Raúl López-Antón

Retinal alterations in mild cognitive impairment and Alzheimer’s disease: an optical coherence tomography study

Retinal nerve fiber layer thickness (RNFL) measured by means of Optical Coherence Tomography (OCT) has been used as a marker not only of ophthalmologic diseases but also of neurodegenerative diseases such as Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The purpose of this work was to demonstrate that patients with amnestic MCI show an intermediate RNFL thickness between normality and AD, and a macular volume and thickness as well. In a cross-sectional study we consecutively recruited 18 patients with AD, 21 with MCI, and 41 healthy controls. OCT was performed in all of them to measure circumpapillary RNFL thickness in µm, as well as macular volume and thickness. In the analysis of variance we saw that RNFL was thinner in MCI patients compared with controls, and it was also thinner in AD patients compared with MCI patients and controls. With regard to the macular measurements in mm3, MCI patients had the greatest macular volume in comparison with AD patients and controls. In turn the controls had greater macular volume than AD patients. The decreased RNFL thickness in MCI and AD patients suggests loss of retinal neurons and their axons. The increased thickness and macular volume have never been reported before in aMCI. This finding could be explained by inflammation and/or gliosis in early stages of AD. OCT could be a useful marker of AD for early detection and monitoring progression.

Mild cognitive impairment diagnosed with the new DSM-5 criteria: prevalence and associations with non-cognitive psychopathology.

To contrast the prevalence of mild cognitive impairment (MCI) as diagnosed using DSM‐5 criteria (DSM5‐MCI) with MCI as diagnosed using Petersens criteria (P‐MCI) and to explore the association of both with non‐cognitive psychopathological symptoms (NCPS).

The Prevalence of Mild Cognitive Impairment in Diverse Geographical and Ethnocultural Regions: The COSMIC Collaboration

Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%–36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%–10.8%); Clinical Dementia Rating of 0.5 (1.8%–14.9%); Mini-Mental State Examination score of 24–27 (2.1%–20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.

Non-cognitive psychopathological symptoms associated with incident mild cognitive impairment and dementia, alzheimer’s type

Objective: To test the hypothesis that specific psychopathological non-cognitive symptoms are associated with incident mild cognitive impairment (MCI), while different symptoms are associated with incident dementia of Alzheimer’s type (DAT).Methods: A representative community sample of 4,803 individuals aged 55+ years was interviewed in a two-phase screening, in Wave I or ZARADEMP I. This is the baseline, cross-sectional study of the ZARADEMP Project, a longitudinal study to document incidence and risk factors of dementia. The main instrument for assessment of participants was the ZARADEMP Interview, which includes standardized Spanish versions of instruments such as the Mini-Mental Status Examination and the Geriatric Mental State GMS-AGECAT. Two years later, in Wave II or ZARADEMP II, the cognitively non-deteriorated elderly were reassessed in a similar, two-phase procedure. “Incident cases” of both dementia and DAT (DSM-IV-TR criteria), as well as MCI (operationally defined Petersen’s criteria) were diagnosed by a panel of psychiatrists. Statistical, logistic regression models, adjusted by age, sex and education were used to test the hypothesized association.Results: “Irritability”, “neurovegetative symptoms”, “sleep problems”, “concentration ifficulties”, “loneliness” and “subjective slowing” documented at baseline were associated with incident MCI (odds ratio, OR range 1.71-2.67). A different profile of non-cognitive symptoms was associated with incident DAT, specifically “tension” (OR= 2.45), “sleep problems” (OR= 2.81), and “observed slowing” (OR= 4.35). On the contrary, “subjective restriction of activities” seemed to be negatively associated with DAT (OR= 0.12).Conclusions: To our knowledge, this is the first report about some specific psychopathological, non-cognitive symptoms associated with incident MCI and/ or incident DAT, when controlling by each other. The psychopathological profile associated with MCI is different from the profile preceding DAT.

Depression and Incident Alzheimer Disease: The Impact of Disease Severity

OBJECTIVES To test the hypothesis that clinically significant depression (particularly severe depression) increases the risk of Alzheimers disease (AD). METHODS A longitudinal, three-wave epidemiologic study was implemented in a sample of individuals aged 55 years and older (n = 4,803) followed up at 2.5 years and 4.5 years. This was a population-based cohort drawn from the Zaragoza Dementia and Depression (ZARADEMP) Project, in Zaragoza, Spain. Participants included individuals cognitively intact at baseline (n = 3,864). The main outcome measures were depression as assessed by using the diagnostic interview Geriatric Mental State- Automated Geriatric Examination for Computer Assisted Taxonomy package; and AD diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The Fine and Gray multivariate regression model was used in the analysis, accounting for mortality. RESULTS At baseline, clinically significant depression was diagnosed in 452 participants (11.7%); of these, 16.4% had severe depression. Seventy incident cases of AD were found at follow-up. Compared with nondepressed individuals, the incidence rate of AD was significantly higher in the severely depressed subjects (incidence rate ratio: 3.59 [95% confidence interval: 1.30-9.94]). A consistent, significant association was observed between severe depression at baseline and incident AD in the multivariate model (hazard ratio: 4.30 [95% CI: 1.39-13.33]). Untreated depression was associated with incident AD in the unadjusted model; however, in the final model, this association was attenuated and nonsignificant. CONCLUSIONS Severe depression increases the risk of AD, even after controlling for the competing risk of death.

Retinal nerve fiber layer thickness measured by optical coherence tomography in patients with schizophrenia: A short report

Background and Objectives: Our study aims to assess retinal nerve fiber layer (RNFL) thickness in patients affected by schizophrenia. Methods: Ten schizophrenic patients (mean age 39 +/- 13 years, best corrected visual acuity ≥ 20/20, refractive error between +/-2 diopters, and intraocular pressure <18 mmHg) were enrolled. They were compared with 10 age-matched controls. In all subjects, optic nerve head (ONH) measurements, peripapillary RNFL thickness, macular thickness and volume were measured by optical coherence tomography (OCT). Results: Schizophrenic patients showed an statistically significant reduction of the overall RNFL thickness (95+/-13 μm, range: 53-110) compared with those values observed in control eyes (103+/-8 μm, range: 88-119) (p = 0.047, Mann-Whitney U test). We also observed reduced peripapillary RNFL thickness in nasal quadrant in schizophrenic patients (75+/-17 μm, range: 41-111) when compared with controls (84+/-10 μm, range: 67-105) (p = 0.048, Mann-Whitney U test). The remaining peripapillary RNFL quadrants, macular thickness and volume did not reveal differences between both groups. No statistically significant differences were observed between the control group and schizophrenia patients with regard to ONH measurements, macular thickness and volume. Conclusions: Schizophrenia patients had a reduction of peripapillary RNFL thickness evaluated by OCT. To our knowledge, neither reduced RNFL thickness nor macular thickness and volume have been previously documented in patients diagnosed with schizophrenia. These findings suggest that neuronal degeneration could be present in the retina of schizophrenic patients as previously observed in neurodegenerative disorders.

COSMIC (Cohort Studies of Memory in an International Consortium): An international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups

BackgroundA large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.Methods/DesignLongitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress.DiscussionThe challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.

Prevalence and implications of psychopathological non-cognitive symptoms in dementia

Objective:  Clinical experience and recent population studies suggest that psychopathological, non‐cognitive symptoms are both frequent and relevant in dementia.

Retinal nerve fiber layer and macular thickness in patients with schizophrenia: Influence of recent illness episodes.

Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. We aimed to study retinal OCT measures of patients with schizophrenia with respect to healthy controls, and to evaluate possible differences between recent illness episode (RIE) and non-recent illness episode (NRIE) patients. Thirty schizophrenia patients were classified as RIE (n=10) or NRIE (n=20), and compared with 30 matched controls. Statistical analyses included linear mixed-effects models to study the association between OCT measures and group membership. Multivariate models were used to control for potential confounders. In the adjusted linear mixed-effects regression model, patients had a significantly thinner retinal nerve fiber layer (RNFL) in overall measurements, and in the nasal, superior and inferior quadrants. Macular inner ring thickness and macular volume were also significantly smaller in patients than controls. Compared with controls, in the adjusted model only NRIE (but not RIE) patients had significantly reduced RNFL overall measures, superior RNFL, nasal RNFL, macular volume, and macular inner ring thickness. No significant correlation was found between illness duration and retinal measurements after controlling for age. In conclusion, retinal parameters observed using OCT in schizophrenia patients could be related to clinical status and merit attention as potential state biomarkers of the disorder.

Inclusion of Respiratory Frequency Information in Heart Rate Variability Analysis for Stress Assessment

Respiratory rate and heart rate variability (HRV) are studied as stress markers in a database of young healthy volunteers subjected to acute emotional stress, induced by a modification of the Trier Social Stress Test. First, instantaneous frequency domain HRV parameters are computed using time-frequency analysis in the classical bands. Then, the respiratory rate is estimated and this information is included in HRV analysis in two ways: 1) redefining the high-frequency (HF) band to be centered at respiratory frequency; 2) excluding from the analysis those instants where respiratory frequency falls within the low-frequency (LF) band. Classical frequency domain HRV indices scarcely show statistical differences during stress. However, when including respiratory frequency information in HRV analysis, the normalized LF power as well as the LF/HF ratio significantly increase during stress (p-value <; 0.05 according to the Wilcoxon test), revealing higher sympathetic dominance. The LF power increases during stress, only being significantly different in a stress anticipation stage, while the HF power decreases during stress, only being significantly different during the stress task demanding attention. Our results support that joint analysis of respiration and HRV obtains a more reliable characterization of autonomic nervous response to stress. In addition, the respiratory rate is observed to be higher and less stable during stress than during relax (p-value <; 0.05 according to the Wilcoxon test) being the most discriminative index for stress stratification (AUC = 88.2%).