Mild Alzheimer's Disease Group Research Articles

Changes in colour perception in Alzheimer's disease continuum

Aims/Purpose: The progression of Alzheimer's disease (AD) manifests from a preclinical stage, characterized by asymptomatic pathological alterations, to an advanced stage of AD accompanied by cognitive impairment. The aim of this study was to explore visual function along the entire AD continuum, from individuals with a high genetic predisposition to those in the moderate phase of the disease.Methods: All participants underwent a visual examination and had to be visually healthy to be included. The study contained five groups: controls (n = 53), individuals with a positive family history of AD (HF+) (n = 13), mild cognitive impairment (MCI) (n = 23), mild AD (n = 25) and moderate AD (n = 21). The study analysed the results of errors in colour perception.Results: A significant increase in the total number of errors was observed between the control group and the moderate AD group. And also when comparing the FH+ group with the MCI group, the mild AD group and the moderate AD group. Significant differences were found on the tritan axis between the control group and the mild AD group, as well as in the moderate AD group. Significant differences were observed between the FH+ group and the mild AD group, as well as in the moderate AD group. A significant increase in the number of errors on the deutan axis was observed between the control group and both the mild and moderate AD groups. In addition, a statistically significant increase was observed when comparing the FH+ group with the moderate AD group. The test correlated with the MMSE score and also showed good predictive value when memory impairment was present.Conclusions: Understanding the importance of changes in colour perception in AD continuum can aid in the early detection and treatment of AD, potentially improving patient outcomes and facilitating targeted interventions.

Visual function changes along the continuum of Alzheimer's disease

Aims/Purpose: The progression of Alzheimer's disease (AD) is manifested by a gradual transition from a preclinical phase, characterized by asymptomatic pathological alterations, to an advanced phase of AD accompanied by cognitive impairment. The aim of this study was to explore visual function along the entire AD continuum.Methods: Each participant underwent a comprehensive visual examination, with only visually healthy individuals being selected for the study. The study comprised the following groups: controls (n = 53), positive family history of AD (FH+) (n = 13), mild cognitive impairment (MCI) (n = 23), mild AD (n = 25), and moderate AD (n = 21). The study analysed the results of visual acuity (VA) and contrast sensitivity (CS).Results: A significant reduction in VA was identified between the control group and the MCI, mild AD and moderate AD groups. CS showed significant changes in all cognitive impairment groups compared to the control group and the FH+ group at spatial frequencies of 12 and 18 cpd. In contrast, significant differences were only observed at spatial frequencies of 3 and 6 cpd between the cognitively impaired groups, starting from moderate AD, with no detectable decrease in CS during the MCI phase. No differences were detected between the control group and the FH+ group. The tests showed a positive correlation with the Mini Mental State Examination score and exhibited a favourable predictive ability in the presence of memory impairment, with higher predictive performance observed in the advance stages of AD.Conclusions: The presence of alterations in VA and CS can be observed as early as the MCI stage in individuals with AD. Recognizing the continuum of AD holds significant significance in early detection, with visual examination offering a straightforward and cost‐effective diagnostic tool for AD. Healthcare professionals can leverage this knowledge to gain a better understanding of the progressive nature of the disease.

Affective theory of mind in people with mild and moderate Alzheimer's disease.

This study compared the affective theory of mind (ToM) of people with mild and moderate Alzheimer's disease (AD) and healthy older adults and also investigated the relationship between affective ToM and cognitive and clinical functioning in AD people. This cross-sectional study included 156 older adults with AD and 40 healthy older adults. We used an experimental task involving reasoning processes in different contextual situations. The affective ToM was impaired in AD groups compared with healthy group, with moderate AD group showing lower performance than mild AD group. The affective ToM task of mild AD group was significantly correlated with the Mini-Mental State Examination (MMSE) and education years. Linear regression showed only education years as a predictor of ToM task performance. The neuropsychiatric symptoms and functionality were not correlated with the affective ToM. Our findings demonstrated that people with mild and moderate AD presented impairments in affective ToM that can be explained by the difficulties to infer emotion from reasoning processes. In addition, the education years variable proved to be an affective ToM performance's predictor for the mild AD group, but not for the moderate AD group, indicating that ToM abilities are affected differently in different stages of AD. Neuropsychiatric symptoms and functionality seem to have no influence on affective ToM impairments in people with AD.

The role of visual rating and automated brain volumetry in early detection and differential diagnosis of Alzheimer's disease.

Medial temporal lobe atrophy (MTA) is a diagnostic marker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the accuracy of quantitative MTA (QMTA) in diagnosing early AD is unclear. This study aimed to investigate the accuracy of QMTA and its related components (inferior lateral ventricle [ILV] and hippocampus) with MTA in the early diagnosis of MCI and AD. This study included four groups: normal (NC), MCI stable (MCIs), MCI converted to AD (MCIs), and mild AD (M-AD) groups. Magnetic resonance image analysis software was used to quantify the hippocampus, ILV, and QMTA. MTA was rated by two experienced neurologists. Receiver operating characteristic area under the curve (AUC) analysis was performed to compare their capability in differentiating AD from NC and MCI, and optimal thresholds were determined using the Youden index. QMTA distinguished M-AD from NC and MCI with higher diagnostic accuracy than MTA, hippocampus, and ILV (AUCNC = 0.976, AUCMCI = 0.836, AUCMCIs = 0.894, AUCMCIc = 0.730). The diagnostic accuracy of QMTA was superior to that of MTA, the hippocampus, and ILV in differentiating MCI from AD. The diagnostic accuracy of QMTA was found to remain the best across age, sex, and pathological subgroups analyzed. The sensitivity (92.45%) and specificity (90.64%) were higher in this study when a cutoff value of 0.635 was chosen for QMTA. QMTA may be a better choice than the MTA scale or the associated quantitative components alone in identifying AD patients and MCI individuals with higher progression risk.

Brain Representation of Animal and Non-Animal Images in Patients with Mild Cognitive Impairment and Alzheimer's Disease.

In early Alzheimer's disease (AD), high-level visual functions and processing speed are impacted. Few functional magnetic resonance imaging (fMRI) studies have investigated high-level visual deficits in AD, yet none have explored brain activity patterns during rapid animal/non-animal categorization tasks. To address this, we utilized the previously known Integrated Cognitive Assessment (ICA) to collect fMRI data and compare healthy controls (HC) to individuals with mild cognitive impairment (MCI) and mild AD. The ICA encompasses a rapid visual categorization task that involves distinguishing between animals and non-animals within natural scenes. To comprehensively explore variations in brain activity levels and patterns, we conducted both univariate and multivariate analyses of fMRI data. The ICA task elicited activation across a range of brain regions, encompassing the temporal, parietal, occipital, and frontal lobes. Univariate analysis, which compared responses to animal versus non-animal stimuli, showed no significant differences in the regions of interest (ROIs) across all groups, with the exception of the left anterior supramarginal gyrus in the HC group. In contrast, multivariate analysis revealed that in both HC and MCI groups, several regions could differentiate between animals and non-animals based on distinct patterns of activity. Notably, such differentiation was absent within the mild AD group. Our study highlights the ICA task's potential as a valuable cognitive assessment tool designed for MCI and AD. Additionally, our use of fMRI pattern analysis provides valuable insights into the complex changes in brain function associated with AD. This approach holds promise for enhancing our understanding of the disease's progression.

Alzheimer's disease: a continuum with visual involvements.

Alzheimer's disease (AD) is the most common form of dementia affecting the central nervous system, and alteration of several visual structures has been reported. Structural retinal changes are usually accompanied by changes in visual function in this disease. The aim of this study was to analyse the differences in visual function at different stages of the pathology (family history group (FH+), mild cognitive impairment (MCI), mild AD and moderate AD) in comparison with a control group of subjects with no cognitive decline and no family history of AD. We included 53 controls, 13 subjects with FH+, 23 patients with MCI, 25 patients with mild AD and, 21 patients with moderate AD. All were ophthalmologically healthy. Visual acuity (VA), contrast sensitivity (CS), colour perception, visual integration, and fundus examination were performed. The analysis showed a statistically significant decrease in VA, CS and visual integration score between the MCI, mild AD and moderate AD groups compared to the control group. In the CS higher frequencies and in the colour perception test (total errors number), statistically significant differences were also observed in the MCI, mild AD and moderate AD groups with respect to the FH+ group and also between the control and AD groups. The FH+ group showed no statistically significant difference in visual functions compared to the control group. All the test correlated with the Mini Mental State Examination score and showed good predictive value when memory decline was present, with better values when AD was at a more advanced stage. Alterations in visual function appear in subjects with MCI and evolve when AD is established, being stable in the initial stages of the disease (mild AD and moderate AD). Therefore, visual psychophysical tests are a useful, simple and complementary tool to neuropsychological tests to facilitate diagnosis in the preclinical and early stages of AD.

Quantifying AD‐related brain amyloid with linearised progression models: model‐based vs. data‐based.

AbstractBackgroundBrain amyloid‐β (Aβ) is the pathological hallmark of Alzheimer's disease (AD). In logistic disease models, Aβ accumulation is a sigmoid function of time‐since‐disease‐onset (TSDO) (figure 1). Previous positron emission tomography (PET)‐based models vary accumulation onset(t50) and duration(r) globally; capacity(K) and baseline(NS) regionally (Whittington2018). We confirm existing approaches and propose a more powerful ICA‐based approach to quantify disease severity and estimate TSDO.MethodWe used 1071 18F‐florbetapir standard uptake value ratio (SUVR) images from the ADNI‐2 study (adni.loni.usc.edu/data‐samples/data‐types/pet). Images were mapped into MNI space. Averages were extracted using the Harvard‐Oxford brain‐atlas. Whole‐brain tracer‐specific sigmoid parameters (Jack2013) obtained from the literature were used to estimate TSDO.Of 16 models of regional Aβ accumulation (each of the 4 regional sigmoid parameters varied either regionally or globally), the optimal Bayesian information criterion was found with global t50 and r, and regional NS and K (figure 1) with global values r=6.16y and t50=4.10y.Linearised maps of NS and K were obtained by regressing the SUVR maps onto the global sigmoid. We also estimated these maps as independent components, using a 2‐component ICA on the SUVR maps. Both outcomes were used to quantify Aβ accumulation from SUVR images as weighting factors of the accumulation map.We compared the weights from the logistic model and the ICA model in ADNI, using effect size measured with Hedges' g between cognitively normal (CN), subjective memory complaints (SMC), mild cognitive impairment (EMCI/MCI/LMCI) and AD groups. We compared 3 longitudinal visits (N=112) in the OASIS‐3 study (see www.oasis‐brains.org) with both methods, global SUVR and Centiloid (Klunk2015) using 11C‐PiB PET SUVR images.ResultMaps of accumulation capacity from both models had spatial correlation of 0.86 (figure 2); baseline maps had spatial correlation of 0.95. Hedges' g between ADNI groups was 2.25 for K, and 2.42 for ICA (1.46 for global SUVR). In OASIS‐3, Hedges' g between visits was 1.24 for K, 1.46 for ICA (global SUVR 0.15, Centiloid 0.4).ConclusionWe demonstrate that linear accumulation models can be used to quantify brain Aβ with PET; maps obtained by ICA yield larger effect sizes than the logistic method for differentiating groups and measuring changes between visits.

Correlation of muscle strength with cognitive function and medial temporal lobe atrophy in patients with mild to moderate Alzheimer's disease

Objective: To analyze the correlation of muscle strength with cognitive function and medial temporal lobe atrophy (MTA) in patients with mild to moderate Alzheimer's disease (AD). Methods: General information, sarcopenia-related indicators, neuropsychological tests and MTA score were collected in 80 confirmed AD patients (41 mild and 39 moderate patients) and 43 normal controls (NC) from the Memory Disorders Clinic of Department Of Neurology in the Second Affiliated Hospital of Soochow University between January and December 2021. Appendicular skeletal muscle mass index (ASMI), grip strength and 5-times sit-to-stand time and 6-m gait speed were used for assessing muscle mass, muscle strength and physical function, respectively. Cognitive function was assessed by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Memory and Executive Screening Scale (MES), Digit Symbol Substitution Test (DSST), Digital Span Test (DST) and Verbal Fluency Task (VFT), respectively. DST included Forward Digit Span Test (FDST) and Backward Digit Span Test (BDST). All the subjects underwent 3.0T coronal three-dimensional gradient echo sequence MRI. MTA scale was performed to evaluate the degree of medial temporal lobe atrophy. The differences in the sarcopenia-related indicators, cognitive score and MTA score were analyzed among the three groups, and the partial correlation analysis was performed between the inter-groups. Results: Eighty AD patients (24 males and 56 females) were included, aged (72±7) years old, with 41 mild and 39 moderate patients. Meanwhile, 43 NC included 19 males and 24 females, with a mean age of (70±6) years old. The disease duration in moderate AD patients was longer than that of mild AD patients [34.0 (25.0, 43.5) months vs 24.0 (11.0, 34.0) months, P<0.001]. The differences of sarcopenia-related indicators and MTA score among the three groups were statistically significant (all P<0.001), including 5-times sit-to-stand time [(13.6±1.8) s vs (11.5±1.7) s vs (10.3±1.9) s, P<0.001] and MTA score [2.0 (2.0, 3.0) vs 1.0 (1.0, 2.0) vs 0 (0, 0), P<0.001]. In neuropsychological tests, compared to the NC group, MMSE, MoCA, MES and VFT scores in mild and moderate AD groups were lower (all P<0.001); meanwhile, compared to the mild AD group, the moderate group had lower MMSE, MoCA, MES, DSST and VFT scores (all P<0.001). In sarcopenia-related indicators, muscle strength in particular was correlated with widespread cognitive functioning domains and MTA score in AD patients. Grip strength was positively correlated with MMSE, MoCA , MES, FDST (r=0.387, 0.418, 0.522 and 0.484, respectively, all P<0.001), DSST (r=0.327, P=0.006) and VFT score (r=0.354, P=0.003), and negatively correlated with MTA score (r=-0.631, P<0.001). 5-times sit-to-stand time was negatively correlated with MMSE, MoCA, MES, DSST, FDST, VFT score (r=-0.583, -0.587, -0.814, -0.591, -0.552 and -0.485, respectively, all P<0.001), and BDST (r=-0.355, P=0.003) strongly positively correlated with MTA score (r=0.836, P<0.001). ASMI was positively correlated with MMSE, MoCA, MES, DSST, FDST score (r=0.257, 0.238, 0.428, 0.282 and 0.364, respectively, all P<0.05), and negatively correlated with MTA score (r=-0.377, P=0.001). 6-m gait speed was positively correlated with MMSE, MoCA, MES, DSST, FDST score (r=0.419, 0.486, 0.699, 0.559 and 0.500, respectively, all P<0.001), BDST and VFT score (r=0.384、0.377, respectively, both P=0.001), and strongly negatively correlated with MTA score (r=-0.803, P<0.001). Conclusions: Patients with mild to moderate AD have widespread cognitive impairment. Muscle mass, muscle strength and physical function are all significantly impaired. Compared to muscle mass and physical function, decreased muscle strength is significantly associated with widespread cognitive decline and increased degree of medial temporal lobe atrophy.

Retention and impairment of neurocognitive functions in mild cognitive impairment and Alzheimer's disease with a comprehensive neuropsychological test.

AimMATRICS Consensus Cognitive Battery was developed by the National Institute of Mental Health to establish acceptance criteria for measuring cognitive changes in schizophrenia and can be used to assess cognitive functions in other psychiatric disorders. We used a Japanese version of MATRICS Consensus Cognitive Battery to explore the changes in multiple cognitive functions in patients with mild cognitive impairment and mild Alzheimer's disease.MethodsWe administered the Japanese version of MATRICS Consensus Cognitive Battery to 11 patients with mild cognitive impairment (MCI), 11 patients with Alzheimer's disease, and 27 healthy controls. All Japanese versions of MATRICS Consensus Cognitive Battery domain scores were converted to t‐scores using sample means and standard deviations and were compared for significant performance differences among healthy control, MCI, and mild Alzheimer's disease groups.ResultsCompared with healthy controls, patients with MCI and mild Alzheimer's disease demonstrated the same degree of impairment to processing speed, verbal learning, and visual learning. Reasoning and problem‐solving showed significant impairments only in mild Alzheimer's disease. Verbal and visual abilities in working memory showed different performances in the MCI and mild Alzheimer's disease groups, with the Alzheimer's disease group demonstrating significantly more deficits in these domains. No significant difference was found among the groups in attention/vigilance and social cognition.ConclusionsThe Japanese version of MATRICS Consensus Cognitive Battery can be used to elucidate the characteristics of cognitive dysfunction of normal aging, MCI, and mild dementia in clinical practice.

Gestures analysis during a picture description task: Capacity to discriminate between healthy controls, mild cognitive impairment, and Alzheimer's disease

The main objective of this study is to compare the gesticulation of the five study groups that conform the evolution from healthy ageing to a moderate stage of Alzheimer's disease (AD). As a secondary aim we intend to assess the capacity of co-speech gestures to discriminate between the two main groups of amnestic Mild Cognitive Impairment (MCI), executive MCI (ex-MCI) and temporo-medial MCI (tm-MCI), since this last group is the one with the highest rate of progression to AD. 52 participants were divided into five groups, according to their global cognition state (healthy controls, ex-MCI, tm-MCI, mild AD, and moderate AD). They were videotaped during a picture description task and their verbal (speech fluency and lexical diversity measures) and non-verbal communication (gestural production) performances were analysed. Statistical analysis confirmed that the global cognition performance was worse in patients with greater cognitive impairment, and MCI groups differ from each other in delayed recall memory. Concerning verbal communication, time of speech was lower in the healthy control group when compared with the rest of the groups. In the non-verbal communication aspect, a trend toward statistical significance was found in iconic gestures per minute, iconic gestures per word and iconic gestures for word substitution. Pairwise comparison highlighted these variables as potential differentiating factor between ex-MCI, tm-MCI and mild AD groups. As for the first objective, our study results demonstrated there was not a linear progression in gestural production among groups. In relation to the second objective, outcomes pointed to a great value, since iconic gestures variables have been identified as a potential marker for the specific identification of tm-MCI individuals, who are a subgroup of amnestic MCI with a greater predisposition to progress to Alzheimer's disease.

Coupling analysis between functional and structural brain networks in Alzheimer's disease.

The coupling between functional and structural brain networks is difficult to clarify due to the complicated alterations in gray matter and white matter for the development of Alzheimer's disease (AD). A cohort of 112 participants [normal control group (NC, 62 cases), mild cognitive impairment group (MCI, 31 cases) and AD group (19 cases)], was recruited in our study. The brain networks of rsfMRI functional connectivity (rsfMRI-FC) and diffusion tensor imaging structural connectivity (DTI-SC) across the three groups were constructed, and their correlations were evaluated by Pearson's correlation analyses and multiple comparison with Bonferroni correction. Furthermore, the correlations between rsfMRI-SC/DTI-FC coupling and four neuropsychological scores of mini-mental state examination (MMSE), clinical dementia rating-sum of boxes (CDR-SB), functional activities questionnaire (FAQ) and montreal cognitive assessment (MoCA) were inferred by partial correlation analyses, respectively. The results demonstrated that there existed significant correlation between rsfMRI-FC and DTI-SC (p < 0.05), and the coupling of rsfMRI-FC/DTI-SC showed negative correlation with MMSE score (p < 0.05), positive correlations with CDR-SB and FAQ scores (p < 0.05), and no correlation with MoCA score (p > 0.05). It was concluded that there existed FC/SC coupling and varied network characteristics for rsfMRI and DTI, and this would provide the clues to understand the underlying mechanisms of cognitive deficits of AD.

Impairment of Episodic-Specific Autobiographical Memory in Individuals with Subjective Cognitive Decline and in Patients with Prodromal or Mild Alzheimer's Disease.

Autobiographical memory (AM) is a personal form of memory that becomes impaired in the early, clinical stages of Alzheimer's disease (AD). In the "preclinical" phase of AD, neuropathological hallmarks are present (especially in a brain network underpinning AM), but performance on standardized neuropsychological tests is normal. Even so, some patients have subjective cognitive decline (SCD). The aim was to 1) investigate AM performance on two tests with different approaches in SCD, and in prodromal and mild AD, and 2) examine the association between the AM tests. We included 17 SCD patients with heightened risk of AD, 17 amnestic mild cognitive impairment (aMCI) patients, 17 patients with mild dementia due to AD, and 30 healthy controls. Patients were diagnosed according to international criteria, and all participants had MMSE scores≥24. AM was assessed using the Columbia Autobiographical Memory Interview-Short Form (CAMI-SF) and the Three Events Test. These tests measure the production of contextual details. Significant group effects were found for the Three Events Test and the CAMI-SF. All patient groups produced significantly fewer contextual details than the controls on the Three Events Test. On CAMI-SF, the aMCI and mild AD groups were able to answer fewer questions or gave significantly less detailed answers than the other groups. The SCD patients performed below the controls on CAMI-SF, but the difference was not significant. AM may be impaired in very early AD, even in the phases where standardized episodic memory tests show no decline.

Cognitive Impairment in Late-Life Depression: A Comparative Study of Healthy Older People, Late-Life Depression, and Mild Alzheimer's Disease Using Multivariate Base Rates of Low Scores.

Late-Life Depression (LLD) is often associated with cognitive impairment. However, distinction between cognitive impairment due to LLD and those due to normal aging or mild Alzheimer's Disease (AD) remain difficult. The aim of this study was to present and compare the multivariate base rates of low scores in LLD, mild AD, and healthy control groups on a battery of neuropsychological tests. Participants (ages 60–89) were 352 older healthy adults, 390 patients with LLD, and 234 patients with mild AD (i.e., MMSE ≥ 20). Multivariate base rates of low scores (i.e., ≤ 5th percentile) were calculated for each participant group within different cognitive domains (verbal episodic memory, executive skills, mental processing speed, constructional praxis, and language/semantic memory). Obtaining at least one low score was relatively common in healthy older people controls (from 9.4 to 17.6%), and may thus result in a large number of false positives. By contrast, having at least two low scores was unusual (from 0.3 to 4.6%) and seems to be a more reliable criterion for identifying cognitive impairment in LLD. Having at least three low memory scores was poorly associated with LLD (5.9%) compared to mild AD (76.1%) and may provide a useful way to differentiate between these two conditions [ = 329.8, p < 0.001; Odds Ratio = 50.7, 95% CI = 38.2–77.5]. The multivariate base rate information about low scores in healthy older people and mild AD may help clinicians to identify cognitive impairments in LLD patients, improve the clinical decision-making, and target those who require regular cognitive and clinical follow-up.

Reduced serum miR-202 may promote the progression of Alzheimer's disease patients via targeting amyloid precursor protein.

The current study investigated whether the expression of miR-202 was abnormal in the serum of patients with Alzheimer's disease (AD) and evaluated the potential clinical significance, thereby shedding light on the diagnosis of AD. Here, our data showed that the level of miR-202 decreased significantly in the serum of AD patients (n=121) compared with that of healthy controls (n=86). Further analysis showed that the level of serum miR-202 was gradually decreased in the mild AD group (n=31), moderate AD group (n=52) and severe AD group (n=38) compared with the healthy control group. Receiver operating characteristic (ROC) curve analysis demonstrated that serum miR-202 could differentiate AD patients from healthy controls, with an AUC of 0.892. Spearman correlation analysis showed that serum miR-202 was positively correlated with the Mini-Mental State Examination (MMSE). Based on TargetScan, a conserved binding site was identified in the 3'UTR of amyloid precursor protein (APP). The dual luciferase assay showed that miR-202 suppressed the relative luciferase activity of pmirGLO-APP-3'UTR. Western blot assays indicated that overexpression of miR-202 suppressed the expression of APP, while the expression of APP was enhanced after inhibition of miR-202 in PC12 cells, indicating that APP was a possible target gene of miR-202. Moreover, the cell apoptosis induced by transfection of miR-202 inhibitor was abolished by silencing APP. In summary, we showed novel data that downregulation of serum miR-202 may be used as a potential biomarker for AD and may promote the development of AD by targeting APP.

Characteristics of Regional Cerebral Blood Flow in Alzheimer Disease and Amnestic Mild Cognitive Impairment by Single-Photon Emission Computerized Tomography: A Cross-Sectional Study

Introduction: The regional cerebral blood flow (rCBF) distribution can affect brain functioning, leading to amnestic mild cognitive impairment (aMCI) and mild Alzheimer disease (AD). This study aimed to clarify the detailed characteristics of rCBF distribution in patients with mild AD and aMCI. Methods: This cross-sectional study from April 2015 to March 2018 included 103 older adults (mean age 78.9 years; 60% females), out of a total of 302 adults, and categorized them into 3 groups according to cognitive symptoms. The normal control (NC), aMCI, and mild AD groups included 20, 50, and 33 participants, respectively. The primary outcome was rCBF, which was compared among the 3 groups using a 2-sample t test without correction for multiple comparisons. Results: In the aMCI group, the rCBF decreased in the bilateral parietal and left frontal association cortex and the bilateral premotor cortex (p < 0.01) but increased in the bilateral cerebellum (p < 0.01). In the mild AD group, the rCBF decreased in the bilateral parietal and occipital association cortex, the bilateral premotor cortex, the left temporal and frontal association cortex, and the left limbic lobe (p < 0.01). Conversely, the rCBF increased in some parts of the cerebellum, the bilateral frontal and temporal association cortex, the left occipital association cortex, and the right premotor cortex (p < 0.01). Conclusion: Based on the analysis of the values obtained, it was inferred that the rCBF undergoes reduction and elevation in aMCI and AD patients.

Mild Alzheimer Disease, Financial Capacity, and the Role of Depression: Eyes Wide Shut?

The aim of this study was to assess whether comorbid depression in patients with mild Alzheimer disease (AD) can influence financial capacity. The sample comprised 109 participants divided into 4 groups: mild AD with and without depressive symptoms, and cognitive normal elderly with and without depression. Participants were examined using a number of neuropsychological tests, with an emphasis on the Mini-Mental State Examination, the 15-item Geriatric Depression Scale, and the Legal Capacity for Property Law Transactions Assessment Scale. Financial capacity ascertained as performance in the Legal Capacity for Property Law Transactions Assessment Scale in the group of mild AD patients was severely impaired when depression coexisted, thus clearly differentiating the mild AD group from mild AD with comorbid depression.

Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

[18F]FDG-PET and [11C]PIB-PET are validated as neurodegeneration and amyloid biomarkers of Alzheimer's disease (AD). We used a PET staging system based on the 2018 NIA-AA research framework to compare the proportion of amyloid positivity (A+) and hypometabolism ((N)+) in cases of mild probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls, incorporating an additional classification of abnormal [18F]FDG-PET patterns and investigating the co-occurrence of such with A+, exploring [18F]FDG-PET to generate hypotheses in cases presenting with clinical-biomarker "mismatches." Elderly individuals (N = 108) clinically classified as controls (N = 27), aMCI (N = 43) or mild probable AD (N = 38) were included. Authors assessed their A(N) profiles and classified [18F]FDG-PET neurodegenerative patterns as typical or non-typical of AD, performing re-assessments of images whenever clinical classification was in disagreement with the PET staging (clinical-biomarker "mismatches"). We also investigated associations between "mismatches" and sociodemographic and educational characteristics. AD presented with higher rates of A+ and (N)+. There was also a higher proportion of A+ and (N)+ individuals in the aMCI group in comparison to controls, however without statistical significance regarding the A staging. There was a significant association between amyloid positivity and AD (N)+ hypometabolic patterns typical of AD. Non-AD (N)+ hypometabolism was seen in all A- (N)+ cases in the mild probable AD and control groups and [18F]FDG-PET patterns classified such individuals as "SNAP" and one as probable frontotemporal lobar degeneration. All A- (N)- cases in the probable AD group had less than 4years of formal education and lower socioeconomic status (SES). The PET-based staging system unveiled significant A(N) differences between AD and the other groups, whereas aMCI and controls had different (N) staging, explaining the cognitive impairment in aMCI. [18F]FDG-PET could be used beyond simple (N) staging, since it provided alternative hypotheses to cases with clinical-biomarker "mismatches." An AD hypometabolic pattern correlated with amyloid positivity. Low education and SES were related to dementia in the absence of biomarker changes.

Facial Expression Recognition Patterns in Mild and Moderate Alzheimer's Disease.

Facial expression recognition is one of the essential abilities for social cognition. We aimed to compare facial expression recognition among people with mild and moderate Alzheimer's disease (AD) and to identify which factors were associated with impairment according to disease severity. We included 52 participants with either mild or moderate AD. FACES includes four subtasks requiring matching expressions with picture stimuli (tasks 1 and 2), labelling emotions (task 3), and recognizing situations with evident emotional content (task 4). There were significant differences between groups in FACES global scores, task 2 and task 4. In the mild AD group, FACES global score was influenced by educational background and cognitive performance, task 1 was associated with comprehension and constructive praxis, task 2 was associated with cognitive flexibility, and task 3 was associated with word finding. In subtask 4, no significant associations were found after adjusting for level of cognitive decline. In the moderate AD group, the awareness of emotional state domain was associated with FACES global score, task 1 was associated with constructive praxis, task 3 was associated with neuropsychiatric symptoms, and task 4 was associated with the ability to recognize emotions through situations. No significant associations were found on task 2, after adjusting for level of cognitive decline. Our findings suggest emotional processing difficulties across AD stages. However, when participants needed to recognize the most preponderant emotion in a situation with evident emotional content, our results suggest that in both groups there was no influence of cognitive impairment.

Application of local gyrification index in the early diagnosis of Alzheimer disease

Objective To evaluate the role of local gyrification index (LGI) in the early diagnosis of Alzheimer disease(AD). Methods Thirty-five amnestic-type mild cognitive impairment patients (aMCI group), 34 mild AD patients (mild AD group) and 33 healthy volunteers (normal control group) were studied. All patients underwent high resolution MRI examination and mini-mental state examination (MMSE). Using surface-based morphometry, the FreeSurfer was employed to access LGI of vertex over every participant′s whole cortical surface, then we calculated the mean LGI (mLGI) of each subject′s left and right hemisphere separately. Taking age, gender and educational year as covariance, analysis of covariance was used to compare the difference of mLGI of left and right brain among 3 groups, then Bonferroni was done between every two groups. Analysis of covariance was applied to compare the difference of LGI of every participant among 3 groups, and Monte Carlo method was employed to perform multiple comparison corrections. The correlations between the MMSE scores and LGIs of the three groups were analyzed. Results Compared with normal control group(left 3.03±0.12,right 3.02±0.13), the mLGI of hemispheres in mild AD group(left 2.94±0.11,right 2.93±0.10) decreased respectively(P 0.05). The difference of mLGI of hemispheres between aMCI group and mild AD group also had no statistical significance(P>0.05). The aMCI group showed decrease of LGI in some brain regions located at the right temporal lobe, bilateral frontal and parietal lobe compared with the normal control group. While compared with aMCI group, decreased LGIs was presented in some brain regions located at bilateral temporal, occipital, frontal lobe and the right parietal lobe of mild AD group. There was a positive correlation between MMSE scores and LGIs of some brain regions in the bilateral temporal, occipital lobe, the left frontal lobe and the right parietal lobe in the three groups. Conclusion LGI is conductive in the early diagnosis of AD and can serve as an imaging marker for monitoring disease progresses. Key words: Alzheimer disease; Mild cognitive impairment; Magnetic resonance imaging; Local gyrification index

Impaired comprehension of metaphorical expressions in very mild Alzheimer's disease.

BackgroundBrain-damaged patients often have difficulty understanding non-literal language. However, whether patients with Alzheimer’s disease (AD) have comprehension deficits of metaphorical expressions, in contrast with non-metaphorical (literal) expressions, remains unclear.Patients and methodsThe subjects were 40 AD patients; 20 had mild AD (17–23 points on the Mini-Mental State Examination [MMSE]), and 20 had very mild AD (≥24 points). Twenty normal elderly controls were also enrolled as a control group. Thirty sentences that contained novel similes (Items) were prepared. For each Item, four explanatory choices, consisting of one correct response and three foils, were provided. The participants were asked to choose the written statement that best represented the Item’s meaning. In addition, all the subjects completed the Token Test.ResultsThe patients with mild AD had significantly lower scores than the normal controls on both the simile comprehension test and the Token Test. However, the patients with very mild AD exhibited significantly lower scores on the simile comprehension test, but not on the Token Test. The distributions of error types for the simile test differed between the mild AD group and the other groups. The mild AD patients made more errors that were “far” from the correct responses.ConclusionPatients with AD are more likely to have comprehension deficits of metaphorical expressions than comprehension deficits of non-metaphorical expressions. Pragmatic language dysfunction may precede formal language dysfunction during the progression of AD.