Cerebellar Volume Is Associated with Cognitive Decline in Mild Cognitive Impairment: Results from ADNI.
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ABSTRACT:
SUBMITTER: Lin CY
PROVIDER: S-EPMC7085462 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPrevious work examining normal controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) identified substantial biological heterogeneity. We hypothesized that ADNI mild cognitive impairment (MCI) subjects would also exhibit heterogeneity with possible clinical implications.MethodsADNI subjects diagnosed with amnestic MCI (n=138) were clustered based on baseline magnetic resonance imaging, cerebrospinal fluid, and serum biomarkers. The clusters were compared with respect to longitudinal atrophy, cognitive trajectory, and time to conversion.ResultsFour clusters emerged with distinct biomarker patterns: The first cluster was biologically similar to normal controls and rarely converted to Alzheimer's disease (AD) during follow-up. The second cluster had characteristics of early Alzheimer's pathology. The third cluster showed the most severe atrophy but barely abnormal tau levels and a substantial proportion converted to clinical AD. The fourth cluster appeared to be pre-AD and nearly all converted to AD.ConclusionsSubjects with MCI who were clinically similar showed substantial heterogeneity in biomarkers.
| S-EPMC4092059 | biostudies-literature
Project description:ObjectiveWe examined whether sarcopenia is associated with the occurrence of late-life cognitive impairment.MethodsNondemented older adults (N = 1175) underwent annual testing with 17 cognitive tests summarized as a global cognitive score. A composite sarcopenia score was constructed based on muscle mass measured with bioelectrical impedance and muscle function based on grip strength. Cox proportional hazard models were employed to examine associations of sarcopenia with incident Alzheimer's dementia (AD) and incident mild cognitive impairment (MCI). Linear mixed-effect models determined the association of sarcopenia with cognitive decline. All models controlled for age, sex, education, race, and height squared.ResultsAverage follow-up was 5.6 years. More severe sarcopenia at baseline was associated with a higher risk of incident AD (hazard ratio [HR], 1.50 [95% confidence interval 1.20-1.86]; p < 0.001) and of MCI (1.21 [1.01-1.45]; 0.04) and a faster rate of cognitive decline (estimate = -0.013; p = 0.01). Analyses of the individual components of sarcopenia showed that muscle function was associated with incident AD, incident MCI, and cognitive decline with and without a term for lean muscle mass in the model. In contrast, lean muscle mass was not associated with incident cognitive impairment or cognitive decline when a term for muscle function was included in the model.ConclusionsPoor muscle function, but not reduced lean muscle mass, drives the association of sarcopenia with late-life cognitive impairment. Further work is needed to identify features of muscle structure, which may increase the specificity of sarcopenia for identifying older adults at risk for late-life cognitive impairment.
| S-EPMC8286176 | biostudies-literature
Project description:Mild Cognitive Impairment (MCI) is a border or precursor state of dementia. To optimize implemented interventions for MCI, it is essential to clarify the underlying neural mechanisms. However, knowledge regarding the brain regions responsible for MCI is still limited. Here, we implemented the Montreal Cognitive Assessment (MoCA) test, a screening tool for MCI, in 20 healthy elderly participants (mean age, 67.5 years), and then recorded magnetoencephalograms (MEG) while they performed a visual sequential memory task. In the task, each participant memorized the four possible directions of seven sequentially presented arrow images. Recall accuracy for beginning items of the memory sequence was significantly positively related with MoCA score. Meanwhile, MEG revealed stronger alpha-band (8-13 Hz) rhythm desynchronization bilaterally in the precuneus (PCu) for higher MoCA (normal) participants. Most importantly, this PCu desynchronization response weakened in correspondence with lower MoCA score during the beginning of sequential memory encoding, a time period that should rely on working memory and be affected by declined cognitive function. Our results suggest that deactivation of the PCu is associated with early MCI, and corroborate pathophysiological findings based on post-mortem tissue which have implicated hypoperfusion of the PCu in early stages of Alzheimer disease. Our results indicate the possibility that cognitive decline can be detected early and non-invasively by monitoring PCu activity with electrophysiological methods.
| S-EPMC7521706 | biostudies-literature
Project description:In this paper, we explore the utility of resting-state EEG measures as potential biomarkers for the detection and assessment of cognitive decline in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Neurophysiological biomarkers of AD derived from EEG and FDG-PET, once characterized and validated, would expand the set of existing diagnostic molecular biomarkers of AD pathology with associated biomarkers of disease progression and neural dysfunction. Since symptoms of AD often begin to appear later in life, successful identification of EEG-based biomarkers must account for age-related neurophysiological changes that occur even in healthy individuals. To this end, we collected EEG data from individuals with AD (n = 26), MCI (n = 53), and cognitively normal healthy controls stratified by age into three groups: 18-40 (n = 129), 40-60 (n = 62) and 60-90 (= 55) years old. For each participant, we computed power spectral density at each channel and spectral coherence between pairs of channels. Compared to age matched controls, in the AD group, we found increases in both spectral power and coherence at the slower frequencies (Delta, Theta). A smaller but significant increase in power of slow frequencies was observed for the MCI group, localized to temporal areas. These effects on slow frequency spectral power opposed that of normal aging observed by a decrease in the power of slow frequencies in our control groups. The AD group showed a significant decrease in the spectral power and coherence in the Alpha band consistent with the same effect in normal aging. However, the MCI group did not show any significant change in the Alpha band. Overall, Theta to Alpha ratio (TAR) provided the largest and most significant differences between the AD group and controls. However, differences in the MCI group remained small and localized. We proposed a novel method to quantify these small differences between Theta and Alpha bands' power using empirically derived distributions of spectral power across the time domain as opposed to averaging power across time. We defined Power Distribution Distance Measure (PDDM) as a distance measure between probability distribution functions (pdf) of Theta and Alpha power. Compared to average TAR, using PDDF enhanced the statistical significance, the effect size, and the spatial distribution of significant effects in the MCI group. We designed classifiers for differentiating individual MCI and AD participants from age-matched controls. The classification performance measured by the area under ROC curve after cross-validation were AUC = 0.85 and AUC = 0.6, for AD and MCI classifiers, respectively. Posterior probability of AD, TAR, and the proposed PDDM measure were all significantly correlated with MMSE score and neuropsychological tests in the AD group.
| S-EPMC7864432 | biostudies-literature
Project description:Copy number variants (CNVs) are DNA sequence alterations, resulting in gains (duplications) and losses (deletions) of genomic segments. They often overlap genes and may play important roles in disease. Only one published study has examined CNVs in late-onset Alzheimer's disease (AD), and none have examined mild cognitive impairment (MCI). CNV calls were generated in 288 AD, 183 MCI, and 184 healthy control (HC) non-Hispanic Caucasian Alzheimer's Disease Neuroimaging Initiative participants. After quality control, 222 AD, 136 MCI, and 143 HC participants were entered into case/control association analyses, including candidate gene and whole genome approaches. Although no excess CNV burden was observed in cases (AD and/or MCI) relative to controls (HC), gene-based analyses revealed CNVs overlapping the candidate gene CHRFAM7A, as well as CSMD1, SLC35F2, HNRNPCL1, NRXN1, and ERBB4 regions, only in cases. Replication in larger samples is important, after which regions detected here may be promising targets for resequencing.
| S-EPMC3109875 | biostudies-literature
Project description:We investigated the relationship between regional atrophy rates and 2-year cognitive decline in a large cohort of patients with mild cognitive impairment (MCI; n = 103) and healthy controls (n = 90). Longitudinal magnetic resonance image (MRI) scans were analyzed using high-throughput image analysis procedures. Atrophy rates were derived by calculating percent cortical volume loss between baseline and 24 month scans. Stepwise regressions were performed to investigate the contribution of atrophy rates to language, memory, and executive functioning decline, controlling for age, gender, baseline performances, and disease progression. In MCI, left temporal lobe atrophy rates were associated with naming decline, whereas bilateral temporal, left frontal, and left anterior cingulate atrophy rates were associated with semantic fluency decline. Left entorhinal atrophy rate was associated with memory decline and bilateral frontal atrophy rates were associated with executive function decline. These data provide evidence that regional atrophy rates in MCI contribute to domain-specific cognitive decline, which appears to be partially independent of disease progression. MRI measures of regional atrophy can provide valuable information for understanding the neural basis of cognitive impairment in MCI.
| S-EPMC2923665 | biostudies-literature
Project description:Introduction: Mild cognitive impairment is often associated with affective and other neuropsychiatric symptoms (NPS). This co-occurrence might have a relevant impact on disease progression, from MCI to dementia. Objective: The aim of this study was to explore the trajectories of cognitive decline in an MCI sample from a memory clinic, taking into consideration a perspective of isolated cognitive functions and based on NPS clusters, accounting for the different comorbid symptoms collected at their baseline visit. Methods: A total of 2,137 MCI patients were monitored over a 2.4-year period. Four clusters of NPS (i.e., Irritability, Apathy, Anxiety/Depression and Asymptomatic) were used to run linear mixed models to explore the interaction of cluster with time on cognitive trajectories using a comprehensive neuropsychological battery (NBACE) administered at baseline and at the three subsequent follow-ups. Results: A significant interaction between cluster and time in cognitive decline was found when verbal learning and cued-recall were explored (p = 0.002 for both memory functions). For verbal learning, the Irritability cluster had the largest effect size (0.69), whereas the Asymptomatic cluster showed the smallest effect size (0.22). For cued-recall, the Irritability cluster had the largest effect size among groups (0.64), and Anxiety/Depression had the smallest effect size (0.21). Conclusions: In MCI patients, the Irritability and Apathy NPS clusters shared similar patterns of worsening in memory functioning, which could point to these NPS as risk factors of a faster cognitive decline, acting as early prognostic markers and helping in the diagnostic process.
| S-EPMC8693625 | biostudies-literature
Project description:IntroductionThe growing public threat of Alzheimer's disease (AD) has raised the urgency to quantify the degree of cognitive decline during the conversion process of mild cognitive impairment (MCI) to AD and its underlying genetic pathway. The aim of this article was to test genetic common variants associated with accelerated cognitive decline after the conversion of MCI to AD.MethodsIn 583 subjects with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI; ADNI-1, ADNI-Go, and ADNI-2), 245 MCI participants converted to AD at follow-up. We tested the interaction effects between individual single-nucleotide polymorphisms and AD diagnosis trajectory on the longitudinal Alzheimer's Disease Assessment Scale-Cognition scores.ResultsOur findings reveal six genes, including BDH1, ST6GAL1, RAB20, PDS5B, ADARB2, and SPSB1, which are directly or indirectly related to MCI conversion to AD.DiscussionThis genome-wide association study sheds light on a genetic mechanism of longitudinal cognitive changes during the transition period from MCI to AD.
| S-EPMC5440281 | biostudies-literature
Project description:ObjectiveA variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants.MethodsAPOE epsilon4 allele frequency, CSF proteins (Abeta(1-42), total tau, hyperphosphorylated tau [p-tau(181p)]), glucose metabolism (FDG-PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n = 85), using data from a large multisite study (Alzheimer's Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer's Disease Assessment Scale-Cognitive Subscale) during a variable follow-up period (1.9 +/- 0.4 years).ResultsPatients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (p <or= 0.02). In addition, the CSF ratio p-tau(181p)/Abeta(1-42) (beta = 1.10 +/- 0.53; p = 0.04) and, marginally, FDG-PET predicted cognitive decline.ConclusionsBaseline FDG-PET and episodic memory predict conversion to AD, whereas p-tau(181p)/Abeta(1-42) and, marginally, FDG-PET predict longitudinal cognitive decline. Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention.
| S-EPMC2906178 | biostudies-literature
Project description:Background and Purpose: It is well known that there is a wide range of different pathological stages related to Alzheimer's disease (AD) among patients with amnestic mild cognitive impairment (aMCI). Further refinement of the stages based on neuropsychological and neuroimaging methods is important for earlier disease detection, as well as for the development and evaluation of disease-modifying interventions. Materials and Methods: In this cross-sectional study, 125 aMCI patients were classified into declined progressively three stages of mild, moderate and severe, utilizing the extreme groups approach (EGA) based on their memory function. Fifty-two patients, in addition to 24 cognitively normal subjects, were included in further structural MRI analyses. Characteristics of cognitive functions and brain structures across these newly defined stages were explored through general linear models. Results: Almost all the non-memory cognitive functions showed progressive decline as memory function deteriorated. In addition, medial structures including the right hippocampus, right lingual and left fusiform gyrus, presented with greater gray matter (GM) atrophy during the later stages of aMCI (corrected p < 0.05). Correlations were found between GM volume of the lingual gyrus and processing speed (r = 0.419, p = 0.003) and between the fusiform gyrus and general cognitive function (r = 0.281, p = 0.046). Moreover, both cognitive function and GM volume presented non-linear trajectories over stages of aMCI. Conclusion: Our study characterized the cognitive profiles along with the degree of episodic memory impairment, and these three stages of aMCI showed non-linear progressive decline in cognitive functions and GM volumes.
| S-EPMC5222841 | biostudies-literature