Subjective and objective cognitive function among older adults with a history of traumatic brain injury: A population-based cohort study

<div><p>Background</p><p>Traumatic brain injury (TBI) is extremely common across the lifespan and is an established risk factor for dementia. The cognitive profile of the large and growing population of older adults with prior TBI who do not have a diagnosis of dementia, however, has not been well described. Our aim was to describe the cognitive profile associated with prior TBI exposure among community-dwelling older adults without dementia—an understudied but potentially vulnerable population.</p><p>Methods and findings</p><p>In this population-based cohort study, we studied 984 community-dwelling older adults (age 51 y and older and their spouses) without dementia who had been randomly selected from respondents to the 2014 wave of the Health and Retirement Study to participate in a comprehensive TBI survey and who either reported no prior TBI (<i>n</i> = 737) or prior symptomatic TBI resulting in treatment in a hospital (<i>n =</i> 247). Mean time since first TBI was 38 ± 19 y. Outcomes assessed included measures of global cognitive function, verbal episodic memory, semantic fluency, and calculation as well as a measure of subjective memory (“How would you rate your memory at the present time?”). We compared outcomes between the two TBI groups using regression models adjusting for demographics, medical comorbidities, and depression. Sensitivity analyses were performed stratified by TBI severity (no TBI, TBI without loss of consciousness [LOC], and TBI with LOC). Respondents with TBI were younger (mean age 64 ± 10 y versus 68 ± 11 y), were less likely to be female, and had higher prevalence of medical comorbidities and depression than respondents without TBI. Respondents with TBI did not perform significantly differently from respondents without TBI on any measure of objective cognitive function in either raw or adjusted models (fully adjusted: global cognitive function score 15.4 versus 15.2, <i>p</i> = 0.68; verbal episodic memory score 4.4 versus 4.3, <i>p</i> = 0.79; semantic fluency score 15.7 versus 14.0, <i>p</i> = 0.21; calculation impairment 22% versus 26%, risk ratio [RR] [95% CI] = 0.86 [0.67–1.11], <i>p</i> = 0.24). Sensitivity analyses stratified by TBI severity produced similar results. TBI was associated with significantly increased risk for subjective memory impairment in models adjusted for demographics and medical comorbidities (29% versus 24%; RR [95% CI]: 1.26 [1.02–1.57], <i>p =</i> 0.036). After further adjustment for active depression, however, risk for subjective memory impairment was no longer significant (RR [95% CI]: 1.18 [0.95–1.47], <i>p =</i> 0.13). Sensitivity analyses revealed that risk of subjective memory impairment was increased only among respondents with TBI with LOC and not among those with TBI without LOC. Furthermore, the risk of subjective memory impairment was significantly greater among those with TBI with LOC versus those without TBI even after adjustment for depression (RR [95% CI]: partially adjusted, 1.38 [1.09–1.74], <i>p =</i> 0.008; fully adjusted, 1.28 [1.01–1.61], <i>p =</i> 0.039).</p><p>Conclusions</p><p>In this population-based study of community-dwelling older adults without dementia, those with prior TBI with LOC were more likely to report subjective memory impairment compared to those without TBI even after adjustment for demographics, medical comorbidities, and active depression. Lack of greater objective cognitive impairment among those with versus without TBI may be due to poor sensitivity of the cognitive battery or survival bias, or may suggest that post-TBI cognitive impairment primarily affects executive function and processing speed, which were not rigorously assessed in this study. Our findings show that among community-dwelling non-demented older adults, history of TBI is common but may not preferentially impact cognitive domains of episodic memory, attention, working memory, verbal semantic fluency, or calculation.</p></div

Characteristics of respondents with and without traumatic brain injury.

<p>Characteristics of respondents with and without traumatic brain injury.</p

Objective and subjective cognitive outcomes by traumatic brain injury status.

<p>Objective and subjective cognitive outcomes by traumatic brain injury status.</p

Sampling of respondents.

<p>The cohort for this study was derived from a random sub-sample of non-proxy respondents to the 2014 wave of the Health and Retirement Study (HRS) who were randomly assigned to participate in a traumatic brain injury (TBI) module. Text in grey represents respondents excluded from this study.</p

Traumatic brain injury features.

<p>Traumatic brain injury features.</p

A Clinical Index to Predict Progression from Mild Cognitive Impairment to Dementia Due to Alzheimer's Disease

<div><p>Background</p><p>Mild cognitive impairment is often a precursor to dementia due to Alzheimer's disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment.</p><p>Objective</p><p>To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings.</p><p>Design and Participants</p><p>382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study.</p><p>Main Predictors Measures</p><p>Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales.</p><p>Main Outcome Measure</p><p>Progression to probable Alzheimer's disease.</p><p>Key Results</p><p>Subjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer's disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell's c-statistic was 0.71(95% CI: 0.68–0.75). Fourteen percent of subjects with low risk scores (0–2 points, n = 124) converted to probable Alzheimer's disease over 3 years, compared to 51% of those with moderate risk scores (3–8 points, n = 223) and 91% of those with high risk scores (9–16 points, n = 35).</p><p>Conclusions</p><p>An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer's disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression.</p></div

Observed versus Predicted Conversion from Amnestic MCI to AD over 3 Years by Brief Clinical Index Point Score.

<p>The solid line shows the proportion of subjects predicted to progress from amnestic mild cognitive impairment (MCI) to probable Alzheimer's disease (AD) over three years as function of their brief clinical index point score, while the dotted line shows the actual proportions that progressed at each point score value based on three-year Kaplan-Meier (KM) estimates. The vertical bars show the number of individuals at each point score value (right vertical axis).</p

Factors Associated with Conversion from Amnestic MCI to AD^*.

<p>AD, Alzheimer's disease; ADAS-cog, Alzheimer's Disease Assessment Scale – cognitive subscale; CI, confidence interval; MCI, mild cognitive impairment.</p><p>*Only factors retained in the final model are included.</p><p>Factors Associated with Conversion from Amnestic MCI to AD^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113535#nt103" target="_blank">*</a>}.</p

Distribution of participant characteristics by BDNF tertile.

<p>P-values come from ANOVA and Chi-square tests, as appropriate. BDNF = brain derived neurotrophic factor, 3MS = Teng Modified Mini-Mental Status Exam, DSST = Digit Symbol Substitution Test, CVD = cerebrovascular disease, MI = myocardial infarction.</p

Baseline Characteristics of 382 Participants with Amnestic Mild Cognitive Impairment (MCI).

<p>Table includes selected demographic and medical history variables and all items from within each domain that were associated with conversion to AD (p<0.20). AD, Alzheimer's disease; ADAS-Cog, Alzheimer's Disease Assessment Scale – cognitive subscale; FAQ, Functional Assessment Questionnaire; NPI, Neuropsychiatric Inventory; SD, standard deviation. Data missing as follows: Blood pressure (4), pulse (1), FAQ (3).</p><p>Baseline Characteristics of 382 Participants with Amnestic Mild Cognitive Impairment (MCI).</p