Kelsey R. Thomas

CogSMART Compensatory Cognitive Training for Traumatic Brain Injury: Effects Over 1 Year

Objective:There are very few evidence-based treatments for individuals with mild to moderate traumatic brain injuries. We developed and tested a 12-week, manualized, compensatory cognitive training intervention, Cognitive Symptom Management and Rehabilitation Therapy (CogSMART), which targeted postconcussive symptom management, prospective memory, attention, learning/memory, and executive functioning. The intervention focused on psychoeducation and compensatory strategies such as calendar use, self-talk, note taking, and a 6-step problem-solving method. Setting:VA Healthcare System. Participants:A total of 50 Veterans with mild to moderate traumatic brain injuries receiving supported employment. Design:Twelve-month randomized controlled trial with participants assigned to receive CogSMART or additional supported employment sessions for the first 12 weeks. Outcome assessments were administered at baseline and 3, 6, and 12 months. Main Measures:Assessments measured postconcussive symptoms, neuropsychological performance, functional capacity, psychiatric symptom severity, quality of life, and weeks worked during the 12-month trial. Results:Hierarchical linear modeling analyses using all 4 time points demonstrated significant CogSMART-associated reductions in postconcussive symptoms (r = −0.28, P = .026, d = 0.64) and improvements in prospective memory (r = 0.35, P = .031, d = 0.55) and quality of life (r = 0.34, P = .009, d = 1.0). The groups did not differ on weeks worked during the trial. Conclusion:CogSMART has the potential to improve postconcussive symptoms, cognitive performance, and self-rated quality of life in individuals with mild to moderate traumatic brain injuries.

Identification of Mild Cognitive Impairment in ACTIVE: Algorithmic Classification and Stability

Rates of mild cognitive impairment (MCI) have varied substantially, depending on the criteria used and the samples surveyed. The present investigation used a psychometric algorithm for identifying MCI and its stability to determine if low cognitive functioning was related to poorer longitudinal outcomes. The Advanced Cognitive Training of Independent and Vital Elders (ACTIVE) study is a multi-site longitudinal investigation of long-term effects of cognitive training with older adults. ACTIVE exclusion criteria eliminated participants at highest risk for dementia (i.e., Mini-Mental State Examination < 23). Using composite normative for sample- and training-corrected psychometric data, 8.07% of the sample had amnestic impairment, while 25.09% had a non-amnestic impairment at baseline. Poorer baseline functional scores were observed in those with impairment at the first visit, including a higher rate of attrition, depressive symptoms, and self-reported physical functioning. Participants were then classified based upon the stability of their classification. Those who were stably impaired over the 5-year interval had the worst functional outcomes (e.g., Instrumental Activities of Daily Living performance), and inconsistency in classification over time also appeared to be associated increased risk. These findings suggest that there is prognostic value in assessing and tracking cognition to assist in identifying the critical baseline features associated with poorer outcomes.

Cerebral Blood Flow and Amyloid-β Interact to Affect Memory Performance in Cognitively Normal Older Adults

Cerebral blood flow (CBF) alterations and amyloid-β (Aβ) accumulation have been independently linked to cognitive deficits in older adults at risk for dementia. Less is known about how CBF and Aβ may interact to affect cognition in cognitively normal older adults. Therefore, we examined potential statistical interactions between CBF and Aβ status in regions typically affected in Alzheimer’s disease (AD) within a sample of older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Sixty-two cognitively normal participants (mean age = 72 years) underwent neuroimaging and memory testing. Arterial spin labeling magnetic resonance imaging was used to quantify CBF and florbetapir PET amyloid imaging was used to measure Aβ deposition. Aβ status (i.e., positivity versus negativity) was determined based on established cutoffs (Landau et al., 2013). The Rey Auditory Verbal Learning Test was used to assess memory. Linear regression models adjusted for age, education, and sex, demonstrated significant interactions between CBF and Aβ status on memory performance. Among Aβ positive older adults, there were significant negative associations between higher CBF in hippocampus, posterior cingulate, and precuneus and poorer memory performance. In contrast, among Aβ negative older adults, there were no significant associations between CBF and cognition. Our findings extend previous CBF studies of dementia risk by reporting interactions between Aβ status and CBF on memory performance in a sample of well-characterized, cognitively normal older adults. Results suggest that differential CBF-cognition associations can be identified in healthy, asymptomatic Aβ positive older adults relative to Aβ negative individuals. Associations between higherCBF and poorer memory among Aβ positive older adults may reflect a cellular and/or vascular compensatory response to pathologic processes whereby higher CBF is needed to maintain normal memory abilities. Findings indicate that CBF and its associations with cognition may have utility as a reliable marker of brain function early in the AD process when interventions are likely to be beneficial.

Race-related disparities in 5-year cognitive level and change in untrained ACTIVE participants.

Objective: The current study examined a 5-year cognitive change in untrained African American and White participants from the Advanced Cognitive Training in Independent and Vital Elderly (ACTIVE) study. Method: Five-year trajectories of memory, reasoning, visual processing speed/useful field of view, digit-symbol substitution, and vocabulary were investigated. Education, health, gender, age, and retest/practice effects were controlled for, and a missing data pattern mixture approach was used to adjust for dropout effects. Results: After considering age, education, health, and gender, being African American uniquely explained 2% to 7% of the variance in cognitive performance. There were virtually no significant race differences in the rates of change. Discussion: Race-related results in the current study are consistent with previous research suggesting that social advantage factors such as education have a stronger influence on the level of performance than the rate of change. The small remaining effects of being African American on performance levels likely reflect uncontrolled variation in factors like literacy and financial advantage.

Compensatory cognitive training for people with severe mental illnesses in supported employment: A randomized controlled trial

Treatments for cognitive and functional impairments associated with severe mental illnesses are urgently needed. We tested a 12-week, manualized, Compensatory Cognitive Training (CCT) intervention targeting prospective memory, attention, learning/memory, and executive functioning in the context of supported employment for people with severe mental illnesses who were seeking work. 153 unemployed, work-seeking outpatients with schizophrenia/schizoaffective disorder (n=58), bipolar disorder (n=37), or major depression (n=58) were randomized to receive supported employment plus CCT or enhanced supported employment, a robust control group. Assessments of neuropsychological performance, functional capacity, psychiatric symptom severity, and self-reported functioning and quality of life were administered at baseline and multiple follow-up assessments over two years; work outcomes were collected for two years. Forty-seven percent of the participants obtained competitive work, but there were no differences in work attainment, weeks worked, or wages earned between the CCT and the enhanced supported employment group. ANCOVAs assessing immediate post-treatment effects demonstrated significant, medium to large, CCT-associated improvements on measures of working memory (p=0.038), depressive symptom severity (p=0.023), and quality of life (p=0.003). Longer-term results revealed no statistically significant CCT-associated improvements, but a trend (p=0.058) toward a small to medium CCT-associated improvement in learning. Diagnostic group (schizophrenia-spectrum vs. mood disorder) did not affect outcomes. We conclude that CCT has the potential to improve cognitive performance, psychiatric symptom severity, and quality of life in people with severe mental illnesses. Receiving CCT did not result in better work outcomes, suggesting that supported employment can result in competitive work regardless of cognitive status.

Self-perceived Difficulties in Everyday Function Precede Cognitive Decline among Older Adults in the ACTIVE Study.

OBJECTIVES Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. METHODS The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. RESULTS Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. CONCLUSIONS Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2018, 24, 104-112).

Age and Improved Attention Predict Work Attainment in Combined Compensatory Cognitive Training and Supported Employment for People With Severe Mental Illness.

Abstract The objective of this study was to examine whether cognitive change and age predicted work outcome in the context of supported employment (SE) and compensatory cognitive training (CCT) in severe mental illness. Forty unemployed outpatients receiving SE (7 young [20–35 years], 15 middle-aged [36–50 years], and 18 older [51–66 years] patients) completed cognitive assessments at baseline and after 12 weeks of CCT. Logistic regression analyses showed that improvement in attention/vigilance significantly predicted work attainment (B = 2.35, SE = 1.16, p = 0.043). Young and older participants were more likely to obtain work than middle-aged participants (B = 4.03, SE = 1.43, p = 0.005; B = 2.16, SE = 0.93, p = 0.021, respectively). Improved attention and age group (young and old) were associated with better work outcomes after SE + CCT. Improving attention may be an important target for improving work outcome in severe mental illness. Middle-aged individuals may need additional support to return to work.

Word-list intrusion errors predict progression to mild cognitive impairment.

Objective: Preclinical Alzheimer’s disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI. Method: Cognitively normal participants (n = 525) from the Alzheimer’s Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on the Rey Auditory Verbal Learning Test (AVLT; intrusion errors, learning slope, proactive interference, retroactive interference) predicted progression to MCI and a Clinical Dementia Rating (CDR) score of 1 after considering demographic characteristics, apolipoprotein E &egr;4 status, cerebrospinal fluid AD biomarkers, ischemia risk, mood, functional difficulty, and standard neuropsychological total test scores for the model. Results: Baseline AVLT intrusion errors predicted progression to MCI (hazard ratio = 1.04, 95% confidence interval 1.01–1.07, p = .008) and improved model fit after the other valuable predictors were already in the model, &khgr;2(df = 1) = 6.330, p = .012. AVLT intrusion errors also predicted progression to CDR = 1 (hazard ratio = 1.10, 95% confidence interval 1.02–1.18, p = .016) and again improved model fit, &khgr;2(df = 1) = 4.682, p = .030. Conclusions: Intrusion errors on the AVLT contribute unique value for predicting progression from normal cognition to MCI and normal cognition to mild dementia (CDR = 1). Intrusion errors appear to reflect subtle change and inefficiencies in cognition that precede impairment detected by neuropsychological total scores.

Age as a Moderator of Change Following Compensatory Cognitive Training in Individuals With Severe Mental Illnesses.

Objective: This study explored whether age moderated cognitive, symptom, and functional changes over a 12-week compensatory cognitive training (CCT) intervention for participants with severe mental illnesses. CCT focused on the cognitive domains of attention, learning, prospective memory, and executive functioning, often impaired in this population. Method: Seventy-seven unemployed individuals (46 participants with severe mood disorders and 31 participants with schizophrenia/schizoaffective disorder; mean age = 44 years) received CCT for 12 weeks in the context of a supported employment program. Participants were administered cognitive, symptom severity, and functional measures at baseline and 3-, 6-, and 12-month follow-ups, as well as at 18 and 24 months for symptom/functional measures. Mixed effects models, controlling for diagnosis, examined whether age impacted the trajectories of change following CCT. Results: Analyses showed several significant time by age interactions; younger participants improved more over time on category fluency, &bgr; = −.280, t(42.10) = −2.76, p = .008, and financial capacity (UCSD Performance-Based Skills Assessment), &bgr; = −.194, t(54.02) = −2.21, p = .031, whereas older participants showed greater reduction in positive symptom severity (Positive and Negative Syndrome Scale), &bgr; = −.109, t(78.35) = −2.34, p = .022, and less functional decline on the Independent Living Skills Survey, &bgr; = .118, t(109.77) = 2.05, p = .043. Conclusions and Implications for Practice: Age moderated the effects of CCT over time on measures of cognition, symptom severity, and functioning. Younger participants improved on objective measures of verbal processing speed and financial capacity, whereas older participants showed reduced positive symptom severity and less decline in self-reported daily functioning. These findings suggest that CCT may differentially benefit persons with severe mental illnesses depending on age.

Reduced Regional Cerebral Blood Flow Relates to Poorer Cognition in Older Adults With Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) increases risk for dementia, including Alzheimer’s disease (AD). Many previous studies of brain changes underlying cognitive impairment in T2DM have applied conventional structural magnetic resonance imaging (MRI) to detect macrostructural changes associated with cerebrovascular disease such as white matter hyperintensities or infarcts. However, such pathology likely reflects end-stage manifestations of chronic decrements in cerebral blood flow (CBF). MRI techniques that measure CBF may (1) elucidate mechanisms that precede irreversible parenchymal damage and (2) serve as a marker of risk for cognitive decline. CBF measured with arterial spin labeling (ASL) MRI may be a useful marker of perfusion deficits in T2DM and related conditions. We examined associations among T2DM, CBF, and cognition in a sample of 49 well-characterized nondemented older adults. Along with a standard T1-weighted scan, a pseudocontinuous ASL sequence optimized for older adults (by increasing post-labeling delays to allow more time for the blood to reach brain tissue) was obtained on a 3T GE scanner to measure regional CBF in FreeSurfer derived regions of interest. Participants also completed a neuropsychological assessment. Results showed no significant differences between individuals with and without T2DM in terms of cortical thickness or regional brain volume. However, adjusting for age, sex, comorbid vascular risk factors, and reference CBF (postcentral gyrus) older adults with T2DM demonstrated reduced CBF in the hippocampus, and inferior temporal, inferior parietal, and frontal cortices. Lower CBF was associated with poorer memory and executive function/processing speed. When adjusting for diabetes, the significant associations between lower regional CBF and poorer executive function/processing speed remained. Results demonstrate that CBF is reduced in older adults with T2DM, and suggest that CBF alterations likely precede volumetric changes. Notably, relative to nondiabetic control participants, those with T2DM showed lower CBF in predilection sites for AD pathology (medial temporal lobe and inferior parietal regions). Findings augment recent research suggesting that perfusion deficits may underlie cognitive decrements frequently observed among older adults with T2DM. Results also suggest that CBF measured with ASL MRI may reflect an early and important marker of risk of cognitive impairment in T2DM and related conditions.