Neuropsychological Protocol Research Articles

Impact of Neuropsychological Assessment on Subjective Memory Complaints in Patients With Mild Cognitive Impairment.

Patients with Alzheimer's disease (AD), namely at an initial stage like amnestic cognitive impairment (aMCI), typically present with memory complaints. They also have difficulties regarding self-knowledge about their cognitive deficits. In clinical practice, a formal neuropsychological assessment is often done. The present study aimed to understand whether patients with aMCI retain the ability to monitor the success or failure in their performance during the neuropsychological assessment and adjust the report of memory complaints accordingly, as compared to healthy controls. Participants were patients with aMCI and healthy controls who were questioned about their own memory abilities using the Subjective Memory Complaints (SMC) scale, applied before and after the neuropsychological assessment protocol. A repeated measures General Linear Model was performed to analyze changes in SMC (within-subjects effects) after the neuropsychological assessment, in patients with aMCI and healthy controls (between-subjects effects). Eighty volunteers, 40 patients with aMCI and 40 healthy controls, participated in the study. Patients with aMCI showed lower MMSE scores, more depressive symptoms, and deficits in memory and learning, language and executive domains. Patients with aMCI had higher SMC scores [9.4(3.6)] than healthy controls [4.4(2.3)] before the neuropsychological assessment. A statistically significant interaction was found between the SMC and the diagnostic group, meaning that healthy controls decreased SMC [3.4(1.9)] after the neuropsychological assessment, whereas patients with aMCI kept high levels of SMC [9.6(3.9)]. In patients with aMCI, an inverse correlation between logical memory and the change in SMC was found, so that patients with lower scores in the logical memory test tended to increase their memory complaints after the assessment. Both patients with aMCI and healthy controls can monitor and update the impression about their memory abilities following a formal neuropsychological assessment. Patients with aMCI maintain a high SMC level, which is inversely associated with their memory performance. In practical terms, SMC should be measured consistently at a particular moment in time, preferably preceding the objective neuropsychological assessment.

Everyday forgetfulness and memory complaints: A randomized controlled cognitive intervention study

ABSTRACT The results of Cognitive Intervention (CI) programs vary considerably; thus, it is helpful to assess the characteristics that enhance the effectiveness of these programs. Our objectives were to analyze the effectiveness of a multicomponent CI program called UMAM on cognitive performance, subjective memory, daily forgetfulness, and mood of individuals with memory complaints. Older adults with no cognitive impairment were separated into two groups by simple random assignment, a control (n = 111) and a parallel experimental (n = 115) group. They were assessed with an extended neuropsychological protocol and the Memory Failures of Everyday Questionnaire (MFE); evaluation pre and post intervention (at six months). We performed a multifactorial cognitive intervention (30 sessions) based on memory strategies, stimulation of cognitive processes, instruction in basic concepts about memory, interventions for everyday memory failures, and Metamemory. The Results showed improvements in objective measures, including logical memory (Cohen’s d = .30); processing speed (d = .26); phonological (d = .33) and semantic verbal fluency (d = .27); and general cognitive performance (d = .82) (all, p < .05). In subjective measures, we found improvements in mood state (d = .25) and everyday memory failures (MFE: d = .29) (all, p < .05). Several everyday failures improve: ‘Forgetting where you have put something,’ “finding a word that is on the ‘tip of the tongue,’ and ‘checking again if something has been done’ (all, p < .05). We found positive results when a cognitive process was directly trained intensely using exercises that focus on real life, with adaptive activities that aim to resolve everyday memory failures. This program has proved effective in promoting health and well-being and preventing cognitive impairment. Trial registration: Trial retrospectively registered on January 29, 2020; (ClinicalTrials.gov -NCT04245579).

Cognitive outcome after stereo-electroencephalography-guided radiofrequency thermocoagulation in temporal lobe epilepsy.

Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) is being used incrementally in the invasive diagnosis of epilepsy. There is currently a lack of information regarding the potential cognitive consequences of the extended use of this technique. This work describes, for the first time, the cognitive outcomes after RFTC in patients with temporal lobe epilepsy (TLE), evaluated longitudinally and using a control group. Forty-eight adult patients with drug-resistant unilateral TLE (30 RFTC-treated patients and 18 controls) were evaluated using a comprehensive neuropsychological protocol at baseline. In the RFTC group, two follow-up assessments were performed at 3 months and 1 year. The control group was reevaluated after 1 year. Two analyses were performed: 1) group-level analyses, in which linear mixed models were applied according to TLE lateralization (intragroup and intergroup [RFTC vs control] comparisons), and 2) individual-level analyses, in which the Reliable Change Index (RCI) algorithm was developed and a 90% CI (cutoff ± 1.64) was used to describe neuropsychological outcomes at 1 year post-RFTC. A memory subanalysis was performed in hippocampal RFTC patients (25/30). A Spearman coefficient study was conducted to determine the correlation between cognitive change and thermocoagulated contacts. Left- and right-sided TLE patients treated with RFTC showed cognitive preservation at baseline. At a group level, the short-term evaluation, including verbal and visual memory, language, and executive functions, showed preservation in these domains and no significant differences compared with baseline. In the long-term follow-up assessment (1 year after RFTC), no significant intragroup changes were found, nor were significant changes found in comparison with the control group. The RCI algorithm showed that significant individual cognitive losses and gains were infrequent. Three patients presented with naming deficits, only 1 (3.3%) of whom showed a clinically significant deficit. Significant gains were more prevalent in executive function tests with a speed component (4/20 left-sided RFTC patients). Twenty-five of the 30 (83%) patients were treated with hippocampal RFTC. No patients experienced significant loss in verbal delayed memory in the left-sided RFTC sample or in visual delayed memory in the right-sided RFTC sample. The correlations between cognitive change and RFTC contacts were mostly nonsignificant. In the group-level comparisons, discernible cognitive impairment following RFTC was not evidenced. The majority of patients did not exhibit significant individual declines during the 1-year follow-up period. Notably, the procedural intervention yielded no substantial repercussions on memory functioning following hippocampal RFTC. These findings underscore the evidence supporting the cognitive preservation associated with SEEG-guided RFTC.

APOE genotype, hippocampal volume, and cognitive reserve predict improvement by cognitive training in older adults without dementia: a randomized controlled trial.

Cognitive training (CT) programs aim to improve cognitive performance and impede its decline. Thus, defining the characteristics of individuals who can benefit from these interventions is essential. Our objectives were to assess if the cognitive reserve (CR), APOE genotype (e4 carriers/non-carriers) and/or hippocampal volume might predict the effectiveness of a CT program. Participants were older adults without dementia (n = 226), randomized into parallel experimental and control groups. The assessment consisted of a neuropsychological protocol and additional data regarding total intracranial, gray matter, left/right hippocampus volume; APOE genotype; and Cognitive Reserve (CR). The intervention involved multifactorial CT (30 sessions, 90min each), with an evaluation pre- and post-training (at six months); the control group simply following the center's routine activities. The primary outcome measures were the change in cognitive performance and the predictors of change. The results show that APOE-e4 non-carriers (79.1%) with a larger left hippocampal volume achieved better gains in semantic verbal fluency (R2 = .19). Subjects with a larger CR and a greater gray matter volume better improved their processing speed (R2 = .18). Age was correlated with the improvement in executive functions, such that older age predicts less improvement (R2 = .07). Subjects with a larger left hippocampal volume achieved more significant gains in general cognitive performance (R2 = .087). In conclusion, besides the program itself, the effectiveness of CT depends on age, biological factors like genotype and brain volume, and CR. Thus, to achieve better results through a CT, it is essential to consider the different characteristics of the participants, including genetic factors.Trial registration: Trial retrospectively registered on January 29th, 2020-(ClinicalTrials.gov -NCT04245579).

Cognitive dysfunction characteristics of multiple sclerosis with aging

BackgroundWe aimed to investigate the characteristics of cognitive impairment in older people with multiple sclerosis (MS). MethodsCross-sectional study that included participants that were examined with a common and comprehensive neuropsychological protocol. The subjects were matched by sociodemographic variables and the following groups were generated for comparisons: young MS versus healthy controls (HC) (n = 246), old MS versus HC (n = 198), young MS vs old MS (n = 226), MS vs Alzheimer's disease (AD)(n = 70), and MS vs Parkinson's disease (PD) (n = 62). The ICCoDiMS criteria were used to define cognitive impairment in MS. ResultsCognitive impairment was more frequent in young than old patients (70.8 % vs 52.2 %). Attention and speed processing is the most frequent cognitive domain impaired in MS (54.9 % of young MS vs 32.7 % of old MS). The frequency of impairment in attention/processing speed (54.9 % vs 32.7 %) and episodic memory (27.9 % vs 14.3) was higher in the young group than in the old group. There were no statistically significant differences in the distribution of impairment in executive function (46.0 % vs 35.3 %), visuospatial (17.9 % vs 9.5 %), and language (12.4 % vs 17.7 %). In those patients meeting the criteria for cognitive impairment, young MS patients showed lower performance in attention/processing speed tests. Conversely, old MS patients showed lower performance in episodic memory, verbal fluency, and planning. There were no differences in the correlations between SDMT and other neuropsychological tests in young and old patients, which suggests similar cognitive processes underlying SDMT performance in both groups. There were differences between old MS and prodromal AD, especially in episodic memory, while the cognitive profile of old MS was largely shared with PD. ConclusionsOur study found that the cognitive profile of MS is defined by a characteristic impairment in attention and processing speed, which is present during the lifespan. The impairment in processing speed is less prominent in old age, whereas the impairment of other cognitive functions becomes more relevant. These findings suggest potential differences in the pathophysiological processes associated with cognitive impairment between young and old ages that warrant further investigation.

The Neuropsychological Assessment Battery Driving Scenes Test in a Dementia Clinic.

In dementia research, the Driving Scenes test from the Neuropsychological Assessment Battery has been shown to relate to memory, dementia diagnosis, and functional impairment. The aim of the current study was to examine Driving Scenes and its component scores, and their relationships with cognition and daily functioning, in a mixed dementia clinic sample. One hundred U.S. military veterans between the ages of 55 and 88 were administered a full neuropsychological protocol that included Driving Scenes. The Driving Scenes score and its subscores were strongly related to memory skills, and there were additional subscore associations with language and visuospatial functions. Driving Scenes uniquely predicted reported bill payment difficulties and tendency to get lost while driving, which were not predicted by other performances across cognitive domains. Driving Scenes is a clinically and functionally relevant measure of memory. Although the Driving Scenes total score remains useful in dementia evaluations, component scores and error scores contribute additional practical information.

Cognitive profile in multiple sclerosis and post-COVID condition: a comparative study using a unified taxonomy

Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.

Short-term memory binding is insensitive to the socioeconomic status of older adults with and without mild cognitive impairment

Objective: The Visual Short-Term Memory Binding (VSTMB) Test is a useful tool in the assessment of Alzheimer’s disease (AD). Research has suggested that short-term memory binding is insensitive to the sociocultural characteristics of the assessed individuals. Such earlier studies addressed this influence by considering years of education. The current study aims to determine the influence of sociocultural factors via a measure of Socioeconomic Status (SES) which provides a more holistic approach to these common confounders. Methods: A sample of 126 older adults, both with (n = 59) and without (n = 67) amnestic mild cognitive impairment (aMCI), underwent assessment using a neuropsychological protocol including VSTMB test. All participants were classified as either high SES or low SES, employing the Standard Demographic Classification from the European Society for Opinion and Marketing Research. Results: ANOVA/ANCOVA models confirmed that performance of healthy and aMCI participants on traditional neuropsychological tests were sensitive to SES whereas the VSTMB Test was not. The results add to the growing array of evidence suggesting that there are cognitive abilities which are unaffected by socioeconomic factors, regardless of clinical condition. Conclusions: The lack of sensitivity to sociocultural factors previously reported for the VSTMB test is accompanied by a lack of sensitivity to socioeconomic factors thus broadening the scope of this test to aid in the detection of dementia across populations with different backgrounds. Future studies should take these findings forward and explore the potential influences of AD biomarkers (A/T/N) on the association between cognitive functions and demographic variables.

Specific cognitive and psychological alterations are more strongly linked to increased migraine disability than chronic migraine diagnosis

IntroductionThe efficiency of The International Classification of Headache Disorders (ICHD-3) in reflecting patients’ disability has recently been questioned. This prompts consideration that clinical features beyond pain may more accurately indicate the extent of underlying brain impairment than the mere frequency of headache days. Important cognitive dysfunctions and psychological impairment have been reported in burdensome cases of migraine, and the presence of these alterations has been associated with biological changes in the nervous system. This study aimed to compare migraine-related disability within a specific patient group, classified using ICHD-3 criteria or classified based on findings from a neuropsychological evaluation using machine learning. Additionally, a complementary voxel-based morphometry (VBM) comparison was conducted to explore potential neuroanatomical differences between the resulting groups.Patients and methodsThe study included episodic and chronic migraine patients seeking consultation at a specialized headache department. A neuropsychological evaluation protocol, encompassing validated standardized tests for cognition, anxiety, depression, perceived stress, and headache-related impact (HIT-6) and disability (MIDAS), was administered. Results from this evaluation were input into an automated K-means clustering algorithm, with a predefined K=2 for comparative purposes. A supplementary Voxel-based Morphometry (VBM) evaluation was conducted to investigate neuroanatomical contrasts between the two distinct grouping configurations.ResultsThe study involved 111 participants, with 49 having chronic migraine and 62 having episodic migraine. Seventy-four patients were assigned to cluster one, and 37 patients were assigned to cluster two. Cluster two exhibited significantly higher levels of depression, anxiety, and perceived stress, and performed worse in alternating and focalized attention tests. Differences in HIT-6 and MIDAS scores between episodic and chronic migraine patients did not reach statistical significance (HIT-6: 64.39 (±7,31) vs 62.92 (±11,61); p= 0. 42 / MIDAS: 73.63 (±68,61) vs 84.33 (±63,62); p=0.40). In contrast, patients in cluster two exhibited significantly higher HIT-6 (62.32 (±10,11) vs 66.57 (±7,21); p=0.03) and MIDAS (68.69 (±62,58) vs 97.68 (±70,31); p=0.03) scores than patients in cluster one. Furthermore, significant differences in grey matter volume between the two clusters were noted, particularly involving the precuneus, while differences between chronic and episodic migraine patients did not withstand correction for multiple comparisons.ConclusionsThe classification of migraine patients based on neuropsychological characteristics demonstrates a more effective separation of groups in terms of disability compared to categorizing them based on the chronic or episodic diagnosis of ICHD-3. These findings could reveal biological changes that might explain differences in treatment responses among apparently similar patients.

Cognitive profile in cerebral small vessel disease: comparison between cerebral amyloid angiopathy and hypertension-related microangiopathy

Cerebral amyloid angiopathy (CAA) is recognized as a cause of cognitive impairment, but its cognitive profile needs to be characterized, also respect to hypertension-related microangiopathy (HA). We aimed at comparing difference or similarity of CAA and HA patients’ cognitive profiles, and their associated factors. Participants underwent an extensive clinical, neuropsychological, and neuroimaging protocol. HA patients (n = 39) were more frequently males, with history of vascular risk factors than CAA (n = 32). Compared to HA, CAA patients presented worse performance at MoCA (p = 0.001) and semantic fluency (p = 0.043), and a higher prevalence of amnestic MCI (46% vs. 68%). In univariate analyses, multi-domain MCI was associated with worse performance at MoCA, Rey Auditory Verbal Learning Test (RAVLT), and semantic fluency in CAA patients, and with worse performance at Symbol Digit Modalities Test (SDMT) and phonemic fluency in HA ones. In multivariate models, multi-domain deficit remained as the only factor associated with RAVLT (β = − 0.574) in CAA, while with SDMT (β = − 0.364) and phonemic fluency (β = − 0.351) in HA. Our results highlight different patterns of cognitive deficits in CAA or HA patients. While HA patients’ cognitive profile was confirmed as mainly attentional/executive, a complex cognitive profile, characterized also by deficit in semantic memory, seems the hallmark of CAA patients.

In search of a neuropsychological profile for migraine: A scoping review.

Migraine is commonly overlooked by the general population and by professionals in research and clinical practice. Moreover, it is difficult to grasp the neuropsychological profile of migraineurs due to the cyclic nature of the disorder. With this in mind, a scoping review of the literature was conducted with the goal of characterizing cognitive domains associated with deficits in migraine. PubMed, PsychInfo, Scopus, EMBASE and OpenGrey databases were searched for studies published from 1st January 2006 to 30th November 2022. Following the review process, 52 eligible studies were included in the review. Studies included in this review show mixed and sometimes contradictory findings. Overall, both visual and auditory perception appear to be impaired. Deficits on attention, many memory processes, visuospatial function and spatial navigation and on a wide range of executive functions (set-shifting and cognitive flexibility, decision-making and reasoning, working memory and prospective memory) complete a complex cognitive profile in migraine. Lack of consistency across studies in sample selection and sizes, lack of detailed links between cognitive deficits and specific migraine phases, or length and chronicity, inconsistencies on the role of aura in cognitive function; and heterogeneity and sometimes questionable reliability and validity of some of the cognitive measures used may affect the clarity and consistency of results observed. Further research properly addressing the role of gender and age, migraine stage, length and chronicity of the condition, the effect of aura and comorbidities is needed, alongside increasing consistency across diverse neuropsychological assessment protocols. This review provides a comprehensive, up-to-date picture of the current status of knowledge in relation to the characterization of the complex cognitive profile of migraine. It offers detailed information of the existing research gaps and challenges to improve the cognitive characterization of migraine across its different stages and leads clinicians to carefully consider the selection of relevant cognitive tasks, in order to grasp more accurately the patient's cognitive profile; an assessment that should be an integral part of any protocol developed for the clinical assessment and subsequent treatment planning for migraine.

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.

Cognitive flexibility impairment in temporal lobe epilepsy: The impact of epileptic foci lateralization on executive functions

IntroductionTemporal Lobe Epilepsy (TLE) has been associated with memory impairments, which are typically linked to hippocampal and mesial temporal cortex lesions. Considering the presence of extensive bidirectional frontotemporal connections, it can be hypothesized that executive dysfunction in TLE is modulated by the lateralization of the epileptic foci. Material and MethodsA comprehensive neuropsychological executive functions protocol was administered to 63 participants, including 42 individuals with temporal lobe epilepsy (20 with right-TLE and 22 with left-TLE) and 21 healthy controls aged 20–49. ResultsThe results indicate that TLE patients exhibit poorer executive performance compared to healthy controls in working memory (F(2,60) = 4.18, p <.01), planning (F(2,60) = 4.71, p <.05), set shifting (F(2,60) = 10.1, p <.001), phonetic verbal fluency (F(2,60) = 11.71, p <.01) and semantic verbal fluency (F(2,60) = 9.61, p <.001. No significant differences were found in cognitive inhibition. Furthermore, right-TLE patients showed lower performance than left-TLE in set shifting (F(1,61) = 6.45, p <.05), while no significant differences were observed in working memory, planning, inhibition, and verbal fluency. ConclusionsThis research emphasize the importance of considering the lateralization of the temporal lobe focus to achieve a more accurate neuropsychological characterization. The cognitive differences between left and right TLE patients highlight the need for individualized approaches in their treatment and care.

Prevalence of Mild Cognitive Impairment in Southern Regions of Colombia.

Recent reports suggest that by 2050 there will be an increase of around 310% of cases affected by dementia in Latin American countries. A previous study in a Southern region reported one of the highest prevalences of dementia in Latin America. To investigate the prevalence of mild cognitive impairment associated with low education, rurality, and demographic characteristics. A cross-sectional study recruited a community-dwelling sample of 823 adults from rural and urban areas of two Southern provinces of Colombia from 2020-2022. Participants were assessed with a neuropsychological protocol validated in Colombia. To obtain general and region-specific prevalence rates, age, sex, schooling, and socioeconomic level were considered and controlled for. Most of the participants reported low education and socioeconomic level, the participation of women was higher. It was determined that the prevalence of mild cognitive impairment (MCI) was 53.6%, with 56.6% in the province of Caquetá followed by 51.9% in the province of Huila. The amnestic MCI represented 42.6%, the amnestic multi-domain was 39%, the non-amnestic 16.55%, and the non-amnestic multi-domain 1.81%. Our participants reported comorbidities such as diabetes and hypertension. We also observed a relationship between exposure to pesticides and MCI. We observed one of the highest prevalences of MCI in Latin America reported to date. Variables such as age, gender, and education proved risk factors for MCI in the explored regions. Our findings are very much in line with recent studies that highlight the influence of non-canonical risk factors of dementia in underrepresented countries from Latin America.

Neuropsychological Rehabilitation Improves Memory and Action Naming in Patients With Post-COVID-19 Syndrome.

Post-COVID-19 syndrome (PCS-19) is a condition characterized by both physical and cognitive alterations in patients who have overcome COVID-19. Despite the high incidence of this disorder and the inconveniences it produces to those affected, there are few studies investigating the efficacy of cognitive stimulation in these patients. The aim of this study was to compare two groups of patients with PCS-19. One of them was treated with neuropsychological intervention for 6 months, whereas the other did not receive treatment. Both groups shared similar clinical characteristics and cognitive profiles. The study included 15 participants. Eight (seven women and one man, with a mean age of 50.13 years) made up the experimental group and received neuropsychological rehabilitation sessions once a week with the aim of recovering or compensating for their impaired functions. The control group consisted of seven patients (six women and one man, with a mean age of 52.86 years) who did not undergo neuropsychological rehabilitation sessions. The neuropsychological assessment protocol included tests for all cognitive domains. In comparison with the assessment prior to the neuropsychological intervention, significant differences were found in the experimental group both in verbal memory and in the action naming task. As for the control group, improvements in action fluency performance were observed. Neither group showed significant improvement in pre- versus posttest Stroop scores. However, the control group did perform higher than the treatment group in the final assessment. Despite the small sample size, our results suggest that patients with PCS-19 may benefit from neuropsychological rehabilitation, as it may help them to improve several cognitive functions that do not recover spontaneously.

Bilingualism and APOE4 alelle as a risk‐protective factor in dementia among Peruvian Andean aging population

AbstractBackgroundBilingualism has been considered as a protective factor against dementia. But the evidence in Native American populations is spare and to our knowledge, there are no studies analyzing risk factors, as the APOE4 genotype and environmental protective factors as the bilingualism and education. Our objective was to analyze the risk/protective association between bilingualism and APOE4 status (carrier/non‐Carrier) on Alzheimer Dementia Related Disorders (ADRD). In addition, we analyzed the impact of the bilingual/monolingual condition on cognition.MethodWe used the data of the ongoing study “Genetics of Alzheimer’s disease in Peruvian Populations study” (GAPP). 275 older adults (mean age = 71.57, SD = 8.3) were recruited from 3 Peruvian cities: Lima, Arequipa and Puno. These last located in the southern of Peru where Quechua and Aymara ethnics are the most important population. Bilingual condition was evaluated as a dichotomous condition (yes/no). A clinical and neuropsychological protocol was applied which included brief cognitive test, functional status measures and clinical dementia scales (CDR). Cognitive measures included attention, memory, abstract reasoning, language and visuoconstruction. Genotyping was conducted on The Infinium Global Screening Array‐24 BeadChip, which combines multi‐ethnic genome‐wide content. Binary logistic regression was performed taking the CDR 1 score as the dependent variable and gender, education, being bilingual/monolingual, and APOE4 Carrier/non‐Carrier status as predictors. Finally, we use mean comparison test in cognition measures according the bilingual/monolingual condition.ResultWe observed that bilingualism (OR = 0.23, p&lt;.001), APOE non‐carrier status (OR = 0.26, p&lt;.001) and more years of schooling (OR = 0.92, p&lt;.01) are associated with a lower risk of dementia. We also see that bilinguals have better scores than monolinguals in orientation tasks (t = 2.65, p&lt;.01), memory total recall (t = 2.02, p&lt;.05), semantic fluency‐animals (t = 2.71, p&lt;. 01) and visuoconstructional abilities (t = 6.62, p&lt;.001). Likewise, only in perception recognition tasks, monolinguals scored higher than bilinguals (t = 3.17, p&lt;.01).ConclusionEnvironmental factors seem to have a significant protective effect along with biological known risk factor in dementia and have a significant effect on cognition.

Discovery‐based proteomics identifies plasma proteins that predict longitudinal cognitive decline in older adults over a 7‐year follow‐up period

AbstractBackgroundRecent technological advances have enabled large‐scale proteomic profiling of plasma and especially in studies of Alzheimer’s disease. However, studies that have comprehensively examined longitudinal cognitive decline as an outcome from plasma protein levels prior to the onset of clinical dementia are limited. This project aimed to identify plasma proteins predictive of cognitive decline across a robust neuropsychological protocol over a 7‐year follow‐up period.MethodsVanderbilt Memory and Aging Project participants (n = 333, 73±7 years, 41% female) free of clinical dementia at study entry underwent fasting blood draw and comprehensive serial neuropsychological assessment over a 7‐year period (mean follow‐up = 5.8 years). Plasma samples were subjected to multiplex liquid chromatography tandem mass spectrometry analysis to quantify cross‐sectional protein abundances for each participant at study entry. Normalization of proteomic data adjusted for batch effects, high levels of missingness, and log2 transformation. Linear mixed‐effects regressions related protein levels to longitudinal neuropsychological outcomes, adjusting for age, sex, race/ethnicity, education, baseline cognitive status, apolipoprotein E ε4 status, and follow‐up time. False discovery rate correction was applied to the a priori significance threshold.ResultsInitial proteomics analyses yielded 3,784 proteins, of which 686 were used as analytical predictors following quality control, post‐acquisition filtering, and data normalization. Regression analyses resulted in 86 proteins which predicted longitudinal decline in global cognition, as assessed by the Montreal Cognitive Assessment. In analyses with individual neuropsychological domains as outcomes, 144 proteins predicted longitudinal decline in at least one neuropsychological domain [episodic memory (40 proteins), language (72 proteins), information processing speed (99 proteins), executive function (22 proteins), visuospatial skills (55 proteins)]. There was a smaller number of proteins (i.e., five) that were predictive of longitudinal cognitive decline across all domains.ConclusionWe conducted large‐scale proteomics analyses and identified 144 plasma proteins at study entry among a cohort of older adults free of clinical dementia that predict subsequent decline in cognition over a 7‐year follow‐up period. Five of these proteins were predictive of decline across all domains suggesting these proteins may represent biological pathways that adversely affect brain health with increasing age. Replication is needed to validate identified proteins as potential biomarkers of cognitive decline.

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 effect of age and years of schooling on CERAD‐MX performance of Mexican preclinical carriers and non‐carriers’ relatives of the V717I APP mutation

AbstractBackgroundIn a previous study in a sample of young neurotypical adults (18 to 59 years), we found that years of schooling (YoS) have a greater effect than age on the tasks included in the neuropsychological protocol of the Mexican adaptation of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD‐MX).MethodThirty‐eight participants (Mage = 31.08 years; MYoS = 8.27 years), from Jalisco State in Mexico, identified as first‐degree relatives of symptomatic autosomal dominant Alzheimer’s disease (ADAD) carriers of the V71 7I APP mutation were divided into two groups, MC (n = 15) and NC (n = 23). Eight CERAD‐MX tasks were used: the Mini‐mental State Examination (MMSE), Semantic Verbal Fluency (SVF), Verbal Boston Naming (VBN), Word List Memory (WLM) with delayed recall (WLD) and recognition (WLR), as well as Constructional Praxis copy (CPC) and recall (CPR). We used z‐scores, then defined random vectors with Sklar’s theorem and a Gaussian dome from simulations of new samples obtained by inverse transform sampling.ResultIn both groups, YoS had a greater positive effect on the MMSE, WLM, WLD z‐scores. In the MC group only, this same effect was evident in the SVF and CPR scores, while in the NC group this effect was seen in the VBN, and CPC z‐scores. Age effect was more pronounced that YoS in MC performance on the CPC, while in NC, on SVF performance.ConclusionFor both groups, YoS has a greater effect than age on several tasks, showing that YoS is a confounding variable when analyzing performance on CERAD‐MX tasks. Moreover, in the MC group, age has a positive effect on CPC task performance suggesting that graphic abilities are not vulnerable to the presence of V717I APP mutation at the preclinical stage.

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.