Non-amnestic Mild Cognitive Impairment Research Articles

Analysis of the prevalence of anticoagulant therapy in patients with cognitive disorders and cerebral amyloid angiopathy (CAA)

To investigate the prevalence of coincident anticoagulation in patients with cognitive disorders and possible or probable cerebral amyloid angiopathy (CAA) as well as the relationship between the presence of oral anticoagulation and CAA-specific lesion load. Patients with subjective cognitive decline (SCD), amnestic and non-amnestic mild cognitive impairment (aMCI/naMCI), Alzheimer's disease (AD), mixed dementia (MD) and vascular dementia (VD) who presented to our outpatient dementia clinic between February 2016 and October 2020 were included in this retrospective analysis. Patients underwent cranial magnetic resonance imaging (MRI). MRI data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. Presence of anticoagulant therapy was determined by chart review. Within the study period, 458 patients (209 male, 249 female, mean age 73.2 ± 9.9years) with SCD (n = 44), naMCI (n = 40), aMCI (n = 182), AD (n = 120), MD (n = 68) and VD (n = 4) were analyzed. Atotal of 109 patients (23.8%) were diagnosed with possible or probable CAA. CAA prevalence was highest in aMCI (39.4%) and MD (28.4%). Of patients with possible or probable CAA, 30.3% were under platelet aggregation inhibition, 12.8% were treated with novel oral anticoagulants and 3.7% received phenprocoumon treatment. Regarding the whole study cohort, patients under oral anticoagulation showed more cerebral microbleeds (p = 0.047). There was no relationship between oral anticoagulation therapy and the frequency of cortical superficial siderosis (p = 0.634). CAA is afrequent phenomenon in older patients with cognitive disorders. Almost half of CAA patients receive anticoagulant therapy. Oral anticoagulation is associated with ahigher number of cortical and subcortical microbleeds.

Premorbid personality traits as predictors for incident predementia syndromes: a multistate model approach.

Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states. Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded. Mann-Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI. FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.

Differential diagnosis of mild cognitive impairment of Alzheimer's disease by Simoa p-tau181 measurements with matching plasma and CSF.

Alzheimer's disease (AD) is characterized by a long preclinical phase. Although late-stage AD/dementia may be robustly differentiated from cognitively normal individuals by means of a clinical evaluation, PET imaging, and established biofluid biomarkers, disease differentiation between cognitively normal and various subtypes of mild cognitive impairment (MCI) remains a challenging task. Differential biomarkers for early-stage AD diagnosis with accessible biofluid samples are urgently needed. Misfolded phosphorylated tau aggregates (p-tau) are present in multiple neurodegenerative diseases known as "tauopathies", with the most common being AD. P-tau181 is a well-established p-tau biomarker to differentiate AD dementia from non-AD pathology. However, it is unclear if p-tau181 is capable of diagnosing MCI, an early AD stage, from cognitively normal subjects, or if it can discriminate MCI subtypes amnestic MCI (aMCI) from non-amnestic MCI (naMCI). Here we evaluated the capability of p-tau181 in diagnosing MCI from cognitively normal subjects and discriminating aMCI from naMCI subtypes. We collected matching plasma and CSF samples of a clinically diagnosed cohort of 35 cognitively normal, 34 aMCI, 17 naMCI, and 31 AD dementia cases (total 117 participants) with supplemental CSF Aβ42 and total tau AD biomarker levels and performed Simoa p-tau181 assays. The diagnostic capabilities of Simoa p-tau181 assays to differentiate these cohorts were evaluated. We found (i) p-tau181 can robustly differentiate MCI or aMCI from cognitively normal cohorts with matching plasma and CSF samples, but such differentiation is weaker in diagnosing naMCI from cognitively normal groups, (ii) p-tau181 is not capable of differentiating aMCI from naMCI cohorts, and (iii) either factor of Aβ or total tau burden markedly improved differentiation power to diagnose aMCI from cognitively normal group. Plasma and CSF p-tau181 levels may serve as a promising biomarker for diagnosing aMCI from normal controls in the preclinical phase. But more robust new biomarkers are needed to differentiate naMCI from cognitively normal cases or to discriminate between MCI subtypes, aMCI from naMCI.

Connectivity changes in two-channel prefrontal ERP associated with early cognitive decline in the elderly population: beta band responses to the auditory oddball stimuli.

This study utilized recent advancements in electroencephalography (EEG) technology that enable the measurement of prefrontal event-related potentials (ERPs) to facilitate the early detection of mild cognitive impairment (MCI). We investigated two-channel prefrontal ERP signals obtained from a large cohort of elderly participants and compare among cognitively normal (CN), subjective cognitive decline (SCD), amnestic MCI (aMCI), and nonamnestic MCI (naMCI) groups. Signal processing and ERP component analyses, specifically adapted for two-channel prefrontal ERP signals evoked by the auditory oddball task, were performed on a total of 1,754 elderly participants. Connectivity analyses were conducted to assess brain synchronization, especially in the beta band involving the phase locking value (PLV) and coherence (COH). Time-frequency, time-trial, grand average, and further statistical analyses of the standard and target epochs were also conducted to explore differences among the cognition groups. The MCI group's response to target stimuli was characterized by greater response time variability (p < 0.001) and greater variability in the P300 latency (p < 0.05), leading to less consistent responses than those of the healthy control (HC) group (CN+SCD subgroups). In the connectivity analyses of PLV and COH waveforms, significant differences were observed, indicating a loss of synchronization in the beta band in response to standard stimuli in the MCI group. In addition, the absence of event-related desynchronization (ERD) indicated that information processing related to readiness and task performance in the beta band was not efficient in the MCI group. Furthermore, the observed decline in the P200 amplitude as the standard trials progressed suggests the impaired attention and inhibitory processes in the MCI group compared to the HC group. The aMCI subgroup showed high variability in COH values, while the naMCI subgroup showed impairments in their overall behavioral performance. These findings highlight the variability and connectivity measures can be used as markers of early cognitive decline; such measures can be assessed with simple and fast two-channel prefrontal ERP signals evoked by both standard and target stimuli. Our study provides deeper insight of cognitive impairment and the potential use of the prefrontal ERP connectivity measures to assess early cognitive decline.

An IoT-based cognitive impairment detection device: A newly proposed method in older adults care-choice reaction time-device development and data-driven validation.

Research shows that older adults' performance on choice reaction time (CRT) tests can predict cognitive decline. A simple CRT tool could help detect mild cognitive impairment (MCI) and preclinical dementia, allowing for further stratification of cognitive disorders on-site or via telemedicine. The primary objective was to develop a CRT testing device and protocol to differentiate between two cognitive impairment categories: (a) subjective cognitive decline (SCD) and non-amnestic mild cognitive impairment (na-MCI), and (b) amnestic mild cognitive impairment (a-MCI) and multiple-domain a-MCI (a-MCI-MD). A pilot study in Italy and Romania with 35 older adults (ages 61-85) assessed cognitive function using the Mini-Mental State Examination (MMSE) and a CRT color response task. Reaction time, accuracy, and demographics were recorded, and machine learning classifiers analyzed performance differences to predict preclinical dementia and screen for mild cognitive deficits. Moderate correlations were found between the MMSE score and both mean reaction time and mean accuracy rate. There was a significant difference between the two groups' reaction time for blue light, but not for any other colors or for mean accuracy rate. SVM and RUSBoosted trees were found to have the best preclinical dementia prediction capabilities among the tested classifier algorithms, both presenting an accuracy rate of 77.1%. CRT testing with machine learning effectively differentiates cognitive capacities in older adults, facilitating early diagnosis and stratification of neurocognitive diseases and can also identify impairments from stressors like dehydration and sleep deprivation. This study highlights the potential of portable CRT devices for monitoring cognitive function, including SCD and MCI.

PREVALENCE OF METABOLIC COMORBIDITIES AMONG COGNITIVELY NORMAL AND IMPAIRED WHITE AND AFRICAN AMERICANS

Abstract Assessing comorbidities associated with a MCI diagnosis is crucial for diagnostic accuracy and for understanding the role of comorbidities in cognitive decline. In this study of amnestic (aMCI) and non-amnestic (naMCI) MCI participants and persons with normal cognition (CN), we compared the prevalence of three primary comorbidities: Hypertension (HTN), Hyperlipidemia (HLD), and Diabetes Mellitus (DM) across African American and White populations using Chi-squares. Participant data (N = 9,342, 17% African American) were available through the National Alzheimer’s Coordinating Center and included: CN (n = 5,963; MOCA mean=27), aMCI (2,694; MOCA=22), and naMCI (685; MOCA=24) with diagnosis and data per their first Uniform Data Set (Version 3) visit. Significant differences in the distribution of HTN, HLD, and DM were found among the diagnostic groups for the total cohort and racial groups, separately; however, diagnostic differences across races were not always consistent. The relative rates of DM and HLD across the diagnostic groups for both races were generally similar, though higher percentages were seen in African Americans (25% of African Americans, 10% of Whites). As for HTN (52% of African Americans, 39% of Whites), however, the distributions differ across the diagnostic groups and race (%yes for diagnosis; White Americans: CN 35%, aMCI 47%, naMCI 44%; African Americans: CN 66%, aMCI 70%, naMCI 79%, p&amp;lt; 0.001). These findings highlight the importance of considering the contributions of both race and diagnosis when evaluating the role of comorbid factors and metabolic disorders in NC and MCI groups, in particular when considering blood pressure-related measures.

Characteristic early changes of Glu and Cho in brain regions affected by different types of subjective cognitive decline and their clinical significance.

To discuss the early changes of Glu and Cho in the affected areas of different types of subjective cognitive decline, including amnestic MCI (aMCl), non-amnestic MCI (naMCI) and vascular cognitive impairment no dementia (VCIND), using Proton Magnetic Resonance Spectroscopy (1H-MRS) technology. Routine head MRI and lH-MRS examinations were performed on 50 clearly diagnosed aMCI patients, 44 naMCI patients, 44 VCIND patients, and 44 elderly individuals with normal cognitive function. Measure the volume of the patient bilateral hippocampus. Using the bilateral hippocampus, left posterior cingulate gyrus (PCG), and frontal lobe as regions of interest, the scope under the peak of N-acetylaspartate (NAA), choline complex (Cho), glutamate (Glu), Metabolic Images (mI), and creatine (Cr) was tested. Perform a correlation analysis between the NAA/Cho/Cr values of the VCIND group and the MoCA score. All experimental subjects were right-handed. The NAACr values in both hippocampus of the VCIND were greatly lower than those in control (P < .05). The NAA/Cr values on both sides of the VCIND were correlated with the MoCA score (P < .05). The NAA/Cr values in the LHp and PCG of subjects in the aMCI and naMCI groups were lower than those in the NC group (P < .05). The NAA/Cr values in the left frontal lobe of the aMCI and naMCI showed no obvious decrease compared to the NC. The Glu/Cr of subjects in the aMCI was lower in the left PCG than those in the naMCI and NC (P < .05). The discrepancy between the naMCI and the NC was P > .05. In the LHp and frontal lobe, in contrast with the naMCI and NC, the mI/Cr values in the LHp and PCG of subjects in the aMCI were higher (P < .05). In the left frontal lobe, relative to the aMCI and NC, the mI/Cr values in the naMCI were higher (P < .05). The changes in the concentration of 1H-MRS metabolites in the hippocampus can indicate the presence of hippocampal neuronal damage before morphological changes occur in the hippocampus. 1H-MRS NAA/Cr can reflect the cognitive function changes of patients to a certain extent. There are regional differences in mI and Glu metabolism in the brain between aMCI and naMCI groups. 1H-MRS provides an effective basis for clinical differentiation between aMCI and naMCI.

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population-based study.

To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults. This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n=1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio= 1.22; 95% confidence interval [CI]= 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p<0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p<0.05). Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults. We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.

Comparison of Baseline Cognitive Testing Results in Mild Cognitive Impairment Subtypes in the NACC Database

AbstractBackgroundMild cognitive impairment (MCI) reflects cognitive deficits without significant functional decline in activities of daily living. MCI subtypes correspond to phenotypic cognitive impairment patterns in memory, attention, language, executive, and visuospatial compared to age‐adjusted norms: Amnestic single domain (ASD) or multi‐domain (AMD), Nonamestic single domain (NASD), or Nonamnestic multi‐domain (NAMD). Previous studies have suggested Nonanmestic subtypes demonstrate more likely represent non‐AD prodromes, but conclusions have been limited by small sample sizes. The present study attempts to see correlates of htese proposed differences as evident by cognitive testing battery.MethodUsing the National Alzheimer’s Coordinating Center (NACC) database (grant U24 AG072122), we selected all initial Uniform Data Set (UDS) assessments diagnosed as MCI with subtyping. The NACC data was collected from 37 participating Alzheimer’s disease Research Centers. Baseline demographic, clinical features, Neuropsychiatric symptoms, and AD biomarkers were collected. One‐way ANOVA analyses were used to compare cognitive performance on all UDS cognitive tests across MCI subtypes.Result9852 individuals with MCI on baseline UDS visits were analyzed: 45.4% AMD, 33.7% ASD, 12.6% NASD, 8.2% NAMD. There were significant differences (P&lt;.001 or greater) on all measures which is not unexpected given large sample size. Notable differences between ASD/AMD, NASD/NAMD were prominent on Trails B, Craft story immediate and delayed recall, and Benton immediate recall minus delayed recall. See table for complete summary of scores.Trails B, mean (SD) times were ASD (113±62), AMD (157±82), NASD (143±78),NAMD (171±83). Craft story showed clear differences between groups on immediate recall (ASD14.9 (6.4)/AMD 14.2 (6.76)/NASD 18.0 (8.0/NAMD 17.9 (6.9)) and delayed recall (ASD 9.9 (7.0)/AMD 10.1 (6.7)/NASD 15.2 (6.4)/NAMD 15.5 (6.2)). Benton immediate minus delayed recall differences were ASD 8.1/AMD 7.9 versus NASD 4.2, NAMD 4.9)ConclusionNonamnestic MCI subtypes are characterized by lower performance on executive tasks such as Trails B. Conversely, memory tasks show lower performance in NACC UDS participants with amnestic subtypes of MCI. This would support the concept that Nonamnestic MCI may represent prodromal stages of non‐AD dementia more frequently.

Cardiovascular and Metabolic Disorders in Mild Cognitive Impairment among Older African‐American Adults

AbstractBackgroundMild Cognitive Impairment (MCI) is one of the early predictors of Alzheimer’s disease (AD) and dementia. Assessing comorbidities associated with an MCI diagnosis is crucial not only for diagnostic accuracy but also for understanding the role of comorbidities for evident cognitive impairment. In this study we investigated the association between MCI (amnestic and/or non‐amnestic) and primary comorbidities of hypertension (HTN), hyperlipidaemia (HLD), and Diabetes Mellitus (DM).MethodsWe recruited 116 community‐dwelling older African American adults with subjective complaints (103 females, 13 males, mean age = 73.93, range = 65‐91) through the Wayne State Institute of Gerontology and Michigan Alzheimer’s Disease Research Center. Participants were consensus diagnosed as 57 healthy controls (HC), 32 amnestic MCI (aMCI), and 27 nonamnestic MCI (naMCI) based on NAAC Unified Data Set3 protocol. NIH Toolbox‐Cognition battery (NIHTB‐C) also was administered, but not used for consensus.ResultsAcross all the participants, UDS3 forms noted 69% with hypertension (HTN), 56% hyperlipidaemia (HLD), and 28% Type II Diabetes. Among the normal group: 65% had HTN, 51% had HLD, and 28% had DM. Among those diagnosed with aMCI: 66% had HTN, 53% had HLD, and 34% had DM. Among naMCI: 81% had HTN, 63% had HLD, and 22% had DM. Comorbidities did not differ significantly across diagnostic groups. Regarding NIHTB‐C, significant ANOVA interactions did show that aMCI and naMCI with DM were lower in Fluid Intelligence than scores for controls with DM (p = .017). Also, as compared to controls with HTN, naMCI with HTN were lower on Fluid Intelligence (p = .024).ConclusionOur findings did not demonstrate differences in cardiovascular‐ or diabetes‐related comorbidities across MCI groups and controls in this group of community‐dwelling African Americans. However, DM and HTN, but not HLD, did affect the relationship among the diagnostic groups for fluid intelligence, a summary measure of higher cognitive functioning. This suggests that comorbid medical factors can affect cognitive performance, particularly for MCI groups. Further research is needed to fully understand the scope of risk factors influencing cognitive decline in African Americans. Further analyses will assess relationships between cognitive diagnoses, race, health conditions, and demographic risk factors.

Divergent brain regional atrophy and associated fiber disruption in amnestic and non-amnestic MCI

BackgroundUnderstanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI).MethodsT1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed.ResultsThe aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language.ConclusionsThe divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions.

26 Correlates of Neuropsychological Decline Following Deep Brain Stimulation in Patients with Parkinson's Disease

Objective:Deep Brain Stimulation (DBS) is an FDA-approved treatment for Parkinson's Disease (PD), for which the medical workup includes routine pre- and post- operative neuropsychological assessment to determine potential surgical cognitive risk. Existing research suggests that cognitively normal individuals experience good cognitive outcome, whereas those with pre-existing cognitive deficits are prone to accelerated cognitive decline post-DBS. The goal of this study is to identify characteristics that determine which individuals with PD are at risk for accelerated post-DBS cognitive loss, and to characterize the nature of the decline in this population.Participants and Methods:We conducted a retrospective chart review of PD- DBS patients who completed their DBS workup and surgery at Mount Sinai Hospital NYC between 2015 and 2022. Non-English speakers were excluded from this study due to small sample size and use of a neurocognitive battery different from that of English speakers. Using repeated measures t-tests, chi square, and regression analyses, we explored variables related to disease (e.g., duration, L-Dopa burden, DBS target), socio-demographic background (e.g., age onset, current age, education), assessment modality (telehealth vs in-office), neurocognitive performances (e.g., WMS-IV Logical Memory (LM), HVLT-R, WASI-II Matrix &amp; Similarities, WAIS-IV Digit Span), and cognitive diagnosis (amnestic vs non-amnestic MCI) for all individuals in the sample. At the individual level, we utilized Reliable Change Indices (RCI) to identify clinically significant cognitive differences from pre- to post-DBS exam. We considered LM- Delayed Recall (LMDR) as a proxy for memory loss, as this cognitive function is expected to remain generally unchanged post PD-DBS. Therefore, decline on this measure in the first year after DBS could indicate a change in global memory function and possible evidence of accelerated postoperative decline.Results:Of 65 charts reviewed, 44 patients were native English-speaking and included in our analyses. At the group level, there were no significant differences in disease characteristics, socio-demographic variables, or cognitive classification between those who declined versus those who did not decline on LMDR. Regression statistics for predictors of cognitive decline also were non-significant. Of the eight individuals who declined on LMDR, one patient declined on a total of one neuropsychological measure, four declined on a total of two measures, two declined on a total of three measures, and one declined on a total of four measures. Two of these eight individuals had a diagnosis that changed to amnestic MCI based on concomitant interval history of ADL compromise. Of these two individuals, one declined in two tests and the other declined in four tests. Six of the eight individuals who declined also showed abnormalities in their imaging with either edema or hemorrhage.Conclusions:Our analysis is unique in that we explored cognitive decline at both the group and individual levels. Despite this, we did not find predictors of post-DBS cognitive decline. Further detailed analysis of additional post-operative factors that might play a greater role in our understanding of this phenomenon is warranted. This said, our data do support that the majority of individuals with non-amnestic MCI did not decline cognitively.

77 Differentiating Amnestic Versus Non-Amnestic Mild Cognitive Impairment Using the NIH Toolbox Cognition Battery

Objective:In research, and particularly clinical trials, it is important to identify persons at high risk for developing Alzheimer’s Disease (AD), such as those with Mild Cognitive Impairment (MCI). However, not all persons with this diagnosis have a high risk of AD as MCI can be broken down further into amnestic MCI (aMCI), who have a high risk specifically for AD, and non-amnestic MCI (naMCI), who are predominantly at risk for other dementias. People with aMCI largely differ from healthy controls and naMCI on memory tasks as it is the hallmark criteria for an amnestic diagnosis. Given the growing use of the NIH Toolbox Cognition battery in research trials, this project investigated which Toolbox Cognition measures best differentiated aMCI from naMCI and in comparison to persons with normal cognition.Participants and Methods:A retrospective data analysis was conducted investigating performance on NIH Toolbox Cognition tasks among 199 participants enrolled in the Michigan Alzheimer’s Disease Research Center. All participants were over age 50 (51-89 years, M=70.64) and had a diagnosis of aMCI (N=74), naMCI (N=24), or Normal Cognition (N=101). Potential demographic differences were investigated using chi-square and ANOVAs. Repeated measure general linear model was used to look at potential group differences in Toolbox Cognition performance, covarying for age which was statistically different in aMCI versus Normal participants. Linear regression was used to determine which cognitive abilities, as measured by the Uniform Data Set-3 (UDS3), might contribute to Toolbox differences noted in naMCI versus aMCI groups.Results:As expected, aMCI had lower Toolbox memory scores compared to naMCI (p=0.007) and Normals (p&lt;0.001). Interestingly, naMCI had lower Oral Reading scores than both aMCI (p=0.008) and Normals (p&lt;0.001). There were no other Toolbox performance differences between the MCI groups. 19.4% of the variance in Oral Reading scores was explained by performance on the following UDS3 measures: Benson delayed recall (inverse relationship) and backward digit span and phonemic fluency (positive relationship).Conclusions:In this study, Toolbox Picture Sequence Memory and Oral Reading scores differentiated aMCI and naMCI groups. While the difference in memory was expected, it was surprising that the naMCI group performed worse than the aMCI and normal groups on the Toolbox Oral Reading task, a task presumed to reflect Crystalized abilities resistive to cognitive decline. Results suggest that Oral Reading is primarily positively associated with working memory and executive tasks from the UDS3, but negatively associated with visual memory. It is possible that the Oral Reading subtest is sensitive to domains of deficit aside from memory that can best distinguish aMCI from naMCI. A better understanding of the underlying features in the Oral Reading task will assist in better characterizing deficit patterns seen in naMCI, making selection of aMCI participants more effective in clinical trials.

89 The Effect of Personality Traits on the Development of Predementia Cognitive States: Results from the Einstein Aging Study

Objective:Recent research has found associations between the Five Factor Model (FFM) personality traits (Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism) and risk of developing subjective cognitive decline (SCD), mild cognitive impairment (MCI), and/or dementia. It has therefore been proposed that personality should be incorporated into conceptual models of dementia risk, as personality assessments have utility as readily available, low-cost measures to predict who is at greater risk for developing pathological cognitive decline. The objective of the present study was to explore the relationship between FFM personality traits and predementia cognitive syndromes including SCD, amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The first aim was to compare baseline personality traits between participants who transitioned from healthy cognition or SCD to aMCI vs. naMCI. The second aim was to determine the relationship between FFM personality traits and risk of transition between predementia cognitive states. The third aim was to explore relationships between levels of FFM personality traits and performance on a comprehensive cognitive battery.Participants and Methods:The participants for this study were 562 (Aim 3; Mean Age = 78.90) older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment (Aims 1 &amp; 2; Mean Age = 78.60). Baseline levels of FFM personality traits were measured in the EAS using the 50-item International Personality Item Pool (IPIP) version of the NEO-Personality Inventory. Baseline levels of anxiety and depressive symptoms, medical history, performance on a cognitive battery and age sex, and years of education were also collected. A multistate Markov approach was used to model the risk of transition across the four predementia states (cognitively healthy, SCD, aMCI, and naMCI) with each FFM personality trait as covariates.Results:Regarding Aim 1, Mann-Whitney U tests revealed no differences in levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. Regarding Aim 2, the multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, the model revealed that higher levels of extraversion were protective against developing naMCI. Finally, regarding Aim 3, exploratory correlations revealed many positive associations between levels of openness to experience and performance on neuropsychological tests. Few associations were found for the other FFM personality traits.Conclusions:Results from this study suggest that premorbid personality traits may play a predictive role in the risk for or protection against specific predementia syndromes. Thus, FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. These personality measures could be used (in addition to other established risk factors for cognitive decline) to enrich clinical trials by targeting individuals who are at greatest risk for developing specific forms of cognitive decline. Such measures may also be useful in diagnostic prediction models for predementia syndromes. These results should be replicated in future studies with larger sample sizes and younger participants.

1 Associations of Locus of Control and Memory Self-Awareness in Older Adults with and without MCI

Objective:While loss of insight into one’s cognitive impairment (anosognosia) is a feature in Alzheimer’s disease dementia, less is known about memory self-awareness in cognitively unimpaired (CU) older adults or mild cognitive impairment (MCI) or factors that may impact self-awareness. Locus of control, specifically external locus of control, has been linked to worse cognitive/health outcomes, though little work has examined locus of control as it relates to self-awareness of memory functioning or across cognitive impairment status. Therefore, we examined associations between locus of control and memory self-awareness and whether MCI status impacted these associations.Participants and Methods:Participants from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (mean age=73.51; 76% women; 26% Black/African American) were classified as CU (n=2177) or MCI (amnestic n=313; non-amnestic n=170) using Neuropsychological Criteria. A memory composite score measured objective memory performance and the Memory Functioning Questionnaire measured subjective memory. Memory self-awareness was defined as objective memory minus subjective memory, with positive values indicating overreporting of memory difficulties relative to actual performance (hypernosognosia) and negative values indicating underreporting (hyponosognosia). Internal (i.e., personal skills/attributes dictate life events) and external (i.e., environment/others dictate life events) locus of control scores came from the Personality in Intellectual Aging Contexts Inventory. General linear models, adjusting for age, education, sex/gender, depressive symptoms, general health, and vocabulary examined the effects of internal and external locus of control on memory self-awareness and whether MCI status moderated these associations.Results:Amnestic and non-amnestic MCI participants reported lower internal and higher external locus of control than CU participants. There was a main effect of MCI status on memory self-awareness such that amnestic MCI participants showed the greatest degree of hyponosognosia/underreporting, followed by non-amnestic MCI, and CU participants slightly overreported their memory difficulties. While, on average, participants were fairly accurate at reporting their degree of memory difficulty, internal locus of control was negatively associated with self-awareness such that higher internal locus of control was associated with greater underreporting (ß=-.127, 95% CI [-.164, -.089], p&lt;.001). MCI status did not moderate this association. External locus of control was positively associated with self-awareness such that higher external locus of control was associated with greater hypernosonosia/overreporting (ß=.259, 95% CI [.218, .300], p&lt;.001). Relative to CU, amnestic, but not non-amnestic, MCI showed a stronger association between external locus of control and memory self-awareness. Specifically, higher external locus of control was associated with less underreporting of cognitive difficulties in amnestic MCI (ß=.107, 95% CI [.006, .208], p=.038).Conclusions:In CU participants, higher external locus of control was associated with greater hypernosognosia/overreporting. In amnestic MCI, the lower external locus of control associations with greater underreporting of objective cognitive difficulties suggests that perhaps reduced insight in some people with MCI may result in not realizing the need for external supports, and therefore not asking for help from others. Alternatively, in amnestic participants with greater external locus of control, perhaps the environmental cues/feedback translate to greater accuracy in their memory self-perceptions. Longitudinal analyses are needed to determine how memory self-awareness is related to future cognitive declines.

Exploring Verbal Fluency Strategies among Individuals with Normal Cognition, Amnestic and Non-Amnestic Mild Cognitive Impairment, and Alzheimer's Disease.

Background and Objectives: The present study explored the utilization of verbal fluency (VF) cognitive strategies, including clustering, switching, intrusions, and perseverations, within both semantic (SVF) and phonemic (PVF) conditions, across a continuum of neurocognitive decline, spanning from normal cognitive ageing (NC) to mild cognitive impairment (MCI) and its subtypes, amnestic (aMCI) and non-amnestic (naMCI), as well as AD. Materials and Methods: The study sample was derived from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. The sample included 1607 NC individuals, 146 with aMCI (46 single-domain and 100 multi-domain), 92 with naMCI (41 single-domain and 51 multi-domain), and 79 with AD. Statistical analyses, adjusting for sex, age, and education, employed multivariate general linear models to probe differences among these groups. Results: Results showed that AD patients exhibited poorer performance in switching in both VF tasks and SVF clustering compared to NC. Similarly, the aMCI group performed worse than the NC in switching and clustering in both tasks, with aMCI performing similarly to AD, except for SVF switching. In contrast, the naMCI subgroup performed similarly to those with NC across most strategies, surpassing AD patients. Notably, the aMCI subgroup's poor performance in SVF switching was mainly due to the subpar performance of the multi-domain aMCI subgroup. This subgroup was outperformed in switching in both VF tasks by the single-domain naMCI, who also performed better than the multi-domain naMCI in SVF switching. No significant differences emerged in terms of perseverations and intrusions. Conclusions: Overall, these findings suggest a continuum of declining switching ability in the SVF task, with NC surpassing both aMCI and AD, and aMCI outperforming those with AD. The challenges in SVF switching suggest executive function impairment associated with multi-domain MCI, particularly driven by the multi-domain aMCI.

Openness and age influence cognitive progression: a longitudinal study.

Some psychological and personality characteristics of individuals seem to determine behavioral patterns that are associated with better health throughout life and, consequently, prevent the progression of early cognitive changes to dementia. To identify which individuals have modified cognitive ratings after 24 months of follow-up and correlating with personality traits. One hundred and two volunteers were evaluated clinically and for personality characteristics and neuropsychological testing. Of these, 25 subjects were classified as cognitively normal (CN), 25 as subjective cognitive decline (SCD), 28 as nonamnestic mild cognitive impairment (naMCI), and 24 as amnestic mild cognitive impairment (amMCI) at baseline. Follow-up occurred over 2 years from the initial assessment, and the cognitive categories of the participants were re-analyzed every 6 months to observe differences in their classification. Out of the 102 subjects, 65 remained at follow-up. The sample followed-up longitudinally was composed predominantly of women (65%), white (74%), with a mean age of 78 (±7.5) years old and 12 (±4.8) years of schooling. Throughout the process, 23% of CN, 15% of SDC, and 27% of naMCI individuals worsened cognitively. Amnestic with mild cognitive impairment volunteers remained stable or improved. Individuals with older age show more significant cognitive deterioration, and those with very low or high rates of the openness personality trait are associated with cognitive decline utilizing the Fisher exact test, probably because the open extremes influence choices, stress management, and behavioral maintenance. The factors most associated with cognitive change in this group of older adults were age and the intensity of the openness aspects of personality.

Comorbid cerebral amyloid angiopathy in dementia and prodromal stages-Prevalence and effects on cognition.

To determine the contribution of cerebral amyloid angiopathy to cognitive impairment in MCI and dementia. Patients with subjective memory impairment (SMI), amnestic and non-amnestic mild cognitive impairment ((n)aMCI), Alzheimer's disease (AD), mixed and vascular dementia (MD/VD) from our memory clinic were included in this retrospective analysis. Patients underwent neuropsychological testing and cranial magnetic resonance imaging (MRI). Magnetic resonance imaging data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. ANOVAs were used to investigate the contribution of CAA to cognitive impairment within diagnostic groups and to determine whether differences in cognitive test performance between the diagnostic groups are mediated by total CAA burden. 475 patients (222 male, 253 female) with SMI (n=47), naMCI (n=41), aMCI (n=189), early AD (n=9), AD (n=114), MD (n=71) and VD (n=4) were included. Mean age was 73.2 (9.9) years. CAA prevalence was 14.9% in SMI, 14.6% in naMCI, 24.3% in aMCI, 22.2% in early onset AD, 18.4% in late onset AD, 46.5% in MD and 25% in VD. Patients with possible and probable CAA were older than patients without CAA. In particular, diagnosis of aMCI, early onset AD, MD and VD showed high CAA prevalence. In AD but not in aMCI, CAA diagnosis significantly influenced test performance in the CERAD word list recall (F (1,78)=4505; p=0.037; partial eta-square=0.055). Differences in cognitive test performance between the diagnostic groups of naMCI, aMCI, AD and MD were mediated by total CAA burden within AAT simply nouns subtest (F (2,39)=4059; p=0.025; partial eta-square=0.172) and in CERAD verbal fluency test (F (3,129)=3533; p=0.017; partial eta-square=0.076). This retrospective analysis demonstrates high prevalence rates of CAA in cognitive diagnoses. Our data suggest that comorbid CAA independently impacts cognitive test performance in the course of AD with presumably stage-dependent effects. Especially in patients with AD comorbid CAA additionally impairs memory function. Total CAA small vessel disease burden further modulates psychometric differences in cognitive test performance between diagnostic groups regarding word finding and word fluency capabilities.

Mild Cognitive Impairment Subtype Performance in Comparison to Healthy Older Controls on the NIH Toolbox and Cogstate.

Early detection is necessary for the treatment of dementia. Computerized testing has become more widely used in clinical trials; however, it is unclear how sensitive these measures are to early signs of neurodegeneration. We investigated the use of the NIH Toolbox-Cognition (NIHTB-CB) and Cogstate-Brief computerized neuropsychological batteries in the identification of mild cognitive impairment (MCI) versus healthy older adults [healthy control (HC)] and amnestic (aMCI) versus nonamnestic MCI (naMCI). Exploratory analyses include investigating potential racial differences. Two hundred six older adults were diagnosed as aMCI (n = 58), naMCI (n = 15), or cognitively healthy (HC; n = 133). The NIH Toolbox-CB subtests of Flanker, Picture Sequence Memory, and Picture Vocabulary significantly differentiated MCI from HC. Further, subtests from both computerized batteries differentiated patients with aMCI from those with naMCI. Although the main effect of race differences was noted on tests and in diagnostic groups was significant, there were no significant race-by-test interactions. Computer-based subtests vary in their ability to help distinguish MCI subtypes, though these tests provide less expensive and easier-to-administer clinical screeners to help identify patients early who may qualify for more comprehensive evaluations. Further work is needed, however, to refine computerized tests to achieve better precision in distinguishing impairment subtypes.

Clinical characteristics of pathological confirmed prodromal dementia with Lewy bodies

IntroductionMisdiagnosis rate of Dementia with Lewy Bodies (DLB) remains high despite being second most common cause of neurodegenerative dementia. To date, understanding of clinical profile of pathologically confirmed prodromal DLB remains limited. The main objective of this study was to describe and compare it with pathologically confirmed Alzheimer's disease (AD). MethodsWe accessed the National Alzheimer's Coordinating Center database from 2005 to December 2022 data freeze and included 111 and 501 prodromal DLB and AD patients respectively. First visit data was analyzed. ResultsClinician-determined memory impairment is common in prodromal DLB (>70%) but associated with higher risk for AD diagnosis (OR 0.355, p = 0.0003). DLB had a higher proportion of non-amnestic mild cognitive impairment (MCI) diagnoses but statistically insignificance in differentiating the two. Inattention (OR 2.273, p = 0.0015), and neuropsychiatric features, such as visual hallucinations (OR 11.98, p < 0.0001), depressed mood (OR1.709, p = 0.0292), apathy (1.824, p = 0.0345), and night/REM sleep behaviors, are associated with DLB diagnosis. Hallucinations are infrequent (7–11%). Motor symptoms, particularly gait disorders (OR 4.570, p < 0.001), falls (OR3.939, p = 0.0003), tremors (OR2.237, p = 0.0154), slowness (OR3.573, p < 0.0001), and parkinsonism signs (OR2.443, p < 0.0001), are common. 32% showed no parkinsonism during initial presentation. Neuropsychological examination revealed less impaired memory and language but impaired executive function in DLB. ConclusionIn clinical practice, it is important to note that memory symptoms although being higher risk associated with AD diagnosis, are prominent in prodromal DLB. Psychosis is infrequent, and non-amnestic MCI is not necessarily associated with higher risk of DLB diagnosis. A careful clinical approach is key to improve the diagnosis of prodromal DLB.