Anne-Cécile Troussière

Treatment of sleep apnoea syndrome decreases cognitive decline in patients with Alzheimer's disease

Background It is essential to detect and then treat factors that aggravate Alzheimers disease (AD). Here, we sought to determine whether or not continuous positive airway pressure (CPAP) therapy for sleep apnoea syndrome (SAS) slows the rate of cognitive decline in mild-to-moderate AD patients. Methods Between January 2003 and June 2011, we included consecutive, mild-to-moderate AD patients (a Mini Mental State Examination (MMSE) score at inclusion ≥15) with severe SAS as determined by video-polysomnography (an apnoea-hypopnoea index ≥30). In this single-blind, proof-of-concept trial, we analysed the mean decline in the annual MMSE score (the main outcome measure) according to whether or not the patients had received CPAP therapy. The decline was computed for each patient and for the first 3 years of follow-up. Results Of the 23 included patients, 14 underwent CPAP treatment. The CPAP and non-CPAP groups did not differ significantly in terms of their demographic characteristics or MMSE score at baseline. The median annual MMSE decline was significantly slower in the CPAP group (−0.7 (−1.7; +0.8)) than in the non-CPAP group (−2.2 (−3.3; −1.9); p=0.013). Conclusions In this pilot study, CPAP treatment of severe SAS in mild-to-moderate AD patients was associated with significantly slower cognitive decline over a three-year follow-up period. Our results emphasise the importance of detecting and treating SAS in this population.

Ictal changes in parasympathetic tone: Prediction of postictal oxygen desaturation.

Objective: To measure changes in parasympathetic tone before, during, and after temporal seizures, and to determine whether changes in high-frequency heart rate variability are correlated with postictal oxygen desaturation. Methods: We recorded the electrocardiogram and peripheral oxygen saturation during 55 temporal lobe seizures and calculated a high-frequency variability index (HFVI) as a marker of parasympathetic tone for periods of 20 minutes (centered on seizure onset). We then compared HFVI values in seizures with and without postictal hypoxemia, and looked for correlations between HFVI changes and the risk of sudden unexpected death in epilepsy (SUDEP) (as assessed with the SUDEP-7 Inventory). Results: Parasympathetic tone decreased rapidly at the onset of temporal lobe seizures, reached its minimum value at the end of the seizure, and then gradually returned to its preictal value. Changes in parasympathetic tone were more intense and longer-lasting in older patients with a longer duration of epilepsy. The HFVI was significantly lower during seizures with hypoxemia, and remained significantly lower 5 minutes after the end of the seizure. The change in the HFVI slope over the first 30 seconds of the seizure was predictive of postictal oxygen desaturation. Postictal autonomic changes were correlated with the SUDEP-7 scores. Conclusion: Our results showed that ictal autonomic dysfunction is correlated with postictal hypoxemia. A prolonged impairment of parasympathetic tone might expose a patient to a greater risk of postictal sudden unexpected death. The real-time measurement of parasympathetic tone in patients with epilepsy may be of value to medical staff as an early warning system.

CLINICAL IMPACT OF CEREBROSPINAL FLUID BIOMARKERS IN MILD COGNITIVE IMPAIRMENT DIAGNOSIS

TDP had lower levels of sAPPb and higher levels of YKL-40 in CSF compared to controls (Fig. 1). The sAPPb/YKL-40 ratio was lower in both FTLD groups compared to controls. In the ROC analysis (Fig. 2), the sAPPb/YKL-40 ratio had an area under the curve of 0.91 (95%CI 0.86-0.96) to distinguish FTLD subjects from controls, but lower values to distinguish FTLD from AD (AUC 0.70; 95%CI 0.61-0.79) and to discriminate FTLDTau from FTLD-TDP (AUC 0.67; 95%CI 0.51-0.82). Conclusions:These findings suggest that the sAPPb/YKL-40 ratio could be of interest to distinguish patients with FTLD from those with similar clinical phenotypes. Although the ratio cannot be used to discriminate between the main pathologies underlying FTLD, it might be useful to interrogate the neuropathological substrate in some clinical scenarios and, eventually, to select potential candidates for clinical trials.

Ralentissement du déclin cognitif avec l’appareillage du syndrome d’apnées du sommeil dans la maladie d’Alzheimer légère à modérée

Objectif.— Etudier la qualite du sommeil et la vigilance d’une population parkinsonienne depourvue de troubles non moteurs majeurs. Methode.— Vingt-trois patients (14 hommes et neuf femmes âges de 67± 8,6 ans) presentant une maladie de Parkinson idiopathique de severite moderee (Hoehn et Yahr 2,26± 0,8), traites par 620± 319mg/j de DOPA (et un agoniste dopaminergique, n = 16) ont ete inclus dans l’etude sans tenir compte de la qualite subjective de leur sommeil. Une evaluation prealable montrait l’absence de troubles cognitifs (MMS > 24) ou psychiatriques majeurs et une polysomnographie (PSG) un AHI inferieur a 15 h. L’etude comportait 3 PSG consecutives avec TIDE et dosage nocturne de la 6-SMT, precedees de sept jours d’evaluation actimetrique en ambulatoire. Resultats.— Au niveau subjectif, 56 % des patients se plaignaient de somnolence selon l’echelle d’Epworth et 32 % presentaient une insomnie moderee a severe selon l’echelle de Morin (EM). La somnolence n’etait pas objectivee a la TIDE sauf pour un patient. A l’inverse, la polysomnographie confirmait les plaintes d’insomnie, 48 % des patients ayant un temps total de sommeil (TTS) inferieur a cinq heures, et 35 % ayant en sus une efficience de sommeil inferieure a 60%. En general le TTS etait de 322± 83minutes. Une analyse statistique montre que les principaux determinants du TTS sont l’EM, la duree de la maladie et une atteinte motrice plus severe. Conclusions.— Ces resultats montrent une incidence elevee de perturbation du sommeil dans cet echantillon de patients presentant une maladie de Parkinson de severite moderee. La relation inverse entre duree de la maladie et TTS suggerent l’influence du processus neurodegeneratif sur les mecanismes du sommeil. En revanche, le niveau de vigilance diurne ne semble pas compromis par la maladie.

Indications and use of CSF biomarkers in French memory clinics

RR intervals(SDNN) and the square root of the mean of the squares of successive RR intervals differences(rMSSD) mean values were significantly lower in patients with AD than in those with MCI or in controls. There were no significant differences between MCI and control groups in mean R-R interval, 5-min total power, VLF, LF and HF or LF/HF ratio. MMSE was negatively correlation with age and duration with illness. HF power emerged as the parameters better related to MMSE. Conclusions: These results suggest that the presence of autonomic cardiac dysfunction in AD patients might be due to a cholinergic deficit in the peripheral autonomic nervous system. The ongoing follow-up of this study population will verify the potential role of the HRV parameters in predicting the degeneration of cognitive functions and mortality rates.