Alertamientos y movimientos periódicos de las piernas durante las etapas de sueño y deterioro cognitivo leve en adultos mayores. Estudio preliminar / Arousals and periodic leg movements during sleep stages and mild cognitive impairment in older adults: a preliminary study

RESUMEN La fragmentación del sueño puede asociarse con distintas enfermedades, entre ellas, la demencia. En este sentido, la fragmentación de sueño, indicada por el índice de alertamientos y/o movimientos periódicos de las piernas (MPP), podría ser un marcador temprano de deterioro cognitivo leve (DCL), un síndrome precursor de la demencia. El objetivo del presente estudio fue medir el índice de prevalencia de los alertamientos y de los MPP durante el sueño en un grupo control y un grupo con DCL, así como determinar si hay diferencia entre los grupos en ambos índices y establecer si existe una correlación entre los dos fenómenos. En 9 participantes (3 mujeres controles y 3 mujeres con DCL; y 3 hombres con DCL) (edad: 69.1 ± 5; años de educación: 8 ± 2) se registró una noche de polisomnografía. Se obtuvieron los índices por hora de alertamientos y para cada etapa de sueño, así como los MPP globales y por hora; además se realizaron análisis entre y dentro de cada grupo. Se encontró una correlación positiva y un mayor número de MPP que de alertamientos durante toda la noche en los participantes con DCL. Conocer la prevalencia y asociación de ambos fenómenos contribuye en la formulación de una evaluación más cuidadosa y profunda de los adultos mayores en riesgo de desarrollar DCL y/o demencia.

ABSTRACT Sleep fragmentation may be associated with several diseases, including dementia. In this sense, sleep fragmentation, indicated by the rates of arousals and/or periodic leg movements (PLM), could be an early marker of Mild Cognitive Impairment (MCI), a syndromic stage prior to dementia. Therefore, the objective of this study was to compare the index of PLM with that of arousals and correlate both indexes in people with MCI and without MCI during all sleep stages. In 9 participants (3 control women and 3 women with MCI; and 3 men with MCI) (ages: 69.1 ± 5; years of education: 8 ± 2), one night of polysomnography was performed. Hourly rates of arousals and PLM were scored from each sleep stage. Analyses were performed within and between PLM and arousals for each group. Significant differences and a positive correlation were found between the arousal and the PLM rates for the group with MCI during the whole night. Knowledge of the prevalence and the association of both phenomena may contribute to a more careful and thorough evaluation of older adults at risk of developing MCI and/or dementia.

Dissociation of Arousal Index Between REM and NREM Sleep in Elderly Adults with Cognitive Impairment, No Dementia: A Pilot Study.

BACKGROUND: Sleep disruption in elderly has been associated with an increased risk of cognitive impairment and its transition into Alzheimer's disease (AD). High arousal indices (AIs) during sleep may serve as an early-stage biomarker of cognitive impairment non-dementia (CIND). OBJECTIVE: Using full-night polysomnography (PSG), we investigated whether CIND is related to different AIs between NREM and REM sleep stages. METHODS: Fourteen older adults voluntarily participated in this population-based study that included Mini-Mental State Examination, Neuropsi battery, Katz Index of Independence in Activities of Daily Living, and single-night PSG. Subjects were divided into two groups (n = 7 each) according to their results in Neuropsi memory and attention subtests: cognitively unimpaired (CU), with normal results; and CIND, with -2.5 standard deviations in memory and/or attention subtests. AIs per hour of sleep during N1, N2, N3, and REM stages were obtained and correlated with Neuropsi total score (NTS). RESULTS: AI (REM)  was significantly higher in CU group than in CIND group. For the total sample, a positive correlation between AI (REM)  and NTS was found (r = 0.68, p = 0.006), which remained significant when controlling for the effect of age and education. In CIND group, the AI (N2)  was significantly higher than the AI (REM) . CONCLUSION: In CIND older adults, this attenuation of normal arousal mechanisms in REM sleep are dissociated from the relative excess of arousals observed in stage N2. We propose as probable etiology an early hypoactivity at the locus coeruleus noradrenergic system, associated to its early pathological damage, present in the AD continuum.

Prevention of Neurological Sequelae in Preterm Infants.

BACKGROUND: Preterm birth is one of the world's critical health problems, with an incidence of 5% to 18% of living newborns according to various countries. White matter injuries due to preoligodendrocytes deficits cause hypomyelination in children born preterm. Preterm infants also have multiple neurodevelopmental sequelae due to prenatal and perinatal risk factors for brain damage. The purpose of this work was to explore the effects of the brain risk factors and MRI volumes and abnormalities on the posterior motor and cognitive development at 3 years of age. METHODS: A total of 166 preterm infants were examined before 4 months and clinical and MRI evaluations were performed. MRI showed abnormal findings in 89% of the infants. Parents of all infants were invited to receive the Katona neurohabilitation treatment. The parents of 128 infants accepted and received Katona's neurohabilitation treatment. The remaining 38 infants did not receive treatment for a variety of reasons. At the three-year follow-up, Bayley's II Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) were compared between treated and untreated subjects. RESULTS: The treated children had higher values of both indices than the untreated. Linear regression showed that the antecedents of placenta disorders and sepsis as well as volumes of the corpus callosum and of the left lateral ventricle significantly predicted both MDI and PDI, while Apgar < 7 and volume of the right lateral ventricle predicted the PDI. CONCLUSIONS: (1) The results indicate that preterm infants who received Katona's neurohabilitation procedure exhibited significantly better outcomes at 3 years of age compared to those who did not receive the treatment. (2) The presence of sepsis and the volumes of the corpus callosum and lateral ventricles at 3-4 months were significant predictors of the outcome at 3 years of age.

Week-by-week changes in sleep EEG in healthy full-term newborns.

Spectral analysis of neonatal sleep is useful for studying brain maturation; however, most studies have analyzed conventional broad bands described for awake adults, so a distinct approach for EEG analysis may disclose new findings. STUDY OBJECTIVES: To extract independent EEG broad bands using principal component analysis (PCA) and describe week-by-week EEG changes in quiet sleep (QS) and active sleep (AS) during the first 5 weeks of postnatal life in healthy, full-term newborns. METHODS: Polysomnography of spontaneous sleep was recorded in 60 newborns in 5 groups at 41, 42, 43, 44, and 45 weeks (n = 12 each) postconceptional age (POST-C). QS and AS stages were identified. Absolute power (AP) for 1 Hz bins between 1 and 30 Hz was subjected to PCA to extract independent broad bands. RESULTS: PCA rendered three independent broad bands distinct from conventional bands. They explained 82.8% of variance: 2-10 Hz, 10-16 Hz, and 17-30 Hz. ANOVAs (group × age × derivations) showed significant higher power at 2-10 Hz with greater age, higher power in QS than AS in all three bands, and significantly higher AP in the left central region, and in the right occipital and temporal areas, in both sleep stages. CONCLUSION: A different method of analyzing sleep EEG generated new information on brain maturation. The Sigma frequencies identified suggest that sleep spindle maturation begins by at least 41 weeks of POST-C age. Interhemispheric asymmetries during sleep suggest earlier development of the central left region and the right occipital and temporal areas.

How to Obtain Reliable Visual Event-related Potentials in Newborns.

The present study discusses the characteristics of visual event-related potentials (VEPs) and outlines methodological steps for obtaining reliable measurements in newborns. Obtaining high-quality, reliable VEPs is crucial for the early detection of abnormal development of the central nervous system in at-risk newborns, and for implementing successful early interventions. Recommendations are based on a previous study which showed that when post-conceptional age, polysomnography-identified sleep stages, and light-emitting diodes (LEDs) googles as the luminous source are controlled, no more than 4 repetitions of VEP averages are required to obtain replicable recordings, variability decreases, and reliable VEPs can be obtained. By controlling for these sources of variability and using statistical analyses, we were able to clearly and reliably identify the amplitude and latency of three main components (NII, PII and NIII) present in 100% of newborns (n = 20) during active sleep. Recording VEPs during awake states, quiet sleep and transitional sleep is not recommended because VEP morphology may differ significantly from one average to the next, leading to the risk of misleading clinical prognoses. Moreover, it is easier to obtain VEPs during active sleep because this state can be clearly and reliably identified at this stage of development, sleep cycles are short enough to allow measurements to be taken in a reasonable time, and the method does not require new o expensive equipment.

The Color of Noise and Weak Stationarity at the NREM to REM Sleep Transition in Mild Cognitive Impaired Subjects.

In Older Adults (OAs), Electroencephalogram (EEG) slowing in frontal lobes and a diminished muscle atonia during Rapid Eye Movement sleep (REM) have each been effective tracers of Mild Cognitive Impairment (MCI), but this relationship remains to be explored by non-linear analysis. Likewise, data provided by EEG, EMG (Electromyogram) and EOG (Electrooculogram)-the three required sleep indicators-during the transition from REM to Non-REM (NREM) sleep have not been related jointly to MCI. Therefore, the main aim of the study was to explore, with results for Detrended Fluctuation Analysis (DFA) and multichannel DFA (mDFA), the Color of Noise (CN) at the NREM to REM transition in OAs with MCI vs. subjects with good performances. The comparisons for the transition from NREM to REM were made for each group at each cerebral area, taking bilateral derivations to evaluate interhemispheric coupling and anteroposterior and posterior networks. In addition, stationarity analysis was carried out to explore if the three markers distinguished between the groups. Neuropsi and the Mini-Mental State Examination (MMSE) were administered, as well as other geriatric tests. One night polysomnography was applied to 6 OAs with MCI (68.1 ± 3) and to 7 subjects without it (CTRL) (64.5 ± 9), and pre-REM and REM epochs were analyzed for each subject. Lower scores for attention, memory and executive funcions and a greater index of arousals during sleep were found for the MCI group. Results confirmed that EOGs constituted significant markers of MCI, increasing the CN for the MCI group in REM sleep. The CN of the EEG from the pre-REM to REM was higher for the MCI group vs. the opposite for the CTRL group at frontotemporal areas. Frontopolar interhemispheric scaling values also followed this trend as well as right anteroposterior networks. EMG Hurst values for both groups were lower than those for EEG and EOG. Stationarity analyses showed differences between stages in frontal areas and right and left EOGs for both groups. These results may demonstrate the breakdown of fractality of areas especially involved in executive functioning and the way weak stationarity analyses may help to distinguish between sleep stages in OAs.

Visual evoked potentials are similar in polysomnographically defined quiet and active sleep in healthy newborns.

Morphology and late components of evoked potentials change depending on wake-sleep stages in adults. Visual Evoked potentials (VEPs) have been frequently studied in newborns to identify abnormal development of visual pathways; however, large variability has been reported and there is uncertainty as to the effect of sleep stages on VEPs in neonates. OBJECTIVE: To describe the characteristics of VEPs in one month old, healthy full-term newborns during active sleep (AS) and quiet sleep (QS), defined by simultaneous polysomnography (PSG). METHODS: VEPs were obtained by monocular LEDs stimulation of each eye during AS and QS, in 20 healthy full-term newborns (gestational age 37-40 weeks) with normal birth weights and normal prenatal Doppler ultrasound indices. Latencies and amplitudes of N2, P2 and N3 components in AS and QS were compared, and their association with absolute power of EEG frequency bands, assessed. RESULTS: There were no significant differences in VEP morphology, latencies and amplitudes between sleep states. Typical wave forms were obtained in all newborns in AS; however, no VEPs could be identified clearly in 3 newborns in QS; QS VEPs were less reliable than in AS: more averaging was required; correlation was significantly lower between the VEP averages; and a larger number of babies needed more than two averages to obtain replicable responses needed for clinical purposes. CONCLUSIONS: These results indicate that changes in amplitude and latency of some VEP components observed in NREM and REM sleep in adults are not yet present in one month old newborns probably due to immaturity of cortical and sleep mechanisms. VEPs are more reliable during AS than QS in newborns. Systematic VEP recording during AS, and polysomnographic control to identify this stage, are highly recommended as methods that can increase there liability of neonatal VEPs.

Improving the efficiency of Auditory Brainstem Responses in newborns, using a 60clicks/s stimulation rate.

Recent evidence suggests that Auditory Brainstem Responses (ABR), in neonates with risk factors for neurological damage, may show auditory brainstem abnormalities, even in patients with normal hearing. To compare the recording and diagnostic accuracy of neonatal Auditory Brainstem Responses (ABR), using 10 and 60clicks/s stimulation rates, two groups of neonates were prospectively studied: 30 healthy full-term neonates, with no peri- or postnatal complications; and 30 high-risk newborns with two or more of the following conditions: hyperbilirubinemia, use of ototoxic drugs, birth weight inferior to 1500g, perinatal sepsis, intraventricular hemorrhage, and/or mechanical ventilation. Correlation between ABR trials, recording duration, and the absolute and interpeak latencies of ABR waves I, III and V, were measured. ROC-curve analysis assessed the diagnostic accuracy of both stimulation rates. The correlations between ABRs trials were significantly higher at 60clicks/s than at 10clicks/s (F(1,116)=14.5, p<0.0002). Recording duration at 60clicks/s was significantly lower (t=20.9, p<0.0001). ROC-curve comparisons showed increased diagnostic accuracy at the stimulation rate of 60clicks/s, for waves I (D=2.04, p=0.04), V (D=2.02, p=0.04), interpeak latencies III-V (D=2.2, p=0.02), and I-V (D=2.86, p=0.004). In neonates, the use of 60clicks/s stimulation rate permits a substantial shortening of the ABR recording, with greater diagnostic accuracy and replicability.