Christian LoBue

Self-Reported Traumatic Brain Injury and Mild Cognitive Impairment: Increased Risk and Earlier Age of Diagnosis

This study examined whether history of traumatic brain injury (TBI) is associated with increased risk and earlier onset of mild cognitive impairment (MCI). Subjects with MCI (n = 3,187) and normal cognition (n = 3,244) were obtained from the National Alzheimers Coordinating Center database. TBI was categorized based on lifetime reported TBI with loss of consciousness (LOC) without chronic deficit. Logistic regression was used to examine TBI history as a predictor of MCI, adjusted for demographics, apolipoprotein E-ɛ4 (ApoE4), a composite vascular risk score, and history of psychiatric factors. ANCOVA was used to examine whether age at MCI diagnosis and estimated age of onset differed between those with (TBI+) and without (TBI-) a history of TBI. TBI history was a significant predictor (p <  0.01) and associated with increased odds of MCI diagnosis in unadjusted (OR = 1.25; 95% CI = 1.05-1.49) and adjusted models, accounting for age, education, ApoE4, and a composite vascular score (OR = 1.32; 95% CI = 1.10-1.58). This association, however, was largely attenuated (OR = 1.14; 95% CI = 0.94-1.37; p = 0.18) after adjustment for reported history of depression. MCI was diagnosed a mean of 2.3 years earlier (p <  0.001) in the TBI+ group, and although TBI+ subjects had an estimated mean of decline 1.7 years earlier, clinician-estimated age of onset failed to differ (p = 0.13) when gender and psychiatric factors were controlled. This is the first report of a possible role for TBI as a risk factor in MCI, but its association may be related to other factors such as gender and depression and requires further investigation.

Traumatic brain injury history is associated with earlier age of onset of Alzheimer disease

Abstract Objective: This study examined whether a history of traumatic brain injury (TBI) is associated with earlier onset of Alzheimer disease (AD), independent of apolipoprotein ε4 status (Apoe4) and gender.Method: Participants with a clinical diagnosis of AD (n = 7625) were obtained from the National Alzheimer’s Coordinating Center Uniform Data Set, and categorized based on self-reported lifetime TBI with loss of consciousness (LOC) (TBI+ vs. TBI−) and presence of Apoe4. ANCOVAs, controlling for gender, race, and education were used to examine the association between history of TBI, presence of Apoe4, and an interaction of both risk factors on estimated age of AD onset.Results: Estimated AD onset differed by TBI history and Apoe4 independently (p’s < .001). The TBI+ group had a mean age of onset 2.5 years earlier than the TBI− group. Likewise, Apoe4 carriers had a mean age of onset 2.3 years earlier than non-carriers. While the interaction was non-significant (p = .34), participants having both a history of TBI and Apoe4 had the earliest mean age of onset compared to those with a TBI history or Apoe4 alone (MDifference = 2.8 and 2.7 years, respectively). These results remained unchanged when stratified by gender.Conclusions: History of self-reported TBI can be associated with an earlier onset of AD-related cognitive decline, regardless of Apoe4 status and gender. TBI may be related to an underlying neurodegenerative process in AD, but the implications of age at time of injury, severity, and repetitive injuries remain unclear.

Traumatic brain injury history is associated with earlier age of onset of frontotemporal dementia

Objective We retrospectively examined whether a history of traumatic brain injury (TBI) is associated with an earlier age of symptom onset and diagnosis in a large sample of patients with behavioural variant frontotemporal dementia (bvFTD). Methods Data on patients with bvFTD (n=678) were obtained from the National Alzheimers Coordinating Center Uniform Data Set. TBI was categorised based on reported lifetime history of TBI with loss of consciousness (LOC) but no chronic deficits occurring more than 1 year prior to diagnosis of bvFTD. Analysis of covariance (ANCOVA) was used to determine if clinician-estimated age of symptom onset and age at diagnosis of bvFTD differed between those who reported a history of TBI with LOC (TBI+) and those who did not (TBI−). Results Controlling for sex, the TBI+ bvFTD group had an age of symptom onset and age of diagnosis that was on average 2.8 and 3.2 years earlier (p<0.01) than the TBI− bvFTD group. Conclusions TBI history with LOC occurring more than 1 year prior to diagnosis is associated with an earlier age of symptom onset and diagnosis in patients with bvFTD. TBI may be related to the underlying neurodegenerative processes in bvFTD, but the implications of age at time of injury, severity and repetitive injuries remain unclear.

Optimal neurocognitive, personality and behavioral measures for assessing impulsivity in cocaine dependence.

Abstract Background: Impulsivity may underlie the poor treatment retention and high relapse rates observed in cocaine-dependent persons. However, observed differences in measures of impulsivity between cocaine-dependent and healthy control participants often do not reach clinical significance, suggesting that the clinical relevance of these differences may be limited. Objectives: To examine which measures of impulsivity (i.e. self-report impulsivity, self-report personality, neurocognitive testing) best distinguish cocaine-dependent and healthy control participants (i.e. showing differences at least 1.5 standard deviations [SD] from controls). Optimal measures were considered to demonstrate sufficient classification accuracy. Methods: Sixty-five recently abstinent cocaine-dependent and 25 healthy control participants were assessed using select neurocognitive tests and self-report questionnaires including the NEO Personality Inventory-Revised (NEO-PI-R), Temperament and Character Inventory (TCI), Barratt Impulsiveness Scale (BIS-11a), and the Frontal Systems Behavior Scale (FrSBe). Results: When corrected for years of education and gender, neurocognitive measures did not demonstrate clinically significant differences between cocaine-dependent and control participants. The personality measures TCI Purposefulness and Congruent Second Nature and NEO-PI-R Impulsiveness, and the self-rating measures FrSBe Disinhibition and BIS-11 Motor Impulsivity and Total successfully identified clinically meaningful elevations in impulsivity within cocaine-dependent participants (>1.5 SDs from controls). Furthermore, these measures achieved 84–93% accuracy in discriminating cocaine-dependent from control participants. Conclusion: Clinically significant neurocognitive impairment in cocaine-dependent participants was not observed in this sample. As the BIS-11 or FrSBe are brief to administer, accurate, and have been shown to predict treatment retention and relapse, these measures appear to be optimal, relative to the personality measures, for examining trait impulsivity in cocaine dependence.

Neurodegenerative Dementias After Traumatic Brain Injury

Traumatic brain injury (TBI) is often considered to be a risk factor for the later development of neurodegenerative conditions, but some findings do not support a link. Differences in research methods, clinical samples, and limitations encountered when assessing and documenting TBI details likely contribute to the mixed reports in the literature. Despite some variability in findings, a review of the literature does provide support for the notion that TBI appears to be associated with earlier onset of some neurodegenerative disorders, although clearly not everyone with a TBI appears to be at an increased risk. Whereas a mechanistic link remains unknown, TBI has been found to initiate an accumulation of pathological processes related to several neurodegenerative disorders. The authors propose a hypothetical model that relates TBI to the development of pathological burden overlapping with some neurodegenerative conditions, in which onset of cognitive/behavioral impairments is hastened in some individuals, but pathological processes stabilize afterward, resulting in a similar course of decline to individuals with dementia who do not have a history of TBI.

Traumatic Brain Injury History Is Associated With an Earlier Age of Dementia Onset in Autopsy-Confirmed Alzheimer’s Disease.

Objective: To evaluate whether a history of traumatic brain injury (TBI) with reported loss of consciousness (LOC) is a risk factor for earlier onset of Alzheimer’s disease (AD) in an autopsy-confirmed sample. Method: Data from 2,133 participants with autopsy-confirmed AD (i.e., at least Braak neurofibrillary tangle stages III to VI and CERAD neuritic plaque score moderate to frequent) were obtained from the National Alzheimer’s Coordinating Center (NACC). Participants were categorized by presence/absence of self-reported remote (i.e., >1 year prior to their first Alzheimer’s Disease Center visit) history of TBI with LOC (TBI+ vs. TBI−). Analyses of Covariance (ANCOVA) controlling for sex, education, and race compared groups on clinician-estimated age of symptom onset and age of diagnosis. Results: Average age of onset was 2.34 years earlier (p = .01) for the TBI+ group (n = 194) versus the TBI− group (n = 1900). Dementia was diagnosed on average 2.83 years earlier (p = .002) in the TBI+ group (n = 197) versus the TBI− group (n = 1936). Using more stringent neuropathological criteria (i.e., Braak stages V-VI and CERAD frequent), both age of AD onset and diagnosis were 3.6 years earlier in the TBI+ group (both p’s < .001). Conclusions: History of TBI with reported LOC appears to be a risk factor for earlier AD onset. This is the first study to use autopsy-confirmed cases, supporting previous investigations that used clinical criteria for the diagnosis of AD. Further investigation as to possible underlying mechanisms of association is needed.

Traumatic brain injury history and progression from mild cognitive impairment to Alzheimer disease.

Objective: To examine whether history of traumatic brain injury (TBI) is associated with more rapid progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Method: Data from 2,719 subjects with MCI were obtained from the National Alzheimer’s Coordinating Center. TBI was categorized based on presence (TBI+) or absence (TBI–) of reported TBI with loss of consciousness (LOC) without chronic deficit occurring >1 year prior to diagnosis of MCI. Survival analyses were used to determine if a history of TBI predicted progression from MCI to AD up to 8 years. Random regression models were used to examine whether TBI history also predicted rate of decline on the Clinical Dementia Rating scale Sum of Boxes score (CDR-SB) among subjects who progress to AD. Results: Across 8 years, TBI history was not significantly associated with progression from MCI to a diagnosis of AD in unadjusted (HR = 0.80; 95% CI [0.63, 1.01]; p = .06) and adjusted (p = .15) models. Similarly, a history of TBI was a nonsignificant predictor for rate of decline on CDR-SB among subjects who progressed to AD (b = 0.15, p = .38). MCI was, however, diagnosed a mean of 2.6 years earlier (p < .001) in TBI+ subjects compared with the TBI– group. Conclusions: A history of TBI with LOC was not associated with progression from MCI to AD, but was linked to an earlier age of MCI diagnosis. These findings add to a growing literature suggesting that TBI might reduce the threshold for onset of MCI and certain neurodegenerative conditions, but appears unrelated to progression from MCI to AD.

Consistency of traumatic brain injury reporting in older adults with and without cognitive impairment

Abstract Objective: Medical history information regarding prior traumatic brain injury (TBI) usually relies on self-report, although little is known about the reliability of this information with regard to injuries sustained years or decades earlier. Even less is known about the reliability of self-reported medical history information in older individuals with cognitive impairment. To this end, we assessed the test-retest reliability of self-reported TBI history in a large, national sample. Methods: Participants (n = 4309) were older adults with intact cognition, mild cognitive impairment (MCI) and Alzheimer’s disease (AD) from the National Alzheimer’s Coordinating Center. Subjects provided TBI history information at baseline and one annual follow-up visit. Consistency of self-reported history of TBI with <5 minutes loss of consciousness (mLOC) and TBI with ≥5 mLOC reported at time 1 and 2 was analyzed across diagnostic groups. Results: Overall, subjects provided reports of TBI history at follow-up that were highly consistent with baseline reports (97.8–99.6% agreement), and Cohen’s kappa coefficients were all larger than .80 and statistically significant, maximum p < .001. Furthermore, level of cognitive impairment was not a significant predictor of consistency in reporting. Conclusions: These data are some of the first to suggest that self-report may be a consistent method of obtaining remote TBI history in the absence of medical records for older individuals, regardless of cognitive impairment.

Traumatic brain injury history and age of mild cognitive impairment diagnosis

Background: Alzheimer’s disease (AD) clinical trial functional measures require careful cross-cultural adaptation prior to their use in multinational trials to ensure the scales measure equivalent concepts across cultures. However, adaptation alone does not guarantee the measurement characteristics of a measure will be retained. Thorough evaluation of newly adapted measures’ psychometric properties should be assessed to determine to what extent the measure will perform as expected in clinical trials. The aim of this analysis is to investigate the validity and reliability of a culturally adapted ADCS-ADL in a cohort of mild-to-moderate (M2M) AD subjects in China. Methods: An observational study enrolled 150 male and female M2M AD subjects and 100 healthy controls ages 55 to 85 at 15 sites in mainland China. Subjects had a diagnosis of probable AD, Mini-Mental State Examination (MMSE) score 15 and 26, equivalent of >6th grade reading level and if treated, pharmacologically stable. The ADCS-ADL, along with cognitive measures, were administered by raters trained and certified prior to study start. Aspects of reliability and validity assessed include construct and known-groups validity and test-retest reliability. Results: The AD cohort was older (p<.05) and had more females than the control group. The mean ADCS-ADL total score for the M2MAD subjects (60.8610.2) was significantly lower (p<.0001) than that of the healthy controls (77.062.0). There was a significant correlation (p<.0001) between the AD subject ADCS-ADL scores and MMSE (0.53), CDR (-0.58), ADAS-cog (-0.42). Test-retest reliability for ADCS-ADL total score was found to be acceptable (0.84, p<.0001). Conclusions: The data reported here suggest this adaptation of the Chinese ADCS-ADL is both valid and reliable in a population of mild-to-moderate AD subjects in mainland China. Future analyses will include a comparison of the psychometric properties between these data and data collected in other languages.