are needed to clarify our findings and identify factors (e.g. older age) that may modify cognitive changes following surgery. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is common in heart failure. Obesity is a known risk factor for cognitive dysfunction in heart failure, though the mechanisms remain unclear. Obesity increases risk for conditions like hypertension and type 2 diabetes mellitus (T2DM) as well as poor fitness levels, and this may serve as one possible pathway accounting for association between obesity and cognitive dysfunction. Aims: We used structural equation modeling to test whether the combination of hypertension, T2DM, and reduced fitness mediate the association between obesity and cognitive dysfunction. Methods: Two hundred heart failure patients completed neuropsychological testing and a physical fitness assessment. Hypertension and T2DM were ascertained via self-report and medical records. Body mass index (BMI) was calculated. Results: Forty-three percent of the sample was obese. Hypertension (70%) and T2DM (36%) were common, and fitness levels were reduced. The structural equation model with these factors as mediators between BMI and cognitive function demonstrated excellent fit (comparative fit index = 0.98; root mean-square error of approximations = 0.03). Higher BMI correlated with hypertension, T2DM, and poorer fitness. Each of these factors predicted worse cognition. Models that isolated medical comorbidities and physical fitness as the mediator were weaker than the full model. Conclusions: Increased risk for medical comorbidities and reduced fitness levels helped to explain the negative effects of obesity on cognitive dysfunction in heart failure. Prospective studies should confirm this pattern and examine how weight loss benefits cognitive function in heart failure. [ABSTRACT FROM AUTHOR]

This study longitudinally examined participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who underwent a conversion in amyloid-beta (Aβ) status in comparison to a group of ADNI participants who did not show a change in amyloid status over the same follow-up period. Participants included 136 ADNI dementia-free participants with 2 florbetapir positron emission tomography (PET) scans. Of these participants, 68 showed amyloid conversion as measured on florbetapir PET, and the other 68 did not. Amyloid converters and non-converters were chosen to have representative demographic data (age, education, sex, diagnostic status, and race). The amyloid converter group showed increased prevalence of APOE ε4 (p < 0.001), greater annualized percent volume loss in selected magnetic resonance imaging (MRI) regions (p < 0.05), lower cerebrospinal fluid Aβ 1–42 (p < 0.001), and greater amyloid retention (as measured by standard uptake value ratios) on florbetapir PET scans (p < 0.001) in comparison to the non-converter group. These results provide compelling evidence that important neuropathological changes are occurring alongside amyloid conversion. [ABSTRACT FROM AUTHOR]

Purpose/Aim: Heart failure patients often require assistance with activities of daily living, including driving. Recent work shows heart failure patients commit more errors on a simulated driving task relative to controls and cognitive dysfunction contributed to these errors. We sought to extend these findings by examining whether structural magnetic resonance imaging indices correlate with driving independence and performance in heart failure. Materials and Methods: Forty-nine heart failure patients underwent brain magnetic resonance imaging and performed a battery assessing attention/executive function and memory. A self-report instrument was used to assess independence in transportation. A subset of heart failure participants ( N = 8) completed a validated driving simulator scenario. Results: Among the larger sample ( N = 49), reduced gray matter correlated with greater dependence in transportation and worse attention/executive function; in turn, worse attention/executive function predicted greater assistance with transportation ( p < 0.05). Among the subset that completed the driving simulator ( N = 8), reduced gray matter correlated with more stop signs missed and increased white matter hyperintensities correlated with greater collisions, centerline crossings and time out of lane ( p < 0.05). Poorer attention/executive function was also associated with more time over the speed limit on the driving simulation ( p < 0.05). Follow-up analyses showed the above effects were largely independent of age. Conclusions: Reduced structural brain integrity is associated with poorer reported and simulated driving in persons with heart failure. Larger prospective studies that employ on-road testing are needed to clarify brain changes and risk for unsafe driving in heart failure. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is associated with cognitive impairment, and bariatric surgery has been shown to improve cognitive functioning. Rapid improvements in glycemic control are common after bariatric surgery and likely contribute to these cognitive gains. We examined whether improvements in glucose regulation are associated with better cognitive function following bariatric surgery. Method: A total of 85 adult bariatric surgery patients underwent computerized cognitive testing and fasting blood draw for glucose, insulin, and glycated hemoglobin (HbA1c) at baseline and 12 months postoperatively. Results: Significant improvements in both cognitive function and glycemic control were observed among patients. After controlling for baseline factors, 12-month homeostatic model assessment of insulin resistance HOMA-IR predicted 12-month digits backward (β = –.253, p <.05), switching of attention–A (β =.156, p <.05), and switching of attention–B (β = –.181, p <.05). Specifically, as HOMA-IR decreased over time, working memory, psychomotor speed, and cognitive flexibility improved. Decreases in HbA1c were not associated with postoperative cognitive improvements. After controlling for baseline cognitive test performance, changes in body mass index (BMI) were also not associated with 12-month cognitive function. Conclusions: Small effects of improved glycemic control on improved aspects of attention and executive function were observed following bariatric surgery among severely obese individuals. Future research is needed to identify the underlying mechanisms for the neurocognitive benefits of these procedures. [ABSTRACT FROM AUTHOR]

We investigated the internal structure comparability of Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) scores derived from the MMPI-2 and MMPI-2-RF booklets in a sample of 320 criminal defendants (229 males and 54 females). After exclusion of invalid protocols, the final sample consisted of 96 defendants who were administered the MMPI-2-RF booklet and 83 who completed the MMPI-2. No statistically significant differences in MMPI-2-RF invalidity rates were observed between the two forms. Individuals in the final sample who completed the MMPI-2-RF did not statistically differ on demographics or referral question from those who were administered the MMPI-2 booklet. Independent t tests showed no statistically significant differences between MMPI-2-RF scores generated with the MMPI-2 and MMPI-2-RF booklets on the test’s substantive scales. Statistically significant small differences were observed on the revised Variable Response Inconsistency (VRIN-r) and True Response Inconsistency (TRIN-r) scales. Cronbach’s alpha and standard errors of measurement were approximately equal between the booklets for all MMPI-2-RF scales. Finally, MMPI-2-RF intercorrelations produced from the two forms yielded mostly small and a few medium differences, indicating that discriminant validity and test structure are maintained. Overall, our findings reflect the internal structure comparability of MMPI-2-RF scale scores generated from MMPI-2 and MMPI-2-RF booklets. Implications of these results and limitations of these findings are discussed. [ABSTRACT FROM AUTHOR]

Aim Heart failure ( HF) patients require assistance with activities of daily living ( ADL). Poor physical fitness has recently been identified as a contributor to the high rates of disability in HF, though the mechanisms for such effects are unclear. Although not previously examined, decreased fitness might adversely impact ADL in HF through its known association with cognitive impairment, a key correlate of self-care abilities in this population. We sought to test this possibility using a model-based approach. Methods A total of 197 patients with HF completed a physical fitness test and a neuropsychological test battery. A total ADL composite was derived from the Lawton Brody scale. Structural equation modeling tested whether cognitive function mediated the association between physical fitness and total ADL. Results Fitness was reduced, and cognitive dysfunction and impaired ADL were prevalent. The initially significant association between fitness and total ADL was attenuated when cognitive function was introduced as a mediator. This model showed good fit (comparative fit index = 0.91: root mean-square error of approximations = 0.077) with a significant indirect pathway between physical fitness and total ADL through cognitive function: Decreased physical fitness was associated with cognitive dysfunction (β = 0.35), which predicted greater assistance with ADL (β = 0.22). Conclusions Poor physical fitness might lead to decreased functional independence in HF through its negative effects on cognitive function. Prospective studies are required to confirm our findings, identify other mechanisms by which poor fitness impacts ADL, and examine whether exercise interventions can improve cognition and help preserve ADL independence in HF. Geriatr Gerontol Int 2015; 15: 174-181. [ABSTRACT FROM AUTHOR]

Background Heart failure (HF) increases risk for cognitive impairment in part due to the negative effects of cardiac dysfunction on cerebral perfusion. Atrial fibrillation (AF), an independent risk factor for cognitive impairment, often accompanies HF and is associated with lower systemic perfusion. However, no study has examined the associations among AF, cognitive function, and cerebral perfusion in patients with HF. Methods A total of 187 HF patients completed neuropsychological testing and underwent transcranial Doppler ultrasonography. Cerebral blood flow velocity of the middle cerebral artery (CBF-V) operationalized cerebral perfusion. A medical chart review ascertained AF. Results History of AF was found in 32.1% of HF patients. HF patients with AF exhibited worse global cognition, memory, and CBF-V relative to patients without AF. These effects remained after HF severity and other demographic and medical factors were taken into account. Partial correlations controlling for possible confounds showed decreased CBF-V predicted worse cognition in multiple domains in the overall sample (r = 0.13 to 0.15, P < 0.05) and in the subgroup of HF patients with AF (r = 0.26 to r = 0.28, P < 0.05), but not among HF patients without AF. Conclusions AF exacerbates cognitive deficits in HF, possibly through its association with decreased cerebral perfusion. Longitudinal studies are needed to determine whether AF accelerates cognitive decline in HF and whether medical (e.g., ablation) and lifestyle interventions (e.g., exercise programs) that target cerebral perfusion improve cognitive outcomes in patients with HF and AF. [ABSTRACT FROM AUTHOR]

Evidence suggests that both obesity and binge eating disorder (BED) may be associated with deficits in cognitive functioning. The purpose of this study was to examine whether a lifetime history of BED would be associated with changes in several domains of cognitive functioning (attention, executive function, language, and memory) following bariatric surgery. Participants were 68 bariatric surgery patients who completed a computerized battery of cognitive tests within 30 days prior to undergoing surgery and again at a 12-Month postoperative follow-up. Results revealed that on the whole, participants displayed improvements from baseline to follow-up in attention, executive function, and memory, even after controlling for diagnostic history of depression; no changes were observed for language. However, individuals with and without a history of BED did not differ in changes in body mass index or in the degree of improvement in cognitive functioning from baseline to follow-up. Such results suggest that a history of BED does not influence changes in cognitive functioning following bariatric surgery. Future research will be needed to further clarify the role of BED in predicting cognitive function over time. [ABSTRACT FROM AUTHOR]

Introduction: Treatment nonadherence is common in heart failure (HF) and is associated with poor health outcomes in this population. Recent cross-sectional work in heart failure and past work in other medical populations suggest that cognitive function is a key determinant of a patient’s ability to adhere to treatment recommendations. However, it is also possible that treatment adherence is an important modifier and predictor of cognitive function, though no study has examined this possibility, and we sought to do so in a sample of heart failure patients.Method: A total of 115 patients with heart failure self-reported adherence to treatment recommendations. The Modified Mini Mental State Examination (3MS), Trail Making Test Parts A and B, and the California Verbal Learning Test–II (CVLT–II) assessed cognitive function. These procedures were performed at baseline and a 12-month follow-up.Results:Global cognition and memory abilities improved over the 12-month period. Regression analyses controlling for baseline and medical and demographic factors showed that better baseline treatment adherence predicted improved 12-month performances on the 3MS and CVLT–II. Adherence to medication and diet regimens and smoking abstinence emerged as the most important contributors.Conclusions:Better treatment adherence predicted improved cognition one year later in HF. Prospective studies that utilize objective assessments of treatment adherence are needed to confirm our findings and examine whether improved treatment adherence preserves cognitive function in heart failure. [ABSTRACT FROM PUBLISHER]

Background: Occurrences of impaired activities of daily living (ADL) are common in heart failure (HF) patients and contribute to the elevated mortality and hospitalization rates in this population. Cognitive impairment is also prevalent in HF, though its ability to predict functional decline over time is unknown. Aims: This study examined the longitudinal pattern of activities of daily living (ADL) in HF persons and whether reduced baseline cognitive status predicts functional decline in this population. Methods: Altogether 110 persons with HF completed the Lawton-Brody Instrumental Activities of Daily Living (IADL) scale and were administered the Modified Mini-Mental Status Examination (3MS) at baseline and a 12-month follow-up. Three composite scores were derived from the Lawton-Brody scale, including total, instrumental, and basic ADL. Results: HF patients reported high rates of baseline impairments in instrumental ADL, including shopping, food preparation, housekeeping duties, laundry, among others. Repeated measures analyses showed significant declines in total and instrumental ADL from baseline to the 12-month follow-up in HF (p<0.05). Hierarchical regression analyses showed that poorer baseline performance on the 3MS predicted worse total ADL performance at 12-months (β=0.15, p=0.049), including greater dependence in shopping, driving, feeding, and physical ambulation (p<0.05 for all). Conclusion: The current results show that HF patients report significant functional decline over a 12-month period and brief cognitive tests can identify those patients at highest risk for decline. If replicated, such findings encourage the use of cognitive screening measures to identify HF patients most likely to require assistance with ADL tasks. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bariatric surgery is associated with improved cognition, and it is possible that such improvements are found at extended follow-ups. We hypothesized that cognitive improvement would be maintained 3 years after bariatric surgery. METHODS: Fifty bariatric patients were recruited from the Longitudinal Assessment of Bariatric Surgery parent project. Participants completed a computerized cognitive test battery to assess cognitive function at 12 weeks, 12 months, 24 months, and 36 months after surgery. RESULTS: Repeated measures revealed main effects for attention, executive function, and memory. Attention improved up to 24 months and then slightly declined although it still fell within the average range at 36 months. Improvements in executive function reached their peak at 36 months after surgery. Short-term improvements in memory were maintained at 36 months. No main effect emerged for language. CONCLUSIONS: Bariatric surgery may lead to lasting improvements in cognition. Prospective studies with extended follow-ups (eg, 10 years) should examine whether bariatric surgery can attenuate cognitive decline in severely obese patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Cognitive impairment in heart failure (HF) is believed to result from brain hypoperfusion subsequent to cardiac dysfunction. Physical inactivity is prevalent in HF and correlated with reduced cardiac and cognitive function. Yet, no longitudinal studies have examined the neurocognitive effects of physical inactivity in HF. The current study examined whether reduced physical activity increases risk for cognitive impairment and brain hypoperfusion over time in HF. Methods: At baseline and 12months later, 65 HF patients underwent neuropsychological testing, transcranial Doppler ultrasonography, and were asked to wear an accelerometer for seven days. Results: Lower baseline step count and less time spent in moderate free-living activity best predicted worse attention/executive function and decreased cerebral perfusion at the 12-month follow-up. Decreased baseline cerebral perfusion also emerged as a strong predictor of poorer 12-month attention/executive function. Conclusions: Lower physical activity predicted worse cognition and cerebral perfusion 12months later in HF. Physical inactivity in HF may contribute to cognitive impairment and exacerbate risk for conditions such as Alzheimer's disease. Larger studies are needed to elucidate the mechanisms by which physical inactivity leads to cognitive dysfunction in HF, including clarification of the role of cerebral hypoperfusion. [Copyright &y& Elsevier]

Objective Cerebral hypoperfusion is common in heart failure (HF) and believed to underlie poor neurocognitive outcomes in this population. Up to 42% of HF patients also exhibit depressive symptomatology that may stem from reduced cerebral blood flow. However, no study has examined this possibility or whether reduced brain perfusion increases risk for future cognitive dysfunction in older adults with HF. Methods One hundred HF patients underwent transcranial Doppler ultrasonagraphy to quantify global cerebral blood flow velocity (CBF-V) and were administered a cognitive test battery to assess global cognition, attention/executive function, and memory abilities. All participants then completed the Beck Depression Inventory-II to assess depressive symptomatology. These procedures were performed at baseline and at 12-month follow-up. Results Repeated measures revealed that CBF-V declined over the 12-month period. Regression analyses showed that reduced baseline CBF-V predicted worse performances in attention/executive function ( p < 0.05 for all) and a trend for memory ( p = 0.09) in addition to greater depressive symptomatology ( p < 0.05) at the 12-month follow-up, even after controlling for baseline factors and medical and demographic variables. Conclusions Cerebral perfusion declined over time and was associated with poorer cognitive function and greater depressive symptoms at a 1-year follow-up in HF. Prospective studies with long-term follow-ups that employ neuroimaging are needed to examine whether cognitive dysfunction and depression in HF stem from the adverse effects of cerebral hypoperfusion on the cerebral structure. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Cognitive impairment is prevalent in heart failure (HF), though substantial variability in the pattern of cognitive impairment is found across studies. To clarify the nature of cognitive impairment in HF, we examined longitudinal trajectories across multiple domains of cognition in HF patients using latent growth class modeling. 115 HF patients completed a neuropsychological battery at baseline, 3-months and 12-months. Participants also completed the Beck Depression Inventory-II (BDI-II). Latent class growth analyses revealed a three-class model for attention/executive function, four-class model for memory, and a three-class model for language. The slope for attention/executive function and language remained stable, while improvements were noted in memory performance. Education and BDI-II significantly predicted the intercept for attention/executive function and language abilities. The BDI-II also predicted baseline memory. The current findings suggest that multiple performance-based classes of neuropsychological test performance exist within cognitive domains, though case-controlled prospective studies with extended follow-ups are needed to fully elucidate changes and predictors of cognitive function in HF. [ABSTRACT FROM PUBLISHER]

Aims and objectives To examine the independent association between executive function with instrumental activities of daily living and health behaviours in older adults with heart failure. Background Executive function is an important contributor to functional independence as it consists of cognitive processes needed for decision-making, planning, organising and behavioural monitoring. Impairment in this domain is common in heart failure patients and associated with reduced performance of instrumental activities of daily living in many medical and neurological populations. However, the contribution of executive functions to functional independence and healthy lifestyle choices in heart failure patients has not been fully examined. Design Cross-sectional analyses. Methods One hundred and seventy-five heart failure patients completed a neuropsychological battery and echocardiogram. Participants also completed the Lawton- Brody Instrumental Activities of Daily Living Scale and reported current cigarette use. Results Hierarchical regressions revealed that reduced executive function was independently associated with worse instrumental activity of daily living performance with a specific association for decreased ability to manage medications. Partial correlations showed that executive dysfunction was associated with current cigarette use. Conclusions Our findings suggest that executive dysfunction is associated with poorer functional independence and contributes to unhealthy behaviours in heart failure. Future studies should examine whether heart failure patients benefit from formal organisation schema (i.e. pill organisers) to maintain independence. Relevance to clinical practice Screening of executive function in heart failure patients may provide key insight into their ability to perform daily tasks, including the management of treatment recommendations. [ABSTRACT FROM AUTHOR]

Obesity is associated with cognitive dysfunction in children and adolescents, although the mechanisms underlying these deficits remain unclear. This study examined the associations between body mass index (BMI) and regional gray matter volume and white matter integrity in 120 healthy children and adolescents (6-18 years of age) who underwent magnetic resonance and diffusion tensor imaging. Bonferroni-corrected partial correlation analyses controlling for demographic and clinical characteristics revealed significant inverse associations between demographically standardized BMI values and gray matter volume of frontal ( r = −0.31) and limbic ( r = −0.35) brain regions. No such pattern emerged for fractional anisotropy of white matter tracts. Subsequent hierarchical regression analyses indicated that the relationship between standardized BMI and structural gray and white matter brain indices did not vary with age. These findings suggest that obesity in children and adolescents is associated with decreased volume of frontal and limbic cerebral gray matter regions. Further research is much needed to better elucidate possible brain-based mechanisms for cognitive dysfunction associated with obesity. [ABSTRACT FROM AUTHOR]

Aim Cognitive impairment is common among persons with cardiovascular disease ( CVD), and several potential aetiological mechanisms have been described, including contributions of genetic markers such as variations in the brain-derived neurotrophic ( BDNF) gene. This current study examined the associations of BDNF genotype with cognitive function among individuals with CVD. Methods This study included 110 participants with CVD who completed a comprehensive neuropsychological battery that assessed global cognitive function, attention/executive function, memory, language, and visuospatial abilities. All participants also underwent blood draw to provide a DNA sample that was used to determine BDNF genotype. Carriers of either one or two copies of the methionine allele of BDNF were categorized into one group ( n = 33); non-carriers were categorized into a second group ( n = 77). Results After adjustment for demographic and medical characteristics, hierarchical regression analyses revealed persons with one or more methionine alleles displayed better performance than valine/valine individuals for attention/executive function (β = 0.22, P = 0.047) and memory (β = 0.25, P = 0.03), as well as a trend for language (β = 0.19, P = 0.08) and visuospatial abilities (β = 0.21, P = 0.06). Conclusions BDNF Val66Met had little impact on cognitive functioning in a sample of older adults with CVD, and significant findings contradicted that predicted by past work. Future work is much needed to clarify the mechanisms of these findings, particularly studies examining both circulating BDNF levels and genetic variation in the BDNF gene and cognitive function over time. [ABSTRACT FROM AUTHOR]

Context: Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is a computerized cognitive test battery commonly used for concussion evaluation. An important aspect of these procedures is baseline testing, but researchers have suggested that many users do not use validity indices to ensure adequate effort during testing. No one has examined the prevalence of invalid performance for college football players. Objective: To examine the prevalence of invalid scores on ImPACT testing. Design: Cross-sectional study. Setting: National Collegiate Athletic Association Division I university. Patients or Other Participants: A total of 159 athletes (age = 20.3 ± 1.41 years; range = 17.8-23.7 years) from a Division I collegiate football team participated. Intervention(s): An informational intervention regarding the importance of concussion testing to promote safety was administered before testing for the most recent season. Main Outcome Measure(s): We examined preseason ImPACT testing data across a 3-year period (total assessments = 269). Based on invalid and sandbagging indices denoted by the ImPACT manual, protocols were examined to indicate how many invalid indices each athlete had. Results: A total of 27.9% (n = 75) of assessments were suggestive of invalid scores, with 4.1% (n = 11) suggesting invalid responding only, 17.5% (n = 47) indicating "sandbagging" only, and 6.3% (n = 17) showing both invalid and sandbagging responding. The informational intervention did not reduce the prevalence of invalid responding. Conclusions: These findings highlight the need for further information about the ImPACT validity indices and whether they truly reflect poor effort. Future work is needed to identify practices to reliably target and reduce invalid responding. [ABSTRACT FROM AUTHOR]

Obesity is an established risk factor for cognitive impairment. Theories of cognitive reserve suggest that premorbid factors, such as intellectual ability, may attenuate the expression of cognitive impairment due to age or disease. The current study examined whether cognitive reserve, defined as estimated premorbid intellectual ability, moderates the relationship between obesity and cognitive function in obese adults. Participants without major medical or psychological conditions completed a computerized battery of neuropsychological tests. Hierarchical regression models found a significant interaction between BMI and cognitive reserve for attention/executive function and memory, suggesting that cognitive reserve attenuates the expression of obesity-related cognitive impairment. [ABSTRACT FROM AUTHOR]

Background Poor sleep is common in heart failure (HF), though mechanisms of sleep difficulties are not well understood. Adverse brain changes among regions important for sleep have been demonstrated in patients with HF. Cerebral hypoperfusion, a correlate of sleep quality, is also prevalent in HF and a likely contributor to white matter hyperintensities (WMH). However, no study to date has examined the effects of cerebral blood flow, WMH, and brain volume on sleep quality in HF. Methods Fifty-three HF patients completed the Pittsburgh Sleep Quality Index and underwent brain magnetic resonance imaging to quantify brain and WMH volume. Transcranial Doppler ultrasonography assessed cerebral blood flow velocity of the middle cerebral artery (CBF-V of the MCA). Results 75.5% of HF patients reported impaired sleep. Regression analyses adjusting for medical and demographic factors showed decreased CBF-V of the MCA and greater WMH volume were associated with poor sleep quality. No such pattern emerged on total brain or regional volume indices. Conclusions Decreased cerebral perfusion and greater WMH may contribute to sleep difficulties in HF. Future studies are needed to confirm these findings and clarify the effects of cerebral blood flow and WMH on sleep in healthy and patient samples. [ABSTRACT FROM AUTHOR]

Objective: Cerebral hypoperfusion is common in heart failure (HF) and believed to underlie poor neurocognitive outcomes in this population. Up to 42% of HF patients also exhibit depressive symptomatology that may stem from reduced cerebral blood flow. However, no study has examined this possibility or whether reduced brain perfusion increases risk for future cognitive dysfunction in older adults with HF. Methods: One hundred HF patients underwent transcranial Doppler ultrasonagraphy to quantify global cerebral blood flow velocity (CBF-V) and were administered a cognitive test battery to assess global cognition, attention/executive function, and memory abilities. All participants then completed the Beck Depression Inventory-II to assess depressive symptomatology. These procedures were performed at baseline and at 12-month follow-up. Results: Repeated measures revealed that CBF-V declined over the 12-month period. Regression analyses showed that reduced baseline CBF-V predicted worse performances in attention/executive function (p<0.05 for all) and a trend for memory (p =0.09) in addition to greater depressive symptomatology (p<0.05) at the 12-month follow-up, even after controlling for baseline factors and medical and demographic variables. Conclusions: Cerebral perfusion declined over time and was associated with poorer cognitive function and greater depressive symptoms at a 1-year follow-up in HF. Prospective studies with long-term follow-ups that employ neuroimaging are needed to examine whether cognitive dysfunction and depression in HF stem from the adverse effects of cerebral hypoperfusion on the cerebral structure. [ABSTRACT FROM AUTHOR]