Amnestic Mild Cognitive Impairment Research Articles

Module-level structural and functional alternations in amnestic mild cognitive impairment

Module-level structural and functional alternations in amnestic mild cognitive impairment

Identification of amnestic mild cognitive impairment among Black and White community-dwelling older adults using NIH Toolbox Cognition tablet battery.

Identify which NIH Toolbox Cognition Battery (NIHTB-CB) subtest(s) best differentiate healthy controls (HC) from those with amnestic mild cognitive impairment (aMCI) and compare the discriminant accuracy between a model using a priori "Norm Adjusted" scores versus "Unadjusted" standard scores with age, sex, race/ethnicity, and education controlled for within the model. Racial differences were also examined. Participants were Black/African American (B/AA) and White consensus-confirmed (HC = 96; aMCI = 62) adults 60-85 years old that completed the NIHTB-CB for tablet. Discriminant function analysis (DFA) was used in the Total Sample and separately for B/AA (n = 80) and White participants (n = 78). Picture Sequence Memory (an episodic memory task) was the highest loading coefficient across all DFA models. When stratified by race, differences were noted in the pattern of the highest loading coefficients within the DFAs. However, the overall discriminant accuracy of the DFA models in identifying HCs and those with aMCI did not differ significantly by race (B/AA, White) or model/score type (Norm Adjusted versus Unadjusted). Racial differences were noted despite the use of normalized scores or demographic covariates-highlighting the importance of including underrepresented groups in research. While the models were fairly accurate at identifying consensus-confirmed HCs, the models proved less accurate at identifying White participants with an aMCI diagnosis. In clinical settings, further work is needed to optimize computerized batteries and the use of NIHTB-CB norm adjusted scores is recommended. In research settings, demographically corrected scores or within model correction is suggested.

Effect of polycyclic aromatic hydrocarbon exposure on amnestic mild cognitive impairment and Alzheimer’s disease: A matched case-control study

There is an emerging body of evidence concerning the neurological effect of air pollutants on cognitive function and increased risk of neurodegeneration. Although previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) are neurotoxic, the effect of PAHs exposure on neurodegeneration remains unclear. This study aimed to investigate the association between PAH exposure and the risk of developing amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). For this matched case-control cross-sectional study, we recruited patients aged ≥50 years diagnosed with aMCI and AD from the Samsung Medical Center, Seoul, Korea, between 2014 and 2019. For each patient, we randomly selected four cognitively healthy controls through frequency matching based on sex, age group, and education level. Urinary levels of four PAH metabolites, 1-hydroxypyrene (1-OHP), 1-hydroxyphenanthrene (1-OHPhe), 2-hydroxyfluorene (2-OHFlu), and 2-naphthol (2-NAP), were measured. A conditional logistic regression model was used to evaluate the association, adjusting for potential confounders. A total of 212 patients with aMCI with 848 matched controls, and 267 patients with AD with 1068 matched controls were included in the analyses to estimate the risk of PAH exposure. We found that elevated urinary levels of PAH metabolites (specifically, 1-OHP and 2-NAP) were significantly associated with an increased risk of aMCI and AD. An increase of one unit in log-transformed level of urinary 1-OHP was associated with a 1.15- and 1.16-times higher risk of aMCI and AD, respectively. An increase of one unit in log-transformed level of urinary 2-NAP was associated with a 1.11- and 1.13-times higher risk of aMCI and AD, respectively. These findings indicate that PAH exposure may increase the risk of aMCI and AD, especially for the elderly population. Considering the widespread distribution of PAHs in the environment, reducing PAH exposure may be an effective strategy for the prevention of neurodegenerative diseases.

Cerebello-Parietal Functional Connectivity in Amnestic Mild Cognitive Impairment.

The role of the cerebellum in amnestic mild cognitive impairment (aMCI), typically a prodromal stage of Alzheimer's disease, is not fully understood. We studied the lobule-specific cerebello-cerebral connectivity in 15 cognitively normal and 16 aMCI using resting-state functional MRI. Our analysis revealed weaker connectivity between the cognitive cerebellar lobules and parietal lobe in aMCI. However, stronger connectivity was observed in the cognitive cerebellar lobules with certain brain regions, including the precuneus cortex, posterior cingulate gyrus, and caudate nucleus in participants with worse cognition. Leveraging these measurable changes in cerebello-parietal functional networks in aMCI could offer avenues for future therapeutic interventions.

Neural Basis of Agitated Behaviors in Patients with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

Aggression, a common symptom of Alzheimer's disease (AD), can impose a significant burden on caregivers, necessitating early institutionalization. The current study examined the neural basis of aggression and its expression mechanism, to advance the development of effective treatment strategies for aggression in patients with AD. The study sample included 257 patients; 180 were diagnosed with AD and 77 with amnestic mild cognitive impairment (aMCI). Factor analysis of the neuropsychiatric inventory (NPI) aggression scores was performed, and the correlation between each factor and cerebral blood flow (CBF) was examined via diagnosis of AD or aMCI using statistical parametric mapping. Refusal of care was correlated with reduced CBF in the right hippocampus of patients with AD while no specific related regions could be identified in patients with aMCI. Violent behavior was associated with decreased CBF in the right temporal pole and medial frontal lobe of patients with AD and aMCI. These findings suggest that aggression, measured using NPI includes two distinct symptoms, refusal of care and violent behavior, having different underlying neural bases.

Associations Between Free and Cued Selective Reminding Test and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment.

The Free and Cued Selective Reminding Test (FCSRT), assessing verbal episodic memory with controlled learning and semantic cueing, has been recommended for detecting the genuine encoding and storage deficits characterizing AD-related memory disorders. The present study aims at investigating the ability of FCSRT in predicting cerebrospinal fluid (CSF) evidence of amyloid-β positivity in subjects with amnestic mild cognitive impairment (aMCI) and exploring its associations with amyloidopathy, tauopathy and neurodegeneration biomarkers. 120 aMCI subjects underwent comprehensive neurological and neuropsychological examinations, including the FCSRT assessment, and CSF collection; CSF Aβ42/40 ratio, p-tau181, and total-tau quantification were conducted by an automated CLEIA method on Lumipulse G1200. Based on the Aβ42/40 ratio value, subjects were classified as either A+ or A-. All FCSRT subitem scores were significantly lower in A+ group and significantly predicted the amyloid-β status, with Immediate Total Recall (ITR) being the best predictor. No significant correlations were found between FCSRT and CSF biomarkers in the A- aMCI group, while in the A+ aMCI group, all FCSRT subitem scores were negatively correlated with CSF p-tau181 and total-tau, but not with the Aβ42/40 ratio. FCSRT confirms its validity as a tool for the diagnosis of AD, being able to predict the presence of amyloid-β deposition with high specificity. The associations between FCSRT subitem scores and CSF p-tau-181 and total-tau levels in aMCI due to AD could further encourage the clinical use of this simple and cost-effective test in the evaluation of individuals with aMCI.

Brain inflammation co-localizes highly with tau in mild cognitive impairment due to early-onset Alzheimer's disease.

Brain inflammation, with an increased density of microglia and macrophages, is an important component of Alzheimer's disease (AD) and a potential therapeutic target. However, it is incompletely characterized, particularly in patients whose disease begins before the age of 65 years and, thus, have few co-pathologies. Inflammation has been usefully imaged with translocator protein (TSPO) positron emission tomography (PET), but most inflammation PET tracers cannot image subjects with a low-binder TSPO rs6971 genotype. In an important development, participants with any TSPO genotype can be imaged with a novel tracer, [11C]ER176, that has a high binding potential and a more favorable metabolite profile than other TSPO tracers currently available. We applied [11C]ER176 to detect brain inflammation in mild cognitive impairment (MCI) caused by early-onset AD. Furthermore, we sought to correlate the brain localization of inflammation, volume loss, elevated Aβ and tau. We studied brain inflammation in 25 patients with early-onset amnestic MCI (average age 59 ± 4.5 years, 10 women) and 23 healthy controls (average age 65 ± 6.0 years, 12 women), both groups with a similar proportion of all three TSPO-binding affinities. [11C]ER176 total distribution volume (VT), obtained with an arterial input function, was compared across patients and controls using voxel-wise and region-wise analyses. In addition to inflammation PET, most MCI patients had Aβ (n=23), and tau PET (n=21). For Aβ and tau tracers, standard uptake value ratios (SUVRs) were calculated using cerebellar grey matter as region of reference. Regional correlations among the three tracers were determined. Data were corrected for partial volume effect. Cognitive performance was studied with standard neuropsychological tools. In MCI caused by early-onset AD, there was inflammation in the default network, reaching statistical significance in precuneus and lateral temporal and parietal association cortex bilaterally, and in the right amygdala. Topographically, inflammation co-localized most strongly with tau (r= 0.63 ± 0.24). This correlation was higher than the co-localization of Aβ with tau (r= 0.55±0.25) and of inflammation with Aβ (0.43±0.22). Inflammation co-localized least with atrophy (-0.29±0.26). These regional correlations could be detected in participants with any of the three rs6971 TSPO polymorphisms. Inflammation in AD-related regions correlated with impaired cognitive scores. Our data highlight the importance of inflammation, a potential therapeutic target, in the AD process. Furthermore, they support the notion that, as shown in experimental tissue and animal models, the propagation of tau in humans is associated with brain inflammation.

Risk-Taking Behavior Differs Between Older Adults with and without Mild Cognitive Impairment.

Adequately evaluating risk and making decisions is vital but understudied for older adults living independently but with compromised cognition, as seen in those with mild cognitive impairment (MCI), specifically those with amnestic MCI (aMCI) which is associated with higher risk of conversion to Alzheimer's disease. We propose to comprehensively evaluate risk-taking behaviors across domains important for everyday activities between an aMCI group and their cognitively healthy counterparts (HC). A case-control study design. Data on risk-taking behaviors via the Domain-Specific Risk-Taking Scale (DOSPERT), and candidate confounding mental health factors (i.e., neurodegeneration, depression, and fatigue) were collected. Analyses on group difference and interaction between group and confounding factors on risk-taking behaviors were conducted. The aMCI group showed a higher likelihood of risk-taking than HC (t = 4.38, df = 73, p < 0.001). Moderation analysis showed fatigue (F = 5.91, p = 0.018) and presence of depression (F = 4.52, p = 0.037), but not neurodegeneration, as significant moderators for group and DOSPERT total score, controlling for sex. In post-hoc analyses, there was a significant relationship between both fatigue (B = -7.83, SE = 3.65, t = -2.14, p = 0.036), and presence of depression (B = -20.80, SE = 9.97, t = -2.09, p = 0.041), with DOSPERT total score for HC but not for aMCI. There were no significant relationships between neurodegeneration, fatigue, or depression with any specific risk-taking domains after correction for multiple comparisons. Our results show differences in risk-taking behavior between older adults with and without intact cognition, and overall decision-making is affected by fatigue and depression in HC but not aMCI, together suggesting the importance of cognition in the ability to adjust risk-taking behaviors.

Effect of APOE ɛ4 Status on Brain Amyloid‐β and Cognitive Function in Amnestic and Nonamnestic Mild Cognitive Impairment: A [18F] Florbetapir PET‐CT Study

AbstractMild cognitive impairment (MCI) is recognized as a predementia syndrome caused by multiple etiologies and nonmemory symptoms in MCI have recently gained increasing attention. However, the pattern of Aβ deposition and the effect of APOE (apolipoprotein E, APOE) ε4 on cognitive impairment in amnestic MCI (aMCI) and nonamnestic MCI (naMCI) patients has not been demonstrated. In this work, the amyloid‐β (Aβ) load by [18F]florbetapir PET imaging and cognitive performance is compared by comprehensive neuropsychological scales in participants with different MCI types or different APOE ε4 carriage status. According to the Aβ positivity and results of voxel‐wise analysis, higher Aβ loads are observed in aMCI patients than naMCI patients, especially aMCI patients with APOE ε4. Additionally, it is observed that memory domain Z scores show a strong negative correlation with global florbetapir SUVR in the aMCI group (r = – 0.352, p &lt; 0.001) but not in the naMCI group (r = –0.016, p = 0.924). Moreover, this correlation is independent of APOE e4 carriage status. This study aims to identify high‐risk groups at an early stage of AD(Alzheimer's Disease, AD) through cognitive performance and APOE ε4 carrier status, which can be important for guiding clinical intervention trials.

Loneliness and Resting-State Functional Brain Connectivity Among Older Adults: A Proportional Correlation.

Loneliness reportedly increases the risk of dementia, especially Alzheimer's disease (AD). The authors' previous study demonstrated associations between loneliness and structural abnormalities observed in early-stage AD. The present study examined associations between the brain's functional characteristics and loneliness among older adults with concerns about cognitive decline. This single-center study included 43 participants (13 with amnestic mild cognitive impairment and 30 with normal cognition). Participants were assessed with the revised University of California Los Angeles (UCLA) Loneliness Scale and underwent resting-state functional MRI. Functional images were preprocessed with the CONN toolbox. The selected seeds were within brain regions reportedly associated with loneliness. One-sample general linear model analysis was performed to examine regressions of UCLA Loneliness Scale scores and functional connectivity between the seeds and regions of interest. The revised UCLA Loneliness Scale scores were positively correlated with functional connectivity between the right hippocampus and left lateral parietal lobe and were negatively correlated with functional connectivity between the left amygdala and left frontal operculum and between the left amygdala and right supramarginal gyrus. Analyses were adjusted for age, sex, and education and scores on the Mini-Mental State Examination and Clinical Dementia Rating scale. Loneliness was associated with abnormal function of the hippocampus, parts of the parietal lobe and frontal cortex, and the amygdala. These findings may suggest a possible correlation between loneliness and neurological changes associated with dementia.

Elevated plasma neurofilament light was associated with multi-modal neuroimaging features in Alzheimer’s disease signature regions and predicted future tau deposition

BackgroundNeurofilament Light (NfL) is a biomarker for early neurodegeneration in Alzheimer’s disease (AD). This study aims to examine the association between plasma NfL and multi-modal neuroimaging features across the AD spectrum and whether NfL predicts future tau deposition.MethodsThe present study recruited 517 participants comprising Aβ negative cognitively normal (CN-) participants (n = 135), Aβ positive cognitively normal (CN +) participants (n = 64), individuals with amnestic mild cognitive impairment (aMCI) (n = 212), and those diagnosed with AD dementia (n = 106). All the participants underwent multi-modal neuroimaging examinations. Cross-sectional and longitudinal associations between plasma NfL and multi-modal neuro-imaging features were evaluated using partial correlation analysis and linear mixed effects models. We also used linear regression analysis to investigate the association of baseline plasma NfL with future PET tau load. Mediation analysis was used to explore whether the effect of NfL on cognition was mediated by these imaging biomarkers.ResultsThe results showed that baseline NfL levels and the rate of change were associated with Aβ deposition, brain atrophy, brain connectome, glucose metabolism, and brain perfusion in AD signature regions (P<0.05). In both Aβ positive CN and MCI participants, baseline NfL showed a significant predictive value of elevating tau burden in the left medial orbitofrontal cortex and para-hippocampus (β = 0.336, P = 0.032; β = 0.313, P = 0.047). Lastly, the multi-modal neuroimaging features mediated the association between plasma NfL and cognitive performance.ConclusionsThe study supports the association between plasma NfL and multi-modal neuroimaging features in AD-vulnerable regions and its predictive value for future tau deposition.

Predicting progression from subjective cognitive decline to mild cognitive impairment or dementia based on brain atrophy patterns

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder where pathophysiological changes begin decades before the onset of clinical symptoms. Analysis of brain atrophy patterns using structural MRI and multivariate data analysis are an effective tool in identifying patients with subjective cognitive decline (SCD) at higher risk of progression to AD dementia. Atrophy patterns obtained from models trained to classify advanced AD versus normal subjects, may not be optimal for subjects at an early stage, like SCD. In this study, we compared the accuracy of the SCD progression prediction using the ‘severity index’ generated using a standard classification model trained on patients with AD dementia versus a new model trained on β-amyloid (Aβ) positive patients with amnestic mild cognitive impairment (aMCI).MethodsWe used structural MRI data of 504 patients from the Swedish BioFINDER-1 study cohort (cognitively normal (CN), Aβ-negative = 220; SCD, Aβ positive and negative = 139; aMCI, Aβ-positive = 106; AD dementia = 39). We applied multivariate data analysis to create two predictive models trained to discriminate CN individuals from either individuals with Aβ positive aMCI or AD dementia. Models were applied to individuals with SCD to classify their atrophy patterns as either high-risk “disease-like” or low-risk “CN-like”. Clinical trajectory and model accuracy were evaluated using 8 years of longitudinal data.ResultsIn predicting progression from SCD to MCI or dementia, the standard, dementia-based model, reached 100% specificity but only 10.6% sensitivity, while the new, aMCI-based model, reached 72.3% sensitivity and 60.9% specificity. The aMCI-based model was superior in predicting progression from SCD to MCI or dementia, reaching a higher receiver operating characteristic area under curve (AUC = 0.72; P = 0.037) in comparison with the dementia-based model (AUC = 0.57).ConclusionWhen predicting conversion from SCD to MCI or dementia using structural MRI data, prediction models based on individuals with milder levels of atrophy (i.e. aMCI) may offer superior clinical value compared to standard dementia-based models.

Distinguishable neural circuit mechanisms associated with the clinical efficacy of rTMS in aMCI patients.

Repetitive transcranial magnetic stimulation is used in early-stage Alzheimer's disease to slow progression, but heterogeneity in response results in different treatment outcomes. The mechanisms underlying this heterogeneity are unclear. This study used resting-state neuroimaging to investigate the variability in episodic memory improvement from angular gyrus repetitive transcranial magnetic stimulation and tracked the neural circuits involved. Thirty-four amnestic mild cognitive impairment patients underwent angular gyrus repetitive transcranial magnetic stimulation (4weeks, 20Hz, 100% resting motor threshold) and were divided into high-response and low-response groups based on minimal clinically important differences in auditory verbal learning test scores. Baseline and pre/post-treatment neural circuit activities were compared. Results indicated that the orbital middle frontal gyrus in the orbitofrontal cortex network and the precuneus in the default mode network had higher local activity in the low-response group. After treatment, changes in local and remote connectivity within brain regions of the orbitofrontal cortex, default mode network, visual network, and sensorimotor network showed opposite trends and were related to treatment effects. This suggests that the activity states of brain regions within the orbitofrontal cortex and default mode network could serve as imaging markers for early cognitive compensation in amnestic mild cognitive impairment patients and predict the aftereffects of repetitive transcranial magnetic stimulation response.

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen’s criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

Vulnerability to semantic and phonological interference in normal aging and amnestic mild cognitive impairment (aMCI).

To determine whether the increased vulnerability to semantic interference previously observed in amnestic mild cognitive impairment (aMCI) is specifically associated with semantic material or if it also affects other types of material, suggesting generalized executive and inhibitory impairment. Seventy-two participants divided into two groups (33 aMCI, 39 normal control [NC]) matched for age and education were included. They completed a comprehensive neuropsychological examination, the French version of the Loewenstein Acevedo Scale for Semantic Interference and Learning (LASSI-L; semantic interference test), and a homologous experimental phonological test, the phonological interference and learning test. Independent sample t tests, mixed analysis of variance (ANOVA), and analysis of covariance (ANCOVA) on memory and interference scores were conducted to compare memory and interference in both conditions for both groups. For memory scores, results revealed significant main effects of group (NC > aMCI) and condition (semantic > phonological) and significant interactions (poorer performance in the semantic condition for aMCI). aMCI committed more phonological false recognition errors, were disproportionately more vulnerable to retroactive semantic interference, and showed a higher percentage of intrusion errors associated with proactive semantic interference than NC. To our knowledge, this is the first study to compare vulnerability to interference in aMCI and normal aging with two similarly designed semantic and phonological word list learning tasks. Taken together, our results suggest that aMCI present with broad difficulties in source memory and inhibition, but that impaired deep semantic processing results in additional semantic intrusion errors during proactive interference and impacts their ability to show good recall after an interference list (greater semantic retroactive interference). Results are discussed according to the level-of-processing and activation/monitoring theories. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Do sex and handedness influence general cognition and financial capacity in patients with aMCI and healthy older adults? Emphasis on women's performance.

The effects of sex and handedness on financial capacity performance remain unexplored both in healthy older adults and in patients with amnestic mild cognitive impairment (aMCI). The aim of this study was to study the effect of the above factors (sex, handedness, and health condition), following a factorial experimental design; hence, eight groups (each with ten individuals) with similar demographic characteristics (age and education level) were formed consisting of right/left-handed, women/men and healthy/not healthy (with a diagnosis of aMCI) older adults. Mini-Mental State Examination (MMSE) was administered as a measure of general cognitive ability, and Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS) was used as an indicator of financial capacity; moreover, GDS-15 was used to assess depressive symptomatology. Self-reports of hand preference were also included. Although as expected healthy men and women regardless of their handedness outperformed aMCI patients on MMSE and LCPLTAS, performance on cash transactions, bank statement management, bill payment, financial decision making, and knowledge of personal assets from LCPLTAS is significantly higher for right-handed aMCI women compared with left-handed aMCI women. Future research should further elucidate the reasons for this left-handed female patient with aMCI profile in larger groups of patients. This is an exploratory study, and the small sample size limits the strength of conclusions; further studies on this topic are needed.

Altered activation of the dorsal anterior cingulate cortex during oddball performance in individuals at risk for Alzheimer's disease

IntroductionThe neural mechanisms underlying neurodegenerative disorders in the elderly remain elusive, despite extensive neuroimaging research in recent decades. Amnestic type mild cognitive impairment (aMCI) and late-life major depressive disorder (MDD) are two such conditions characterized by intersecting cognitive and affective symptomatology, and they are at a higher risk for Alzheimer's disease. Materials and methodsThis study analyzed the neural underpinnings of cognitive and depressive symptoms in a cohort comprising 12 aMCI subjects, 24 late-life MDD patients, and 26 healthy controls (HCs). Participants underwent a detailed neuropsychological assessment and completed a visual attentional oddball task during functional magnetic resonance imaging (fMRI), with evaluations at baseline and at 2-year follow-up. ResultsInitial findings showed that aMCI subjects had reduced dACC activation during oddball (target) stimulus detection, a pattern that persisted in longitudinal analyses and correlated with cognitive functioning measures. For HCs, subsequent dACC activation was linked to depression scores. Furthermore, in the affective-cognitive altered groups, later dACC activation correlated with oddball and memory performance. ConclusionsThese findings enhance our comprehension of the neurobiological basis of cognitive and depressive disturbances in aging, indicating that dACC activation in response to a visual attentional oddball task could serve as a neural marker for assessing cognitive impairment and depression in conditions predisposing to Alzheimer's disease.

Volumetric and functional connectivity changes of the thalamic nuclei in different stages of Alzheimer’s disease

ObjectiveMemory processes known to be impaired in Alzheimer’s disease (AD) are maintained by a large-scale neurocognitive network with subcortical components, including the thalamus. Therefore, we aimed to examine the volumetric and functional changes of the thalamic nuclei at different scales across AD stages. MethodsMRI data of patients diagnosed with 20 AD dementia (ADD), 30 amnestic mild cognitive impairment (MCI), and 30 subjective cognitive impairment (SCI) were used. Volumetric and functional connectivity analyzes were performed by dividing the thalamus into anterior, medial, posterior, lateral and intralaminar nucleus groups and their specific subnuclei. ResultsIn the course of AD, the volume of the medial group nuclei, especially the mediodorsal medial magnocellular (MDm) nucleus, decreases. Medial group nuclei and MDm functional connectivity with frontal areas were decreased both in ADD and MCI compared to SCI group, while both of them increased their functional connectivity with visual areas in the ADD group compared to the MCI group. ConclusionsOur study suggests that the medial group of the thalamus, and specifically the MDm, may be affected in AD. SignificanceSpecific thalamic nuclei may be a critical anatomical region for investigating structural and functional changes in AD.

Machine Learning Classification of Patients with Amnestic Mild Cognitive Impairment and Non-Amnestic Mild Cognitive Impairment from Written Picture Description Tasks.

Individuals with Mild Cognitive Impairment (MCI), a transitional stage between cognitively healthy aging and dementia, are characterized by subtle neurocognitive changes. Clinically, they can be grouped into two main variants, namely patients with amnestic MCI (aMCI) and non-amnestic MCI (naMCI). The distinction of the two variants is known to be clinically significant as they exhibit different progression rates to dementia. However, it has been particularly challenging to classify the two variants robustly. Recent research indicates that linguistic changes may manifest as one of the early indicators of pathology. Therefore, we focused on MCI's discourse-level writing samples in this study. We hypothesized that a written picture description task can provide information that can be used as an ecological, cost-effective classification system between the two variants. We included one hundred sixty-nine individuals diagnosed with either aMCI or naMCI who received neurophysiological evaluations in addition to a short, written picture description task. Natural Language Processing (NLP) and a BERT pre-trained language model were utilized to analyze the writing samples. We showed that the written picture description task provided 90% overall classification accuracy for the best classification models, which performed better than cognitive measures. Written discourses analyzed by AI models can automatically assess individuals with aMCI and naMCI and facilitate diagnosis, prognosis, therapy planning, and evaluation.

Detection of cerebrospinal fluid biomarkers changes of Alzheimer's disease using a cognitive stress test in persons with subjective cognitive decline and mild cognitive impairment.

Timely and accurate diagnosis of the earliest manifestations of Alzheimer's disease (AD) is critically important. Cognitive challenge tests such as the Loewenstein Acevedo Scales for Semantic Interference and Learning (LASSI-L) have shown favorable diagnostic properties in a number of previous investigations using amyloid or FDG PET. However, no studies have examined LASSI-L performance against cerebrospinal fluid biomarkers of AD, which can be affected before the distribution of fibrillar amyloid and other changes that can be observed in brain neuroimaging. Therefore, we aimed to evaluate the relationship between LASSI-L scores and CSF biomarkers and the capacity of the cognitive challenge test to detect the presence of amyloid and tau deposition in patients with subjective cognitive decline and amnestic mild cognitive impairment (MCI). One hundred and seventy-nine patients consulting for memory loss without functional impairment were enrolled. Patients were examined using comprehensive neuropsychological assessment, the LASSI-L, and cerebrospinal fluid (CSF) biomarkers (Aβ1-42/Aβ1-40 and ptau181). Means comparisons, correlations, effect sizes, and ROC curves were calculated. LASSI-L scores were significantly associated with CSF biomarkers Aβ1-42/Aβ1-40 in patients diagnosed with MCI and subjective cognitive decline, especially those scores evaluating the capacity to recover from proactive semantic interference effects and delayed recall. A logistic regression model for the entire sample including LASSI-L and age showed an accuracy of 0.749 and an area under the curve of 0.785 to detect abnormal amyloid deposition. Our study supports the biological validity of the LASSI-L and its semantic interference paradigm in the context of the early stages of AD. These findings emphasize the utility and the convenience of including sensitive cognitive challenge tests in the assessment of patients with suspicion of early stages of AD.