Dataset Information

Morphometric Changes to Corneal Dendritic Cells in Individuals With Mild Cognitive Impairment.

ABSTRACT:

Purpose

There has been increasing interest in identifying non-invasive, imaging biomarkers for neurodegenerative disorders of the central nervous system (CNS). The aim of this proof-of-concept study was to investigate whether corneal sensory nerve and dendritic cell (DC) parameters, captured using in vivo confocal microscopy (IVCM), are altered in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Methods

Fifteen participants were recruited from the Australian Imaging Biomarkers and Lifestyle (AIBL) study in Melbourne, VIC, Australia. The cohort consisted of cognitively normal (CN) individuals (n = 5), and those with MCI (n = 5) and AD (n = 5). Participants underwent a slit lamp examination of the anterior segment, followed by corneal imaging using laser-scanning in vivo confocal microscopy (IVCM) of the central and inferior whorl regions. Corneal DC density, field area, perimeter, circularity index, aspect ratio, and roundness were quantified using Image J. Quantitative data were derived for corneal nerve parameters, including nerve fiber length (CNFL), fiber density (CNFD), branch density (CNBD), and diameter.

Results

Corneal DC field area and perimeter were greater in individuals with MCI, relative to CN controls, in both the central and inferior whorl regions (p < 0.05 for all comparisons). In addition, corneal DCs in the whorl region of MCI eyes had lower circularity and roundness indices and a higher aspect ratio relative to CNs (p < 0.05 for all comparisons). DC density was similar across participant groups in both corneal regions. There was a trend toward lower quantitative parameters for corneal nerve architecture in the AD and MCI groups compared with CN participants, however, the inter-group differences did not reach statistical significance. Central corneal nerve diameters were similar between groups.

Conclusion

This study is the first to report morphological differences in corneal DCs in humans with MCI. These differences were evident in both the central and mid-peripheral cornea, and in the absence of significant nerve abnormalities or a difference in DC density. These findings justify future large-scale studies to assess the utility of corneal IVCM and DC analysis for identifying early stage pathology in neurodegenerative disorders of the CNS.

SUBMITTER: Dehghani C

PROVIDER: S-EPMC7755610 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Morphometric Changes to Corneal Dendritic Cells in Individuals With Mild Cognitive Impairment.

Dehghani Cirous C Frost Shaun S Jayasena Rajiv R Fowler Christopher C Masters Colin L CL Kanagasingam Yogesan Y Jiao Haihan H Lim Jeremiah K H JKH Chinnery Holly R HR Downie Laura E LE

Frontiers in neuroscience 20201209

<h4>Purpose</h4>There has been increasing interest in identifying non-invasive, imaging biomarkers for neurodegenerative disorders of the central nervous system (CNS). The aim of this proof-of-concept study was to investigate whether corneal sensory nerve and dendritic cell (DC) parameters, captured using <i>in vivo</i> confocal microscopy (IVCM), are altered in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD).<h4>Methods</h4>Fifteen participants were recruited from ...[more]

PMID: 33362451

Similar Datasets

Project description:INTRODUCTION:Episodic memory processes are supported by different subregions of the medial temporal lobe (MTL). In contrast to a unitary model of memory recognition supported solely by the hippocampus, a current model suggests that item encoding engages perirhinal cortex, whereas relational encoding engages parahippocampal cortex and the hippocampus. However, this model has not been examined in the context of aging, neurodegeneration, and MTL morphometrics. METHODS:Forty-four healthy subjects (HSs) and 18 cognitively impaired subjects (nine mild cognitive impairment [MCI] and nine Alzheimer's disease [AD] patients) were assessed with the relational and item-specific encoding task (RISE) and underwent 3T magnetic resonance imaging. The RISE assessed the differential contribution of relational and item-specific memory. FreeSurfer was used to obtain measures of cortical thickness of MTL regions and hippocampus volume. RESULTS:Memory accuracies for both item and relational memory were significantly better in the HS group than in the MCI/AD group. In MCI/AD group, relational memory was disproportionately impaired. In HSs, hierarchical regressions demonstrated that memory was predicted by perirhinal thickness after item encoding, and by hippocampus volume after relational encoding (both at trend level) and significantly by parahippocampal thickness at associative recognition. The same brain morphometry profiles predicted memory accuracy in MCI/AD, although more robustly perirhinal thickness for item encoding (R2 = 0.31) and hippocampal volume and parahippocampal thickness for relational encoding (R2 = 0.31). DISCUSSION:Our results supported a model of episodic memory in which item-specific encoding was associated with greater perirhinal cortical thickness, while relational encoding was associated with parahippocampal thickness and hippocampus volume. We identified these relationships not only in HSs but also in individuals with MCI and AD. In the subjects with cognitive impairment, reductions in hippocampal volume and impairments in relational memory were especially prominent.

Project description:Studies have suggested that insulin resistance plays a role in cognitive impairment in individuals with type 2 diabetes. We aimed to determine whether an improvement in insulin resistance could explain cognitive performance variations over 36 weeks in older individuals with mild cognitive impairment (MCI) and type 2 diabetes.A total of 97 older individuals (mean +/- SD age 76 +/- 6 years) who had recently (<2 months) started an antidiabetes treatment of metformin (500 mg twice a day) (n = 30) or metformin (500 mg/day)+rosiglitazone (4 mg/day) (n = 32) or diet (n = 35) volunteered. The neuropsychological test battery consisted of the Mini-Mental State Examination (MMSE), Rey Verbal Auditory Learning Test (RAVLT) total recall, and Trail Making Tests (TMT-A and TMT-B) performed at baseline and every 12 weeks for 36 weeks along with clinical testing.At baseline, no significant differences were found between groups in clinical or neuropsychological parameters. Mean +/- SD values in the entire population were as follows: A1C 7.5 +/- 0.5%, fasting plasma glucose (FPG) 8.6 +/- 1.3 mmol/l, fasting plasma insulin (FPI) 148 +/- 74 pmol/l, MMSE 24.9 +/- 2.4, TMT-A 61.6 +/- 42.0, TMT-B 162.8 +/- 78.7, the difference between TMT-B and TMT-A [DIFFBA] 101.2 +/- 58.1, and RAVLT 24.3 +/- 2.1. At follow-up, ANOVA models tested changes in metabolic control parameters (FPI, FPG, and A1C). Such parameters improved in the metformin and metformin/rosiglitazone groups (P(trend) < 0.05 in both groups). ANCOVA repeated models showed that results for the metformin/rosiglitazone group remained stable for all neuropsychological tests, and results for the diet group remained stable for the MMSE and TMT-A and declined for the TMT-B (P(trend) = 0.024), executive efficiency (DIFFBA) (P(trend) = 0.026), and RAVLT memory test (P(trend) = 0.011). Results for the metformin group remained stable for the MMSE and TMTs but declined for the RAVLT (P(trend) = 0.011). With use of linear mixed-effects models, the interaction term, FPI x time, correlated with cognitive stability on the RAVLT in the metformin/rosiglitazone group (beta = -1.899; P = 0.009).Rosiglitazone may protect against cognitive decline in older individuals with type 2 diabetes and MCI.

Project description:BACKGROUND/OBJECTIVES:Behavioral problems in individuals with Alzheimer's disease (AD) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI). DESIGN:Longitudinal observational cohort study. SETTING:Academic medical center. PARTICIPANTS:Members of an apolipoprotein E (APOE) ɛ4 genetically enriched cohort of Maricopa County residents who were neuropsychiatrically healthy at entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had the Neuroticism, Extraversion, and Openness Personality Inventory-Revised (NEO-PI-R) before and during the MCI transition epoch were compared with 252 nontransitioners also with serial NEO-PI-R administrations. INTERVENTION:Longitudinal administration of the NEO-PI-R and neuropsychological test battery. MEASUREMENTS:Change in NEO-PI-R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from entry to the epoch of MCI diagnosis or an equivalent follow-up duration in nontransitioners. RESULTS:NEO-PI-R neuroticism T-scores increased significantly more in MCI transitioners than in nontransitioners (mean 2.9, 95% confidence interval (CI) = 0.9-4.9 vs 0, 95% CI = -0.7-0.7, P = .02), and openness decreased more in MCI transitioners than in nontransitioners (-4.8, 95% CI = -7.3 to -2.4 vs -1.0, 95% CI = -1.6 to -0.4, P < .001). Concurrent subclinical but statistically significant changes in behavioral scores worsened more in MCI transitioners than nontransitioners for measures of depression, somatization, irritability, anxiety, and aggressive attitude. CONCLUSION:Personality and subclinical behavioral changes begin during the transition from preclinical AD to incident MCI and qualitatively resemble the clinically manifest behavioral disorders that subsequently arise in individuals with frank dementia.

Project description:ImportanceMild cognitive impairment (MCI) is a transition state between normal cognitive aging and dementia that increases the risk for progressive cognitive decline. Preventing cognitive decline is a public health priority.ObjectiveTo determine whether behavioral activation prevents cognitive and functional decline over 2 years in black individuals with MCI.Design, setting, and participantsSingle-center, single-masked, attention-controlled randomized clinical trial. Participants were enrolled from June 21, 2011, to October 3, 2014, and follow-up ended December 13, 2016. Community-based recruitment and treatment of black individuals older than 65 years with amnestic MCI. Volunteer sample of 1390 persons with memory complaints were screened. Overall, 536 individuals had baseline assessment, and 315 (58.8%) were ineligible, most often owing to normal cognition (205 of 315 [65%]) or dementia (59 of 315 [18.7%]); 221 fully eligible participants were randomized. Analyses were intention to treat.InterventionsParticipants were randomized to behavioral activation, which aimed to increase cognitive, physical, and social activity (111 [50.2%]), or supportive therapy, an attention control treatment (110 [49.8%]).Main outcomes and measuresThe prespecified primary outcome was a decline of 6 or more recalled words on the total recall score of the Hopkins Verbal Learning Test-Revised assessed at 6, 12, 18, and 24 months. The secondary outcome was functional decline.ResultsOf 221 randomized participants (mean [SD] age, 75.8 [7.0] years, 175 women [79%]), 77 behavioral activation participants (69.4%) and 87 supportive therapy participants (79.1%) had 2-year outcome assessments. After baseline, behavioral activation participants engaged in significantly more cognitive activities than supportive therapy participants. The 2-year incidence of memory decline was 1.2% (95% CI, 0.2-6.4) for behavioral activation vs 9.3% (95% CI, 5.30-16.4) for supportive therapy (relative risk, 0.12; 95% CI, 0.02-0.74; P = .02). Behavioral activation was associated with stable everyday function, whereas supportive therapy was associated with decline (difference in slopes, 2.71; 95% CI, 0.12-5.30; P = .04). Rates of serious adverse events for behavioral activation and supportive therapy, respectively, were: falls (14 [13%] vs 28 [25%]), emergency department visits (24 [22%] vs 24 [22%]), hospitalizations (36 [32%] vs 31 [28%]), and deaths (7 [5%] vs 3 [4%]).Conclusions and relevanceBehavioral activation prevented cognitive and functional decline, but this finding requires further investigation. Black individuals have almost twice the rate of dementia as white individuals; behavioral activation may reduce this health disparity.Trial registrationClinicalTrials.gov Identifier: NCT01299766.

Dataset Information

Morphometric Changes to Corneal Dendritic Cells in Individuals With Mild Cognitive Impairment.

Purpose

Methods

Results

Conclusion

Publications

Morphometric Changes to Corneal Dendritic Cells in Individuals With Mild Cognitive Impairment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets