Search Results (19)

Background/Objectives: The study examined the relationships between specific Theory-of-Mind (ToM) dimensions, cognitive planning, and sleep duration in aging adults. Methods: The sample included 179 participants, comprising 46 cognitively healthy individuals, 75 diagnosed with amnestic Mild Cognitive Impairment (aMCI), and 58 with non-amnestic (naMCI). The mean age of the participants was 70.23 years (SD = 4.74), with a mean educational attainment of 12.35 years (SD = 3.22) and gender distribution of 53 men and 126 women. ToM assessment included tasks measuring the understanding and interpretation of non-literal speech, proverbs and metaphors, as well as an emotion-recognition test. For cognitive planning, a Tower Test was utilized. Sleep duration was measured using actigraphy. Results: We identified significant differences in various ToM tasks’ performance between the groups, particularly in non-literal speech tasks and third-order ToM stories. The HC group consistently outperformed both MCI groups in these tasks, with aMCI showing higher performance than naMCI. Mediation analysis applied to examine potential direct and indirect effects of sleep duration on ToM tasks indicated that total sleep time had significant indirect effects through cognitive planning—mainly as rule violation total score—on specific ToM aspects. Hence, besides the effects of MCI pathologies and especially of naMCI, sleep duration seems also to be associated with ToM performance in aging via specific executive functioning decrements. Conclusions: The findings underscore the social implications of ToM deficits due to MCI and/or sleep duration decrease, particularly in naMCI older adults, as they can seriously impair their social interactions. Targeted interventions could improve emotional understanding, communication, and overall quality of life. Full article

Background: Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are currently underdiagnosed in the community, and early detection of cognitive deficits is crucial for timely intervention. FACEmemory^®, the first completely self-administered online memory test with voice recognition, has been launched as an accessible tool to detect such deficits. This study aims to investigate the neuropsychological associations between FACEmemory subscores and cognitive composites derived from traditional paper-and-pencil neuropsychological tests and to develop an optimal algorithm using FACEmemory data and demographics to discriminate cognitively healthy (CH) individuals from those with MCI. Methods: A total of 669 participants (266 CH, 206 non-amnestic MCI [naMCI], and 197 amnestic MCI [aMCI]) were included. Multiple linear regression analyses were conducted using a cognitive composite as the dependent variable and FACEmemory subscores and demographic data (age, sex, and schooling) as independent variables. Machine learning models were compared to identify an optimal algorithm for distinguishing between CH and MCI (whole MCI, aMCI, and naMCI). Results: Multiple regression analyses showed associations between FACEmemory scores and the domains of memory (ρ = 0.67), executive functions (ρ = 0.63), visuospatial/visuoperceptual abilities (ρ = 0.55), language (ρ = 0.43), praxis (ρ = 0.52), and attention (ρ = 0.31). An optimal algorithm distinguished between CH and aMCI, achieving a FACEmemory cutoff score of 44.5, with sensitivity and specificity values of 0.81 and 0.72, respectively. Conclusions: FACEmemory is a promising online tool for identifying early cognitive impairment, particularly aMCI. It may contribute to addressing the underdiagnosis of MCI and dementia in the community and in promoting preventive strategies. Full article

This study aimed to examine the associations between specific sleep parameters and specific aspects of cognitive functioning in individuals diagnosed with mild cognitive impairment (MCI), compared with healthy controls (HCs) by using cognitive, subjective, and objective sleep measures. A total of 179 participants were enrolled, all aged ≥ 65 years (mean age = 70.23; SD = 4.74) and with a minimum of six years of education (mean = 12.35; SD = 3.22). The sample included 46 HCs (36 females), 75 individuals with amnestic MCI (aMCI) (51 females), and 58 individuals with non-amnestic MCI (naMCI) (39 females). Inhibition, cognitive flexibility as a combined application of inhibitory control and set shifting or task/rule switching, and planning were examined. The following D-KEFS subtests were administered for their evaluation: Verbal Fluency Test, Color–Word Interference Test, and Tower Test. Self-reported sleep questionnaires (Athens Insomnia Scale, Stop-Bang questionnaire, and Pittsburg Sleep Quality Index) were used for subjective sleep assessments. Actigraphy was used for objective sleep measurements. Mixed-measures ANOVA, MANOVA, and one-way ANOVA, as well as the Scheffe post hoc test, were applied to the data. The results showed that the three groups exhibited statistically significant differences in the Tower Test (total achievement score, total number of administered problems, and total rule violations). As regards objective sleep measurements, the total sleep time (TST) was measured using actigraphy, and indicated that there are significant differences, with the HC group having a significantly higher mean TST compared to the naMCI group. The relationships evaluated in the TST Tower Test were found to be statistically significant. The findings are discussed in the context of potential parameters that can support the connection between sleep duration, measured as TST, and cognitive planning, as measured using the Tower Test. Full article

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. Full article

Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer’s disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did not have a clinically determined diagnosis of dementia by the end of the three-year study. Additionally, we explored the connection between baseline plasma concentration of NfL and AD dementia patients, considering their demographics, clinical features, and cognitive profiles. A total of 350 participants from the Biomarker of AmyLoid pepTide and AlZheimer’s diseAse Risk (BALTAZAR) multicenter prospective study were investigated: 161 AD dementia participants and 189 MCI participants (of which 141 had amnestic MCI and 48 non-amnestic MCI). Plasma biomarkers were measured at baseline and the progression of clinical and cognitive profiles was followed over the three years of follow-up. Baseline plasma NfL concentration increased across the Alzheimer’s disease continuum with a mean NfL value of 17.1 ng/mL [SD = 6.1] in non-amnestic MCI, 20.7 ng/mL [SD = 12.0] in amnestic MCI, and 23.1 ng/mL [SD = 22.7] in AD dementia patients. Plasma NfL concentration correlated with age, body mass index (BMI), and global cognitive performance and decline, as measured by the Mini-Mental State Examination (MMSE). MMSE scores decreased in parallel with increasing plasma NfL concentration, independently of age and BMI. However, NfL concentration did not predict MCI participants’ conversion to dementia within three years. Discussion: Baseline plasma NfL concentration is associated with cognitive status along the AD continuum, suggesting its usefulness as a potential informative biomarker for cognitive decline follow-up in patients. Full article

Mild cognitive impairment (MCI) is a transitional clinical stage prior to dementia. Patients with amnestic MCI have a high risk of progression toward Alzheimer’s disease. Both amnestic mild cognitive impairment and sporadic Alzheimer’s disease are multifactorial disorders consequential from a multifaceted cross-talk among molecular and biological processes. Non-coding RNAs play an important role in the regulation of gene expression, mainly long non-coding RNAs (lncRNAs), that regulate other RNA transcripts through binding microRNAs. Cross-talk between RNAs, including coding RNAs and non-coding RNAs, produces a significant regulatory network all through the transcriptome. The relationship of genes and non-coding RNAs could improve the knowledge of the genetic factors contributing to the predisposition and pathophysiology of MCI. The objective of this study was to identify the expression patterns and relevant lncRNA-associated miRNA regulatory axes in the blood of MCI patients, which includes lncRNA-SNHG16, lncRNA-H19, and lncRNA-NEAT1. Microarray investigations have demonstrated modifications in the expression of long non-coding RNAs (lncRNA) in the blood of patients with MCI compared with control samples. This is the first study to explore lncRNA profiles in mild cognitive impairment blood. Our study proposes RNAs targets involved in molecular pathways connected to the pathogenesis of MCI. Full article

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. Full article

Objectives: This pilot study aims to explore the potential of a positive psychology intervention (PPI) in enhancing the subjective well-being of older individuals with amnestic mild cognitive impairment (MCI), a precursor to dementia. Design and Setting: A randomized trial was conducted, initially recruiting 51 participants aged 65 and above from the Greek Association of Alzheimer’s Disease and Related Disorders in Thessaloniki, Greece. The study employed a control-experimental group setup. To ensure randomization, each participant was assigned a unique number, and a random number generator was used for group allocation. Participants: A total of 41 eligible participants with amnestic mild cognitive impairment (MCI) were included in the study after screening. Intervention: The intervention consisted of a 3-week positive psychology program (PPI) where the PERMA Profiler questionnaire was administered at three intervals: pre-intervention, post-intervention, and one month after completion. Main Outcome Measures: The subjective well-being of participants. Results: The analysis, conducted mainly through mixed-measures ANOVAs, supported the study’s hypotheses, revealing that the 3-week PPI led to increased PERMA model scores and overall well-being, which persisted even after one month. Conversely, non-participants experienced declines in most domains except for Positive Emotion and Meaning, which demonstrated improvement and recovery during follow-up. Conclusions: These findings suggest the potential of PPI in enhancing the subjective well-being of older adults with amnestic MCI, with implications for addressing dementia-related challenges. Further investigation is warranted to pinpoint PPI effects on MCI and tailor interventions for improved subjective well-being. Full article

Growing evidence suggests that neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases. Peripheral markers of inflammation, including blood cell counts and their ratios, such as the neutrophil-to-lymphocyte ratio (NLR), have been reported as an easily accessible and reliable proxy of central nervous system inflammation. However, the role of peripheral inflammation in dementia and Mild Cognitive Impairment (MCI) still needs to be clarified. In the current study, we aimed to assess the prognostic role of the NLR and other peripheral markers of inflammation in a sample of 130 amnestic MCI, followed up for two to five years. The Mini-Mental state examination (MMSE) score at baseline and follow-up visits was used to assess global cognitive status at each visit and the degree of cognitive decline over time. Baseline peripheral markers of inflammation included blood cell counts and ratios, specifically the NLR, the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), and the systemic immune inflammation index (SII). After classifying subjects into CONVERTERS and non-CONVERTERS (respectively, patients converting to dementia and subjects showing stability at the last available follow-up), we compared peripheral markers of inflammation among groups ed correlated them with cognitive measures, testing the ability of significant factors to predict conversion to dementia. In our cohort, CONVERTERS showed lower baseline MMSE scores (p-value = 0.004) than non-CONVERTERS. In addition, CONVERTERS had statistically elevated NLR (p-value = 0.005), PLR (p-value = 0.002), and SII levels (p-value = 0.015), besides a lower number of lymphocytes (p-value = 0.004) compared with non-CONVERTERS. In a logistic regression analysis, baseline MMSE scores and NLR predicted conversion to dementia. Tertiles analysis showed that MCI with the highest NLR values had a higher conversion risk. Our study supports the hypothesis that a dysregulation of peripheral inflammation involving both lymphocytes and neutrophils may play a role in the pathogenesis of dementia, even at the early stages of neurodegeneration, as in the MCI condition. Full article

Studies demonstrated impairment in the control of saccadic eye movements in Alzheimer’s disease (AD) and people with mild cognitive impairment (MCI) when conducting the pro-saccade and antisaccade tasks. Research showed that changes in the pro and antisaccade latencies may be particularly sensitive to dementia and general executive functioning. These tasks show potential for diagnostic use, as they provide a rich set of potential eye tracking markers. One such marker, the coefficient of variation (CV), is so far overlooked. For biological markers to be reliable, they must be able to detect abnormalities in preclinical stages. MCI is often viewed as a predecessor to AD, with certain classifications of MCI more likely than others to progress to AD. The current study examined the potential of CV scores on pro and antisaccade tasks to distinguish participants with AD, amnestic MCI (aMCI), non-amnesiac MCI (naMCI), and older controls. The analyses revealed no significant differences in CV scores across the groups using the pro or antisaccade task. Antisaccade mean latencies were able to distinguish participants with AD and the MCI subgroups. Future research is needed on CV measures and attentional fluctuations in AD and MCI individuals to fully assess this measure’s potential to robustly distinguish clinical groups with high sensitivity and specificity. Full article

Mild Cognitive Impairment (MCI) is a transition stage between normal aging and dementia and can be useful to monitor the cognitive status of people at risk of dementias. Our aims were to investigate the prevalence of amnestic and non-amnestic MCI in a South Italian elderly population, and to identify socio-demographic, clinical and lifestyle factors associated with MCI. A cross-sectional retrospective population study on 839 community-dwelling participants over 60 years of age was carried out. Elderly people were administered a brief neuropsychological screening to identify their cognitive and functional status, and a questionnaire to investigate several socio-demographic, clinical, and lifestyle factors. Prevalence estimate for MCI was 12.0% (95% CI: 10.0–14.5%), for amnestic MCI was 7.4% (95% CI: 5.8–9.4%), and for non-amnestic MCI was 4.6% (95% CI: 3.4–6.4%), for people older than 60 years of age. Logistic regression models, corrected for age, sex, and education, revealed a significant association of MCI with the following factors: age, education, intellectual activities, and topographical disorientation. On the other hand, education, clinical factors (e.g., depression level and perceived physical pain), lifestyle factors (e.g., smoking, alcohol, and leisure/productive activities), dietary habits, quality of life, and self-reported topographical disorientation were non-significantly associated with MCI. Prevalence estimates and the association of MCI and its subtypes with risk and protective factors were discussed in comparison with the most recent systematic reviews and meta-analyses. Full article

The Aberdeen birth cohorts of 1921 and 1936 (ABC21 and ABC36) were subjected to IQ tests in 1932 or 1947 when they were aged about 11y. They were recruited between 1997–2001 among cognitively healthy community residents and comprehensively phenotyped in a long-term study of brain aging and health up to 2017. Here, we report associations between baseline cognitive test scores and long-term cognitive outcomes. On recruitment, significant sex differences within and between the ABC21 and ABC36 cohorts supported advantages in verbal ability and learning among the ABC36 women that were not significant in ABC21. Comorbid physical disorders were self-reported in both ABC21 and ABC36 but did not contribute to differences in terms of performance in cognitive tests. When used alone without other criteria, cognitive tests scores which fell below the −1.5 SD criterion for tests of progressive matrices, namely verbal learning, digit symbol and block design, did not support the concept that Mild Cognitive Impairment (MCI) is a stable class of acquired loss of function with significant links to the later emergence of a clinical dementia syndrome. This is consistent with many previous reports. Furthermore, because childhood IQ-type data were available, we showed that a lower cognitive performance at about 64 or 78 y than that predicted by IQ at 11 ± 0.5 y did not improve the prediction of progress to MCI or greater cognitive loss. We used binary logistic regression to explore how MCI might contribute to the prediction of later progress to a clinical dementia syndrome. In a fully adjusted model using ABC21 data, we found that non-amnestic MCI, along with factors such as female sex and depressive symptoms, contributed to the prediction of later dementia. A comparable model using ABC36 data did not do so. We propose that (1) MCI criteria restricted to cognitive test scores do not improve the temporal stability of MCI classifications; (2) pathways towards dementia may differ according to age at dementia onset and (3) the concept of MCI may require measures (not captured here) that underly self-reported subjective age-related cognitive decline. Full article

Older adults with amnestic mild cognitive impairment (aMCI) who in addition to their memory deficits also suffer from frontal-executive dysfunctions have a higher risk of developing dementia later in their lives than older adults with aMCI without executive deficits and older adults with non-amnestic MCI (naMCI). Handgrip strength (HGS) is also correlated with the risk of cognitive decline in the elderly. Hence, the current study aimed to investigate the associations between HGS and executive functioning in individuals with aMCI, naMCI and healthy controls. Older, right-handed adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and healthy controls (HC) conducted a handgrip strength measurement via a handheld dynamometer. Executive functions were assessed with the Trail Making Test (TMT A&B). Normalized handgrip strength (nHGS, normalized to Body Mass Index (BMI)) was calculated and its associations with executive functions (operationalized through z-scores of TMT B/A ratio) were investigated through partial correlation analyses (i.e., accounting for age, sex, and severity of depressive symptoms). A positive and low-to-moderate correlation between right nHGS (rp (22) = 0.364; p = 0.063) and left nHGS (rp (22) = 0.420; p = 0.037) and executive functioning in older adults with aMCI but not in naMCI or HC was observed. Our results suggest that higher levels of nHGS are linked to better executive functioning in aMCI but not naMCI and HC. This relationship is perhaps driven by alterations in the integrity of the hippocampal-prefrontal network occurring in older adults with aMCI. Further research is needed to provide empirical evidence for this assumption. Full article

Age-related spatial navigation decline is more pronounced in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. We used a realistic-looking virtual navigation test suite to analyze different aspects of visuospatial processing in typical and atypical aging. A total of 219 older adults were recruited from the Czech Brain Aging Study cohort. Cognitively normal older adults (CN; n = 78), patients with amnestic MCI (n = 75), and those with mild AD dementia (n = 66) underwent three navigational tasks, cognitive assessment, and brain MRI. Route learning and wayfinding/perspective-taking tasks distinguished the groups as performance and learning declined and specific visuospatial strategies were less utilized with increasing cognitive impairment. Increased perspective shift and utilization of non-specific strategies were associated with worse task performance across the groups. Primacy and recency effects were observed across the groups in the route learning and the wayfinding/perspective-taking task, respectively. In addition, a primacy effect was present in the wayfinding/perspective-taking task in the CN older adults. More effective spatial navigation was associated with better memory and executive functions. The results demonstrate that a realistic and ecologically valid spatial navigation test suite can reveal different aspects of visuospatial processing in typical and atypical aging. Full article

ADAM10 is the main α-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of β-amyloid peptide (Aβ) in Alzheimer’s disease (AD). Strong recent evidence indicates the importance of the localization of ADAM10 for its activity as a protease. In this study, we investigated ADAM10 activity in plasma and CSF samples of patients with amnestic mild cognitive impairment (aMCI) and mild AD compared with cognitively healthy controls. Our results indicated that plasma levels of soluble ADAM10 were significantly increased in the mild AD group, and that in these samples the protease was inactive, as determined by activity assays. The same results were observed in CSF samples, indicating that the increased plasma ADAM10 levels reflect the levels found in the central nervous system. In SH-SY5Y neuroblastoma cells, ADAM10 achieves its major protease activity in the fraction obtained from plasma membrane lysis, where the mature form of the enzyme is detected, confirming the importance of ADAM10 localization for its activity. Taken together, our results demonstrate the potential of plasma ADAM10 to act as a biomarker for AD, highlighting its advantages as a less invasive, easier, faster, and lower-cost processing procedure, compared to existing biomarkers. Full article