Logical Memory Test 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.

Post-stroke fatigue severity is associated with executive dysfunction in chronic stroke

ABSTRACT Following stroke, fatigue is highly prevalent and managing fatigue is consistently rated a key unmet need by stroke survivors and professionals. Domain-specific cognitive impairments have been associated with greater fatigue severity in earlier stages of stroke recovery, but it is unclear whether these associations hold in chronic (>2 years) stroke. The present cross-sectional observational study evaluates the relationship between domain-specific cognitive functioning and the severity of self-reported fatigue among chronic stroke survivors. Participants (N = 105; mean age = 72.92, 41.90% female; mean years post-stroke = 4.57) were assessed in domains of attention (Hearts Cancellation test), language (Boston Naming Test), episodic memory (Logical Memory Test), working memory (Digit Span Backwards task), and executive functioning (set-shifting: Trail Making Test, Part B), as part of the OX-CHRONIC study, a longitudinal stroke cohort. Fatigue was assessed using the Fatigue Severity Scale. In a multiple linear regression analysis inclusive of above cognitive domains, only poorer executive functioning was associated with increased fatigue severity. This provides insight into the cognitive impairment profile of post-stroke fatigue long-term after stroke, with executive functioning deficits as the key hallmark.

Voice biomarkers in middle and later adulthood as predictors of cognitive changes.

Prosody voice measures, especially jitter and shimmer, have been associated with cognitive impairment and hold potential as early indicators of risk for cognitive decline. Prior research suggests that voice measures assessed concurrently with longitudinal cognitive outcomes are associated with 10-year cognitive declines in middle-age and older adults from Midlife in the U.S. (MIDUS) study. Using a subsample from the same study, we expanded previous research to examine voice measures that were (1) collected 8 years before cognitive outcomes, (2) derived from narrative speech in logical memory tests instead of word list recall tests, and (3) independent of the cognitive outcomes. Multilevel analyses controlled for covariates of age, sex, education, neurological conditions, depressive symptoms, and chronic conditions. The results indicated that higher jitter and lower shimmer predicted greater 10-year declines in episodic memory and working memory. These findings extend previous research by highlighting prosody voice measures assessed 8 years earlier as predictors of subsequent cognitive declines over a decade.

Story recall performance and AT classification via positron emission tomography: A comparison of logical memory and Craft Story 21

BackgroundEarly detection of Alzheimer's disease (AD) is one of the critical components of the global response to the growing dementia crisis. Analysis of serial position performance in story recall tests has yielded sensitive metrics for the prediction of AD at low cost. In this study, we examined whether serial position markers in two story recall tests (the logical memory test, LMT, and the Craft Story 21 test, CST) were sensitive to cross-sectional biomarker-based assessment of in vivo neuropathology. MethodsParticipants were selected from the Wisconsin Registry of Alzheimer's Prevention (n = 288; WRAP) and the Alzheimer's Disease Research Center (n = 156; ADRC), both from the University of Wisconsin–Madison. Average age at PET was 68.9 (6.7) and 67.0 (8.0), respectively. Data included tau and PiB PET, and LMT for WRAP participants and CST for ADRC participants. Two sets of Bayesian analyses (logistic regressions and ANCOVAs) were conducted within each cohort, separately. ResultsResults indicated that the A+T+ classification was best predicted, cross-sectionally, by the recency ratio (Rr), indexing how much of the end of the story was forgotten between initial learning and delayed assessment. Rr outperformed traditional scores and discriminated between A+T+ and A+T−/A-T-, in both cohorts. ConclusionsOverall, this study confirms that serial position analysis of LMT and CST data, and particularly Rr as an index of recency loss, is a valuable tool for the identification of in vivo tau pathology in individuals free of dementia. Diagnostic considerations are discussed.

Association between oral health and cognitive impairment in older adults: Insights from a Six-year prospective cohort study

ObjectiveThis study aims to investigate the relationships between four baseline oral conditions (periodontal status, dental caries, tooth wear, and dentition) and repeated global cognition or domain-specific cognition (memory, executive function, attention, and verbal fluency) in non-demented older adults over time. MethodsThis prospective cohort study (2011–2019) enrolled 516 non-demented community-dwelling older adults (age ≥ 65) to explore the association between oral health and cognitive function. Global and domain-specific cognition were assessed biennially (four repeats) using a battery of neuropsychological tests. The baseline oral health conditions were examined, including periodontal status, dental caries, tooth wear, and dentition. The association of these oral conditions with cognition was evaluated by generalized linear mixed models. Stratified analyses were performed by important covariates. ResultsOver time, dental caries was associated with poor memory in two different logical memory tests (β^= -0.06 and β^= -0.04). Incomplete dentition with less than 28 teeth was associated with poor performance in attention (β^= -0.05) and verbal fluency (β^= -0.03). These associations became more evident in those with an elevated inflammatory marker (IL-6, β^= -0.11 to -0.08). In contrast, tooth wear was associated with better memory in two different logical memory tests (β^= 0.33 and β^= 0.36) and better executive function (β^= 0.06) over time, and this association became more evident in those with the lowest inflammatory marker (IL-6, β^= 0.10). ConclusionsDental caries and incomplete dentition were associated with poor memory, attention, and verbal fluency performance. Conversely, tooth wear was associated with better memory performance and executive function. Clinical SignificanceFor early prevention of dementia, an evaluation of multiple dental and periodontal status in older adults helps predict the risk of dementia in the preclinical phase. Maintaining intact tooth structure without caries progression and eventually tooth loss may help prevent the worsening of memory, attention, and verbal fluency over time.

Transcranial direct current stimulation-efficacy in mild cognitive impairment: A meta-analysis.

Mild cognitive impairment (MCI) is a transition state in which individuals have cognitive abilities that are in between those of normal aging and dementia. Although not everyone with MCI develops dementia, the risk of progression to dementia is higher in people with MCI. Interventions at this stage can prevent or delay the onset of dementia. In recent years, studies on non-invasive brain stimulation techniques, namely transcranial direct current stimulation (tDCS), have gained momentum for cognitive enhancement in MCI. Since there are very few studies that also report varied results, it becomes important to analyze the effect of tDCS in MCI. The aim of this study was to systematically review the available evidence about using tDCS for MCI and to assess its efficacy using meta-analysis. Eight single- or double-blinded randomized controlled trials were included in the study. Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) for global cognition; and digit span test forward and backward, trail-making test (TMT) A and B; and logical memory test (LMT) assessing specific cognitive domains were considered. A random-effects model was used wherein the standardized mean difference (SMD) and its 95% confidence intervals were reported. The effect of the active tDCS (MoCA [SMD 0.37, 95% CI -0.22-0.95], MMSE [SMD 0.26, 95% CI 0.25-0.77], TMT-A [SMD -0.01, 95% CI -0.42-0.40], and LMT [SMD 0.80, 95% CI -0.24-1.83]) when compared with the sham tDCS was statistically insignificant. The current meta-analysis identified insignificant improvement in cognitive performance with active tDCS treatment as compared to sham tDCS among people with MCI.

Influence of TMX2-CTNND1 polymorphism on cortical thickness in schizophrenia patients and unaffected siblings: an exploratory study based on target region sequencing.

The advancement of neuroimaging and genetic research has revealed the presence of morphological abnormalities and numerous risk genes, along with their associations. We aimed to estimate magnetic resonance imaging-derived cortical thickness across multiple brain regions. The cortical thickness of 129 schizophrenia patients, 42 of their unaffected siblings, and 112 healthy controls was measured and the candidate genes were sequenced. Comparisons were made of cortical thickness (including 68 regions of the Desikan-Killiany Atlas) and genetic variants (in 108 risk genes for schizophrenia) among the three groups, and correlation analyses were performed regarding cortical thickness, clinical symptoms, cognitive tests (such as the N-back task and the logical memory test), and genetic variants. Schizophrenia patients had significantly thinner bilateral frontal, temporal, and parietal gyri than healthy controls and unaffected siblings. Association analyses in target genes showed that four single nucleotide variants (SNVs) were significantly associated with schizophrenia, including thioredoxin-related transmembrane protein 2-catenin, cadherin-associated protein, delta 1 (SNV20673) (positive false discovery rate [PFDR] = 0.008) and centromere protein M (rs35542507, rs41277477, rs73165153) (PFDR = 0.030). Additionally, cortical thickness in the right pars triangularis was lower in carriers of the SNV20673 variant than in non-carriers (PFDR = 0.048). Finally, a positive correlation was found between right pars triangularis cortical thickness and logical memory in schizophrenia patients (r = 0.199, p = 0.032). This study identified regional morphological abnormalities in schizophrenia, including the right homologue of Broca's area, which was associated with a risk variant that affected delta-1 catenin and logical memory. These findings suggest a potential association between candidate gene loci, cortical thickness, and schizophrenia.

Relationships of Physical Activity and Type 2 Diabetes With Cognition in Mexican Americans and Non-Hispanic Whites.

Problem, Research Strategy, and Findings: Low physical activity (PA) and Type 2 diabetes are associated with cognitive aging and Alzheimer's disease, but the evidence is inconsistent and particularly limited by ethnicity. The purpose of this study was to examine the relationships of PA and Type 2 diabetes with cognition in Mexican Americans and non-Hispanic Whites. The study was a cross-sectional analysis of the Health and Aging Brain Study-Health Disparities (n = 1,982-2,000 after removing outliers). Predictors included Rapid Assessment of Physical Activity and hemoglobin A1c (HbA1c). Episodic memory was assessed by Weschler Memory Scale-Third Edition Logical Memory and Spanish-English Verbal Learning Test, executive function by Weschler Memory Scale-Third Edition Digit Span and Digit Symbol Substitution Test, verbal fluency by FAS and animal naming,and global cognition by the Mini-Mental State Examination. Results show that aerobic PA and HbA1c were not associated with domain-specific, or global cognition, but strength/flexibility PA was associated with FAS (b = 0.404, 95% CI [0.023, 0.761]). Higher aerobic PA was associated with greater verbal fluency for Mexican Americans (b = 0.294, 95% CI [0.96, 0.497]) only. HbA1c was negatively associated with Mini-Mental State Examination (b = 0.838, 95% CI [0.008, 1.656]). For low HbA1c, the association between aerobic PA and Digit Symbol Substitution Test was significant for non-Hispanic Whites (b = 0.838, 95% CI [0.008, 1.656]) in comparison to Mexican Americans. Takeaway for Practice: The relationships between PA, Type 2 diabetes, and cognition vary by cognitive domains and ethnicity. Increasing aerobic activities may be particularly important for Mexican Americans who have elevated HbA1c to potentially improve fluency or executive function.

Executive function performance depends on hypertension in individuals with sub‐threshold total Hachinski score

AbstractBackgroundThe Hachinski Ischemia Scale (HIS) differentiates AD and vascular dementia and is used to include individuals with minimal vascular risk factors in ADNI i.e., HIS ≤ 4. HIS score includes history of hypertension (HMHYPERT), a known risk for mild cognitive impairment (MCI) and vascular dementia. Cerebrovascular disease affects performance on tasks involving executive function, such as, planning and processing speed more than memory. Here, we determined if HMHYPERT scores influences executive functioning in all ADNI3 participants with normal cognition (CN) and MCI even with minimal vascular risks.MethodWe included a total of 272 participants (102 MCI, age = 74± 8 [42F, 50 HMHYPERT>0], MoCA = 23 ±3 and 170 CN, age = 73 ±6, [109F, 62 HMHYPERT>0], MoCA = 26 ±3), who underwent HIS, Trails Making Test B, Clock Drawing and Copy scores for executive function, and The Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LOGMEM) scores for memory performance within 12 months. We converted both memory tests into z‐scores and created a composite memory score. Similarly, we created a composite executive function score. To determine if HMHYPERT was associated particularly with executive function, we ran the linear regression analyses twice for the two composite cognitive scores. The following model was used: Composite score ∼ Normalized Age + Sex + Cognitive status * HMHYPERT.Result Executive function: Fig. 1 A shows scores for Trails B, Clock Draw and Clock Copy. The regression analysis showed that executive function was associated with only sex and HYMHYPERT (p<0.05).Memory function Fig. 1 B shows scores for Logical Memory and RAVLT tests in CN and MCI. As expected, MCI groups demonstrate the lowest averages compared to CN groups. As expected, regression analysis showed that memory performance was strongly determined by diagnostic status (p<0.001). Age was significantly associated with memory performance (p<0.05). HMHYPERT was only marginally significantly associated with memory performance (p = 0.08).ConclusionUsing HMHYPERT score as a measure of vascular risk, we observed notable differences in executive function. Although HIS scores ≤ 4 minimize vascular pathology in ADNI3, cognitive performance is still associated with these scores.

Efficacy of transcranial direct current stimulation in mild cognitive impairment – a meta‐analysis

AbstractBackgroundMCI or Mild Cognitive Impairment is a state of cognitive decline which is in between that of normal ageing and dementia. People with MCI have a higher chance of progressing to dementia because of which introducing interventions at this stage becomes increasingly important. Transcranial Direct Current Stimulation (tDCS) is one non‐invasive brain stimulation technique that is considered as an effective intervention strategy for people with MCI to prevent their progression to dementia.MethodFrom 221 and 686 results obtained from PubMed and Google Scholar respectively using the search term ‘(“tDCS”) AND (“MCI”) AND (Randomized) AND (sham controlled)’, 8 studies were included for the current meta‐analysis. Among these studies, the most commonly used cognitive tests namely MMSE (Mini Mental State Examination), MoCA (Montreal Cognitive Assessment), TMT (Trail Making Test) A and B, DST (Digit Span Test) forward and backward and Logical Memory Test were considered for the analysis. The standard mean difference between active and sham treatments in different tests were computed.ResultThe standard mean difference and the 95% confidence interval for the test scores are MoCA: 0.37 (‐0.22,0.95), MMSE: 0.26 (‐0.25, 0.77), TMT A: ‐0.01 (‐0.42, 0.40), TMT B: 0.07 (‐0.41, 0.55), DST F: ‐0.09 (‐0.44, 0.25), DST B: ‐0.11 (‐0.54, 0.31) and Logical memory test: 0.80 (‐0.24, 1.83). It is found that there is an improvement in the performance in MoCA, MMSE, TMT A and logical memory test after treatment with active tDCS but the improvement is statistically insignificant.ConclusionAlthough there is an evident clinical effectiveness, the study identified no significant improvement in cognitive performance with active tDCS in comparison with sham tDCS. This might be due to difference in protocols followed among studies, lower duration of stimulation in a few studies and smaller sample size in each.

Predicting progression to Alzheimer’s disease dementia using cognitive measures: findings from the Essex Memory Clinic

AbstractBackgroundTimely diagnosis of Alzheimer’s disease (AD) is important for patients, carers and healthcare systems. It is therefore imperative to identify measures with the greatest power to predict future AD dementia. In contrast to research settings, expensive biomarkers are not always available in memory clinics. It is therefore vital to identify predictive measures which can be used in ordinary clinical settings.MethodThis study utilized clinical assessment data from 328 patients assessed in the Essex Memory Clinic between 2002 and 2019. Only patients with a diagnosis of subjective cognitive decline (SCD) or mild cognitive impairment (MCI) at baseline and a minimum of two follow‐up visits were included in analyses. Lasso logistic regression (using AD at visit 3 as the outcome) and Lasso Cox proportional hazards models (using time to AD at visit 3 and beyond as outcome) were fitted in two stages. The first stage included baseline cognitive scores only, while the second stage also included change scores for these measures (derived by subtracting scores at baseline from those at the first follow‐up visit).ResultIn the first stage models, lower Mini‐Mental State Examination (MMSE) and Logical Memory Test (LMT) delayed recall scores, and longer Trail‐Making Test part A (TMT‐A) time were associated with greater odds (logistic regression) and hazards (Cox proportional hazards) of progression to AD. In addition, in the Cox model (only), lower baseline Cambridge Cognitive Examination‐Revised (CAMCOG‐R) score was associated with greater hazard of AD. In the second stage models, worsening CAMCOG‐R and LMT (delayed recall) scores were independently associated with both the odds/hazards of AD.ConclusionIn this memory clinic cohort, the cognitive scores most predictive of progression to AD were the delayed LMT, TMT‐A, CAMCOG‐R and MMSE. These results are in‐keeping with earlier work conducted in research cohorts. The inclusion of cognitive change scores over one year follow‐up improved predictive accuracy versus baseline scores alone.

Optimising speech‐testing to predict prodromal Alzheimer’s disease: head‐to‐head comparison study of tasks and analysis methods

AbstractBackgroundChanges in speech occur in early‐stage Alzheimer’s disease. A range of approaches have been used for eliciting and automatically analysing speech, but limited research has directly compared these methods.MethodParticipants from the AMYPRED‐UK (NCT04828122) and AMYPRED‐US (NCT04928976) studies completed four speech‐elicitation tasks: the Automatic Story Recall Task (ASRT), the Logical Memory Test (LMT), Semantic (Animals, Vegetables, Fruit) and Phonemic Verbal Fluency (F, A, S) Tasks. Responses were recorded and automatically transcribed. Analyses were completed with Novoic’s speech analysis software, using four key approaches: (1) feature extraction, (2) representations from large language models (LLM), (3) text‐similarity evaluation, and (4) autoscoring. Together, these evaluated audio, linguistic, and temporal speech domains. Outputs were entered into logistic regression models predicting Mild Cognitive Impairment (MCI)/mild AD and Amyloid positivity in MCI/mild AD. Area under the ROC curves (AUC) were evaluated via 5‐fold cross‐validation.Result165 older adults (including N = 74 MCI and 9 mild AD; of which N = 38 MCI/mild AD and amyloid beta positive) provided data for all tasks. Strength of model predictions varied by task, analytic approach and domain (Fig 1). AUCs predicting MCI/mild AD were generally higher for ASRTs compared to other tasks (Fig 1A). Text‐similarity approaches (G‐match: similarity of word embeddings between the source text and retelling, and V‐match: string‐based matching), produced the highest AUC for ASRTs (G‐match AUC = 0.87‐0.88), and the LMT (V‐match AUC = 0.83‐85). Autoscoring tasks produced the strongest predictor for the semantic fluency (AUC = 0.85), and also one of the strongest for phonemic fluency (AUC = 0.72). Changes in linguistic and temporal characteristics were more sensitive to MCI/mild AD, compared to audio‐only metrics. Amyloid in MCI/mild AD predictions were overall less strong (Fig 1B), with the most consistent pattern being better performance of text‐similarity approaches on story recall tasks (up to AUC = 0.77 for ASRTs, 0.73 for LMT).ConclusionSelection of task and analytic approach is important for developing more sensitive speech‐based testing. The best performing tasks (ASRT, Semantic Fluency) and metrics (text‐similarity metrics and autoscoring) have been incorporated in Novoic’s Storyteller automated remote speech‐based test.

Optimising speech‐testing to predict prodromal Alzheimer’s disease: head‐to‐head comparison study of tasks and analysis methods

AbstractBackgroundChanges in speech occur in early‐stage Alzheimer’s disease. A range of approaches have been used for eliciting and automatically analysing speech, but limited research has directly compared these methods.MethodParticipants from the AMYPRED‐UK (NCT04828122) and AMYPRED‐US (NCT04928976) studies completed four speech‐elicitation tasks: the Automatic Story Recall Task (ASRT), the Logical Memory Test (LMT), Semantic (Animals, Vegetables, Fruit) and Phonemic Verbal Fluency (F, A, S) Tasks. Responses were recorded and automatically transcribed. Analyses were completed with Novoic’s speech analysis software, using four key approaches: (1) feature extraction, (2) representations from large language models (LLM), (3) text‐similarity evaluation, and (4) autoscoring. Together, these evaluated audio, linguistic, and temporal speech domains. Outputs were entered into logistic regression models predicting Mild Cognitive Impairment (MCI)/mild AD and Amyloid positivity in MCI/mild AD. Area under the ROC curves (AUC) were evaluated via 5‐fold cross‐validation.Result165 older adults (including N = 74 MCI and 9 mild AD; of which N = 38 MCI/mild AD and amyloid beta positive) provided data for all tasks. Strength of model predictions varied by task, analytic approach and domain (Fig 1). AUCs predicting MCI/mild AD were generally higher for ASRTs compared to other tasks (Fig 1A). Text‐similarity approaches (G‐match: similarity of word embeddings between the source text and retelling, and V‐match: string‐based matching), produced the highest AUC for ASRTs (G‐match AUC = 0.87‐0.88), and the LMT (V‐match AUC = 0.83‐85). Autoscoring tasks produced the strongest predictor for the semantic fluency (AUC = 0.85), and also one of the strongest for phonemic fluency (AUC = 0.72). Changes in linguistic and temporal characteristics were more sensitive to MCI/mild AD, compared to audio‐only metrics. Amyloid in MCI/mild AD predictions were overall less strong (Fig 1B), with the most consistent pattern being better performance of text‐similarity approaches on story recall tasks (up to AUC = 0.77 for ASRTs, 0.73 for LMT).ConclusionSelection of task and analytic approach is important for developing more sensitive speech‐based testing. The best performing tasks (ASRT, Semantic Fluency) and metrics (text‐similarity metrics and autoscoring) have been incorporated in Novoic’s Storyteller automated remote speech‐based test.

Cerebrovascular disease is associated with memory function in the Health and Aging in Africa Longitudinal Study of an INDEPTH community in rural South Africa

AbstractBackgroundHealth and Aging in Africa Longitudinal Study of an INDEPTH community in South Africa (HAALSI) is a sister study to the US‐based Health and Retirement Study. The purpose of HAALSI is to characterize the social, economic, biological, physical, and mental health factors in a population‐representative cohort of older adults in a rural community in Agincourt, South Africa. Beginning in 2020, as part of an Alzheimer’s disease and related disorders (ADRD) substudy, we conducted neuropsychological evaluations and structural magnetic resonance imaging (MRI) in a subset of HAALSI participants. Here, we report preliminary observations on the relationship of white matter hyperintensity (WMH) volume, a marker of small vessel cerebrovascular disease, and hippocampal volume, a marker of neurodegeneration, on memory function in a group of substudy participants.MethodNinety‐nine HAALSI ADRD participants with available MRI scans and neuropsychological outcomes at time of analysis (mean ± SD; age = 70.3 ± 10.9, 87% with no formal education or some primary education) were included in these analyses. Participants received research‐grade, harmonized 1.5T MRI scanning at a private hospital and were evaluated with a battery of neuropsychological tests. Using in‐house developed software and FreeSurfer, respectively, we derived total WMH volume and total hippocampal volume. We examined the association of these variables with memory function, operationalized as the delayed recall score of the Logical Memory Test, adapted for context.ResultAdjusting for education level, increased WMH volume was associated with poorer performance on the Logical Memory Test (standardized β = ‐0.21, p<0.05) but hippocampal volume was not (standardized β = 0.09, p = 0.41). Associations of these MRI markers with memory function did not interact with education level.ConclusionIn these preliminary analyses of older adults in a rural South African community, markers of small vessel cerebrovascular disease but not neurodegeneration are associated with poorer cognitive outcomes. Future work will examine the pathways that give rise to cognitive impairment and dementia in this rural South African population and track cognitive trajectories over time.

A comparison of word‐list and story recall tests for prediction of biomarker‐determined Alzheimer’s disease

AbstractBackgroundWord‐list and story recall tests are routinely employed in clinical practice for dementia screening. Previous research has shown that both types of tests are predictive of subsequent clinical diagnoses of dementia, including when examining process scores such as forgetting rate. In this study, our aim was to establish how well standard clinical metrics compared to process scores derived from word‐list and story recall tests in predicting biomarker‐determined Alzheimer’s disease (bdAD), as defined by CSF p‐tau/Abeta42 ratio.MethodData from 381 participants (mean age = 65, ± 9) were drawn from the University of Wisconsin – Madison Alzheimer’s Disease Research Center (ADRC) and Wisconsin Registry for Alzheimer’s Prevention (WRAP). Rey’s Auditory Verbal Learning Test (AVLT; word‐list) and Logical Memory Test (LMT; story) data were available. The conventional clinical scores examined were: AVLT total recall, AVLT delayed recall, LMT immediate recall, and LMT delayed recall. The process scores examined were: AVLT recency ratio (i.e., recency forgetting), AVLT total forgetting, LMT recency ratio, LMT total forgetting, and LMT primacy ratio (i.e., primacy forgetting). Bayesian linear regression analyses were carried out with either the nearest or farthest CSF p‐tau/Abeta42 ratio as outcome; the standard and process baseline memory scores as predictors; and baseline age, time elapsed from baseline to lumbar puncture, APOE risk score, sex, and years of education as control variables. Sensitivity analyses were carried out with logistic regressions using a cut‐off of 0.038 CSF p‐tau/Abeta42 ratio as outcome, to assess diagnosticity. CSF biomarkers were measured using the NeuroToolKit (Roche Diagnostics International Ltd, Rotkreuz, Switzerland).ResultLMT recency ratio and LMT primacy ratio were the best performing predictors (BF10 > 1 billion) both when evaluating the nearest (Figure 1a) and the farthest (Figure 1b) outcomes. However, sensitivity analyses with a binary cut‐off favored the primacy ratio. Areas under the curve (AUCs) ranged from 0.86 to 0.87 (including covariates). Specificity was consistently high for primacy ratio with 94% probability of correctly identifying individuals without bdAD.ConclusionOur study shows that story recall tests may be better than word‐list tests for dementia screening, especially when employing process scores alongside conventional clinical scores.

A comparative study of medication profiles from AD, MCI, and non‐demented patients

AbstractBackgroundThe ever‐increasing incidence of Alzheimer’s disease (AD) and the lack of effective therapeutics to treat the disease are leading to a “silver tsunami”. Current FDA‐approved drugs to treat the disease are limited as their benefit is simply momentary relief of the symptoms. Due to the chronic and progressive nature of AD, patients are routinely prescribed multiple non‐AD medications to preserve their ability to perform daily activities and to improve their quality of life. However, how those medications affect AD pathology remains unknown. In the present study, we have compared medication profiles of AD (n = 135), mild cognitive declined (MCI; n = 120), and non‐demented (n = 259) patients, with an aim to determine the effects of top‐ranked drugs on AD pathology.MethodsStudy subjects (≥65 years) were recruited from an academic geriatric practice that is heavily focused on memory disorders. All subjects underwent for the following cognitive assessments: a) Clinical dementia rating scale (CDR), b) Mini‐Mental Status Examination (MMSE), c) logical memory test, d) digit span forward and backward, e) category fluency test, f) ordering test, g) trails A&B, and finally the Geriatric Depression Scale. Individual medication for each subject was listed and they were categorized into major drug classes. Statistical analysis was performed to determine the frequency of each drug in each class.ResultsEight top‐ranked drug classes were categorized from a list of 453 individual medications. Vitamins (30‐40%) and anti‐inflammatory (∼30%) drugs were the major categories for each cohort. Interestingly, 11% of drugs were proton pump inhibitors in non‐demented patients, and this decreased by 8% in MCI, and 5% in AD. We found a reduced (8%) Lipitor prescriptions for AD patients compared MCI (11%) and non‐demented (13%) patients. We are investigating the effects of these highly prescribed drugs on β‐amyloid production/aggregation, cytotoxicity, plaque load, and tau phosphorylation in vitro and in vivo using cell culture and AD mouse models.ConclusionWhile the effects of routinely prescribed drugs on AD pathology are not well known, we found reduced vitamins, proton pump inhibitors, and Lipitor in the medication profiles of AD patients compared to the non‐AD population.

3 Towards Detecting a Pre-clinical Signature of Dementia: Accelerated Forgetting in Healthy Older Samples -Implications for Methodology, Future Ageing Studies and Early Identification of Dementia

Objective:Accelerated long-term forgetting (ALF) has been reported in healthy older individuals, and is a possible early marker for risk of developing Alzheimer’s disease (AD). The Verbal Associative Learning & Memory Test (VALMT; McGibbon & Jansari, 2013) addresses methodological weaknesses in existing clinical tests and has detected ALF in epilepsy within an hour. We used VALMT to investigate learning and forgetting in healthy older participants.Participants and Methods:Older (60-69yrs) and Younger (19-31yrs) participants were compared. Using VALMT, unrelated word-pairs were learned to criterion, then cued-recall was tested at delays of 5, 30 and 55 minutes. Unique pairs were tested at each delay. Subjective memory complaints data were gathered, and the Wechsler Memory Scale Logical Memory test (WMS-LM; a standard clinical measure) was administered.Results:VALMT identified a significant difference in delayed recall between Younger and Older groups by 55 minutes (d = 1.32). While 'fast-learning’ Older participants scored similarly to Younger participants, 'slow-learning’ Older participants were impaired at all delays. Forgetting rates suggested degradation of memory starts during early synaptic consolidation rather than later system-level consolidation. Increased subjective memory complaints were associated with reduced VALMT scores. By contrast, WMS-LM failed to identify significant differences between any groups, and did not correlate with memory complaints.Conclusions:We conclude VALMT may be better able than WMS-LM to identify subtle impairments in healthy older adults within a single clinical visit, and VALMT results better reflect subjective experience. Older slow-learners forget faster and report more subjective memory complaints, which may indicate a group at risk of developing AD.

52 Open Access, Normative Morphometric Software Indicate Neurodegeneration Associated with Episodic Memory Dysfunction in Amnestic MCI

Objective:Neurodegeneration in Alzheimer’s disease (AD) is typically assessed through brain MRI, and proprietary software can provide normative quantification of regional atrophy. However, proprietary software can be cost-prohibitive for research settings. Thus, we used the freely available software NOrmative Morphometry Image Statistics (NOMIS) which generates normative z-scores of segmented T1-weighted images from FreeSurfer to determine if these scores replicate established patterns of neurodegeneration in the context of amnestic mild cognitive impairment (aMCI), and whether these measures correlate with episodic memory test performance.Participants and Methods:Patients with aMCI (n = 25) and cognitively normal controls (CN; n = 74) completed brain MRI and two neuropsychological tests of episodic memory (the Rey Auditory Verbal Learning Test and the Wechsler Logical Memory Tests I & II), from which a single composite of normed scores was computed. A subset returned for follow-up (aMCI n = 11, CN n = 52) after ∼15 months and completed the same procedures. T1-weighted images were segmented using FreeSurfer v6.0 and the outputs were submitted to NOMIS to generate normative morphometric estimates for AD-relevant regions (i.e., hippocampus, parahippocampus, entorhinal cortex, amygdala) and control regions (i.e., cuneus, lingual gyrus, pericalcarine gyrus), controlling for age, sex, head size, scanner manufacturer, and field strength. Baseline data were used to test for differences in ROI volumes and memory between groups and to assess the within-group associations between ROI volumes and memory performance. We also evaluated changes in ROI volumes and memory over the follow-up interval by testing the main effects of time, group, and the group X time interactions. Lastly, we tested whether change in volume was associated with declines in memory.Results:At baseline, the aMCI group performed 2 SD below the CN group on episodic memory and exhibited smaller volumes in all AD-relevant regions (volumes 0.4 - 1.2 SD below CN group, ps < .041). There were no group differences in control region volumes. Memory performance was associated with volumes of the AD-relevant regions in the aMCI group (average rho = .51) but not with control regions. ROI volumes were not associated with memory in the CN group. At follow-up, the aMCI group continued to perform 2 SD below the CN group on episodic memory tests; however, change of performance over time did not differ between groups. The aMCI group continued to exhibit smaller volumes in all AD-relevant regions than the CN group, with greater declines in hippocampal volume (17% annual decline vs. 8% annual decline) and entorhinal volume (54% annual decline vs. 5% annual decline). There was a trending Group X Time interaction such that decrease in hippocampal volume was marginally associated with decline in memory for the aMCI group but not the CN group.Conclusions:Normative morphometric values generated from freely available software demonstrated expected patterns of group differences in AD-related volumes and associations with memory. Significant effects were localized to AD-relevant brain regions and only occurred in the aMCI group. These findings support the validity of these free tools as reliable and cost-effective alternatives to proprietary software.

SAT406 Evaluation Of The Emotional And Cognitive Effects Of Hormone Therapy In Transgender Men And Women

Abstract Disclosure: I. Yaish: None. G. Keltch: None. Y. Greenman: None. K.M. Tordjman: None. Background:- Sex hormones have far-reaching effects on the brain, both emotionally and cognitively. - Varying levels of sex hormones are associated with altered emotional states and cognitive abilities. -No longitudinal study has assessed the impact of cross-sex hormone on these issues in young transgender people. Aim:•To prospectively evaluate the effect of gender-affirming hormonal therapy (GAHT) on cognition and emotional state in transgender men and women initiating therapy Subjects and Methods:- Transgender men (TM) aged 24.6±7.8 y (18-37), and 11 transgender women (TW) 27.3±9.4 (19-46).- Mood questionnaires (PHQ9 and GAD-7), and cognitive tests (short-term logical memory test, sub-tests of knowledge, forward and backward digit recall, number-coding and random learning from WAIS-III, a verbal fluency test and CTMT test) were administered prior to GAHT, and 3-6 months into treatment. - Scores were calculated for emotional stress, memory, attention, and executive functions. - Wilcoxon tests for paired samples assessed the impact of GAHT on these variables. Results - In TM, GAHT significantly improved executive functions but had no effect on memory, attention, and emotional stress. - In TW, GAHT significantly improved memory but had no effect on attention, executive functions, and emotional stress. - Despite a trend for improved emotional stress with GAHT in both groups, over this short study period, this was not significant. Conclusions:- - In keeping with the literature, this short preliminary study showed that estrogen contributes to memory, and testosterone to executive functions.-- This is the first time this has been shown in transgender individuals. -The lack of effect on emotional stress is probably due to the small sample size and short duration, larger studies should elucidate this point. Presentation: Saturday, June 17, 2023

Effects of a 10-week musical instrument training on cognitive function in healthy older adults: implications for desirable tests and period of training.

Previous studies have shown that musical instrument training programs of 16 or more weeks improve verbal memory (Logical Memory Test delayed recall), processing speed (Digit Symbol Coding Test), and executive function (Trail Making Test Part B) of musically untrained healthy older adults. However, it is unclear whether shorter-period instrument training can yield similar effects. We sought to (1) verify those results and (2) clarify if intervention effects could be detected using other measures such as reaction time. Healthy older adults (mean age = 73.28 years) were pseudo-randomly assigned to an untrained control group (n = 30) or an intervention group (n = 30) that received a weekly 10-session musical instrument training program (using melodica). We conducted neuropsychological tests on which intervention effects or association with musical training were reported in previous studies. We newly included two reaction time tasks to assess verbal working memory (Sternberg task) and rhythm entrainment (timing task). Intervention effects were determined using a "group × time" analysis of variance (ANOVA). The intervention effects were detected on the reaction time in Sternberg task and phonological verbal fluency. Although intervention effects had been reported on Logical Memory test, Digit Symbol Coding Test and Trail Making Test in previous studies with longer training periods, the present study did not show such effects. Instead, the test-retest practice effect, indicated by significant improvement in the control group, was significant on these tests. The present results indicated the usefulness of working memory assessments (Verbal Fluency Test and Sternberg task) in detecting the effects of short-term melodica training in healthy older adults. The practice effect detected on those three tasks may be due to the shorter interval between pre- and post-intervention assessments and may have obscured intervention effects. Additionally, the findings suggested the requirement for an extended interval between pre- and post-tests to capture rigorous intervention effects, although this should be justified by a manipulation of training period.