Subtle Cognitive Changes Research Articles

Identifying older adults at risk for dementia based on smartphone data obtained during a wayfinding task in the real world.

Alzheimer's disease (AD), as the most common form of dementia and leading cause for disability and death in old age, represents a major burden to healthcare systems worldwide. For the development of disease-modifying interventions and treatments, the detection of cognitive changes at the earliest disease stages is crucial. Recent advancements in mobile consumer technologies provide new opportunities to collect multi-dimensional data in real-life settings to identify and monitor at-risk individuals. Based on evidence showing that deficits in spatial navigation are a common hallmark of dementia, we assessed whether a memory clinic sample of patients with subjective cognitive decline (SCD) who still scored normally on neuropsychological assessments show differences in smartphone-assisted wayfinding behavior compared with cognitively healthy older and younger adults. Guided by a mobile application, participants had to find locations along a short route on the medical campus of the Magdeburg university. We show that performance measures that were extracted from GPS and user input data distinguish between the groups. In particular, the number of orientation stops was predictive of the SCD status in older participants. Our data suggest that subtle cognitive changes in patients with SCD, whose risk to develop dementia in the future is elevated, can be inferred from smartphone data, collected during a brief wayfinding task in the real world.

A scoping review of remote and unsupervised digital cognitive assessments in preclinical Alzheimer's disease.

Subtle cognitive changes in preclinical Alzheimer's disease (AD) are difficult to detect using traditional pen-and-paper neuropsychological assessments. Remote and unsupervised digital assessments can improve scalability, measurement reliability, and ecological validity, enabling the detection and monitoring of subtle cognitive change. Here, we evaluate such tools deployed in preclinical AD samples, defined as cognitively unimpaired individuals with abnormal levels of amyloid-β (Aβ), or Aβ and tau. In this scoping review, we screened 1,680 unique reports for studies using remote and unsupervised cognitive assessment tools in preclinical AD samples; 23 tools were found. We describe each tool's usability, validity, and reported metrics of reliability. Construct and criterion validity according to associations with established neuropsychological assessments and measures of Aβ and tau are reported. With this review, we aim to present a necessary update to a rapidly evolving field, following a previous review by Öhman and colleagues (2021; Alzheimers Dement. Diagn. Assess. Dis. Monit ) and addressing the open questions of feasibility and reliability of remote testing in the target population. We discuss future directions for using remote and unsupervised digital cognitive assessments in preclinical AD and how such tools may be used for longitudinal monitoring of cognitive function, scalable case finding, and individualized prognostics in both clinical trials and healthcare contexts.

On the lasting impact of mild traumatic brain injury on working memory: Behavioural and electrophysiological evidence

Despite increasing recognition of the significance of mild traumatic brain injury (mTBI), the long-term cognitive consequences of the injury remain unclear. More sensitive measures that can detect subtle cognitive changes and consideration of individual variability are needed to properly characterise cognitive outcomes following mTBI. Here, we used complex behavioural tasks, individual differences approaches, and electrophysiology to investigate the long-term cognitive effects of a history of mTBI. In Experiment 1, participants with self-reported mTBI history (n=82) showed poorer verbal working memory performance on the operation span task compared to control participants (n=88), but there were no group differences in visual working memory, multitasking, cognitive flexibility, attentional control, visuospatial ability, or information processing speed. Individual differences analyses revealed that time since injury and presence of memory loss predicted visual working memory capacity and visuospatial ability, respectively, in those with mTBI history. In Experiment 2, participants with mTBI history (n=20) again demonstrated poorer verbal working memory on the operation span task compared to control participants (n=38), but no group differences were revealed on a visuospatial complex span task or simpler visual working memory measures. We also explored the electrophysiological indices of visual working memory using EEG during a change detection task. No differences were observed in early sensory event-related potentials (P1, N1) or the later negative slow wave associated with visual working memory capacity. Together, these findings suggest that mTBI history may be associated with a lasting, isolated disruption in the subsystem underlying verbal working memory storage. The results emphasise the importance of sensitive cognitive measures and accounting for individual variability in injury characteristics when assessing mTBI outcomes.

Analysis of the effectiveness of a computerized cognitive stimulation program designed from Occupational Therapy according to the level of cognitive reserve in older adults in Primary Care: Stratified randomized clinical trial protocol

Normal aging presents subtle cognitive changes that can be detected before meeting the criteria for Mild cognitive impairment (MCI). Older people with low cognitive reserve and who receive limited cognitive stimulation are at greater risk of deterioration. In this regard, cognitive stimulation (CS) has been identified as an intervention that reduces this risk, provided that its design takes into account the differences in the level of cognitive reserve (CR) acquired throughout life and the baseline level of cognitive functioning. The general objective of this study is to evaluate, through a randomized clinical trial, the effectiveness of a computerized cognitive stimulation program, designed and adapted from Occupational Therapy based on the level of cognitive reserve in older adults in Primary Care. 100 participants will be randomized in a stratified manner according to the level of cognitive reserve (low/moderate/high), assigning 50 participants to the control group and 50 participants to the intervention group. The intervention group will carry out a computerized cognitive stimulation intervention designed and adapted from occupational therapy according to the level of cognitive reserve, through the “stimulus” platform. The main result expected to be achieved is the improvement of higher brain functions. As secondary results, we expect that those cognitive aspects most vulnerable to aging will decrease more slowly (in areas such as memory, executive function, attention and processing speed), and that the cognitive reserve of the participants will increase, in addition to being able to balance gender differences in these aspects. We think that these results can have a positive impact on the creation of adapted, meaningful and stimulating CS programs in older adults to prevent MCI and experience healthier aging.

Influence of daily life and health profile in subtle cognitive decline of women residing in Spanish religious communities: DeCo religious orders study.

Prior to the onset of dementia, individuals commonly undergo a phase marked by subtle cognitive changes, known as subtle cognitive decline. Recognizing these early cognitive alterations is crucial, as they can serve as indicators of an impending decline in cognitive function, warranting timely intervention and support. To determine the incidence of subtle cognitive decline in a population of Spanish women and establish the relationship with possible protective and/or risk factors such as cognitive reserve, cardiovascular risk factors, medication consumption and psychosocial factors. This is a cross-sectional observational study with women from the general population and a more homogeneous population composed of nuns from the Valencian region (Spain). A validated questionnaire was used including lifestyle variables, chronic illnesses, level of education and pharmacological treatments. Three validated subtle cognitive decline screening tests with varying levels of sensitivity and specificity were used: Memory Impairment Screening, Pfeiffer's Short Portable Mental State Questionnaire, and Semantic Verbal Fluency. Our results suggest that nuns may have a significantly reduced risk of cognitive decline compared to the general population (20.67% in nuns vs. 36.63% in the general population). This lower risk for subtle cognitive decline in nuns may be partly attributed to their higher cognitive reserve and long-time engagement in intellectually stimulating activities. Additionally, nuns tend to adopt healthy lifestyles, they are not isolated because they live in community and obtained lower scores for risk factors such as depression, anticholinergic burden, and benzodiazepine consumption. A healthy lifestyle combined with intellectually stimulating activities is related with preserved cognitive function.

Novel measures of cognition and function for the AD spectrum in the Novel Measures for Alzheimer's Disease Prevention Trials (NoMAD) project: Psychometric properties, convergent validation, and contrasts with established measures.

This study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early-stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well-established measures. For 291 older adults with healthy cognition or early mild cognitive impairment, Exploratory factor analyses were used to identify the factor structure of the NPE. Factor and total scores were examined for their psychometric properties and associations with AD risk biomarkers. Composite scores from the novel cognitive and functional measures demonstrated better psychometric properties (distribution and test-retest reliability) and stronger associations with AD-related demographic, genetic, and brain risk markers than well-established measures, DISCUSSION: These novel measures have potential for use as primary cognitive and functional outcomes in early-stage AD clinical trials. Well-established cognitive tests may not accurately detect subtle cognitive changes. No Practice Effect (NPE) and Computerized Functional Skills Assessment and Training are novel measures designed to have improved psychometric properties. NPE had Executive Function, Cognitive Control/Speed, and Episodic Memory domains. Novel measures had better psychometric properties compared to established measures. Significant associations with Alzheimer's disease biomarkers were found with novel measures.

Amyloid-β Deposition Predicts Grocery Shopping Performance in Older Adults Without Cognitive Impairment.

A screening tool sensitive to Alzheimer's disease (AD) risk factors, such as amyloid-β (Aβ) deposition, and subtle cognitive changes, best elicited by complex everyday tasks, is needed. To determine if grocery shopping performance could differentiate older adults at elevated risk of developing AD (OAer), older adults at low risk of developing AD (OAlr), and young adults (YA), and if amount of Aβ deposition could predict grocery shopping performance in older adults (OA). Twenty-one OAer (78±5 years), 33 OAlr (78±5 years), and 28 YA (31±3 years) performed four grocery shopping trials, with the best and worst performances analyzed. Measures included trial time, number of correct items, number of grocery note fixations, and number of fixations and percentage of time fixating on the correct shelving unit, correct brand, and correct shelf. Linear mixed effects models compared measures by performance rank (best, worst) and group (OAer, OAlr, YA), and estimated the effect of Aβ deposition on measures in OA. Relative to their best performance, OAer and OAlr exhibited more correct shelving unit fixations and correct brand fixations during their worst performance, while YA did not. Within OA's worst performance, greater Aβ deposition was associated with a smaller percentage of time fixating on the correct shelving unit, correct shelf, and correct brand. Within OA, greater Aβ deposition was associated with more grocery note fixations. OA with elevated Aβ deposition may exhibit subtle working memory impairments and less efficient visual search strategies while performing a cognitively demanding everyday task.

Dual-task gait has prognostic value for cognitive decline in Parkinson’s disease

IntroductionCognitive decline frequently occurs in individuals with Parkinson’s disease (PD), but the clinical methods to predict the onset of cognitive changes are limited. Given preliminary evidence of the link between gait and cognition, the purpose of this study was to determine if dual task (DT) gait was related to declines in cognition over two years in PD. MethodsA retrospective two-year longitudinal study of 48 individuals with PD using data from the Parkinson’s Progression Markers Initiative of the Michael J. Fox Foundation. The following data were extracted at baseline: spatiotemporal gait (during single and DT), demographics (age, sex), PD disease duration (time since diagnosis), motor function (Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)), and cognition (Montreal Cognitive Assessment (MoCA)), with MoCA scores also extracted after two years. ResultsA binomial logistic regression was conducted, with all covariates (above) in block 1 and DT effect (DTE) of gait characteristics in block 2 entered in a stepwise fashion. The final model was statistically significant (χ2(6) = 23.20, p < 0.001) and correctly classified 78.7 % of participants by cognitive status after two years. Only DTE of arm swing asymmetry (ASA) (p = 0.030) was included in block 2 such that a 1 % decline in DTE resulted in 1.6 % increased odds of cognitive decline. ConclusionsIndividuals with greater change in arm swing asymmetry from single to DT gait may be more likely to experience a decline in cognition within two years. These results suggested that reduced automaticity or poor utilization of attentional resources may be indicative of subtle changes in cognition and indicate that DT paradigms may hold promise as a marker of future cognitive decline.

Continuous Associations between Remote Self-Administered Cognitive Measures and Imaging Biomarkers of Alzheimer’s Disease

BackgroundEasily accessible and self-administered cognitive assessments that can aid early detection for Alzheimer’s disease (AD) dementia risk are critical for timely intervention.Objectives/DesignThis cross-sectional study investigated continuous associations between Mayo Test Drive (MTD)–a remote, self-administered, multi-device compatible, web-based cognitive assessment–and AD-related imaging biomarkers.Participants/Setting684 adults from the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer’s Disease Research Center participated (age=70.4±11.2, 49.7% female). Participants were predominantly cognitively unimpaired (CU; 94.0%).MeasurementsParticipants completed (1) brain amyloid and tau PET scans and MRI scans for hippocampal volume (HV) and white matter hyperintensities (WMH); (2) MTD remotely, consisting of the Stricker Learning Span and Symbols Test which combine into an MTD composite; and (3) in-person neuropsychological assessment including measures to obtain Mayo Preclinical Alzheimer’s disease Cognitive Composite (Mayo-PACC) and Global-z. Multiple regressions adjusted for age, sex, and education queried associations between imaging biomarkers and scores from remote and in-person cognitive measures.ResultsLower performances on MTD were associated with greater amyloid, entorhinal tau, and global tau PET burden, lower HV, and higher WMH. Mayo-PACC and Global-z were associated with all imaging biomarkers except global tau PET burden. MCI/Dementia participants showed lower performance on all MTD measures compared to CU with large effect sizes (Hedge’s g’s=1.65–2.02), with similar findings for CU versus MCI only (Hedge’s g’s=1.46–1.83).ConclusionMTD is associated with continuous measures of AD-related imaging biomarkers, demonstrating ability to detect subtle cognitive change using a brief, remote assessment in predominantly CU individuals and criterion validity for MTD.

423 Innovation in MS Patient Care: Linking Cognitive Health and Myelin Integrity

OBJECTIVES/GOALS: Our objective is to develop a patient-friendly application addressing the progression of cognitive impairments in multiple sclerosis (MS) patients. This initiative aims to augment individualized care and precision management of a major MS comorbidity by generating a cognitive health brain map for each patient. METHODS/STUDY POPULATION: Using the UAMS COMS Database, featuring high-resolution multi-contrast MRIs, and a comprehensive clinical, behavioral, and demographic dataset, we are developing a hierarchical learning-based software tool to compute maps correlating brain structure-function and individual cognitive function. Our MRI analysis employs a three-compartment model (NNLS&gt;0.96). Functional scores are defined by individualized accuracy during the modified information processing speed task (e.g., m-SDMT). We utilize a Bayesian classifier with explicit Pearson’s correlation for tissue classification (BF10&gt;100) to compute an index of the likelihood of correlation with cognitive impairment throughout brain tissue. RESULTS/ANTICIPATED RESULTS: This approach allows us to reveal subtle cognitive changes and their potential links to myelin integrity, offering vital insights into disease progression and management. The m-SDMT strongly correlates with the standard SDMT (r=0.79, p&lt;0.001), confirming reliability as a cognitive assessment tool in clinical and research contexts. Analysis of the COMS dataset emphasized insights into the role of fine myelin structure in MS patients' cognitive functionality. Our findings heightened the pivotal significance of myelin integrity in preserving cognitive abilities and identify disruptions in myelin synthesis and homeostasis as primary contributors to cognitive decline. This discovery stresses the critical role that specialized brain pathways, influenced by myelin integrity, play in the pathology of MS. DISCUSSION/SIGNIFICANCE: This development bridges advanced neuroimaging techniques with practical clinical applications, emphasizing the nuanced role of myelin integrity in MS-related cognitive deficits. Our findings advocate for a multidisciplinary approach to MS management, demanding collaborative workforce development and education in translational science.

Speech patterns during memory recall relates to early tau burden across adulthood.

Early cognitive decline may manifest in subtle differences in speech. We examined 238 cognitively unimpaired adults from the Framingham Heart Study (32-75 years) who completed amyloid and tau PET imaging. Speech patterns during delayed recall of a story memory task were quantified via five speech markers, and their associations with global amyloid status and regional tau signal were examined. Total utterance time, number of between-utterance pauses, speech rate, and percentage of unique words significantly correlated with delayed recall score although the shared variance was low (2%-15%). Delayed recall score was not significantly different between β-amyoid-positive (Aβ+) and -negative (Aβ-) groups and was not associated with regional tau signal. However, longer and more between-utterance pauses, and slower speech rate were associated with increased tau signal across medial temporal and early neocortical regions. Subtle speech changes during memory recall may reflect cognitive impairment associated with early Alzheimer's disease pathology. Speech during delayed memory recall relates to tau PET signal across adulthood. Delayed memory recall score was not associated with tau PET signal. Speech shows greater sensitivity to detecting subtle cognitive changes associated with early tau accumulation. Our cohort spans adulthood, while most PET imaging studies focus on older adults.

Cognitive and Functional Change Over Time in Cognitively Healthy Individuals According to Alzheimer Disease Biomarker-Defined Subgroups.

It is unclear to what extent cognitive outcome measures are sensitive to capture decline in Alzheimer disease (AD) prevention trials. We aimed to analyze the sensitivity to changes over time of a range of neuropsychological tests in several cognitively unimpaired, biomarker-defined patient groups. Cognitively unimpaired individuals from the Amsterdam Dementia Cohort and the SCIENCe project with available AD biomarkers, obtained from CSF, PET scans, and plasma at baseline, were followed over time (4.5 ± 3.1 years, range 0.6-18.9 years). Based on common inclusion criteria for clinical trials, we defined groups (amyloid, phosphorylated tau [p-tau], APOE ε4). Linear mixed models, adjusted for age, sex, and education, were used to estimate change over time in neuropsychological tests, a functional outcome, and 2 cognitive composite measures. Standardized regression coefficients of time in years (βtime) were reported as outcome of interest. We analyzed change over time with full follow-up, as well as with follow-up limited to 1.5 and 3 years. We included 387 individuals (aged 61.7 ± 8.6 years; 44% female) in the following (partly overlapping) biomarker groups: APOE ε4 carriers (n = 212), amyloid-positive individuals (n = 109), amyloid-positive APOE ε4 carriers (n = 66), CSF p-tau-positive individuals (n = 127), plasma p-tau-positive individuals (n = 71), and amyloid and CSF p-tau-positive individuals (n = 50), or in a control group (normal biomarkers; n = 65). An executive functioning task showed most decline in all biomarker groups (βtime range -0.30 to -0.71), followed by delayed word list recognition (βtime range -0.18 to -0.50). Functional decline (βtime range -0.17 to -0.63) was observed in all, except the CSF and plasma tau-positive groups. Both composites showed comparable amounts of change (βtime range -0.12 to -0.62) in all groups, except plasma p-tau-positive individuals. When limiting original follow-up duration, many effects disappeared or even flipped direction. In conclusion, functional, composite, and neuropsychological outcome measures across all cognitive domains detect changes over time in various biomarker-defined groups, with changes being most evident among individuals with more AD pathology. AD prevention trials should use sufficiently long follow-up duration and/or more sensitive outcome measures to optimally capture subtle cognitive changes over time.

The MAPP Room Memory Test: Examining Contextual Memory Using a Novel Computerized Test in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer's Disease.

Contextual memory, the ability to remember spatial or temporal features related to an event, is affected in Alzheimer's disease (AD). There is a shortfall of tests that measure contextual memory. To evaluate visuospatial contextual memory, we developed a computerized cognitive test, the MAPP Room Memory Test, which requires participants to identify in which visual scene target items were previously presented. We hypothesized that cognitively-unimpaired carriers of an autosomal dominant AD mutation (Presenilin-1 E280A, n=15) would perform more poorly on this test than non-carrier family members (n=31). Compared to non-carriers, the carriers had significantly worse delayed room recognition. The results indicate that the MAPP Room Memory Test may be sensitive to subtle cognitive changes associated with risk of AD. Future studies with larger samples using the MAPP Room Memory Test and biomarkers are needed to examine whether this test may also be sensitive to the earliest pathological changes in preclinical AD.

Navigating the diagnostic and therapeutic complexities of autoimmune encephalitis

Characterized by immune-mediated inflammation of the brain, autoimmune encephalitis (AE) encompasses a diverse array of disorders, each presenting with unique as well as overlapping clinical manifestations, and underlying autoantibodies targeting neuronal and glial surface antigens. The clinical spectrum can range from subtle cognitive and behavioural changes to severe seizures, movement disorders, and altered consciousness. However, what truly sets AE apart from other encephalitides is its potential reversibilitywhen identified early and managed appropriately. The identification of N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis in 2007 heralded the discovery of a spectrum of immunotherapy-responsive AE. However, misdiagnosis remains prevalent despite diagnostic algorithms, resulting in unnecessary immunotherapies and delayed treatment of the correct diagnosis. AE diagnosis requires a judicious blend of diagnostic algorithms, antibody testing, and clinical acumen. Testing for antibodies against neuronal surface antigens, preferably in cerebrospinal fluid, is essential, but should be contextual to clinical relevance.Treatment guidelines are largely based on retrospective studies due to a dearth of randomized and prospective data. However, early immunotherapy initiation has proven to be pivotal for optimal outcomes. The therapeutic landscape in AE continues to evolve with the introduction of novel targeted immunotherapies.This review highlights the complexities, and proposes a systematic approach, to the diagnosis and treatment of AE.

REVOLUTIONIZING COGNITIVE ASSESSMENT: THE POWER OF DIGITAL BIOMARKERS AND ECOLOGICALLY VALID METHODS

Abstract Digital technologies have allowed neuropsychologists to utilize process-based approaches to assess cognitive function and change. Traditional methods of neuropsychological assessment involve obtaining single scores (often composites) to represent cognitive function. However, modern process-based techniques involve the use of digital data collection to acquire insights into both the manner and reasoning behind an individual’s performance. The present study will share insights into the task development and validation of active and passive digital cognitive assessments from two longitudinal studies of aging: (1) a study of non-dementia participants (N=322), ultra-brief mobile cognitive tests were administered up to six times per day for two weeks; and (2) a neuro-exergaming study (N=31) enrolling patients with MCI and their co-residing study partner, where participants used a study-provided tablet to complete a neuro-exergaming protocol and digital cognitive assessments (e.g., digital trailmaking and eStroop). We analyzed both traditional and process-based metrics in two studies, including mean response time and patterns of inaccuracy. Study one found significant correlations between MCI status and metrics for survey completion time, working memory, and processing speed. Study two found weak to moderate correlations between cognitive function measures from digital and paper-based neuropsychology. Our findings suggest that remote self-administered digital measures can detect subtle cognitive changes. The event-level data, which is collected through a process-based approach, has enormous untapped potential for discovering and confirming novel digital biomarkers of cognitive health and progression that can be monitored beyond clinical settings.

Cognitive Theory of Mind Deficit Associated with Executive Dysfunction in Cervical Dystonia

Introduction. Cervical dystonia (CD) is viewed as a circumscribed movement disorder. However, beyond motor symptoms, it can imply subtle cognitive change, among others with respect to theory of mind (ToM) capacities. Here, affective and cognitive ToM performances and potential relations to other mental functions were investigated to refine the concept of social cognitive dysfunction in CD. Methods. 20 persons with CD were clinically assessed, together with 20 healthy controls engaged in overview cognitive testing, executive function (EF) tasks, and the Faux Pas Recognition Test (FPRT) as well as the Reading the Mind in the Eyes Tests (RMET) addressing cognitive and affective ToM functions, respectively. Results. Persons with CD showed lower cognitive, but not affective ToM performance than controls. Further, they had abnormally low word production in verbal fluency (VF) tasks, imposing high EF demands. Generally, ToM performance correlated with VF and, further, with the decreased quality of life score in persons with CD. Conclusion. Cognitive ToM deficits seem to occur in the context of executive dysfunction in CD. They belong to an underrecognized spectrum of nonmotor symptoms of likely clinical relevance.

Theory of mind in mild cognitive impairment and Parkinson’s disease: The role of memory impairment

BackgroundSocial cognition is impaired in Parkinson’s disease (PD). Whether social cognitive impairment (iSC) is a by-product of the underlying cognitive deficits in PD or a process independent of cognitive status is unknown. To this end, the present study was designed to investigate the weight of specific cognitive deficits in social cognition, considering different mild cognitive impairment subtypes of PD (PD-MCI).MethodsFifty-eight PD patients underwent a neuropsychological battery assessing executive functions, memory, language, and visuospatial domains, together with social cognitive tests focused on theory of mind (ToM). Patients were divided into subgroups according to their clinical cognitive status: amnestic PD-MCI (PD-aMCI, n = 18), non-amnestic PD-MCI (PD-naMCI, n = 16), and cognitively unimpaired (PD-CU, n = 24). Composite scores for cognitive and social domains were computed to perform mediation analyses.ResultsMemory and language impairments mediated the effect of executive functioning in social cognitive deficits in PD patients. Dividing by MCI subgroups, iSC occurred more frequently in PD-aMCI (77.8%) than in PD-naMCI (18.8%) and PD-CU (8.3%). Moreover, PD-aMCI performed worse than PD-CU in all social cognitive measures, whereas PD-naMCI performed worse than PD-CU in only one subtype of the affective and cognitive ToM tests.ConclusionsOur findings suggest that ToM impairment in PD can be explained by memory dysfunction that mediates executive control. ToM downsides in the amnesic forms of PD-MCI may suggest that subtle changes in social cognition could partly explain future transitions into dementia. Hence, the evaluation of social cognition in PD is critical to characterize a possible behavioral marker of cognitive decline.

In-vehicle Sensing and Data Analysis for Older Drivers with Mild Cognitive Impairment.

Driving is a complex daily activity indicating age and disease-related cognitive declines. Therefore, deficits in driving performance compared with ones without mild cognitive impairment (MCI) can reflect changes in cognitive functioning. There is increasing evidence that unobtrusive monitoring of older adults' driving performance in a daily-life setting may allow us to detect subtle early changes in cognition. The objectives of this paper include designing low-cost in-vehicle sensing hardware capable of obtaining high-precision positioning and telematics data, identifying important indicators for early changes in cognition, and detecting early-warning signs of cognitive impairment in a truly normal, day-to-day driving condition with machine learning approaches. Our statistical analysis comparing drivers with MCI to those without reveals that those with MCI exhibit smoother and safer driving patterns. This suggests that drivers with MCI are cognizant of their condition and tend to avoid erratic driving behaviors. Furthermore, our Random Forest models identified the number of night trips, number of trips, and education as the most influential factors in our data evaluation.

Alternative Endpoints and Models for AD Prevention Trials

AbstractBackgroundThere are several challenges for AD prevention trials. First, the subtle cognitive change in asymptomatic disease stages requires large sample sizes, e.g. 400‐500/arm for two phase 3 confirmatory trials, or 800‐900/arm for a single phase 3 confirmatory trial, using the traditional MMRM. Second, large, international trials may necessitate the use of different tracers for imaging biomarker assessment due to global availability issues, however, statistical models that harmonize tracer differences within clinical trials are still lacking. Third, primary prevention trials using time to event endpoint demands even larger sample sizes, e.g., 1650/arm for TRAILBLAZER‐ALZ 3 with time‐to‐first‐conversion from CDR global 0 to &gt;0 as the outcome. The percentage slowing relative to placebo decline (e.g., lecanemab led to 27% slowing at 18 months) is a popular concept to describe treatment effect. Instead of estimating the absolute difference using MMRM, we proposed to model this percentage treatment effect directly using the percentage or proportional MMRM (pMMRM). pMMRM can harmonize assessments from different tracers by converting the absolute difference into a shared proportional treatment effect across tracers. When using time‐to‐conversion as the primary outcome, instead of using a single event, Cox proportional hazards models for recurrent events can capture the treatment effect after the first event, where a recurrent event is defined as any increment over the previous visit in CDR global.MethodWe first demonstrated that disease modifying treatment effects are essentially proportional retreatment effects. Then, we evaluated the power advantage of pMMRM over MMRM and Cox recurrent events model over single event model through simulations. Finally, we demonstrated how to harmonize data from different tracers using pMMRM.ResultFigure 1 demonstrates that disease modifying treatment effects are like proportional treatment effects, leading to diverged disease progression trajectories and increased absolute differences. Figure 2 shows the power comparison between MMRM and pMMRM. pMMRM led to a power increase up to 30% over MMRM.ConclusionAlternative models such as pMMRM or Cox recurrent event models can yield greater power and pMMRM can harmonize assessment from different tracers, which may help enable global prevention trials in AD with disease modifying drug effects.

LAS‐Face‐ Name Associative Memory Exam: Discriminant validity for the detection of associative memory disorders in people with mild cognitive impairment in Argentina

AbstractBackgroundThe Latin American Spanish version of the Face‐Name Associative Memory Exam (LAS‐FNAME) is a validated version of the test that has been used to detect subtle cognitive changes in cognitively unimpaired adults at increased risk for Alzheimer’s disease (AD). Performance in this test has also been associated with markers of brain pathology in cognitively unimpaired older adults at increased risk for AD due to genetic factors or subjective cognitive decline (Papp et al., 2014;Vila‐Castelar et al., 2020). However, this test has not yet been used for the detection of Mild Cognitive Impairment (MCI) in the Latin American population. This study aims to analyze the discriminative validity and diagnostic performance of the LAS FNAME for the detection of verbal associative memory disorders in patients with MCI.MethodWe recruited 30 patients with MCI according to Petersen’s criteria (2010) and 20 healthy controls matched by age, sex and educational level. All participants completed the LAS‐FNAME, which consists of 12 learning trials of novel pairs of face‐names (immediate learning), followed by a delayed recall condition, and a neuropsychological assessment that included: Montreal Cognitive Assessment (MoCA), Craft Story 21, Multifactorial Memory Questionnaire (MMQ‐S) and a Functional Activity Questionnaire (FAQ).ResultThe groups did not differ in age, sex or education (p = 0.25, p = 0.54, p = 0.54). The age range was 61 to 86 years (M = 74.66; SD = 6.65) and the education range was 7 to 18 years (M = 14.63; SD = 3.41). The LAS‐FNAME showed an ability to discriminate against healthy controls from patients with MCI, both in its immediate (AUC = 0.81) and delayed (AUC = 0.79) conditions. The predictive ability was superior than a screening measure (MoCA, AUC = 0.74). The sensitivity and specificity was 68.4% and 89.3%, respectively. The LAS‐FNAME also showed evidence of concurrent validity with a standard memory test (Craft Story 21) in both immediate (r = 0.52, p&lt;0.01) and delayed (r = 0.63, p&lt;0.01) conditions, and reliability was excellent (α = 0.91).ConclusionPerformance on the LAS‐FNAME was able to distinguish MCI patients from healthy controls, suggesting that the LAS‐FNAME can detect early cognitive changes in prodromal stages of Alzheimer’s disease in Spanish‐speaking individuals.