State Examination Research Articles

Memory problems in elderly people with traumatic brain injury

AbstractThe aim of this study is to assess the effectiveness of various therapy methods in elderly individuals with traumatic brain injury (TBI), taking into account the degree of memory loss and the severity of the injury. The study was conducted in 2022 in Moscow, Russia, and Sofia, Bulgaria, involving six clinics. A total of 200 elderly patients with TBI participated in the study, with a mean age of 72 years. Patients were categorized into groups based on the degree of memory loss and severity of the injury. Standardized tests, including the Mini‐Mental State Examination (MMSE), Clock Drawing Test, Digit Symbol Substitution Test, and Free, and Cued Selective Reminding Test, were used to assess cognitive functions. The Progressive Learning Test evaluated patients' ability to memorize and reproduce information over time. Groups receiving physical therapy and cognitive rehabilitation showed statistically significant improvement in cognitive functions compared to other therapy methods. Specifically, the mean score of the MMSE in these groups increased by 7 points (p < .001). Patients with more severe memory loss demonstrated more pronounced improvement in cognitive functions following the integrated therapy approach. The mean MMSE score increased by 10 points (p < .001), whereas in patients with milder memory loss, the growth was less significant (mean increase of 5 points, p < .05). Groups receiving physical therapy and cognitive rehabilitation consistently demonstrated significantly better results compared to speech therapy and psychological support throughout the study period.

Pareto-principle in rare disease education: assessing the representation of common rare diseases in medical education and coding systems

BackgroundThe Pareto Principle asserts that a large portion of results can be achieved with a small amount of effort. Wakap et al. found that around 80% of individuals with rare diseases (RD) suffer from one of 149 specific rare diseases. A significant challenge in the RD domain is the lack of information, compounded by the fact that most RD are not specifically codifiable in the ICD-10, leading to a deficit in reliable epidemiological data. Additionally, time constraints in medical education hinder the comprehensive teaching of all RD, contributing to the diagnostic odyssey problem through failure of recognizing diseases. We identified the most and second most prevalent RD (prevalences of 1–5/10,000 and 1–9/100,000, respectively) from the Orphanet Epidemiology File, totaling 454 diseases. We investigated the feasibility of specific coding using ICD-10-GM and whether these diseases were explicitly listed in the subject catalog (GK) of the second state examination in human medicine in Germany. A two-sided chi-square test was employed to identify statistically significant differences between prevalence groups.ResultsOut of 454 diseases, a total of 34% could be specifically coded in ICD-10-GM, with 49% of diseases in the 1–5/10,000 prevalence range (153 RD) and 26% in the 1–9/100,000 range (301 RD) having specific codes. Approximately 15% of all investigated diseases were part of the GK, with 25% of the most prevalent and 10% of the second most prevalent RD group, respectively. Statistically significant differences were observed between prevalence groups concerning the presence of a specific ICD-10-GM code and inclusion in the GK.ConclusionOnly 49% of the most prevalent RD can be specifically coded, highlighting the challenge of limited epidemiological data on RD. In Germany, the Alpha-ID was introduced in addition to ICD-10 in the inpatient setting to obtain more valid epidemiological data on RD. Recognizing the Pareto Principle’s applicability, the study emphasizes the importance of including the most common rare diseases in medical education. While recognizing the limitations, especially in covering ultra-rare diseases, the study underscores the potential benefits of enhancing medical curricula to improve rare disease awareness and diagnostic accuracy.

Lifetime physical activity influences Parkinson's disease progression

IntroductionPast studies suggested that Parkinson's disease (PD) patients who engage in physical activity (PA) after diagnosis have slower motor progression. Here, we examine the influence of lifetime PA prior to PD onset on motor, cognitive, and overall functional decline among PD patients. MethodsFor 495 participants in the Parkinson's Environment and Gene (PEG) studies, we collected PA-related measures through interviews and quantified these using metabolic equivalents (MET) scores. PD progression was defined as time to a Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) conversion to ≥ 35 points, Hoehn and Yahr (H&Y) ≥ 3, and a 4-point decline in Mini‐Mental State Examination (MMSE). We used Cox frailty models to estimate hazard ratios and inverse probability weights to account for heterogeneity by enrollment wave and censoring. ResultsFor PD patients reporting the highest lifetime strenuous MET-h/wk (highest quartile), we estimated a lower HR for time-to-UPDRS-III-conversion (Q4 vs. Q1: HR = 0.56, 95 % CI = [0.36, 0.87]). Additionally, having engaged in any competitive sport also reduced the risk of reaching a UPDRS-III ≥ 35 points (low vs. none: HR = 0.61, 95 % CI = [0.44, 0.86]; high vs. none: HR = 0.63; 95 % CI = [0.44,0.86]); high levels of sports activities also affected progression on the H&Y scale (high vs. none: HR = 0.73; 95 % CI = [0.46,1.00]). Lifetime PA measures did not affect time-to-MMSE decline. ConclusionOur study suggests that PD patients who engaged in higher levels of lifetime strenuous PA and competitive sports prior to PD diagnosis experience slower motor and overall functional decline, suggesting that lifetime PA may contribute to a physical reserve advantageous for PD patients.

Confronting Medical Diploma Mills: State Licensing Boards, Legislatures, and the Limits of Medical Authority in the 1920s.

In the standard story of the rise of professional authority in medicine in the 1920s, state medical licensing boards were partners in a coalition, led by the American Medical Association, to radically improve medical education. Boards obtained state laws that limited admission to licensing examinations to graduates of schools approved by the AMA, thus bringing about the rapid demise of low-quality schools by about 1925. The reality at the state level was quite different, however. Medical examining boards containing homeopaths, eclectics, and sometimes osteopaths could be far from reliable partners. Passing laws to benefit the medical profession was exceedingly difficult and dependent on local medical politics. Through the lens of a major medical diploma mill scandal revealed by a journalist in 1923, this paper examines reform efforts in three states greatly affected by the scandal: Missouri, where the scandal originated, Connecticut, and Massachusetts. In each of these states, graduates of low-quality schools as well as fake doctors from diploma mills were able to take a state examination and practice. This paper argues that the AMA, far from being the major player in the elimination of inadequate schools, could set standards but had to stay on the sidelines.

Correlations between plasma markers and brain Aβ deposition across the AD continuum: Evidence from SILCODE.

Previous studies have found that Alzheimer's disease (AD)-related plasma markers are associated with amyloid beta (Aβ) deposition, but the change of this association in different Aβ pathological stages remains unclear. Data were obtained from the SILCODE. According to the standardized uptake value ratio (SUVR) and Aβ stage classification, correlation analysis was performed among plasma biomarkers, and voxel/SUVR values in the regions of interest (ROI) and clinical scale information, respectively. Mediation analysis was used to study the possible pathways. The proportion of cognitively normal (CN) and subjective cognitive decline (SCD) was the highest in stages A0 to 1, while in stages A2 to 4, the proportion of mild cognitive impairment (MCI) and AD increased. Plasma phosphorylated tau (p-tau)181 and glial fibrillary acidic protein (GFAP) levels were significantly lower in stage A0 compared to the later phases. Two pathways demonstrated fully mediated effects: positron emission tomography (PET) SUVR-plasma p-tau181-Mini-Mental State Examination (MMSE) and PET SUVR-plasma GFAP-MMSE. This study demonstrated the role of plasma biomarkers in the early stage of AD, especially in SCD, from both the clinical diagnosis and Aβ stage dimensions. Plasma ptau181 and GFAP level serve as indicators of early Alzheimer's disease and the pathologic Aβ staging classification. A possible ceiling effect of GFAP was observed in the mid-to-late stages of the AD course. This study confirms the role of AD plasma markers in promoting Aβ deposition at an early stage, particularly in females with subjective cognitive decline(SCD). The overlapping brain regions of plasma p-tau181, GFAP, and neurofilament light for Aβ deposition in the brain in early AD were distributed across various regions, including the posterior cingulate gyrus, rectus gyrus, and inferior temporal gyrus.

An examination of state and trait urgency in individuals with binge-eating disorder.

Negative urgency (i.e., acting rashly when experiencing negative affect; NU), is a theorised maintenance factor in binge-eating type eating disorders. This study examined the association between trait NU and eating disorder severity, momentary changes in state NU surrounding episodes of binge eating, and the momentary mechanistic link between affect, rash action, and binge-eating risk. Participants were 112 individuals with binge-eating disorder (BED). Baseline measures included the UPPS-P Impulsive Behaviour Scale to assess trait NU and the Eating Disorders Examination to assess binge-eating frequency and global eating disorder severity. Ecological momentary assessment captured real-time data on binge eating, negative affect, and state NU. Multiple regression analysis revealed a strong association between trait NU and eating disorder severity. Generalised estimating equations showed that state NU increased before and decreased after binge-eating episodes, and that this pattern was not moderated by trait-level NU. Finally, a multilevel structural equation model indicated that increases in rash action mediated the momentary relationship between states of high negative affect and episodes of binge eating. These findings underscore the importance of both trait and state NU in binge-eating type eating disorders, and suggest NU as a potential key target for intervention.

The effect of physical therapy with goal attainment scaling on gait function in patients with subacute stroke

Background: Correct goal setting for patients is one of the most important aspects of physical therapy. Objective: The purpose of this study was to investigate the effect of physical therapy using goal attainment scaling (GAS) scores to assess the gait function in patients with subacute stroke and related factors. Methods: This retrospective cohort study was conducted using the medical records of 129 patients with subacute stroke who had been treated with intensive rehabilitation intervention. This study was approved by the Institutional Review Board of Bundang Cha Hospital (2021-06-008). The functional ambulation category (FAC) was used to set goals with the involvement of patients and their caregivers after the initial assessment, and raw GAS scores were calculated according to whether the goals were achieved through assessment one month later based on the FAC score. The groups were then divided according to the raw GAS scores (−1, 0, 1, or 2), and the general characteristics and clinical assessment scores were statistically analysed. Results: From our results, there were differences in clinical assessment scores based on raw scores on the GAS ([Formula: see text]) and correlation between raw scores on the GAS and improvement scores on the clinical assessment items ([Formula: see text]). Moreover, when the gait function measured by FAC was used as a GAS in subacute stroke patients, the better the function of Rivermead mobility index ([Formula: see text], [Formula: see text]) and Korean-mini-mental state examination ([Formula: see text], [Formula: see text]) than the other clinical factors, the higher the goal attainment raw score. Conclusion: Functions, including cognitive function, should be included when setting goals to improve the gait function and should be considered when developing the neurological physiotherapy programmes. This study helps physicians and physical therapists who first apply functional gait assessment as a GAS to set the initial goals and improves patient and caregiver motivations by applying GAS to patients with lower initial cognitive levels.

Validation of the Slovenian version of the Montreal Cognitive Assessment Scale as a screening tool for the detection of mild cognitive impairment

ObjectiveThe Montreal cognitive assessment scale (MoCA) is commonly used for detecting individuals with mild cognitive impairment (MCI). The aim of the present study was to evaluate the validity of the Slovenian MoCA as a screening tool for MCI and to determine the optimal cut-off point to detect MCI in the elderly population.MethodsMini-Mental State Examination (MMSE), MoCA, and neuropsychological testing assessment were conducted on 93 individuals aged ≥ 60 years. MCI was found in 35 individuals with 58 cognitively asymptomatic controls. Cut-off values, sensitivity, and specificity of MoCA were calculated with the receiver operating characteristic curve.ResultsMCI and healthy individuals did not differ with respect to age and education. Healthy individuals (M = 24.5, SD = 1.7) performed significantly better on MoCA compared to MCI individuals (M = 21.4, SD = 3.2) (p < 0.001). The Cronbach’s α of MoCA as an index of internal consistency was 0.64. MoCA distinguished between healthy controls and MCI individuals with a sensitivity of 77% and specificity of 74%, using a cut-off of 23/24 points.ConclusionThe Slovenian version of MoCA demonstrates an optimal cut-off value of 23/24 points for detecting older individuals with MCI. As a screening tool for MCI, its better diagnostic accuracy makes it preferable to using MMSE.

Does This Law Apply to Me? An Examination of States’ Good Samaritan Overdose Laws and a Policy Proposal for a Uniform Approach to Combatting the Opioid Epidemic

Does This Law Apply to Me? An Examination of States’ Good Samaritan Overdose Laws and a Policy Proposal for a Uniform Approach to Combatting the Opioid Epidemic

Facial emotion recognition is associated with executive functions and depression scores, but not staging of dementia, in mild-to-moderate Alzheimer's disease.

Although deficits in facial emotion recognition (FER) significantly affect interpersonal communication and social functioning, there is no consensus on how FER affects Alzheimer's disease (AD). In this study, we aimed to investigate the clinical and neuropsychological factors affecting the possible deficits in the FER abilities of patients with AD. This cross-sectional study included 37 patients with mild [clinical dementia rating (CDR) scale score=1] or moderate (CDR=2) AD, in whom vascular dementia and depression were excluded, and 24 cognitively normal (CDR=0) subjects. FER ability was determined using the facial emotion identification test (FEIT) and facial emotion discrimination test (FEDT). All participants underwent mini-mental state examination (MMSE), frontal assessment battery (FAB), and geriatric depression scale (GDS). The neuropsychiatric inventory-clinician rating scale (NPI-C), Katz index of independence in activities of daily living, and Lawton instrumental activities of daily living were also administered to patients with AD. The FEIT and FEDT total scores showed that patients with mild and moderate AD had significant FER deficits compared to healthy controls. However, no significant difference was observed between patients with mild and moderate AD in the FEIT and FEDT total scores. FEIT and FEDT scores were not correlated with the MMSE and NPI-C total and subscales scores in patients with AD. Linear regression indicated that FEIT and FEDT total scores were significantly related to age and FAB scores. The GDS score negatively moderated the relationship between FAB and FEDT. This study demonstrated a decreased FER ability in patients with AD. The critical point in FER deficits is the presence of dementia, not the dementia stage, in AD. It has been determined that executive functions and depression (even at a subsyndromal level), which have limited knowledge, are associated with FER abilities.

파시즘 시대 이탈리아의 초등학교 역사 교과서와 1차 세계 대전 서술

Mussolini's regime, which aimed to cultivate 'new' Italians to fascistize Italy, had the goal to establish the Fascist interpretation of history as the nation's official historiography through public education. From the early years in power, it therefore tried to control history education at schools and introduced the state's examination and approval of textbooks. However, despite the Central Commission of the Textbook Examination's hard work for years and the frequent change of the examination criteria, most of the textbooks produced under the system failed to satisfy the Fascist regime. What the schoolbooks made the regime particularly disappointed was their view and narrative on the First World War. Thus Mussolini's government finally monopolized the production of textbooks for primary schools all over Italy from 1930 for more direct and concrete teaching of the Fascist view of history. This essay is a study to examine this Fascist state textbook: first, it looks into the regime's ultimate motivation to abandon the textbook exam and approval system and to decide the monopolization, and then it demonstrates what interpretation of history the Fascist regime taught Italian children by comparing and analyzing (how different and why) the narratives on World War I between the 1920s' schoolbooks and the Fascist state textbook, Libro unico di stato.

Microbial Phenolic Metabolites Are Associated with Improved Cognitive Health.

Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk. A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores. These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.

Variations in metabolic risk factors for dementia do not affect APOE‐mediated cognitive or functional decline in patients with Alzheimer’s disease from São Paulo, Brazil

AbstractBackgroundMidlife cerebrovascular risk, low education and copies of APOE‐ε4 are risk factors for Alzheimer’s disease (AD), whereas metabolic derangements have been associated with dementia onset. This prospective study aimed to explore the impacts of variations in metabolic risk factors on progression of AD in São Paulo, Brazil.MethodsOutpatients with late‐onset AD according to National Institute on Aging – Alzheimer’s Association criteria were assessed for APOE haplotypes (rs7412 &amp; rs429358 genotyped by way of TaqMan® Real‐Time Polymerase Chain Reaction technology) and variations in one year of the following potential metabolic predictors: fasting glycemia, TSH, free T4, vitamin B12, and folic acid. Metabolic variations were assessed in accordance with concurrent variations in the Clinical Dementia Rating Sum‐of‐Boxes, the Index of Independence in Activities of Daily Living, Lawton’s Scale for Instrumental Activities of Daily Living, and the Mini‐Mental State Examination in multiple linear regression models for all patients, and after stratification according to APOE‐ε4 carrier status, with the threshold of significance set at p&lt;0.05.ResultsOf 122 patients, there were 81 women (66.4%) and 41 men (33.6%), 69 APOE‐ε4 carriers (56.5%) and 53 APOE‐ε4 non‐carriers (43.5%). The mean estimated age at AD onset was 73.13±7.1 years‐old. Overall, 120 patients used a cholinesterase inhibitor (98.4%), and 90 patients used Memantine (73.8%). All test scores were significantly different at the end of one year (p&lt;0.01), except for the Mini‐Mental State Examination (p = 0.13). None of the potential metabolic predictors varied significantly after one year (p&gt;0.16), and no variations in metabolic risk factors were concurrently associated with variations in the Clinical Dementia Rating Sum‐of‐Boxes (p&gt;0.17), the Index of Independence in Activities of Daily Living (p&gt;0.09), Lawton’s Scale for Instrumental Activities of Daily Living (p&gt;0.22), or the Mini‐Mental State Examination (p&gt;0.40), neither for APOE‐ε4 carriers (p&gt;0.28), nor for APOE‐ε4 non‐carriers (p&gt;0.07).ConclusionsLifetime metabolic risk factors may affect onset of AD, but concurrent variations in metabolic parameters seem to have no associations with cognitive or functional decline in such patients, regardless of APOE‐ε4 carrier status. (Supported by FAPESP grant #2015/10109‐5)

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

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

Association between Grip Strength and Future Cognitive Function in male

AbstractBackgroundFrailty is an aging‐related syndrome of physiological decline, and has been associated with cognitive function.Grip strength, could be used as a marker for frailty and older adult health status. Frailty has been associated with cognitive function. However, its mechanism has not been fully investigated.We aimed to investigate the association between grip strength with cognitive function.MethodWe prospectively recruited 184 participants who underwent a grip strength test, cognitive function test. Data was collected from the Korean Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study which started in 2014. Frailty was represented by grip strength (kg). Cognitive function was assessed using Mini‐Mental State Examination(MMSE) and The Consortium to Establish a Registry for Alzheimer’s Disease‐K(CERAD‐K).Multiple linear regression models were used to analyze the associations between grip strength and cognitive function. We adjusted age, gender, years of education, and BMI.ResultAmong 184 participants, 119 (64.7%) were cognitively normal. 32 (17.4%) were diagnosed with mild cognitive impairment and 33 (17.9) were a probable AD. Mean age of the participants was 69.4 (8.2) years. 43.5% of the participants were female. Grip strength was positively associated with MMSE at 1 year later in male (ß = 0.182 p = 0.004). In terms of cognitive domain, verbal and visual memory, language, visuospatial, and frontal‐executive functions were related to grip strength (vebal memory: ß = 0.037 p = 0.022, visual memory: ß = 0.046 p = 0.002, language: ß = 0.055 p&lt;0.001, visuospatial: ß = 0.068 p = 0.0213, frontal‐executive: ß = 0.050 p&lt;0.001).ConclusionWeakness of grip strength is associated with decreased future cognitive function. This support concept that grip strength could be a marker for cognitive decline.

The molar ratio between PAI‐1 and BDNF is increased in Alzheimer’s disease patients with full dementia and negatively correlates with MMSE score

AbstractBackgroundIn a previous study, we demonstrated that the enzyme plasminogen activator inhibitor‐1 (PAI‐1), which inhibits plasmin synthesis in the central nervous system (CNS), is increased in the serum of patients with Alzheimer’s disease (AD). In addition to reducing the accumulation of Ab, plasmin in the CNS regulates the synthesis of the trophic factor brain‐derived neurotrophic factor (BDNF) which appears to be altered in the brain of patients with AD. We investigated whether BDNF serum levels in AD and amnestic mild cognitive impairment (aMCI) patients are altered compared to cognitively healthy controls. Moreover, we examined the PAI‐1/BDNF ratio in these patient groups and correlated with cognitive scores as measured by Mini‐Mental State Examination (MMSE).Method40 AD, 40 aMCI and 10 healthy controls were recruited. Venous blood was collected and BDNF serum concentration were quantified by sandwich ELISAs. Comparisons among the experimental groups (AD dementia, aMCI patients, and cognitively healthy controls) on BDNF serum levels were performed using univariate analyses of variance (ANOVA). Pearson correlation coefficients were calculated to explore relationships between biochemical and clinical data. The level of statistical significance was set at p&lt;0.05.ResultThe results showed that BDNF serum levels are decreased in AD as compared to aMCI patients (p &lt; .05). In addition, there was a positive correlation between PAI‐1 and BDNF serum levels (r = .190, p &lt; .05). Furthermore, PAI‐1/BDNF ratio was significantly increased in AD patients as compared to aMCI (p &lt; .001) and controls (p &lt; .001). Lastly, PAI‐1/BDNF ratio negatively correlated with MMSE score (r = ‐.508, p &lt; .001).ConclusionThese data suggest that in AD a reduction of plasmin caused by PAI‐1 may negatively affect the production of BDNF and promote disease progression. Our results also demonstrate that the PAI‐1/BDNF ratio is increased in AD patients compared with aMCI and controls. They also suggest that this ratio could be used as a marker of AD in a state of overt cognitive impairment, as supported by the strong negative correlation between PAI‐1/BDNF ratio and MMSE.

Factors Associated With Dementia‐Related Behaviors Among Caregivers Experiencing Poor Sleep

AbstractBackgroundNeuropsychiatric symptoms of dementia are common and have the potential to negatively impact the physical and mental health of family caregivers, hindering their ability to provide care. Such impact may be worse among caregivers experiencing poor sleep. This study aimed to explore factors associated with the frequency of and caregivers’ distress to dementia‐related problematic behaviors.MethodThis was a cross‐sectional study, using data from a clinical trial of dyadic sleep intervention for persons living with dementia (PLWD) and their family caregivers. Dementia‐related behaviors were measured using a 24‐item, Revised Memory and Behavioral Problems Checklist (RMBPC): total scores of frequencies and caregivers’ distress; scores for three subscales (memory‐related, depression, and disruptive behaviors). Caregiver‐related variables included demographic background, Zarit Burden Interview (ZBI), Positive Aspects of Caregiving (PAC), Pittsburgh Sleep Quality Index (PSQI), and Center for Epidemiological Studies of Depression (CESD). Patient‐related variables included activities of daily living (ADLs), instrumental ADLs (IADLs), and Mini‐Mental State Examination (MMSE) scores. A total of 47 dyads were included in the analysis (caregivers: n = 29 spouses, n = 17 non‐spouses; 40% Whites). Pearson correlation analyses were conducted.ResultHigher ZBI and CESD scores were significantly associated with higher RMBPC frequency total (r = 0.41, r = 0.48, respectively; p&lt;0.01) and caregiver distress total scores (r = 0.58, r = 0.43, respectively; p&lt;0.01). Lower PAC (r = ‐0.31, p = 0.04) and higher MMSE scores (r = 0.37, p = 0.03) were also associated with higher caregiver distress total scores. ZBI and CESD scores were associated with RMBPC‐depression subscale scores (frequency/caregiver distress). There were positive associations between CESD and MMSE with RMBPC‐disruptive behaviors (frequency), and ZBI and PAC scores with RMBPC‐disruptive behaviors (caregiver distress). No patient or caregiver‐related factors were associated with RMBPC‐memory subscale scores. There was no significant association between PSQI scores and RMBPC total/subscale scores. Patient factors were not significantly associated with RMBPC frequency total or caregiver distress total scores.ConclusionDementia‐related problems, particularly depressive symptoms and disruptive behaviors of PLWD are associated with both positive and negative aspects of caregiving. Future studies will need to further examine how each RMBPC subscale of behavior contributes to caregiver burden or perceived caregiving experiences among family caregivers.

Predicting Transitions from Mild Cognitive Impairment to Dementia within 5‐years

AbstractBackgroundEarly detection of individuals at high risk of future progression toward dementia is in great need, particularly in the era of emerging treatments for Alzheimer’s disease. Given the easier administration of neuropsychological (NP) tests over invasive and expensive biomarker acquisition, we seek to predict the future cognitive status of an individual based on digital voice recordings of NP exams.MethodWe utilized automatic speech recognition and natural language processing techniques to create an automated tool that predicts if an individual with mild cognitive impairment (MCI) will develop dementia in a fixed follow‐up window (5 years). We characterize the predictive accuracy of this approach using data from the Framingham Heart Study. First, the automated transcription of the digital voice recordings were classified into 8 main NP sub‐tests including memory assessment, naming and language skill, verbal fluency, general questions, etc. Using a large language model, only the participants’ sentences were encoded into quantitative data. These data and the participants’ characteristics, such as age, sex, ApoE4 (+/‐) genotype, and education were employed to train and test a binary classifier, predicting dementia withing 5 years after a positive MCI diagnosis. We also provide a comparison between our approach and alternative models using demographics and ApoE genotype or the Mini‐Mental State Examination (MMSE) score.ResultWe evaluated the performance of the classification task on the data containing 111 stable MCI and 103 progressive MCI subjects. Our method achieved an average accuracy of 75.5% on the held‐out test data while a baseline model using age, sex, education, and ApoE has an average accuracy of 71.8%. The sensitivity and specificity of the proposed method versus the baseline model are 78.2% vs. 81.8% and 72.7% vs. 61.8%, respectively. Our approach also significantly outperforms the model based on the MMSE score by a margin of 14% in accuracy.ConclusionWe have analyzed digital voice recordings of NP exams for participants with MCI to predict their cognitive status in 5 years. The proposed approach offers a fully automated procedure with higher accuracy, providing an opportunity to develop an accessible and easy‐to‐administer screening tool that could be easily adapted to any language.

The effect of short Aβ(1‐38) peptides on cognitive decline and conversion to AD dementia: longitudinal data using the DELCODE cohort

AbstractBackgroundThe current research consensus is that long Aβ(1‐42) peptides are neurotoxic pathological hallmarks of AD. Interestingly, short Aβ peptides, such as Aβ(1‐38), appear to be less neurotoxic and may counteract AD neuropathology. However, research on Aβ(1‐38) is scarce and their effect on AD pathophysiology in humans in vivo remains unclear. Here, we investigate whether higher relative concentrations of Aβ(1‐38) levels in the cerebrospinal fluid (CSF), compared to Aβ(1‐42) alone, with phospho Tau (pTau) or with both, protect against cognitive decline and risk of conversion to AD dementia.MethodParticipants with subjective cognitive decline (n = 56), mild cognitive impairment (n = 60) and AD dementia (n = 61) from the DELCODE study with a likely pathological Aβ42/P‐tau ratio of &gt; 9.68 at baseline were included. Cognitive performance was assessed annually for five years with the Mini‐Mental State Examination (MMSE) and the Preclinical Alzheimer Cognitive Composite (i.e., PACC5), which was derived from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Conversion to AD dementia was assessed with the Clinical Dementia Rating (CDR) and NINCDS‐ARDA criteria. CSF was collected at baseline. Data was analysed using statistical model fitting procedures for linear mixed models, i.e., Likelihood Ratio (LR) testing. Additionally, we controlled for baseline diagnostic status and the relative effect of Aβ(1‐42) and pTau.ResultHigher Aβ(1‐38) baseline levels were associated with better follow‐up performance on the PACC5 in all three groups across the AD continuum (p &lt; .001). For the MMSE, only the MCI group showed significantly better follow‐up performance (p = .003), and a trend was found in the other groups (SCD: p = .090, AD p = .099). Furthermore, higher Aβ(1‐38) baseline levels decreased risk of conversion to AD dementia within three years by 88% (p = .003) in the SCD and MCI groups.ConclusionAcross the AD spectrum, higher Aβ(1‐38) levels protect against cognitive decline and reduce the risk of conversion to AD dementia. This could inform individual risk prediction in memory clinic patients.

Impact of Independent Review on Potential MMSE Score Inflation at Screening in AD trials

AbstractBackgroundThe Mini‐Mental State Examination (MMSE) is widely used as a screening tool in Alzheimer’s Disease (AD) clinical trials. Screening score inflation is documented in clinical trials of depression and anxiety. We investigated whether score distributions on several multi‐site multinational AD trials showed truncated scores around MMSE inclusion criteria cut‐off, and whether Independent Review (IRev), where site assessments are reviewed by independent clinicians, is an effective methodology to mitigate inclusion bias.MethodMMSE screening score distributions from several clinical trials of Early Symptomatic and Mild to Moderate AD were examined. To assess the impact of IRev on screening score distribution, we compared two studies with similar inclusion criteria (Early AD, MMSE ≥ 22; CDR GS = 0.5 or 1) one with no IRev and one with IRev via audio recording.ResultMMSE screening frequency distributions showed a statistically significant difference between IRev and No‐IREV groups (p &lt; 0.001). The distributions for the two groups were also compared using several score ranges around the threshold. Significant group differences were observed across the score ranges; 20‐24 (D = 0.099, p = 0.01), 19‐25 (D = 0.094, p = 0.002), and 18‐26 (D = 0.0987, p &lt; 0001), suggesting a smaller inclusion bias around the threshold in the IRev group.ConclusionWe observed that screening score inflation occurs in AD trials and Independent Review may be an effective strategy to reduce the number of subjects inappropriately enrolled in the study. IRev should be applied to assessments that fall around the required scored for study participation.