Identification of Earlier Biomarkers for Alzheimer’s Disease: A Multimodal Neuroimaging Study of Individuals with Subjective Cognitive Decline

2020 ◽  
Vol 77 (3) ◽  
pp. 1067-1076
Author(s):  
Ashleigh F. Parker ◽  
Colette M. Smart ◽  
Vanessa Scarapicchia ◽  
Jodie R. Gawryluk ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Cognitive Decline ◽  
Functional Mri ◽  
Healthy Aging ◽  
Angular Gyrus ◽  
Subjective Cognitive Decline ◽  
Grey Matter Volume ◽  
Increased Risk

Background: Individuals with subjective cognitive decline (SCD) are thought to be the earliest along the cognitive continuum between healthy aging and Alzheimer’s disease (AD). Objective: The current study used a multi-modal neuroimaging approach to examine differences in brain structure and function between individuals with SCD and healthy controls (HC). Methods: 3T high-resolution anatomical images and resting-state functional MRI scans were retrieved for 23 individuals with SCD and 23 HC from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Results: The SCD and HC groups were not significantly different in age or education level. Voxel-based morphometry results did not show significant differences in grey matter volume between the groups. Functional MRI results revealed significantly greater functional connectivity in the default mode network in regions including the bilateral precuneus cortex, bilateral thalamus, and right hippocampal regions in individuals with SCD relative to controls. Conversely, those with SCD showed decreased functional connectivity in the bilateral frontal pole, caudate, angular gyrus, and lingual gyrus, compared to HC. Conclusion: Findings revealed differences in brain function but not structure between individuals with SCD and HC. Overall, this study represents a crucial step in characterizing individuals with SCD, a group recognized to be at increased risk for AD. It is imperative to identify biomarkers of AD prior to significant decline on clinical assessment, so that disease-delaying interventions may be delivered at the earliest possible time point.

scholarly journals Decreased Dynamic Flexibility of Brain Functional Connectivity in Prodromal Alzheimer’s Disease

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Zachary G. Osborn ◽  
Shannon L. Risacher ◽  
John D. West ◽  
Eileen Tallman ◽  
Liana Apostolova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Cognitive Decline ◽  
Functional Mri ◽  
Information Transfer ◽  
Time Windows ◽  
Parahippocampal Gyrus ◽  
Subjective Cognitive Decline ◽  
Functional Flexibility

Background and Hypothesis:  In neuroimaging, functional connectivity (FC), defined as the correlation between the functional MRI signals of two brain grey matter regions of interest (ROIs), is thought to reflect communication between ROIs. Changes in whole brain FC networks have been detected in Alzheimer’s disease (AD); however, traditional FC networks generated using the entire length of an fMRI scan could miss cognitively relevant fluctuations in FC. Analyzing dynamic patterns of FC within subsets of fMRI scans is hypothesized to enable greater sensitivity to deficits of information transfer and processing in AD compared to static FC.  Project Methods:  Functional MRI data of 58 participants with either subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, or controls were divided into time windows; the FC within each window provides sequential dynamic FC networks (dFC). Each dFC network was partitioned into subnetworks, e.g. visual or motor, whose member ROIs are strongly interconnected, and the functional flexibility of an ROI was estimated by the number of times it switches subnetworks in a scan.  Results:  The flexibility of the left inferior parietal lobule, right rostral lateral orbitofrontal cortex, and right amyglada/parahippocampal gyrus showed the highest correlations with Montreal Cognitive Assessment scores: r = 0.2516, 0.2480, and 2421, respectively. Although no correlations reached conventional significance (p = 0.0568, 0.0605, and 0.0671, uncorrected), this may reflect low power that should be increased with a planned larger sample.  Potential Impact:  Dynamic FC analyses may help clarify the neurophysiological mechanisms underlying cognitive decline, but methodological refinements and higher resolution data are likely needed to realize this potential.

scholarly journals Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

2016 ◽  
Vol 10 (3) ◽  
pp. 170-177 ◽  
Author(s):  
Adalberto Studart Neto ◽  
Ricardo Nitrini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Clinical Manifestation ◽  
Neurodegenerative Disorder ◽  
Subjective Cognitive Decline ◽  
Subjective Memory ◽  
Increased Risk

ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

scholarly journals Regional atrophy and cognitive decline depend on definition of subjective cognitive decline

2021 ◽  
Author(s):  
Cassandra Morrison ◽  
Mahsa Dadar ◽  
Neda Shafiee ◽  
Sylvia Villeneuve ◽  
D. Louis Collins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Cognitive Change ◽  
Disease Assessment ◽  
Subjective Cognitive Decline ◽  
Cognitively Normal ◽  
Increased Risk ◽  
Definition Of

AbstractBackgroundPeople with subjective cognitive decline (SCD) may be at increased risk for Alzheimer’s disease (AD). However, not all studies have observed this increased risk. Inconsistencies may be related to different methods used to define SCD. The current project examined whether four methods of defining SCD (applied to the same sample) results in different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+) and without SCD (SCD-).MethodsMRI scans and questionnaire data for 273 cognitively normal older adults from Alzheimer’s Disease Neuroimaging Initiative were examined. To operationalize SCD we used four common methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry only. A previously validated MRI analysis method (SNIPE) was used to measure hippocampal volume and grading. Deformation-based morphometry was performed to examine volume at regions known to be vulnerable to AD. Logistic regressions were completed to determine whether diagnostic method was associated with volume differences between SCD- and SCD+. Linear mixed effects models were performed to examine the relationship between the definitions of SCD and future cognitive decline.ResultsResults varied between the four methods of defining SCD. Left hippocampal grading was lower in SCD+ than SCD-when using the CCI (p=.041) and Worry (p=.021) definitions. The right (p=.008) and left (p=.003) superior temporal regions were smaller in SCD+ than SCD-, but only with the ECog. SCD+ was associated with greater future cognitive decline measured by Alzheimer’s Disease Assessment Scale, but only with the CCI definition. In contrast, only the ECog definition of SCD was associated with future decline on the Montreal Cognitive Assessment.ConclusionThe current findings suggest that the various methods used to differentiate between SCD- and SCD+ influence whether volume differences and findings of cognitive decline are observed between groups in this retrospective analysis.

Association of Subjective Cognitive Decline with Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease Pathology in Cognitively Intact Older Adults: The CABLE Study

2021 ◽  
pp. 1-9
Author(s):  
Chen Wen ◽  
Yan-Lin Bi ◽  
Hao Hu ◽  
Shu-Yi Huang ◽  
Ya-Hui Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline ◽  
Csf Biomarkers ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Increased Risk ◽  
T Tau

Background: Subjective cognitive decline (SCD) might occur at the early stages of dementia. Individuals with SCD have an increased risk of subsequent objective cognitive decline and greater rates of progression to dementia. Objective: We aimed to explore the associations between SCD and cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology in cognitively normal individuals. Methods: A total of 1,099 cognitively normal elders with available data on CSF biomarkers of AD pathology (Aβ 42, P-tau, and T-tau) were included in our analysis. Linear regression was used to examine the associations of SCD status and SCD severity with CSF biomarkers. Additionally, a review was conducted to discuss the associations between SCD and CSF biomarkers of AD pathology. Results: After adjustments for covariates, SCD and SCD severity showed significant associations with CSF Aβ 42 (SCD: β= –0.0003, p = 0.0263; SCD severity: β= –0.0004, p = 0.0046), CSF T-tau/Aβ 42 ratio (SCD: β= 0.1080, p = 0.1080; SCD severity: β= 0.1129, p = 0.0009) and CSF P-tau/Aβ 42 ratio (SCD: β= 0.0167, p = 0.0103; SCD severity: β= 0.0193, p = 0.0006) rather than T-tau and P-tau compared with cognitively normal individuals. In the review, a total of 28 studies were finally included after reviewing 174 articles. CSF Aβ 42 was lower in SCD than cognitively normal (CN) individuals, but higher than those with objective cognitive decline. However, CSF tau pathology showed no difference between SCD and CN. Conclusion: The results indicated that pathophysiological changes in CSF Aβ pathology occurred in individuals with SCD, which provide new insights into early intervention of AD.

scholarly journals Exploring dynamic functional connectivity alterations in the preclinical stage of Alzheimer’s disease: an exploratory study from SICOLDE

2021 ◽  
Author(s):  
Fan Yang ◽  
Xueyan Jiang ◽  
Feng Yue ◽  
Luyao Wang ◽  
Boecker Henning ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Connectivity ◽  
Cognitive Decline ◽  
Standardized Uptake Value ◽  
Magnetic Resonance Images ◽  
Subjective Cognitive Decline ◽  
Dynamic Functional Connectivity ◽  
Preclinical Stage ◽  
Neuropsychological Assessments

Abstract IntroductionExploring functional connectivity (FC) alterations is important for the understanding of underlying neuronal network alterations in subjective cognitive decline (SCD). The objective of this study was to discover stable and subtle dynamic functional connectivity (FC) changes in the preclinical stage of Alzheimer’s disease (AD), and to explore the associations between dynamic FCs and amyloid accumulation.MethodsNinety-seven normal control (NC) subjects, 101 subjective cognitive decline (SCD) subjects, and 55 cognitive impairment (CI) subjects with neuropsychological assessments and resting-state functional magnetic resonance images constituted the whole cohort. Of these, 29 NCs and 52 SCDs with amyloid images were selected as the sub-cohort. First, independent components (ICs) identified by group independent component analysis (ICA) were used to define static and dynamic brain networks. Static and sliding-window dynamic FCs were then calculated. Second, the connection between each pair of ICs was compared between groups in the two cohorts. Hubs were obtained and considered as seeds in the subsequent seed-based dynamic FC analysis. One-way analysis of variance (ANOVA) was used to compare the seed-based dynamic FC maps between groups in the whole cohort, while a 2×2 ANOVA model was used to measure the group or amyloid effects in the sub-cohort. Post-hoc analysis was applied, and differences were considered significant if the cluster-level FWE-corrected p-value was less than 0.001. Finally, correlation analysis was conducted between the altered dynamic FCs, neuropsychological assessments, and amyloid burden.ResultsThe results showed that 42 ICs were revealed. Compared with the static FCs, the dynamic FCs were found to be more stable and sensitive between groups. The effective dynamic FCs included those between the salience/ventral attention network, the default mode network, and the visual network. Specifically, the dynamic FC of the thalamus/caudate (IC 25) drove the hub role in the group differences between the NC and SCD groups. In the seed-based dynamic FC analysis, the dynamic FC between the thalamus/caudate and the middle temporal/frontal gyrus was observed to be higher in the SCD and CI groups in the whole cohort. Moreover, a higher dynamic FC between the thalamus/caudate and visual cortex was observed in the amyloid positive group. Finally, the altered dynamic FC was associated with the amyloid global level standardized uptake value ratio.ConclusionOur findings indicate that dynamic FCs can reflect subtle changes in the preclinical stage of AD.

scholarly journals Grey Matter Loss at Different Stages of Cognitive Decline: A Role for the Thalamus in Developing Alzheimer’s Disease

2021 ◽  
pp. 1-16
Author(s):  
Laurens Ansem van de Mortel ◽  
Rajat Mani Thomas ◽  
Guido Alexander van Wingen ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Grey Matter ◽  
Brain Regions ◽  
Angular Gyrus ◽  
Grey Matter Volume ◽  
Volume Loss ◽  
Neuroimaging Data

Background: Alzheimer’s disease (AD) is characterized by cognitive impairment and large loss of grey matter volume and is the most prevalent form of dementia worldwide. Mild cognitive impairment (MCI) is the stage that precedes the AD dementia stage, but individuals with MCI do not always convert to the AD dementia stage, and it remains unclear why. Objective: We aimed to assess grey matter loss across the brain at different stages of the clinical continuum of AD to gain a better understanding of disease progression. Methods: In this large-cohort study (N = 1,386) using neuroimaging data from the Alzheimer’s Disease Neuroimaging Initiative, voxel-based morphometry analyses were performed between healthy controls, individuals with early and late and AD dementia stage. Results: Clear patterns of grey matter loss in mostly hippocampal and temporal regions were found across clinical stages, though not yet in early MCI. In contrast, thalamic volume loss seems one of the first signs of cognitive decline already during early MCI, whereas this volume loss does not further progress from late MCI to AD dementia stage. AD dementia stage converters already show grey matter loss in hippocampal and mid-temporal areas as well as the posterior thalamus (pulvinar) and angular gyrus at baseline. Conclusion: This study confirms the role of temporal brain regions in AD development and suggests additional involvement of the thalamus/pulvinar and angular gyrus that may be linked to visuospatial, attentional, and memory related problems in both early MCI and AD dementia stage conversion.

scholarly journals Local Atrophy Observed in Subjective Cognitive Decline Varies Based on Questionnaire Employed in ADNI

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 638-638
Author(s):  
Cassandra Morrison ◽  
Mahsa Dadar ◽  
Neda Shafiee ◽  
Louis Collins
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Cognitive Change ◽  
Subjective Cognitive Decline ◽  
Future Research ◽  
Clinical Practices ◽  
Increased Risk ◽  
Mri Scans ◽  
The Right

Abstract Background Subjective cognitive decline (SCD) may be associated with increased risk for Alzheimer’s disease. However, neither research nor clinical practices have implemented a universal approach to operationalize SCD. This study was designed to determine whether four different methods of defining SCD influence atrophy differences observed between SCD and normal controls (NC). Methods We included MRI scans from 273 participants (NC and SCD) from the Alzheimer’s Disease Neuroimaging Initiative. We used four methods to operationalize SCD: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), Worry, and ECog+Worry. Deformation-based morphometry was performed to examine volumetric change at the lateral ventricles, amygdala, and superior temporal regions (CerebrA atlas; Manera et al., 2020)). A previously validated MRI analysis method (SNIPE) was used for volume and grading of the hippocampus and entorhinal cortex (Coupe et al., 2012). A logistic regression was completed to examine the association between diagnosis and atrophy in SCD and NC. Results Left hippocampal grading was lower in SCD than NC with the CCI (p=.041) and Worry (p=.021). When using ECog+Worry, smaller left entorhinal volume was observed in SCD than NC (p=.025). Both the right (p=.008) and left (p=.003) superior temporal regions were smaller in SCD than NC, with only the ECog. Conclusion Although SCD questionnaires are designed to measure the same construct, the results here suggest otherwise. These results suggest that the SCD questionnaire employed will influence whether atrophy is observed in SCD relative to NC. Future research is warranted to better understand how different methodologies result in inconsistent findings.

Subjective Spatial Navigation Complaints - A Frequent Symptom Reported by Patients with Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer's Disease

2018 ◽  
Vol 15 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Jiri Cerman ◽  
Ross Andel ◽  
Jan Laczo ◽  
Martin Vyhnalek ◽  
Zuzana Nedelska ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Spatial Navigation ◽  
Subjective Cognitive Decline ◽  
Great Effort ◽  
Frequent Symptom ◽  
Normal Controls

Background: Great effort has been put into developing simple and feasible tools capable to detect Alzheimer's disease (AD) in its early clinical stage. Spatial navigation impairment occurs very early in AD and is detectable even in the stage of mild cognitive impairment (MCI). Objective: The aim was to describe the frequency of self-reported spatial navigation complaints in patients with subjective cognitive decline (SCD), amnestic and non-amnestic MCI (aMCI, naMCI) and AD dementia and to assess whether a simple questionnaire based on these complaints may be used to detect early AD. Method: In total 184 subjects: patients with aMCI (n=61), naMCI (n=27), SCD (n=63), dementia due to AD (n=20) and normal controls (n=13) were recruited. The subjects underwent neuropsychological examination and were administered a questionnaire addressing spatial navigation complaints. Responses to the 15 items questionnaire were scaled into four categories (no, minor, moderate and major complaints). Results: 55% of patients with aMCI, 64% with naMCI, 68% with SCD and 72% with AD complained about their spatial navigation. 38-61% of these complaints were moderate or major. Only 33% normal controls expressed complaints and none was ranked as moderate or major. The SCD, aMCI and AD dementia patients were more likely to express complaints than normal controls (p's<0.050) after adjusting for age, education, sex, depressive symptoms (OR for SCD=4.00, aMCI=3.90, AD dementia=7.02) or anxiety (OR for SCD=3.59, aMCI=3.64, AD dementia=6.41). Conclusion: Spatial navigation complaints are a frequent symptom not only in AD, but also in SCD and aMCI and can potentially be detected by a simple and inexpensive questionnaire.

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