Associations between Cortical Thickness and Metamemory in Alzheimer's Disease.

Metacognitive deficits affect Alzheimer's disease (AD) patient safety and increase caregiver burden. The brain areas that support metacognition are not well understood. 112 participants from the Imaging and Genetic Biomarkers for AD (ImaGene) study underwent comprehensive cognitive testing and brain magnetic resonance imaging. A performance-prediction paradigm was used to evaluate metacognitive abilities for California Verbal Learning Test-II learning (CVLT-II 1-5) and delayed recall (CVLT-II DR); Visual Reproduction-I immediate recall (VR-I Copy) and Visual Reproduction-II delayed recall (VR-II DR); Rey-Osterrieth Complex Figure Copy (Rey-O Copy) and delayed recall (Rey-O DR). Vertex-wise multivariable regression of cortical thickness was performed using metacognitive scores as predictors while controlling for age, sex, education, and intracranial volume. Subjects who overestimated CVLT-II DR in prediction showed cortical atrophy, most pronounced in the bilateral temporal and left greater than right (L > R) frontal cortices. Overestimation of CVLT-II 1-5 prediction and DR performance in postdiction showed L > R associations with medial, inferior and lateral temporal and left posterior cingulate cortical atrophy. Overconfident prediction of VR-I Copy performance was associated with right greater than left medial, inferior and lateral temporal, lateral parietal, anterior and posterior cingulate and lateral frontal cortical atrophy. Underestimation of Rey-O Copy performance in prediction was associated with atrophy localizing to the temporal and cingulate areas, and in postdiction, with diffuse cortical atrophy. Impaired metacognition was associated to cortical atrophy. Our results indicate that poor insight into one's cognitive abilities is a pervasive neurodegenerative feature associated with AD across the cognitive spectrum.

Implementation of an Acute Care COPD Exacerbation Patient Mobilization Tool. A Mixed-Methods Study.

Background: Improving the mobility of hospitalized patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a priority of care. AECOPD-Mob is a clinical decision-making tool for physical therapists, especially those who are newly graduated or are new to caring for patients with AECOPDs in acute care settings. Although this tool has been available for several years, dissemination via publication is not sufficient to implement it in clinical practice.Objective: The primary objective of this study was to develop, implement, and evaluate different formats of AECOPD-Mob in an acute care setting.Methods: We used a mixed-methods, convergent parallel design. In addition to the paper format of AECOPD-Mob, we developed a smartphone app, a web-based learner module, and an in-service learning session. Newly graduated physical therapists (PTs) or PTs new to the practice area were recruited from urban acute care hospitals. Participants used the different formats for 3 weeks and then completed the Post-Study System Usability Questionnaire. User data were retrieved for the learning module. Participants participated in focus groups at 3 weeks and 3 months.Results: Eighteen (72% of eligible PTs, 100% female, 94% graduated within 3 yr) PTs participated. Post-Study System Usability Questionnaire scores for the learning module and smartphone indicated that participants were satisfied with these formats (median score 2.0 on 1-7 Likert Scale for both technology formats, lower scores indicating greater satisfaction). However, the participants reported in the focus group that the paper format was preferred over other formats. Concerns with the smartphone app included infection control and the perception of lack of professionalism when using a smartphone during clinical practice. The learning module and in-service were considered helpful as an introduction but not as an ongoing support. The paper format was seen as the most efficient way to access the necessary information and to facilitate communication between other members of the care team about the importance of mobility for hospitalized patients with AECOPDs.Conclusion: Newly graduated PTs strongly preferred the paper format of the AECOPD-Mob tool in the acute care setting. Future research will focus on knowledge translation strategies for other health disciplines.

Recent cocaine use and memory impairment in HIV.

Both Human Immunodeficiency Virus (HIV) and cocaine use have been associated with impairment in neuropsychological functioning. The high comorbidity between HIV and cocaine use highlights the importance of ascertaining whether there is a compounding effect of cocaine use in individuals with HIV. Among neuropsychological domains impacted by HIV, verbal memory deficits have received substantial attention partly because they have been associated with declines in functional status in HIV positive individuals. We collected California Verbal Learning Test-II data from HIV participants who met lifetime diagnostic criteria of cocaine abuse and/or dependence (HIV/CocDx+, N = 80 & HIV/CocDx-, N = 30, respectively) and those with and without recent cocaine use, which was confirmed by toxicology analysis (HIV/Coc+, N = 56 & HIV/Coc-, N = 57, respectively). The Item Specific Deficit Approach (ISDA) was employed to determine any additional cocaine-associated deficits in encoding, consolidation, and retrieval, which attempts to control for potential confounding factors of memory such as attention. Using conventional methods of evaluating memory profiles, we found that the HIV/Coc + group demonstrated worse learning, immediate and delayed free recall, and recognition in contrast to the HIV/Coc - group; although using the ISDA, we found that encoding was the only significant difference between HIV/Coc + and HIV/Coc-participant, with HIV/Coc - performing better. Our data suggest that for individuals with HIV, cocaine use is associated with a temporary decline in verbal memory, is characterized by greater encoding deficits, and these effects may reduce with abstinence. Clinically, our findings suggest that reduced encoding is the likely contributor to verbal memory decline in HIV/Coc + and these effects are partially reversible-at least to the level of their HIV/Coc - counterparts.

Reaction time and response inhibition in autosomal dominant Alzheimer's disease.

OBJECTIVE: Subtle deficits in several cognitive domains characterize the neuropsychological profile of preclinical Alzheimer's disease (AD). Assessment of preclinical individuals with genes causing autosomal dominant AD (ADAD) provides a model for prodromal disease. We sought to sensitively evaluate attention and working memory using a computerized battery in non-demented persons carrying ADAD mutations. METHOD: A total of 71 non-demented Latinos at-risk for ADAD mutations were recruited [40 mutation carriers (MCs), 31 non-mutation carriers (NCs)] and completed a Spanish language chronometric battery of speeded decision and working memory tasks. RESULTS: On two complex reaction time (RT) tasks involving decision-making and response inhibition, MCs exhibited slower RTs than NCs as they approached their anticipated age of dementia diagnosis. Education moderated these effects, but only in younger MCs. APOE ε4 status was not associated with age-related slowing among NCs or MCs on any of the tests. CONCLUSIONS: Our findings indicate MCs respond more slowly as they approach the age of dementia onset on tasks with greater demands on executive function. Our results also suggest these effects were not explained by APOE ε4 status independently of ADAD mutation status. Computerized reaction time tests can provide sensitive measures of the earliest cognitive changes in AD.

Cognitive Correlates of Hippocampal Atrophy and Ventricular Enlargement in Adults with or without Mild Cognitive Impairment.

We analyzed structural magnetic resonance imaging data from 58 cognitively normal and 101 mild cognitive impairment subjects. We used a general linear regression model to study the association between cognitive performance with hippocampal atrophy and ventricular enlargement using the radial distance method. Bilateral hippocampal atrophy was associated with baseline and longitudinal memory performance. Left hippocampal atrophy predicted longitudinal decline in visuospatial function. The multidomain ventricular analysis did not reveal any significant predictors.

The Functional Ability of MCI and Alzheimer's Patients Predicts Caregiver Burden.

Sixty patients and their caregivers participated in this study. Patients completed activities of daily living tasks and several neuropsychological tests assessing memory, abstract reasoning, and language. Caregivers completed self-report measures assessing caregiver burden and psychological distress. Results revealed that the mAD caregivers endorsed greater physical burden and feelings of missing out on life compared to MCI caregivers. The mAD caregivers indicated greater depression and anxiety relative to MCI caregivers. Stepwise regression found that fewer patient neuropsychological scores predicted caregiver burden, as compared to patients' daily functioning. Overall, mAD displayed more severe types of burden and psychological distress relative to MCI caregivers and patients' daily functional abilities better predicated caregivers' burden and psychological distress than patients' neuropsychological functioning.

A comparison of theoretical and statistically derived indices for predicting cognitive decline.

INTRODUCTION: Both theoretical and statistically derived approaches have been used in research settings for predicting cognitive decline. METHODS: Fifty-eight cognitively normal (NC) and 71 mild cognitive impairment (MCI) subjects completed a comprehensive cognitive battery for up to 5 years of follow-up. Composite indices of cognitive function were derived using a classic theoretical approach and exploratory factor analysis (EFA). Cognitive variables comprising each factor were averaged to form the EFA composite indices. Logistic regression was used to investigate whether these cognitive composites can reliably predict cognitive outcomes. RESULTS: Neither method predicted decline in NC. The theoretical memory, executive, attention, and language composites and the EFA-derived "attention/executive" and "verbal memory" composites were significant predictors of decline in MCI. The best models achieved an area under the curve of 0.94 in MCI. CONCLUSIONS: The theoretical and the statistically derived cognitive composite approaches are useful in predicting decline in MCI but not in NC.

Dance Experience and Associations with Cortical Gray Matter Thickness in the Aging Population.

INTRODUCTION: We investigated the effect dance experience may have on cortical gray matter thickness and cognitive performance in elderly participants with and without mild cognitive impairment (MCI). METHODS: 39 cognitively normal and 48 MCI elderly participants completed a questionnaire regarding their lifetime experience with music, dance, and song. Participants identified themselves as either dancers or nondancers. All participants received structural 1.5-tesla MRI scans and detailed clinical and neuropsychological evaluations. An advanced 3D cortical mapping technique was then applied to calculate cortical thickness. RESULTS: Despite having a trend-level significantly thinner cortex, dancers performed better in cognitive tasks involving learning and memory, such as the California Verbal Learning Test-II (CVLT-II) short delay free recall (p = 0.004), the CVLT-II long delay free recall (p = 0.003), and the CVLT-II learning over trials 1-5 (p = 0.001). DISCUSSION: Together, these results suggest that dance may result in an enhancement of cognitive reserve in aging, which may help avert or delay MCI.

Novel verbal fluency scores and structural brain imaging for prediction of cognitive outcome in mild cognitive impairment.

INTRODUCTION: The objective of this study was to assess the utility of novel verbal fluency scores for predicting conversion from mild cognitive impairment (MCI) to clinical Alzheimer's disease (AD). METHOD: Verbal fluency lists (animals, vegetables, F, A, and S) from 107 MCI patients and 51 cognitively normal controls were transcribed into electronic text files and automatically scored with traditional raw scores and five types of novel scores computed using methods from machine learning and natural language processing. Additional scores were derived from structural MRI scans: region of interest measures of hippocampal and ventricular volumes and gray matter scores derived from performing ICA on measures of cortical thickness. Over 4 years of follow-up, 24 MCI patients converted to AD. Using conversion as the outcome variable, ensemble classifiers were constructed by training classifiers on the individual groups of scores and then entering predictions from the primary classifiers into regularized logistic regression models. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) was measured for classifiers trained with five groups of available variables. RESULTS: Classifiers trained with novel scores outperformed those trained with raw scores (AUC 0.872 vs 0.735; P < .05 by DeLong test). Addition of structural brain measurements did not improve performance based on novel scores alone. CONCLUSION: The brevity and cost profile of verbal fluency tasks recommends their use for clinical decision making. The word lists generated are a rich source of information for predicting outcomes in MCI. Further work is needed to assess the utility of verbal fluency for early AD.

An index predictive of cognitive outcome in retired professional American Football players with a history of sports concussion.

OBJECTIVE: Various concussion characteristics and personal factors are associated with cognitive recovery in athletes. We developed an index based on concussion frequency, severity, and timeframe, as well as cognitive reserve (CR), and we assessed its predictive power regarding cognitive ability in retired professional football players. METHOD: Data from 40 retired professional American football players were used in the current study. On average, participants had been retired from football for 20 years. Current neuropsychological performances, indicators of CR, concussion history, and play data were used to create an index for predicting cognitive outcome. RESULTS: The sample displayed a range of concussions, concussion severities, seasons played, CR, and cognitive ability. Many of the participants demonstrated cognitive deficits. The index strongly predicted global cognitive ability (R(2) = .31). The index also predicted the number of areas of neuropsychological deficit, which varied as a function of the deficit classification system used (Heaton: R(2) = .15; Wechsler: R(2) = .28). CONCLUSIONS: The current study demonstrated that a unique combination of CR, sports concussion, and game-related data can predict cognitive outcomes in participants who had been retired from professional American football for an average of 20 years. Such indices may prove to be useful for clinical decision making and research.

Use of the MoCA in Detecting Early Alzheimer's Disease in a Spanish-Speaking Population with Varied Levels of Education.

BACKGROUND/AIMS: Performance on the Montreal Cognitive Assessment (MoCA) has been demonstrated to be dependent on the educational level. The purpose of this study was to identify how to best adjust MoCA scores and to identify MoCA items most sensitive to cognitive decline in incipient Alzheimer's disease (AD) in a Spanish-speaking population with varied levels of education. METHODS: We analyzed data from 50 Spanish-speaking participants. We examined the pattern of diagnosis-adjusted MoCA residuals in relation to education and compared four alternative score adjustments using bootstrap sampling. Sensitivity and specificity analyses were performed for the raw and each adjusted score. The interval reliability of the MoCA as well as item discrimination and item validity were examined. RESULTS: We found that with progressive compensation added for those with lower education, unexplained residuals decreased and education-residual association moved to zero, suggesting that more compensation was necessary to better adjust MoCA scores in those with a lower educational level. Cube copying, sentence repetition, delayed recall, and orientation were most sensitive to cognitive impairment due to AD. CONCLUSION: A compensation of 3-4 points was needed for <6 years of education. Overall, the Spanish version of the MoCA maintained adequate psychometric properties in this population.

Daily Activity Abilities in MCI, Alzheimer's Disease, and Healthy Controls.

Mild cognitive impairment (MCI) is a risk state for dementia. The present study assessed daily functioning in MCI individuals (amnestic [aMCI] and nonamnestic [naMCI]) relative to those with Alzheimer's disease (AD) and healthy controls (NC). Twenty AD participants, 14 aMCI, 12 naMCI, and 30 healthy controls were administered the Direct Assessment of Functional Status (DAFS). The AD group performed poorer than all groups on all DAFS subscales. The aMCI group performed poorer than controls on the shopping subtests, while the naMCI group performed poorer than controls on only the free recall shopping. Finally, DAFS subscales discriminated the AD and aMCI groups well, but only recognition shopping discriminated between naMCI and aMCI individuals. These findings suggest that circumscribed ADL deficits distinguish subtypes of MCI and AD.

Age effects on cortical thickness in cognitively normal elderly individuals.

BACKGROUND/AIMS: Atrophy in both grey and white matter is found in normal aging. The prefrontal cortex and the frontal lobe white matter are thought to be the most affected regions. Our aim was to examine the effects of normal aging on cortical grey matter using a 3D quantitative cortical mapping method. METHODS: We analyzed 1.5-tesla brain magnetic resonance imaging data from 44 cognitively normal elderly subjects using cortical pattern matching and cortical thickness analyses. Linear regression analysis was used to study the effect of age on cortical thickness. 3D map-wide correction for multiple comparisons was conducted with permutation analyses using a threshold of p < 0.01. RESULTS: We found a significant negative association between age and cortical thickness in the right hemisphere (pcorrected = 0.009) and a trend level association in the left hemisphere (pcorrected = 0.081). Age-related changes were greatest in the sensorimotor, bilateral dorsal anterior cingulate and supplementary motor cortices, and the right posterior middle and inferior frontal gyri. Age effects greater in the medial than lateral visual association cortices were also seen bilaterally. CONCLUSION: Our novel method further validates that normal aging results in diffuse cortical thinning that is most pronounced in the frontal and visual association cortices.

The "Alzheimer's type" profile of semantic clustering in amnestic mild cognitive impairment.

Impairments in learning and recall have been well established in amnestic mild cognitive impairment (aMCI). However, a relative dearth of studies has examined the profiles of memory strategy use in persons with aMCI relative to those with Alzheimer's disease (AD). Participants with aMCI, nonamnestic MCI, AD, and healthy older adults were administered the California Verbal Learning Test-II (CVLT-II). Measures of semantic clustering and recall were obtained across learning and delayed recall trials. In addition, we investigated whether deficits in semantic clustering were related to progression from healthy aging to aMCI and from aMCI to AD. The aMCI group displayed similar semantic clustering performance as the AD participants, whereas the AD group showed greater impairments on recall relative to the aMCI participants. Control participants who progressed to aMCI showed reduced semantic clustering at the short delay at baseline compared to individuals who remained diagnostically stable across follow-up visits. These findings show that the ability to engage in an effective memory strategy is compromised in aMCI, before AD has developed, suggesting that disruptions in semantic networks are an early marker of the disease. (JINS, 2014, 20, 1-11).

Memory for performed and observed activities following traumatic brain injury.

Traumatic brain injury (TBI) is associated with deficits in memory for the content of completed activities. However, TBI groups have shown variable memory for the temporal order of activities. We sought to clarify the conditions under which temporal order memory for activities is intact following TBI. Additionally, we evaluated activity source memory and the relationship between activity memory and functional outcome in TBI participants. Thus, we completed a study of activity memory with 18 severe TBI survivors and 18 healthy age- and education-matched comparison participants. Both groups performed eight activities and observed eight activities that were fashioned after routine daily tasks. Incidental encoding conditions for activities were utilized. The activities were drawn from two counterbalanced lists, and both performance and observation were randomly determined and interspersed. After all of the activities were completed, content memory (recall and recognition), source memory (conditional source identification), and temporal order memory (correlation between order reconstruction and actual order) for the activities were assessed. Functional ability was assessed via the Community Integration Questionnaire (CIQ). In terms of content memory, TBI participants recalled and recognized fewer activities than comparison participants. Recognition of performed and observed activities was strongly associated with social integration on the CIQ. There were no between- or within-group differences in temporal order or source memory, although source memory performances were near ceiling. The findings were interpreted as suggesting that temporal order memory following TBI is intact under conditions of both purposeful activity completion and incidental encoding, and that activity memory is related to functional outcomes following TBI.

Cortical thickness and semantic fluency in Alzheimer's disease and mild cognitive impairment.

The hallmark of Alzheimer's disease (AD) is declarative memory loss, but deficits in semantic fluency are also observed. We assessed how semantic fluency relates to cortical atrophy to identify specific regions that play a role in the loss of access to semantic information. Whole-brain structural magnetic resonance imaging (MRI) data were analyzed from 9 Normal Control (NC)(M=76.7, SD=5.6), 40 Mild Cognitive Impairment (MCI) (M=74.4, SD=8.6), and 10 probable AD (M=72.4, SD=8.0) subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). They all were administered the Category Fluency (CF) animals and vegetables tests. Poorer semantic fluency was associated with bilateral cortical atrophy of the inferior parietal lobule (Brodman areas (BA) 39 and 40) and BA 6, 8, and 9 in the frontal lobe, as well as BA 22 in the temporal lobe. More diffuse frontal associations were seen in the left hemisphere involving BA 9, 10, 32, 44, 45, and 46. Additional cortical atrophy was seen in the temporoparietal (BA 37) and the right parastriate (BA 19, 18) cortices. Associations were more diffuse for performance on vegetable fluency than animal fluency. The permutation-corrected map-wise significance for CF animals was pcorrected=0.01 for the left hemisphere, and pcorrected=0.06 for the right hemisphere. The permutation-corrected map-wise significance for CF vegetables was pcorrected=0.009 for the left hemisphere, and pcorrected=0.03 for the right hemisphere. These results demonstrate the profound effect of cortical atrophy on semantic fluency. Specifically, tapping into semantic knowledge involves the frontal lobe in addition to the language cortices of the temporoparietal region.

Antiretroviral adherence and the nature of HIV-associated verbal memory impairment.

The authors investigated the relationship between antiretroviral adherence and HIV-associated verbal memory impairment. HIV-positive participants demonstrated poorer verbal memory than HIV-negative participants. Both good (≥90%) and poor (<90%) adherers displayed encoding deficits as compared with controls, but only poor adherers exhibited retrieval deficits. Encoding deficits primarily accounted for reduced delayed recall in good adherers, but both encoding and retrieval deficits accounted for reduced delayed recall in poor adherers. The retrieval difference between the adherence groups might be explained by a neuroprotective effect of good antiretroviral adherence or preexisting HIV-related retrieval deficits that result in poorer adherence.

Longitudinal change in cognitive function and medication adherence in HIV-infected adults.

Neuropsychological (NP) dysfunction has been linked to poor medication adherence among HIV-infected adults. However, there is a dearth of research examining longitudinal changes in the relationship between NP status and adherence rates. We hypothesized that declines in NP functioning would be associated with a corresponding decline in medication adherence while stable NP functioning would be associated with stable or improving adherence rates. Participants included 215 HIV-infected adults who underwent cognitive testing at study entry and six months later. Compared to the NP stable group, the NP decline group showed a greater drop in adherence rates. Further analysis revealed that, beyond global NP, learning and memory was significantly associated with changes in adherence rates. These findings further support the link between cognitive functioning and medication adherence and illustrates the importance of documenting changes in cognitive abilities for identifying individuals at risk for poor adherence.

Subtle deficits in instrumental activities of daily living in subtypes of mild cognitive impairment.

BACKGROUND/AIMS: Greater cognitive and functional deficits in mild cognitive impairment (MCI) are associated with higher rates of dementia. We explored the relationship between these factors by comparing instrumental activities of daily living (IADLs) among cognitive subtypes of MCI and examining associations between IADL and neuropsychological indices. METHODS: We analyzed data from 1,108 MCI and 3,036 normal control subjects included in the National Alzheimer's Coordinating Center Uniform Data Set who were assessed with the Functional Activities Questionnaire (FAQ). RESULTS: IADL deficits were greater in amnestic than nonamnestic MCI, but within these subgroups, did not differ between those with single or multiple domains of cognitive impairment. FAQ indices correlated significantly with memory and processing speed/executive function. CONCLUSIONS: IADL deficits are present in both amnestic MCI and nonamnestic MCI but are not related to the number of impaired cognitive domains. These cross-sectional findings support previous longitudinal reports suggesting that cognitive and functional impairments in MCI may be independently associated with dementia risk.

Utility of the functional activities questionnaire for distinguishing mild cognitive impairment from very mild Alzheimer disease.

Current criteria for mild cognitive impairment (MCI) require "essentially intact" performance of activities of daily living (ADLs), which has proven difficult to operationalize. We sought to determine how well the Functional Activities Questionnaire (FAQ), a standardized assessment of instrumental ADLs, delineates the clinical distinction between MCI and very mild Alzheimer disease (AD). We identified 1801 individuals in the National Alzheimer's Coordinating Center Uniform Data Set with MCI (n=1108) or very mild AD (n=693) assessed with the FAQ and randomized them to the development or test sets. Receiver-operator curve (ROC) analysis of the development set identified optimal cut-points that maximized the sensitivity and specificity of FAQ measures for differentiating AD from MCI and were validated with the test set. ROC analysis of total FAQ scores in the development set produced an area under the curve of 0.903 and an optimal cut-point of 5/6, which yielded 80.3% sensitivity, 87.0% specificity, and 84.7% classification accuracy in the test set. Bill paying, tracking current events, and transportation (P's<0.005) were the FAQ items of greatest diagnostic utility. These data suggest that the FAQ exhibits adequate sensitivity and specificity when used as a standardized assessment of instrumental ADLs in the diagnosis of AD versus MCI.