Amnesic Mild Cognitive Impairment Patients Research Articles

Evaluation of Mild Cognitive Impairment through Perientorhinal/Hippocampal Imaging and Comprehensive Neuropsychological and Psychophysical Assessment.

Mild cognitive impairment (MCI) is a significant concern as it is a risk factor for AD progression, and early detection is vital in order to delay dementia onset and enable potential therapeutic interventions. Olfactory impairment is recognized as a predictive biomarker in neurodegenerative processes. The aims of this study were to explore the degree of entorhinal cortical atrophy (ERICA) and the severity of MCI symptoms; to analyze magnetic resonance imaging (MRI) results for the entorhinal cortex, parahippocampal gyrus, peri entorhinal cortex, and the cerebellar tentorium; and to perform a comprehensive neuropsychological and psychophysical assessment. The main results highlighted that in our sample-multidomain amnesic MCI patients with hyposmic symptomatology-we found that ERICA scores were associated with the severity of anxiety symptomatology. One possible hypothesis to explain this observation is that anxiety may contribute to neurodegenerative processes by inducing chronic stress and inflammation. Future research should consider the longitudinal development of neuropsychological scores, anxiety disorders, and brain atrophy to determine their potential predictive value for MCI progression. These findings suggest the importance of psychological factors in MCI progression and the utility of neuropsychological assessment alongside neuroimaging techniques for early detection and follow-up in MCI patients.

Sex Difference in General Cognition Associated with Coupling of Whole-brain Functional Connectivity Strength to Cerebral Blood Flow Changes During Alzheimer’s Disease Progression

Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disorder that results in irreversible cognitive impairments. Nonetheless, there are numerous sex-dependent differences in clinical course. We examined potential contributions of neurovascular coupling deficits to sex differences in AD progression. T1-weighted three-dimensional structural magnetic resonance images, functional blood oxygen level dependent and arterial spin labeling images were acquired from 50 AD patients (28 females), 52 amnesic mild cognitive impairment patients (31 females), and 59 healthy controls (36 females). Short- and long-range functional connectivity strength (FCS) and cerebral blood flow (CBF) values were calculated for all participants. Then, the CBF/FCS coupling ratio, which represented the amount of blood supply per unit of connectivity strength, was calculated for each voxel. Two-way ANOVA was performed to identify group × sex interactions and main effects of group. Correlation analysis was used to assess associations between CBF/FCS ratios and Mini-Mental State Examination (MMSE). There were significant group × sex interaction effects on short-range coupling ratios of right middle temporal gyrus, left angular gyrus, left inferior orbital frontal gyrus, and left superior frontal gyrus as well as on the long-range coupling ratios of right middle temporal gyrus, left precuneus, left posterior cingulate cortex, and left angular gyrus. There were significant negative correlations between MMSE scores and CBF/FCS ratios for all regions with significant group × sex interactions among female patients, while positive correlations were found among male patients. Our results demonstrate significant sex differences in neurovascular coupling mechanisms associated with cognitive function during the course of AD.

Cognitive Improvement via Left Angular Gyrus-Navigated Repetitive Transcranial Magnetic Stimulation Inducing the Neuroplasticity of Thalamic System in Amnesic Mild Cognitive Impairment Patients.

Stimulating superficial brain regions highly associated with the hippocampus by repetitive transcranial magnetic stimulation (rTMS) may improve memory of Alzheimer's disease (AD) spectrum patients. We recruited 16 amnesic mild cognitive impairment (aMCI) and 6 AD patients in the study. All the patients were stimulated to the left angular gyrus, which was confirmed a strong link to the hippocampus through neuroimaging studies, by the neuro-navigated rTMS for four weeks. Automated fiber quantification using diffusion tensor imaging metrics and graph theory analysis on functional network were employed to detect the neuroplasticity of brain networks. After neuro-navigated rTMS intervention, the episodic memory of aMCI patients and Montreal Cognitive Assessment score of two groups were significantly improved. Increased FA values of right anterior thalamic radiation among aMCI patients, while decreased functional network properties of thalamus subregions were observed, whereas similar changes not found in AD patients. It is worth noting that the improvement of cognition was associated with the neuroplasticity of thalamic system. We speculated that the rTMS intervention targeting left angular gyrus may be served as a strategy to improve cognitive impairment at the early stage of AD patients, supporting by the neuroplasticity of thalamic system.

Pseudoneglect is maintained in aging but not in mild Alzheimer's disease: new insights from an enumeration task

Neurologically healthy young adults display a behavioral bias, called pseudoneglect, which favors the processing of stimuli appearing in the left visual field. Pseudoneglect arises from the right hemisphere dominance for visuospatial attention. Previous studies investigating the effects of normal aging on pseudoneglect in line bisection and greyscale tasks have produced divergent results. In addition, scarce systematic investigations of visual biases in dementia have been reported. The aim of the present study was to evaluate whether the leftward bias appearing during an enumeration task in young adults would be preserved in normal aging and at different stages of severity of Alzheimer's disease. In Experiment 1, young and older healthy adults showed a comparable pseudoneglect, performing better when targets appeared in the left visual field. In Experiment 2, the leftward bias was maintained in amnesic mild cognitive impairment patients (aMCI), but it vanished in mild Alzheimer's disease patients (AD). The maintenance of pseudoneglect in normal aging and in aMCI patients is consistent with compensatory phenomena involving the right fronto-parietal network, which allow maintaining the right hemisphere dominance. Conversely, the lack of pseudoneglect in the sample of AD patients likely results from a loss of the right hemisphere dominance, caused by the selective degeneration of the right fronto-parietal network. These results highlight the need of further systematic investigations of visuospatial biases along the continuum of normal and pathological aging, both for a better understanding of the changes characterizing cognitive aging and for improvements in the evaluation of neglect in Alzheimer's disease.

In Search of Sleep Biomarkers of Alzheimer's Disease: K-Complexes Do Not Discriminate between Patients with Mild Cognitive Impairment and Healthy Controls.

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer’s disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioration.

Structural and functional brain connectome architecture in Alzheimer’s disease and amnesic mild cognitive impairment patients (P4.091)

Structural and functional brain connectome architecture in Alzheimer’s disease and amnesic mild cognitive impairment patients (P4.091)

DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy in Alzheimer’s disease and amnesic mild cognitive impairment patients

Several studies have noted an effect of DNA methylation on the pathogenesis of Alzheimer’s disease (AD). We have already reported that DNA methylation levels in the NCAPH2/LMF2 promoter region can be a useful biomarker for the diagnosis of AD and amnesic mild cognitive impairment (aMCI). However, there is still uncertainty about the mechanism by which NCAPH2/LMF2 methylation affects the pathogenesis of AD and aMCI. In this study, we investigated relationships between NCAPH2/LMF2 methylation and other factors. AD (n=30) and aMCI (n=28) subjects were included in this study. NCAPH2/LMF2 methylation levels were measured by pyrosequencing. Correlations between methylation levels and other factors including age at onset, sex, duration of disease, education, mini-mental state examination (MMSE) and frontal assessment battery (FAB) scores, APOE genotype, degree of hippocampal atrophy, and total brain atrophy were measured. Degrees of hippocampal atrophy and total brain atrophy were measured by VSRAD (Voxel-Based Specific Regional Analysis System for Alzheimer’s Disease). Regression analysis revealed that only hippocampal atrophy according to VSRAD is a significant dependent variable correlated with NCAPH2/LMF2 methylation levels. Our results suggest that DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy through apoptosis.

Retrieval Deficiency in Brain Activity of Working Memory in Amnesic Mild Cognitive Impairment Patients: A Brain Event-Related Potentials Study.

In the early stage of Alzheimer disease (AD) or mild cognitive impairment (MCI), working memory (WM) deficiency is prominent and could be attributed to failure in encoding, maintenance or retrieval of information. However, evidence for a retention or retrieval deficit remains equivocal. It is also unclear what cognitive mechanism in WM is impaired in MCI or early AD. We enrolled 46 subjects from our Memory Clinics and community, with 24 amnesic MCI patients and 22 normal subjects. After neurological and cognitive assessments, they performed a classic delayed match to sample (DMS) task with simultaneous event-related potential (ERP) recorded. The ERPs in encoding and retrieval epoch during WM were analyzed separately. The latency and amplitude of every ERP component were compared between two groups, and then analyzed to explore their relationship with neuropsychological performance. Finally, the locations of maximal difference in cortex were calculated by standard low-resolution tomographic analysis. A total of five components were found: P1, N1, P2, N2, and P300. The amplitude of P2 and P300 was larger in normal subjects than in MCI patients only during retrieval, not encoding epoch, while the latency did not show statistical difference. The latency and amplitude of P1 and N1 were similar in two groups. P2 amplitude in the retrieval epoch positively correlated with memory test (auditory verbal learning test) and visual spatial score of Chinese Addenbrooke's Cognitive Examination-Revised (ACE-R), while P300 amplitude correlated with ACE-R. The activation difference in P2 time range was maximal at medial frontal gyrus. However, the difference in cortex activation during P300 time range did not show significance. The amplitude of P2 indicated deficiency in memory retrieval process, potentially due to dysfunction of central executive in WM model. Regarding the location of P2 during WM task, medial frontal plays important role in memory retrieval. The findings in the present study suggested that MCI patients have retrieval deficit, probably due to central executive based on medial frontal gyrus. Thus, it may provide new biomarker for early detection and intervention for aMCI.

Parietal Fast Sleep Spindle Density Decrease in Alzheimer's Disease and Amnesic Mild Cognitive Impairment.

Several studies have identified two types of sleep spindles: fast (13–15 Hz) centroparietal and slow (11–13 Hz) frontal spindles. Alterations in spindle activity have been observed in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). Only few studies have separately assessed fast and slow spindles in these patients showing a reduction of fast spindle count, but the possible local specificity of this phenomenon and its relation to cognitive decline severity are not clear. Moreover, fast and slow spindle density have never been assessed in AD/MCI. We have assessed fast and slow spindles in 15 AD patients, 15 amnesic MCI patients, and 15 healthy elderly controls (HC). Participants underwent baseline polysomnographic recording (19 cortical derivations). Spindles during nonrapid eye movements sleep were automatically detected, and spindle densities of the three groups were compared in the derivations where fast and slow spindles exhibited their maximum expression (parietal and frontal, resp.). AD and MCI patients showed a significant parietal fast spindle density decrease, positively correlated with Minimental State Examination scores. Our results suggest that AD-related changes in spindle density are specific for frequency and location, are related to cognitive decline severity, and may have an early onset in the pathology development.

Vitamin D and progression in Mild Cognitive Impairment (MCI)

Background and objective: Data from cross-sectional and longitudinal studies suggest an association between cognitive impairment and vitamin D (VD) deficiency. However, the association of VD status with MCI conversion to dementia has not been fully explored.The aim of this study was to investigate the association between serum 25-hydroxyvitamin D [25(OH)D] status and progression of MCI to dementia in older adults.Patients and methods: We evaluated patients with diagnosis of MCI according to Mayo Clinic criteria (Petersen, 2001), who were followed for at least 5 years and healthy controls (HC). MCI patients were classified as amnesic or non-amnesic according to presence of memory deficit at baseline. Levels of VD were recorded. VD deficiency was defined as 25(OH)D < 20 ng/ml, insufficiency as 20 to 30 ng/ml, normal > 30 ng/ml. We compared VD levels of patients converted to dementia with those who remain stable. Both groups were compared with HC.Results: 216 subjects were included, 103 MCI and 113 HC. Mean age were 74,16 ± 6,7, 84,1% were females, without demographic differences between groups. The values of VD were similar in both groups. We found that MCI patients with VD deficiency had higher rates of conversion to dementia than the other groups (p = 0,003). Amnesic MCI patients converted to Alzheimer and non amnesic to non-Alzheimer dementias (p < 0,0001).Conclusion: Our findings suggest a significant association of lower VD levels with progression to dementia in MCI patients. A long-time major placebo-controlled randomized trial of vitamin D supplementation in patients with MCI should be started. Background and objective: Data from cross-sectional and longitudinal studies suggest an association between cognitive impairment and vitamin D (VD) deficiency. However, the association of VD status with MCI conversion to dementia has not been fully explored. The aim of this study was to investigate the association between serum 25-hydroxyvitamin D [25(OH)D] status and progression of MCI to dementia in older adults. Patients and methods: We evaluated patients with diagnosis of MCI according to Mayo Clinic criteria (Petersen, 2001), who were followed for at least 5 years and healthy controls (HC). MCI patients were classified as amnesic or non-amnesic according to presence of memory deficit at baseline. Levels of VD were recorded. VD deficiency was defined as 25(OH)D < 20 ng/ml, insufficiency as 20 to 30 ng/ml, normal > 30 ng/ml. We compared VD levels of patients converted to dementia with those who remain stable. Both groups were compared with HC. Results: 216 subjects were included, 103 MCI and 113 HC. Mean age were 74,16 ± 6,7, 84,1% were females, without demographic differences between groups. The values of VD were similar in both groups. We found that MCI patients with VD deficiency had higher rates of conversion to dementia than the other groups (p = 0,003). Amnesic MCI patients converted to Alzheimer and non amnesic to non-Alzheimer dementias (p < 0,0001). Conclusion: Our findings suggest a significant association of lower VD levels with progression to dementia in MCI patients. A long-time major placebo-controlled randomized trial of vitamin D supplementation in patients with MCI should be started.

The partial volume effect in the quantification of 1H magnetic resonance spectroscopy in Alzheimer's disease and aging.

1H-MRS variability increases due to normal aging and also as a result of atrophy in grey and white matter caused by neurodegeneration. In this work, an automatic process was developed to integrate data from spectra and high-resolution anatomical images to quantify metabolites, taking into account tissue partial volumes within the voxel of interest avoiding additional spectra acquisitions required for partial volume correction. To evaluate this method, we use a cohort of 135 subjects (47 male and 88 female, aged between 57 and 99 years) classified into 4 groups: 38 healthy participants, 20 amnesic mild cognitive impairment patients, 22 multi-domain mild cognitive impairment patients, and 55 Alzheimer's disease patients. Our findings suggest that knowing the voxel composition of white and grey matter and cerebrospinal fluid is necessary to avoid partial volume variations in a single-voxel study and to decrease part of the variability found in metabolites quantification, particularly in those studies involving elder patients and neurodegenerative diseases. The proposed method facilitates the use of 1H-MRS techniques in statistical studies in Alzheimer's disease, because it provides more accurate quantitative measurements, reduces the inter-subject variability, and improves statistical results when performing group comparisons.

Hypercapnia affects the functional coupling of resting state electroencephalographic rhythms and cerebral haemodynamics in healthy elderly subjects and in patients with amnestic mild cognitive impairment

ObjectiveCerebral vasomotor reactivity (VMR) and coherence of resting state electroencephalographic (EEG) rhythms are impaired in Alzheimer’s disease (AD) patients. Here we tested the hypothesis that these two variables could be related. MethodsWe investigated VMR and coherence of resting state EEG rhythms in nine normal elderly (Nold) and in 10 amnesic mild cognitive impairment (MCI) subjects. Resting state eyes-closed EEG data were recorded at baseline pre-CO2 (ambient air, 2min), during 7% CO2/air mixture inhalation (hypercapnia, 90s) and post-CO2 (ambient air, 2min) conditions. Simultaneous frontal bilateral near-infrared spectroscopy (NIRS) was performed to assess VMR by cortical oxy- and deoxy-haemoglobin concentration changes. EEG coherence across all electrodes was computed at delta (2–4Hz), theta (4–8Hz), alpha 1 (8–10.5Hz), alpha 2 (10.5–13Hz), beta 1 (13–20Hz), beta 2 (20–30Hz) and gamma (30–40Hz) bands. ResultsIn Nold subjects, ‘total coherence’ of EEG across all frequency bands and electrode pairs decreased during hypercapnia, with full recovery during post-CO2. Total coherence resulted lower in pre-CO2 and post-CO2 and presented poor reactivity during CO2 inhalation in MCI patients compared with Nold subjects. Hypercapnia increased oxy-haemoglobin and decreased deoxy-haemoglobin concentrations in both groups. Furthermore, the extent of changes in these variables during CO2 challenge was correlated with the EEG coherence, as a reflection of neurovascular coupling. ConclusionsHypercapnia induced normal frontal VMR that was detected by NIRS in both Nold and amnesic MCI groups, while it produced a reactivity of global functional coupling of resting state EEG rhythms only in the Nold group. SignificanceIn amnesic MCI patients, global EEG functional coupling is basically low in amplitude and does not react to hypercapnia.

Correlation between Cognitive Impairment and CSF Biomarkers in Amnesic MCI, non-Amnesic MCI, and Alzheimer's Disease

Decreased delayed recall, decreased amyloid-β peptides (Aβ1-42), and increased tau protein concentration in cerebrospinal fluid (CSF) are generally regarded to be valid neuropsychological and biological markers for Alzheimer's disease (AD). Previous studies failed to demonstrate clear-cut correlations between neuropsychological impairment and CSF markers. In this study we test recent models of disease progression, that propose that changes in CSF biomarkers already reach a plateau in a preclinical phase, before cognitive decline begins, that is, even before MCI can be diagnosed. We recruited 73 patients with probable AD (n=36) and mild cognitive impairment (MCI) (amnesic MCI=25; non-amnesic MCI=12). We used the CERAD-NP, a widely used neuropsychological battery with norms for different age and education groups, and additional neuropsychological tests for assessing the cognitive profile of these patient groups. We found a significant correlation between Aβ1-42 in the CSF and memory performance for amnesic MCI patients, but not for non-amnesic MCI and AD patients. All other correlations between cognitive tasks and Aβ1-42 were not significant. Tau protein concentration in the CSF was not correlated with any neuropsychological marker in any of the patients groups. We conclude that the decrease of Aβ1-42 in the CSF mirrors disease progression during the early stages up into AD and therefore is not restricted to the preclinical phase. The decrease of Aβ1-42 reaches a plateau only in the full blown demented syndrome and further functional disease progression is then related to neurodegeneration without further reduction of Aβ1-42 in the CSF.

Callosal atrophy in mild cognitive impairment and Alzheimer's disease: Different effects in different stages

Alzheimer's Disease (AD) is a neurodegenerative disorder that mainly affects grey matter (GM). Nevertheless, a number of investigations have documented white matter (WM) pathology associated with AD. The corpus callosum (CC) is the largest WM fiber bundle in the human brain. It has been shown to be susceptible to atrophy in AD mainly as a correlate of Wallerian degeneration of commissural nerve fibers of the neocortex. The aim of this study was to investigate which callosal regions are affected and whether callosal degeneration is associated with the stage of the disease. For this purpose, we analyzed high-resolution MRI data of patients with amnesic mild cognitive impairment (MCI) (n=20), mild AD (n=20), severe AD (n=10), and of healthy controls (n=20). Callosal morphology was investigated applying two different structural techniques: mesh-based geometrical modeling methods and whole-brain voxel-based analyses. Our findings indicate significant reductions in severe AD patients compared to healthy controls in anterior (genu and anterior body) and posterior (splenium) sections. In contrast, differences between healthy controls and mild AD patients or amnesic MCI patients were less pronounced and did not survive corrections for multiple comparisons. When correlating anterior and posterior WM density of the CC with GM density of the cortex in the severe AD group, we detected significant positive relationships between posterior sections of the CC and the cortex. We conclude that callosal atrophy is present predominantly in the latest stage of AD, where two mechanisms might contribute to WM alterations in severe AD: the Wallerian degeneration in posterior subregions and the myelin breakdown process in anterior subregions.