Dataset Information

Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment.

ABSTRACT:

Objective

The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer's disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals.

Method

We included 126 participants from the Consortium for the Early Identification of Alzheimer's disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs).

Results

Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups.

Discussion

As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD's hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD.

SUBMITTER: Caillaud M

PROVIDER: S-EPMC7424270 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment.

Caillaud Marie M Hudon Carol C Boller Benjamin B Brambati Simona S Duchesne Simon S Lorrain Dominique D Gagnon Jean-François JF Maltezos Samantha S Mellah Samira S Phillips Natalie N Belleville Sylvie S

The journals of gerontology. Series B, Psychological sciences and social sciences 20200801 7

<h4>Objective</h4>The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer's disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals.<h4>Method</h4>We included 126 participants from the Consortium for the Early Identification of Alzheimer's disease-Quebe ...[more]

PMID: 31758692

Similar Datasets

Project description:ObjectivesTo study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old.DesignOngoing longitudinal study.SettingIn Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017.ParticipantsIndividuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment).MeasurementsCognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education.ResultsMean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline.ConclusionWe show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827-1834, 2019.

Project description:ImportanceAlthough white matter hyperintensities (WMHs) are associated with the risk for Alzheimer disease, it is unknown whether they represent an independent source of impairment or interact with known markers of disease.ObjectiveTo examine the degree to which WMHs predict aggressive cognitive decline among individuals with mild cognitive impairment, either independently or by modifying the effects of entorhinal cortex volume (ECV), a marker of Alzheimer disease-related neurodegeneration.Design, setting, and participantsThe Alzheimer's Disease Neuroimaging Initiative is a longitudinal study with 6-month follow-up visits. Three hundred thirty-two participants (mean [SD] age, 74.6 [7.4] years; 118 women) of a total of 374 participants diagnosed as having mild cognitive impairment were included. Participants were excluded if they did not have longitudinal data, apolipoprotein E genotype data, or had evidence of supratentorial infarct.Main outcomes and measuresA decline in Mini-Mental State Examination score of 3 points over 6 months or 6 points over 1 year between consecutive visits was defined as aggressive decline. White matter hyperintensity volume and ECV were entered as predictors in Cox proportional hazards models and Wilcoxon-Breslow tests to examine their impact on this outcome, adjusting for sex, age, education, and apolipoprotein E status.ResultsGreater WMH volume at baseline, apolipoprotein E ε4 status, and smaller ECV at baseline were associated with an increased risk for aggressive decline (hazard ratio [HR], 1.23; 95% CI, 1.05-1.43; P = .01 for WMH volume; HR, 1.49; 95% CI, 1.09-2.05; P = .04 for apolipoprotein E ε4 status; HR, 0.66; 95% CI, 0.55-0.79; P < .001 for ECV). White matter hyperintensity volume modified the effect of ECV on aggressive decline risk: individuals with high ECV and low WMH were at particularly low likelihood of decline (χ2 = 15, P = .001). Participants with Mini-Mental State Examination scores that declined by 3 or more points over 6 months or 6 or more points over 12 months were more likely to have converted to Alzheimer disease by the end of the follow-up period (χ2 = 82, P < .001).Conclusions and relevanceWhite matter hyperintensity burden and ECV predict rapid cognitive decline among individuals with mild cognitive impairment both additively and multiplicatively.

Project description:BackgroundAlthough previous studies have demonstrated that the hippocampus plays a role in verbal memory, the role of hippocampal subfields in visual memory is uncertain, especially in those with preclinical Alzheimer's disease (AD). This study aimed to examine relationships between hippocampal subfield volumes and visual memory in SCD (subjective cognitive decline) and aMCI (amnestic mild cognitive impairment).MethodsThe study sample included 47 SCD patients, 62 aMCI patients, and 51 normal controls (NCs) and was recruited from Shanghai Jiao Tong University Affiliated Sixth People's Hospital. Visual memory was measured by the subtests of BVMT-R (Brief Visuospatial Memory Test-Revised), PLT (Pictorial Learning Test), DMS (Delayed Matching to Sample), and PAL (Paired Associates Learning). Hippocampal subfield volumes were estimated using FreeSurfer software (version 6.0). We modeled the association between visual memory and relative hippocampal subfield volumes (dividing by estimated total intracranial volume) using Pearson's correlation and linear regression.ResultsCompared with the NC group, patients with SCD did not find any relative hippocampal subregion atrophy, and the aMCI group found atrophy in CA1, molecular layer, subiculum, GC-ML-DG, CA4, and CA3. After adjusting for covariates (age, sex, and APOE ε4 status) and FDR (false discovery rate) correction of p (q values) < 0.05, in NC group, DMS delay matching scores were significant and negatively associated with presubiculum (r = -0.399, FDR q = 0.024); in SCD group, DMS delay matching scores were negatively associated with CA3 (r = -0.378, FDR q = 0.048); in the aMCI group, BVMT-R immediate recall scores were positively associated with CA1, molecular layer, subiculum, and GC-ML-DG (r = 0.360-0.374, FDR q < 0.036). Stepwise linear regression analysis confirmed the association.ConclusionsOur results indicate a different and specific correction of visual memory with relative hippocampal subfield volumes between SCD and aMCI. The correlations involved different and more subfields as cognitive decline. Whether these associations predict future disease progression needs dynamic longitudinal studies.

Project description:ImportanceSubjective memory complaints (SMCs) are associated with a faster cognitive decline; whether this association is also associated with structural brain alterations, such as white matter hyperintensity (WMH) volumes, requires investigation.ObjectiveTo evaluate the association of SMCs with WMH volumes and cognitive decline and investigate the role of WMH volumes in the association between SMCs and cognitive decline.Design, setting, and participantsThe Chicago Health and Aging Project, a population-based cohort study, enrolled adults aged 65 years or older. Data collection occurred in 3-year cycles from 1993 until 2012. Our study comprised 975 participants with magnetic resonance imaging assessments, of which 900 participants had data on SMCs and covariates, and 713 participants provided 2 or more cognitive assessments during the follow-up. Statistical analyses were conducted from May to October 2021.ExposuresSMCs were obtained from self-reported questionnaire data during clinical evaluations, and the cycle, when reported, constituted the baseline of our study. Based on the frequency and severity of concerns, we categorized participants into 3 groups, (1) no concerns, (2) moderate concerns, and (3) very worried.Main outcomes and measuresVolumetric magnetic resonance imaging measures of WMH volume and neuropsychological testing assessments of global cognition. Linear regression analysis was used to investigate the association between SMCs and WMH volumes in a multivariable model adjusted for age, sex, race and ethnicity, education, APOE4 status, and total intracranial volume. The association of SMCs with cognitive decline was investigated using linear mixed-effects models for age, sex, race and ethnicity, education, APOE4 status, follow-up time, and each variable in interaction with time to estimate the annual longitudinal change in cognitive function.ResultsOf the 900 participants with data on SMCs, covariates, and WMH volumes, 553 (61.4%) were women, 539 (59.9%) were African American, and the mean (SD) age was 79.5 (6.2) years. SMCs were associated with a larger WMH volume and faster cognitive decline. Compared with participants with no concerns, participants who were very worried had higher WMH volumes (β = 0.833; 95% CI, 0.203-1.463) and 174% faster cognitive decline (β = -0.049; 95% CI, -0.076 to -0.022). The association between SMCs and cognitive decline remained statistically significant among individuals with large WMH volumes (ie, within the fourth quartile). Within the fourth quartile of WMH volumes, participants who were very worried had 428% faster cognitive decline (β = -0.077; 95% CI, -0.144 to -0.011) compared with participants with no concerns.Conclusions and relevanceThis cohort study suggests that SMCs, frequently reported by older individuals, are an important sign of cognitive impairment, especially among people with abnormalities in brain structure, such as larger WMH volumes.

Project description:ObjectiveThis study aims to explore whether body mass index (BMI) level affects the executive function and hippocampal subregion volume of subjective cognitive decline (SCD).Materials and methodsA total of 111 participants were included in the analysis, including SCD (38 of normal BMI, 27 of overweight and obesity) and normal cognitive control (NC) (29 of normal BMI, 17 of overweight and obesity). All subjects underwent the Chinese version of the Stroop Color-Word Test (SCWT) to measure the executive function and a high-resolution 3D T1 structural image acquisition. Two-way ANOVA was used to examine the differences in executive function and gray matter volume in hippocampal subregions under different BMI levels between the SCD and NC.ResultThe subdimensions of executive function in which different BMI levels interact with SCD and NC include inhibition control function [SCWT C-B reaction time(s): F (1,104) = 5.732, p = 0.018], and the hippocampal subregion volume of CA1 [F (1,99) = 8.607, p = 0.004], hippocampal tail [F (1,99) = 4.077, p = 0.046], and molecular layer [F (1,99) = 6.309, p = 0.014]. After correction by Bonferroni method, the population × BMI interaction only had a significant effect on the CA1 (p = 0.004). Further analysis found that the SCWT C-B reaction time of SCD was significantly longer than NC no matter whether it is at the normal BMI level [F (1,104) = 4.325, p = 0.040] or the high BMI level [F (1,104) = 21.530, p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [F (1,99) = 4.938, p = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [F (1,104) = 13.499, p < 0.001] and greater CA1 volume compared with the normal BMI group [F (1,99) = 7.619, p = 0.007].ConclusionThe BMI level is related to the inhibition control function and the gray matter volume of CA1 subregion in SCD. Overweight seems to increase the gray matter volume of CA1 in the elderly with SCD, but it is not enough to compensate for the damage to executive function caused by the disease. These data provide new insights into the relationship between BMI level and executive function of SCD from the perspective of imaging.

Project description:BackgroundThe relationship between white matter hyperintensities (WMH) and the core features of Alzheimer's disease (AD) remains controversial. Further, due to the prevalence of co-pathologies, the precise role of WMH in cognition and neurodegeneration also remains uncertain.MethodsHerein, we analyzed 1803 participants with available WMH volume data, extracted from the ADNI database, including 756 cognitively normal controls, 783 patients with mild cognitive impairment (MCI), and 264 patients with dementia. Participants were grouped according to cerebrospinal fluid (CSF) pathology (A/T profile) severity. Linear regression analysis was applied to evaluate the factors associated with WMH volume. Modeled by linear mixed-effects, the increase rates (Δ) of the WMH volume, cognition, and typical neurodegenerative markers were assessed. The predictive effectiveness of WMH volume was subsequently tested using Cox regression analysis, and the relationship between WMH/ΔWMH and other indicators such as cognition was explored through linear regression analyses. Furthermore, we explored the interrelationship among amyloid-β deposition, cognition, and WMH using mediation analysis.ResultsHigher WMH volume was associated with older age, lower CSF amyloid-β levels, hypertension, and smoking history (all p ≤ 0.001), as well as cognitive status (MCI, p < 0.001; dementia, p = 0.008), but not with CSF tau levels. These results were further verified in any clinical stage, except hypertension and smoking history in the dementia stage. Although WMH could not predict dementia conversion, its increased levels at baseline were associated with a worse cognitive performance and a more rapid memory decline. Longitudinal analyses showed that baseline dementia and positive amyloid-β status were associated with a greater accrual of WMH volume, and a higher ΔWMH was also correlated with a faster cognitive decline. In contrast, except entorhinal cortex thickness, the WMH volume was not found to be associated with any other neurodegenerative markers. To a lesser extent, WMH mediates the relationship between amyloid-β and cognition.ConclusionWMH are non-specific lesions that are associated with amyloid-β deposition, cognitive status, and a variety of vascular risk factors. Despite evidence indicating only a weak relationship with neurodegeneration, early intervention to reduce WMH lesions remains a high priority for preserving cognitive function in the elderly.

Dataset Information

Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment.

Objective

Method

Results

Discussion

Publications

Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets