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.

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).

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.

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.

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.

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.

Automated 3D mapping of baseline and 12-month associations between three verbal memory measures and hippocampal atrophy in 490 ADNI subjects.

We used a previously validated automated machine learning algorithm based on adaptive boosting to segment the hippocampi in baseline and 12-month follow-up 3D T1-weighted brain MRIs of 150 cognitively normal elderly (NC), 245 mild cognitive impairment (MCI) and 97 Dementia of the Alzheimer's type (DAT) ADNI subjects. Using the radial distance mapping technique, we examined the hippocampal correlates of delayed recall performance on three well-established verbal memory tests--ADAScog delayed recall (ADAScog-DR), the Rey Auditory Verbal Learning Test -DR (AVLT-DR) and Wechsler Logical Memory II-DR (LM II-DR). We observed no significant correlations between delayed recall performance and hippocampal radial distance on any of the three verbal memory measures in NC. All three measures were associated with hippocampal volumes and radial distance in the full sample and in the MCI group at baseline and at follow-up. In DAT we observed stronger left-sided associations between hippocampal radial distance, LM II-DR and ADAScog-DR both at baseline and at follow-up. The strongest linkage between memory performance and hippocampal atrophy in the MCI sample was observed with the most challenging verbal memory test-the AVLT-DR, as opposed to the DAT sample where the least challenging test the ADAScog-DR showed strongest associations with the hippocampal structure. After controlling for baseline hippocampal atrophy, memory performance showed regionally specific associations with hippocampal radial distance in predominantly CA1 but also in subicular distribution.

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.

Characterizing multiple memory deficits and their relation to everyday functioning in individuals with mild cognitive impairment.

The authors evaluated multiple memory processes and explored their contributions to everyday functional limitations in persons with mild cognitive impairment (MCI). Participants included individuals with amnestic MCI, nonamnestic MCI, and healthy older adults. As expected, the amnestic MCI group performed more poorly than the control and nonamnestic MCI groups on a content memory measure. Both MCI groups, however, performed more poorly than controls on the noncontent memory measures of prospective memory, temporal order memory, and source memory. Informants also reported that the MCI groups were experiencing greater difficulty than controls completing instrumental activities of daily living (IADLs). Noncontent memory measures were found to make an independent contribution to IADL performances over and above that of content memory. These findings demonstrate that impairments in memory beyond the traditionally assessed content memory are present in individuals with amnestic MCI and with nonamnestic MCI. The results further show that these noncontent memory processes, which have been linked with executive functioning, play a role in supporting IADLs.

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.

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.

Memory prediction accuracy in younger and older adults: a cross-sectional and longitudinal analysis.

Across three experiments, the effects of age and normative information on memory prediction accuracy were examined. In Experiment 1, younger and older adults were given an arbitrary midpoint anchor and made global predictions about how they expected to perform on subsequent verbal, visual, and name-face memory tasks. In Experiment 2, the normative information was varied by providing participants with a midpoint anchor, accurate anchor, or no anchor. Across both experiments, older adults successfully adjusted their predictions in accordance with the task demands, regardless of the type of normative information given. In Experiment 3, older adults' prediction accuracy was measured at a 5-year follow-up. Memory performance predictions were found to be just as accurate as they had been at the first assessment. In general, the findings indicate that older adults were as accurate as younger adults in assessing their memory performance abilities. Older adults also did not operate on a negative stereotype of global cognitive decline with age, as they provided varying performance estimates across the different domains and types of memory tasks.

Effects of age and divided attention on memory components derived for the category exemplar generation task.

Age differences in memory performances on a conceptually driven task, the category exemplar generation (CEG) test, were investigated. Thirty-six younger adults and 36 healthy older adults studied word lists in full and divided attention conditions. Recall was tested with category names. The process-dissociation procedure was used to derive estimates of controlled and automatic memory. Old-old adults (70-84 years) exhibited poorer conscious recollection than both younger (18-24) and young-old adults (59-69). In contrast, no age differences were found in estimates of automatic memory. For the younger and older adults, the divided encoding manipulation reduced both the consciously controlled and automatic estimates of memory. The results suggest that the few prior findings of age deficits in priming on the CEG may have been an artifact of contamination from conscious retrieval processes. They also indicate that the opportunity for greater semantic processing enhances the conceptual priming of both younger and older adults.

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.

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.

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.

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.

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.