Verbal Learning Test Research Articles

The presence of cognitive impairments in the acute phase of traumatic upper limb injuries: A cross-sectional observational study

ObjectivesThe purpose of this study was to investigate the association between cognitive impairments and traumatic upper limb injuries of the acute phase. Material and methodsA cross-sectional observational study was conducted with three groups: a nerve-injury group, a without nerve injury group, and a control group (uninjured participants). Demographic characteristics (e.g. age, sex, body mass index, and education) and traumatic characteristics (duration since injury, injury side, pain, light touch sensation, hand motor function) were recorded. Short-term memory and executive functions were assessed using Rey Auditory and Verbal Learning Test (RAVLT) and Stroop Color and Word Test (SCWT, including SIECT and SIECN), respectively. ResultsThe study comprised 43 participants in the nerve-injury group, 30 participants in the group without nerve injury, and 104 participants in the control group. Generalized linear model was applied to explore the difference of cognitive functions among three groups with impactors. Significantly poorer performance on the RAVLT was observed in the nerve-injury group compared to the other two groups, and lower score of SIECT in nerve-injury group was lower compared to the control group. However, there was no significant difference of SIECN among three groups. In addition, traumatic characteristics did not significantly impact RAVLT and SIECT (p > 0.05) in all injured participants. ConclusionTraumatic nerve injury to the upper limb appears to be associated with both short-term memory and executive function impairment, whereas musculoskeletal injuries without nerve damage showed no cognitive impairment. Therefore, it is important to monitor cognitive function following upper limb nerve injuries.

Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use.

The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.

Neutrophil-to-lymphocyte ratio and longitudinal cognitive performance in Parkinson's disease.

Previous studies have suggested a link between peripheral inflammation and cognitive outcomes in the general population and individuals with Parkinson's disease (PD). We sought to test the association between peripheral inflammation, measured by the neutrophil-to-lymphocyte ratio (NLR), cognitive performance, and mild cognitive impairment (MCI) status in individuals with PD. A retrospective, longitudinal analysis was carried out using data from the Parkinson's Progression Markers Initiative (PPMI), including 422 participants with PD followed over 5 years. Cognitive performance was assessed using a neuropsychological battery including the Montreal Cognitive Assessment (MoCA) and tests of verbal learning, visuospatial function, processing speed, and executive function. Mixed-effect regression models were used to analyze the association between NLR, cognitive performance, and MCI status, controlling for age, sex, education, APOE genotype, and motor severity. There was a negative association between NLR and MoCA, even after adjusting for covariates (b = -0.12, p = 0.033). MoCA scores for individuals in the high NLR category exhibited a more rapid decline over time compared to the low NLR group (b = -0.16, p = 0.012). Increased NLR was associated with decreased performance across all cognitive domains. However, NLR was not associated with MCI status over 5 years of follow-up. This study demonstrates a link between elevated NLR and cognitive performance in PD, but not with MCI status over 5 years. This suggests that NLR is more strongly associated with day-to-day cognitive performance than with incident MCI, but this requires further study in more heterogeneous cohorts.

Do pregnancy and motherhood have an impact on cognitive functions in women

ABSTRACT Pregnancy and motherhood are some of the most physically and mentally challenging periods in a woman’s life. The aim of current study was to examine aspects of cognitive functions in pregnancy and motherhood that are controversial in the literature. The study included 30 healthy pregnant women aged between 18–40 years in their second and third trimesters, 30 healthy controls (nulliparous and non-pregnant women) and 30 healthy mothers matched with the pregnant women for age, handedness and education level. Edinburgh Postpartum Depression Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Trail Making, Stroop, Digit Span, Verbal Fluency and Rey Auditory and Verbal Learning Tests (RAVLT) were applied to all participants. The pregnant group showed significantly lower performance in trail making, digit span, verbal fluency as well as RAVLT compared to other two groups suggesting deficiencies in cognitive areas such as attention, set-shifting, planning, learning, language functions, semantic memory, working memory, encoding memory and retrieval. A trend toward increased function in response inhibition was observed in the mothers. Regression analyses revealed that pregnancy significantly decreased performance in verbal fluency, trail making, and RAVLT. Our findings from rigorously selected participants may help comprehend alterations in cognitive functioning during pregnancy and motherhood, as well as shed light on the contradictory literature.

Impact of Cognitive Intervention on Neurocognitive Development of Schoolchildren Exposed to Lead in a Semi-Urban Community in Mexico.

A quasi-experimental study with a control group was conducted in children aged 7 to 12years from 2 communities in Morelos, Mexico. Blood lead levels were determined, and the neurocognitive function was assessed pre- and postintervention with the Wechsler Intelligence Scale for Children and Children's Auditory Verbal Learning Test-2. A cognitive intervention was conducted at the school. The difference-in-differences method adjusted for variables known as priori and evaluated the impact of cognitive intervention. The differences-in-differences models indicated a significant average increase in scores on the Verbal Comprehension Index (9.58 points), Processing Speed Index (5.33 points), intelligence quotient (5.63 points) level of learning (7.66 points), interference trial (10.12 points), immediate memory span (7.98 points), and recognition accuracy (1.18 points) subtests after the cognitive intervention. The results suggest that cognitive intervention improves neurocognitive development in schoolchildren exposed to Pb.

Neuropsychological tests associated with symptomatic HIV-associated neurocognitive disorder (HAND) in a cohort of older adults in Tanzania.

Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting. This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history. Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background. A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

Cognitive and psychological characteristics in patients with Cerebral Amyloid Angiopathy: a literature review.

To review the current data on cognitive and psychological characteristics of patients with CAA and on the instruments used for their evaluation. A systematic search was performed in Embase, Scopus and PubMed with terms related to "cerebral amyloid angiopathy", "neuropsychological measures" and "patient-reported outcome measures" from January 2001 to December 2021. Out of 2851 records, 18 articles were selected. The cognitive evaluation was present in all of which, while the psychological one only in five articles. The MMSE (Mini Mental State Examination), TMT (Trail Making Test), fluency test, verbal learning test, digit span, digit symbol and Rey figure tests were the most used cognitive tests, while executive function, memory, processing speed, visuospatial function, attention and language were the most frequent impaired cognitive functions. Depression was the most considered psychological factor usually measured with BDI (Beck Depression Inventory) and GDS (Geriatric Depression Scale). The results of this study might be used in clinical practice as a guide to choose cognitive and psychological instruments and integrate them in the clinical evaluation. The results might also be used in the research field for studies investigating the impact of cognitive and psychological variables on the disease course and for consensus studies aimed at define a standardized evaluation of these aspects.

Electroconvulsive therapy disrupts functional connectivity between hippocampus and posterior default mode network

BackgroundThe mechanisms underlying memory deficits after electroconvulsive therapy (ECT) remain unclear but altered functional interactions between hippocampus and neocortex may play a role. ObjectivesTo test whether ECT reduces functional connectivity between hippocampus and posterior regions of the default mode network (DMN) and to examine whether altered hippocampal-neocortical functional connectivity correlates with memory impairment. A secondary aim was to explore if these connectivity changes are present 6 months after ECT. MethodsIn-patients with severe depression (n = 35) received bitemporal ECT. Functional connectivity of the hippocampus was probed with resting-state fMRI before the first ECT-session, after the end of ECT, and at a six-month follow-up. Memory was assessed with the Verbal Learning Test – Delayed Recall. Seed-based connectivity analyses established connectivity of four hippocampal seeds, covering the anterior and posterior parts of the right and left hippocampus. ResultsCompared to baseline, three of four hippocampal seeds became less connected to the core nodes of the posterior DMN in the week after ECT with Cohen's d ranging from −0.9 to −1.1. At the group level, patients showed post-ECT memory impairment, but individual changes in delayed recall were not correlated with the reduction in hippocampus-DMN connectivity. At six-month follow-up, no significant hippocampus-DMN reductions in connectivity were evident relative to pre-ECT, and memory scores had returned to baseline. ConclusionECT leads to a temporary disruption of functional hippocampus-DMN connectivity in patients with severe depression, but the change in connectivity strength is not related to the individual memory impairment.

Digital assessment of cognition in neurodegenerative disease: a data driven approach leveraging artificial intelligence.

A rapid and reliable neuropsychological protocol is essential for the efficient assessment of neurocognitive constructs related to emergent neurodegenerative diseases. We developed an AI-assisted, digitally administered/scored neuropsychological protocol that can be remotely administered in ~10 min. This protocol assesses the requisite neurocognitive constructs associated with emergent neurodegenerative illnesses. The protocol was administered to 77 ambulatory care/memory clinic patients (56.40% women; 88.50% Caucasian). The protocol includes a 6-word version of the Philadelphia (repeatable) Verbal Learning Test [P(r)VLT], three trials of 5 digits backward from the Backwards Digit Span Test (BDST), and the "animal" fluency test. The protocol provides a comprehensive set of traditional "core" measures that are typically obtained through paper-and-pencil tests (i.e., serial list learning, immediate and delayed free recall, recognition hits, percent correct serial order backward digit span, and "animal" fluency output). Additionally, the protocol includes variables that quantify errors and detail the processes used in administering the tests. It also features two separate, norm-referenced summary scores specifically designed to measure executive control and memory. Using four core measures, we used cluster analysis to classify participants into four groups: cognitively unimpaired (CU; n = 23), amnestic mild cognitive impairment (MCI; n = 17), dysexecutive MCI (n = 23), and dementia (n = 14). Subsequent analyses of error and process variables operationally defined key features of amnesia (i.e., rapid forgetting, extra-list intrusions, profligate responding to recognition foils); key features underlying reduced executive abilities (i.e., BDST items and dysexecutive errors); and the strength of the semantic association between successive responses on the "animal" fluency test. Executive and memory index scores effectively distinguished between all four groups. There was over 90% agreement between how cluster analysis of digitally obtained measures classified patients compared to classification using a traditional comprehensive neuropsychological protocol. The correlations between digitally obtained outcome variables and analogous paper/pencil measures were robust. The digitally administered protocol demonstrated a capacity to identify patterns of impaired performance and classification similar to those observed with standard paper/pencil neuropsychological tests. The inclusion of both core measures and detailed error/process variables suggests that this protocol can detect subtle, nuanced signs of early emergent neurodegenerative illness efficiently and comprehensively.

Challenges in identification of HIV‐Associated Neurocognitive Disorders, a focus on low and middle income countries

AbstractBackgroundHIV‐associated neurocognitive disorders (HAND) are highly prevalent amongst people living with HIV (PLWH), especially in Sub‐Saharan Africa (SSA) where the majority of PLWH live. Current HAND identification measures lack accuracy in older PLWH on treatment, with substantial heterogeneity observed in SSA prevalence meta‐analyses There is a need to better understand the current cognitive phenotype of this newly emergent population, to develop appropriate screening tools. We report two linked studies.Study 1 compared diagnostic accuracy of the International HIV dementia scale (IHDS), and Identification and Interventions for Dementia in Elderly Africans (IDEA) screen, for identification of HAND in older PLWH in TanzaniaStudy 2 aimed to identify cognitive domains significantly associated with symptomatic HAND (s‐HAND) in older PLWH in Tanzania, with potential utility in future screening measures.MethodA systematic sample of 253 PLWH aged ≥ 50 attending a Government clinic underwent comprehensive HAND evaluation by consensus American Academy of Neurology (AAN) criteria including locally‐normed low‐literacy clinical neuropsychological assessment. A diagnostic accuracy study of the IHDS and IDEA screen versus AAN criteria was completed with strict blinding. Participants were offered identical annual reassessment at Y1 Y2 and Y3 and the relationship of cognitive domains with s‐HAND in a logistic mixed effects modelResultHAND was highly prevalent (47%) at baseline, increasing to 57.9% at year 3.At baseline, both IHDS and IDEA had limited diagnostic accuracy for HAND (AUROC 0.639–0.667 IHDS, 0.647–0.713 IDEA). On secondary analysis of longitudinal data, tests of verbal learning and memory, categorical verbal fluency, visual memory and visuoconstruction had AUROC &gt; 0.7 for s‐HAND (0.70 ‐ 0.72; p&lt;0.001 for all). Tests of visual memory, verbal learning and memory (delayed recall and recognition memory), psychomotor speed, language comprehension and categorical verbal fluency were independently associated with s‐HAND (p&lt;0.01 for all). Neuropsychological impairment pattern varied by education.ConclusionCurrent HAND screening tests no longer perform well in the new population of older PLWH in Africa. Tests most associated with s‐HAND include broad cortical and subcortical domains, some not included in existing HAND screening tests and vary by educational background. This should be considered in future HAND screening measure development.

Further Validation of a Self‐administered Smartphone‐based Verbal Learning and Memory Assessment

AbstractBackgroundThe International Shopping List test (ISLT) is a verbal word list learning test set within a realistic shopping list context, supporting ease of cultural adaptation, and addressing content validity and patient relevance. Improvements to and the wide adoption of natural language processing (NLP) software has enabled the possibility for self‐administered tests of verbal learning. LilaTM a self‐administered, smartphone‐application (app) was developed, using the virtual assistant and NLP. We have previously reported acceptability and usability data from qualitative analysis of concept elicitation interviews. We now seek to provide preliminary validation data around its use.MethodA convenience sample of healthy young adults (n = 40), M(SD)age = 35 (16), were invited to install and complete one assessment of the LilaTM app. A usability survey was also administered to explore participants’ experiences. The sample was predominantly female (70%) and of Asian ethnicity (62.5%). Data were collected in Australia, using an English word pool developed for the USA.ResultAcceptability was generally high with N = 38 completing immediate recall rounds and N = 32 completing the delayed recall round. Eight‐two percent found it extremely or somewhat easy to hear and understand what items were on the shopping list and 95% indicated that it was extremely or somewhat easy to understand what they had to do to complete the assessment. Scoring accuracy was 88% at the word item level, with reprocessing to address accent, context setting, and other NLP approaches to improve accuracy underway e.g., homophones biased to the grocery item.ConclusionWhilst acceptability was high, the importance of localization of test stimuli was confirmed as well as the need for additional data processing options to account for accent. Continued optimization of data processing to score participant responses and word item pools to reduce ambiguity is expected to further improve accuracy e.g., accounting for regional accents and consideration of homophones and compound words. However, specific characteristics of speech including in those for whom English may be a second/foreign language will be an area of focus for future development.

Further Validation of a Self‐administered Smartphone‐based Verbal Learning and Memory Assessment

AbstractBackgroundThe International Shopping List test (ISLT) is a verbal word list learning test set within a realistic shopping list context, supporting ease of cultural adaptation, and addressing content validity and patient relevance. Improvements to and the wide adoption of natural language processing (NLP) software has enabled the possibility for self‐administered tests of verbal learning. LilaTM a self‐administered, smartphone‐application (app) was developed, using the virtual assistant and NLP. We have previously reported acceptability and usability data from qualitative analysis of concept elicitation interviews. We now seek to provide preliminary validation data around its use.MethodA convenience sample of healthy young adults (n = 40), M(SD)age = 35 (16), were invited to install and complete one assessment of the LilaTM app. A usability survey was also administered to explore participants’ experiences. The sample was predominantly female (70%) and of Asian ethnicity (62.5%). Data were collected in Australia, using an English word pool developed for the USA.ResultAcceptability was generally high with N = 38 completing immediate recall rounds and N = 32 completing the delayed recall round. Eight‐two percent found it extremely or somewhat easy to hear and understand what items were on the shopping list and 95% indicated that it was extremely or somewhat easy to understand what they had to do to complete the assessment. Scoring accuracy was 88% at the word item level, with reprocessing to address accent, context setting, and other NLP approaches to improve accuracy underway e.g., homophones biased to the grocery item.ConclusionWhilst acceptability was high, the importance of localization of test stimuli was confirmed as well as the need for additional data processing options to account for accent. Continued optimization of data processing to score participant responses and word item pools to reduce ambiguity is expected to further improve accuracy e.g., accounting for regional accents and consideration of homophones and compound words. However, specific characteristics of speech including in those for whom English may be a second/foreign language will be an area of focus for future development.

Trajectories in Depressive Symptoms and Midlife Brain Health

AbstractBackgroundEvidence in older adults suggests that depressive symptoms may be part of prodromal mood changes in dementia, rather than a risk factor. However, it is unclear whether variations in depressive symptoms in adulthood exhibit distinct characteristics in brain structure and cognitive function in midlife.MethodsFrom the Coronary Artery Risk Development in Young Adults study, we identified 662 Black and White participants (age 23‐36 at baseline) who completed the Center for Epidemiological Studies Depression scale (CES‐D) at six time points over 20 years. 20 years after baseline, the participants underwent magnetic resonance imaging to characterize gray matter (GM) structures (total GM, temporal cortex, hippocampus, and entorhinal cortex) and white matter hyperintensities (WMHs). Participants also completed neuropsychological tests including the Digit Symbol Substitution Test (DSST), Rey‐Auditory Verbal Learning Test (RAVLT), Stroop Test, Montreal Cognitive Assessment (MoCA), and category and letter fluency tests, analyzed as z‐scores.ResultsUsing growth mixture modeling, we identified four trajectories of depressive symptoms (Figure 1): consistently low scorers (“steady low”; n = 509, 76.9%), a class with an early peak and decline in symptoms (“declining”; n = 63, 9.5%), a class with late increases in symptoms (“increasing”; n = 49, 7.4%), and consistently high scorers (“steady high”; n = 41, 6.2%). Compared to the steady low class, the steady high class had lower entorhinal cortex volume (β: ‐180.80, 95% CI: ‐336.69 to ‐24.91). The increasing class, had more WMHs (β: 0.55, 95% CI: 0.22 to 0.89) and less total brain volume (β: ‐9269.25, 95% CI: ‐17104.67 to ‐1444.82). Both the steady high and the increasing classes had poorer performance on the Stroop task (β: ‐0.40, 95% CI: ‐0.70 to ‐0.10; β: ‐0.39, 95% CI: ‐0.64 to ‐0.14, respectively), however the steady high also had poorer DSST performance (β: ‐0.40, 95% CI: ‐0.67 to ‐0.13), while the increasing class had poorer performance on the MoCA (β: ‐1.20, 95% CI: ‐2.04 to ‐0.37). The declining group was not significantly different from the steady low group on any brain or cognitive measures.ConclusionsOur findings suggest that trajectories in depressive symptoms in young to mid‐adulthood show different cognitive and brain phenotypes in midlife.

Sleep‐Disordered Breathing and Cognition in a Diverse Population

AbstractBackgroundSleep‐disordered breathing (SDB) in older adults is associated with worse cognitive performance and dementia risk. Few studies have examined the relationship between SDB and cognition in a diverse population.MethodsWe studied 654 non‐demented participants from the Health and Aging Brain Study‐Health Disparities (HABS‐HD)‐Dormir study, with an in‐home sleep apnea assessment, a peripheral arterial tonometry‐based system (WatchPAT‐200). SDB measurements included: the respiratory event index (REI; 3% desaturation threshold) and the oxygen desaturation index (ODI; 4% threshold), split into mild (&lt;15 events/hour) and moderate/severe (≥15 events/hour) and assessed by REM, non‐REM, and total sleep (via WatchPat algorithm). We examined three cognitive domains, defining worse cognition as negative standardized z‐scores on the Mini‐Mental Status Exam (MMSE; general cognition); the long‐delay Logical Memory and Spanish‐English Verbal Learning Test (memory); and Trails Making Test‐B and Digit Symbol Substitution (executive function). Regression analyses determined the association between SDB and cognition, adjusting for age, race, sex, education, diabetes, and hypertension.ResultsParticipants were 42.7% Non‐Hispanic White, 35.4% Mexican‐American, and 21.9% Black, averaging 66.6 (sd = 8.2) years; 65.2% were female. The average sleep duration was 6.7 (sd = 1.3) hours; 50.4% had moderate/severe REI and 24.7% had moderate/severe ODI. Compared to mild REI, participants with moderate/severe had a trend towards worse executive function (total‐REI β = ‐0.09 (95% confidence intervals ‐0.20,0.01), p = 0.08). Moderate/severe total‐REI was not associated with global cognition (β = ‐0.02 (‐0.12,0.08), p = 0.75), but moderate/severe REM‐REI was (β = ‐0.11 (‐0.20,‐0.01), p = 0.04). Moderate/severe ODI was also associated with a trend towards worse executive function (total‐ODI β = ‐0.10 (‐0.22,0.01), p = 0.08) and global cognition (total‐ODI β = ‐0.11 (‐0.21,0.01), p = 0.06) compared to mild ODI. The association was greater in non‐REM‐ODI for global cognition (β = ‐0.14 (‐0.26,‐0.02), p = 0.02) and REM‐ODI for executive function (β = ‐0.12 (‐0.22,‐0.02), p = 0.02). There were no associations between REI/ODI and memory, and no interactions with race/ethnicity or APOE4 status. Results were similar after adjusting for body mass index.ConclusionsIn an ethnically and racially diverse population, we found that SDB was prevalent and moderate/severe SDB was associated with lower general cognition and executive function. Future studies should assess the relationship between REM/non‐REM SDB and cognition, and if SDB treatment may reduce dementia risk.

P198: Correlation between depressive symptom severity and functional status in patients with mild cognitive impairment.

Objectives:Although depression is a common co-morbid disorder in patients with mild cognitive impairment (MCI), not all patients with MCI exhibit depressive symptoms. This study aimed to investigate the effect of depression on cognitive and functional decline in MCI.Methods:281 patients with MCI (MCI) defined by 0.5 score on Clinical Dementia Rating were included in the study. Patients were divided into three groups based on their Geriatric Depression Scale (GDS) scores: MCI without depression (GDS&lt;10, n=50), MCI with mild depression (GDS10~19, n=120), and MCI with severe depression (GDS&gt;20, n=111). Cognitive function tests (cognitive domains in CERAD-K including letter fluency, trail making test-A and B, and verbal learning test) and Blessed Dementia Scale-Activities of Daily Living (BDS-ADL) were measured. Group differences were analyzed using an analysis of variance (ANOVA). Correlation between GDS scores and BDS-ADL were analyzed.Results:An ANOVA test showed that activities of daily living differed significantly across groups (F(2, 276) = 13.53, p&lt;0.001). Post-hoc analysis showed MCI with severe depression had a significantly higher mean BDS-ADL score compared with both MCI without depression and MCI with mild depression (both, p&lt;0.001). Correlation analysis showed significant positive correlation between GDS and BDS-ADL (r=0.366, p&lt;0.001). However, mean scores of cognitive function tests were not different among three groups.Conclusions:The present study suggests that co-morbid depressive symptoms may have negative impact on functional status in patients with MCI. This may further suggest the importance of evaluation and treatment of depressive symptoms in patients with MCI.

Classifying Memory Clinic Patients Using the Digital Clock Drawing TestTM, Mini‐Mental State Examination, and Philadelphia (repeatable) Verbal Learning Test

AbstractBackgroundDigital cognitive assessments (DCA) enable quick, sensitive, and reliable assessment of neurocognitive operations that underlie dementia and mild cognitive impairment (MCI). We examined how well the DCTclockTM DCA, Mini‐Mental State Examination (MMSE), and Philadelphia (repeatable) Veral Learning Test (PrVLT) can classify memory clinic patients by cognitive impairment profile.Method106 serial referrals to an outpatient memory clinic were assessed with the DCTclock, MMSE, and P(r)VLT. Using statistical criteria for subtle cognitive impairment (SCI, Edmonds et al., 2015) and MCI (Jak et al., 2008), patients were classified into cognitively normal (CN, n = 21), SCI (n = 33), amnestic MCI (aMCI, n = 22), and dysexecutive/mixed MCI (d/mMCI, n = 30) groups. A series of stepwise logistic regression analyses were conducted with CN participants as the criterion group.ResultIn the first analysis (Table 1), P(r)VLT‐recognition (X2 = 24.39, p&lt;0.001) entered the model first followed by the DCTclock Score (X2 = 16.68, p&lt;0.001). P(r)VLT‐recognition classified aMCI patients (Wald = 11.21, p&lt;0.001). DCTclock (Wald = 8.97, p&lt;0.001) and P(r)VLT‐recognition (Wald = 4.06, p&lt;0.001) classified d/mMCI patients. In the second analysis the four command DCTclock composites were analyzed, excluding the MMSE and P(r)VLT‐recognition scores, Spatial Reasoning classified patients into their respective groups (SCI, Wald = 3.68, p&lt;0.055; aMCI, Wald = 8.84, p&lt;0.003; d/mMCI, Wald = 19.12 p&lt;0.001). Third, analyzing DCTclock command Spatial Reasoning, MMSE, and P(r)VLT‐recognition, the P(r)VLT score, again, entered first (X2 = 24.39, p&lt;0.001) followed by DCTclock Spatial Reasoning (X2 = 18.95, p&lt;0.001). DCTclock Spatial Reasoning classified SCI patients (Wald = 4.66, p&lt;0.031), P(r)VLT‐recognition classified aMCI patients (Wald = 9.11, p&lt;0.003), and both DCTclock command Spatial Reasoning (Wald = 10.56, p&lt;0.001) and P(r)VLT‐recognition (Wald = 3.32, p&lt;.068) classified d/mMCI patients.ConclusionUnlike the MMSE that takes 10‐15 minutes to administer and is scored subjectively, all DCTclock data are digitally obtained and automatically scored, requiring no examiner interface for administration and interpretation, thus obviating clinical judgment, ensuring inter‐rater reliability, and enabling more efficient cognitive assessments. In this series of logistic regression analyses, a combination of DCTclock and P(r)VLT clearly outperformed the MMSE in classifying non‐demented memory clinic patients into cognitively normal, subtle cognitive impairment, and MCI subtypes. These results support the efficacy of DCAs in clinical trials and to screen for emergent cognitive impairment in primary care and specialty medical practices.

A 10‐minute Digitally Administered and Scored Neuropsychological Protocol Assessing Executive Control and Episodic Memory

AbstractBackgroundDigital assessment technology provides rapid and reliable assessment of neurocognitive abilities associated with Alzheimer’s Disease and Related Dementia (ADRD) and Mild Cognitive Impairment (MCI). Dysexecutive and amnestic impairment typify many ADRD and MCI disorders. Here, we evaluate a 10‐minute digitally administered protocol assessing these neurocognitive constructs.Method229 community dwelling participants were assessed (age = 68.32+9.85; education = 15.01+2.58, MMSE = 26.84+2.78; 144 females). Executive abilities were assessed with three trials of 5‐digits backward digit span test (BDST) and the ‘animal’ fluency test. Episodic memory was assessed with a 6‐word Philadelphia (repeatable) Verbal Learning Test (PrVLT) consisting of 2 immediate free recall (IFR) trials, delayed free recall (DFR), and delayed recognition. Traditional pencil and paper testing was not used. Data were obtained with an iPad processed using automatic speech recognition.ResultA K‐means cluster analysis (k = 3) classified participants with possible dementia (pDem = 31), MCI (n = 96), and cognitively normal (CN, n = 100; Table 1). Groups differed from each other on all three P(r)VLT parameters (p = 0.001). CN participants outperformed other groups on executive measures (p = 0.001). All between‐group analyses yielded large effect sizes (η2 = 0.277–0.642). Logistic regression analysis using P(r)VLT‐DFR, P(r)VLT‐recognition, BDST, and ‘animal’ fluency parameters classify MCI and pDem participants into their respective groups compared to CN participants (p = 0.003). For the pDem group, within‐group t‐tests found rapid forgetting (PrVLT‐DFT&lt;PrVLT‐IFR trial 2, p = 0.013; PrVLT‐recognition&lt;PrVLT‐DFR (p = 0.013). Additional, within‐group pDem group comparisons found no differences between P(r)VLT‐recognition and either executive tests. Within group comparisons for the MCI group found P(r)VLT delayed recognition improved compared to P(r)VLT delayed free recall (p&lt;0.001), and worse performance on both executive measures compared to P(r)VLT‐ recognition (p = .001). All of these comparisons are consistent with a mild dysexecutive syndrome.ConclusionThe protocol described above is efficient, reliable, removes any inter‐rater reliability issues, and is able to operationally‐define dysexecutive and amnestic cognitive impairment ‐ key neurocognitive constructs related to ADRD and MCI. This 10‐minute digitally administered and automatically scored neuropsychological protocol assessing executive abilities and episodic memory could easily be deployed in clinical trials and in primary‐ and specialty‐care settings to screen for emergent cases of MCI and ADRD by efficient assessment of episodic memory and executive abilities.

Correlation between depressive symptom severity and functional status in patients with mild cognitive impairment

AbstractBackgroundAlthough depression is a common co‐morbid disorder in patients with mild cognitive impairment (MCI), not all patients with MCI exhibit depressive symptoms. This study aimed to investigate the effect of depression on cognitive and functional decline in MCI.Method281 patients with MCI (MCI) defined by 0.5 score on Clinical Dementia Rating were included in the study. Patients were divided into three groups based on their Geriatric Depression Scale (GDS) scores: MCI without depression (GDS&lt;10, n = 50), MCI with mild depression (GDS10∼19, n = 120), and MCI with severe depression (GDS&gt;20, n = 111). Cognitive function tests (cognitive domains in CERAD‐K including letter fluency, trail making test‐A and B, and verbal learning test) and Blessed Dementia Scale‐Activities of Daily Living (BDS‐ADL) were measured. Group differences were analyzed using an analysis of variance (ANOVA). Correlation between GDS scores and BDS‐ADL were analyzed.ResultAn ANOVA test showed that activities of daily living differed significantly across groups (F(2, 276) = 13.53, p&lt;0.001). Post‐hoc analysis showed MCI with severe depression had a significantly higher mean BDS‐ADL score compared with both MCI without depression and MCI with mild depression (both, p&lt;0.001). Correlation analysis showed significant positive correlation between GDS and BDS‐ADL (r = 0.366, p&lt;0.001). However, mean scores of cognitive function tests were not different among three groups.ConclusionThe present study suggests that co‐morbid depressive symptoms may have negative impact on functional status in patients with MCI. This may further suggest the importance of evaluation and treatment of depressive symptoms in patients with MCI.

A 10‐minute Digitally Administered and Scored Neuropsychological Protocol Assessing Executive Control and Episodic Memory

AbstractBackgroundDigital assessment technology provides rapid and reliable assessment of neurocognitive abilities associated with Alzheimer’s Disease and Related Dementia (ADRD) and Mild Cognitive Impairment (MCI). Dysexecutive and amnestic impairment typify many ADRD and MCI disorders. Here, we evaluate a 10‐minute digitally administered protocol assessing these neurocognitive constructs.Method229 community dwelling participants were assessed (age = 68.32+9.85; education = 15.01+2.58, MMSE = 26.84+2.78; 144 females). Executive abilities were assessed with three trials of 5‐digits backward digit span test (BDST) and the ‘animal’ fluency test. Episodic memory was assessed with a 6‐word Philadelphia (repeatable) Verbal Learning Test (PrVLT) consisting of 2 immediate free recall (IFR) trials, delayed free recall (DFR), and delayed recognition. Traditional pencil and paper testing was not used. Data were obtained with an iPad processed using automatic speech recognition.ResultA K‐means cluster analysis (k = 3) classified participants with possible dementia (pDem = 31), MCI (n = 96), and cognitively normal (CN, n = 100; Table 1). Groups differed from each other on all three P(r)VLT parameters (p = 0.001). CN participants outperformed other groups on executive measures (p = 0.001). All between‐group analyses yielded large effect sizes (η2 = 0.277–0.642). Logistic regression analysis using P(r)VLT‐DFR, P(r)VLT‐recognition, BDST, and ‘animal’ fluency parameters classify MCI and pDem participants into their respective groups compared to CN participants (p = 0.003). For the pDem group, within‐group t‐tests found rapid forgetting (PrVLT‐DFT&lt;PrVLT‐IFR trial 2, p = 0.013; PrVLT‐recognition&lt;PrVLT‐DFR (p = 0.013). Additional, within‐group pDem group comparisons found no differences between P(r)VLT‐recognition and either executive tests. Within group comparisons for the MCI group found P(r)VLT delayed recognition improved compared to P(r)VLT delayed free recall (p&lt;0.001), and worse performance on both executive measures compared to P(r)VLT‐ recognition (p = .001). All of these comparisons are consistent with a mild dysexecutive syndrome.ConclusionThe protocol described above is efficient, reliable, removes any inter‐rater reliability issues, and is able to operationally‐define dysexecutive and amnestic cognitive impairment ‐ key neurocognitive constructs related to ADRD and MCI. This 10‐minute digitally administered and automatically scored neuropsychological protocol assessing executive abilities and episodic memory could easily be deployed in clinical trials and in primary‐ and specialty‐care settings to screen for emergent cases of MCI and ADRD by efficient assessment of episodic memory and executive abilities.

The potential cost‐effectiveness of roflumilast drug treatment in mild cognitive impairment

AbstractBackgroundEvidence is needed on the value of new (pharmacological) health technologies in their early stage of development, to support stakeholders (industry, regulators, payers, and health care providers) in decision‐making linked to their further development and introduction in routine care. Early health‐technology assessment supports stakeholders by providing insight into the size and uncertainty of the expected benefits new technologies may have. This can facilitate early guidance on positioning in clinical practice and research recommendations. Our objective was to provide a pragmatic example of the potential cost‐effectiveness of roflumilast treatment in addition to usual care versus usual care alone if prevention of progression to dementia is in part realized in a population of patients diagnosed with a mild cognitive impairment (MCI) at a memory clinic.MethodThe IPECAD open‐source decision‐analytic model was used to simulate the natural disease progression of MCI and dementia and estimate the quality‐adjusted life years (QALYs) and care costs, comparing roflumilast treatment added to usual care with usual care alone. In this model roflumilast proof of concept evidence on a visual 30‐word verbal learning test (0.39 z‐score) was translated using a published risk equation model to a relative risk of 0.93 for developing dementia. The treatment was assumed symptomatic with no effect on mortality.ResultMore lifeyears were spent in MCI in the roflumilast strategy compared with usual care, with 0.2 increment lifeyears (95%CI: 0.0 to 0.6) (see figure 1), and 0.04 incremental lifetime QALYs (95%CI: 0.00 to 0.11) and k€1.3 adjusted societal costs (95%CI: ‐6.3 to 5.5) (see figure 2). This resulted in an incremental cost‐effectiveness ratio of k€34 per QALY (see table 1). Roflumilast was estimated to have a 37% probability of being cost‐effective (net health benefit 95% interval ‐0.27 to 0.42), with uncertainty mainly driven by extrapolating the word learning surrogate outcome to the patient‐relevant outcome of dementia onset, and the efficacy estimate (see figure 3).ConclusionThe potential cost‐effectiveness of roflumilast treatment is uncertain, driven by uncertainty in treatment efficacy and extrapolation to postponing dementia onset. We believe the results indicate a potential for roflumilast and provide several recommendations to consider investing in its future research.