Elsevier

Clinical Neurophysiology

Volume 113, Issue 10, October 2002, Pages 1615-1622
Clinical Neurophysiology

The effects of normal aging on sleep spindle and K-complex production

https://doi.org/10.1016/S1388-2457(02)00237-7Get rights and content

Abstract

Objectives: Despite a relatively large body of literature describing the characteristics of sleep spindles and K-complexes in young adults, relatively little research has been conducted in older individuals. The general consensus from the few studies that have addressed this issue is that there is a progressive decrease in the number of spindles and K-complexes with age, although there is large intra-individual variation. Whether or not these changes are an inevitable consequence of the aging process can be addressed by studying healthy older adults who provide an example of the effects of age independently from those of disease.

Methods: Fourteen young adults (mean age=21.4±2.5 years) and 20 older adults (mean age=75.5±6.3 years) participated in the study. All subjects were neurologically and medically healthy and were not taking any medications with a known effect on the central nervous system or sleep. For each subject, a number of characteristics were determined including the number, density (SS/min), amplitude and frequency of all spindles as well as the number and density of K-complexes (KC/min).

Results: Spindle number, density and duration as well as K-complex number and density were all significantly lower in the elderly compared to the young adults. The EEG frequency within the spindles was significantly higher in the elderly, although the absolute difference was less than 0.5 Hz. Multiple regression analysis indicated that spindle duration and K-complex density were able to predict over 90% of the variance in age.

Conclusions: The age-related decrease in sleep spindle and K-complex density is consistent with previous reports and may be interpreted as an age-related alteration of thalamocortical regulatory mechanisms.

Introduction

Sleep spindles and K-complexes constitute the physiological markers of Stage 2 non-rapid eye movement (NREM) sleep. Sleep spindles, first described by Loomis et al. (1939), are rhythmic 12–14 Hz oscillations lasting from 0.5 to 3 s. There is now reliable evidence that spindle activity is a consequence of the membrane hyperpolarization of thalamocortical and cortical neurons. During sleep, periodic bursts of action potentials converge back to neurons of the reticular thalamic nucleus, which facilitates and synchronizes the rhythmic oscillations. These bursts are then transferred to the cortex where they induce excitatory postsynaptic potentials and thereby generate sleep spindles (Steriade et al., 1993a, Steriade et al., 1993b, Steriade, 1997).

Speculation regarding the functional significance of sleep spindles has focused on inhibitory correlates of this activity, a view that has influenced studies conducted at both cellular and behavioural levels. Early investigations detailing the neuronal basis for spindles highlighted the contribution of inhibitory postsynaptic potentials to the generation of this activity (Andersen and Sears, 1964), and these observations have been confirmed and extended by Steriade et al. (1993b). Consistent with the inhibitory function of spindle activity are reports of diminished auditory evoked responses in association with spindles. Yamadori (1971) observed that the time required to reach deeper levels of sleep was delayed by the presence of external stimuli. The delay was avoided, however, if such stimuli were presented synchronously with sleep spindles. Further, Steriade, 1994, Steriade, 1997 noted that the normal waking response of the forebrain to external stimuli was markedly reduced when stimuli were presented during a spindle. These findings have been interpreted as indicating a sleep protective role for sleep spindles.

Studies investigating the effect of aging on the oscillation frequency within sleep spindles have found contrary results. One study noted that sleep spindles in older people were markedly decreased in terms of frequency (a decrease from 14 to 8 Hz) compared to younger adults (Feinberg, 1974). Another study, however, reported a direct age-related increase in spindle frequency from 13 to >14 Hz and an inverse relationship with spindle amplitude (i.e. a decrease from 27 to 15 μV) (Principe and Smith, 1982). Spindle density comparisons among young and middle aged adults and the elderly have generally reported a progressive decrease in the number of sleep spindles with age (Principe and Smith, 1982, Guazzelli et al., 1986, Wauquier, 1993, Landolt et al., 1996, Wei et al., 1999, Nicolas et al., 2001), although some have reported an increase (Smith et al., 1979, Bowersox et al., 1985), and others no change (Bove et al., 1994, Pivik et al., 1999).

K-complexes are sleep-specific, phasic EEG waveforms that may be spontaneous, or elicited by stimulation. They have a duration of approximately 0.5 s and are characterized by a well-delineated negative component followed by a positive deflection (Loomis et al., 1939, Rechtschaffen and Kales, 1968). Amzica and Steriade (1998) have recently shown that K-complexes result from a synchronized cortical network that impose periodic excitatory and inhibitory actions on cortical neurons, thus creating cortically generated slow oscillations (0.5–0.9 and 1–4 Hz), which spread through the cortex and are transferred to the thalamus. These same oscillations play a role in triggering and synchronizing thalamic or thalamo-cortical rhythms, such as sleep spindles and delta waves (Steriade, 1999).

The functional significance of K-complexes remains unknown. Since their discovery, there has been substantial debate as to whether the appearance of a K-complex in response to a stimulus is indicative of a partial arousal process that leaves the central nervous system more likely to arouse if further stimulation occurs (Church et al., 1978, Halasz et al., 1985, Halasz, 1993), or reflects a sleep maintenance process involving a response to stimulation that inhibits arousal and prevents the fragmentation of sleep (Roth et al., 1956, Wauquier, 1995, Nicholas et al., 1999).

In a review article, Wauquier (1993) indicated that little is known regarding the incidence of K-complexes in the elderly, but they appear less frequently and with large intra-individual variability. In the only study to have systematically investigated K-complexes in the elderly, Kubicki et al. (1989) reported a linear reduction in the density of K-complexes with increasing age. Young adults under the age of 30 had between 1.2 and 3.2 K-complexes per min during non-REM sleep, those aged between 30 and 50 years had between 1.1 and 2.9, while the elderly (aged above 50) had between 0.7 and 1.7. We have recently demonstrated that K-complexes evoked by auditory stimuli are less common and smaller in healthy elderly subjects when compared to young healthy subjects (Crowley et al., 2002).

Both sleep spindles and K-complexes are hypothesized to be produced following hyperpolarization of thalamo-cortical circuits via activation of GABAergic pathways (McCormick and Bal, 1997, Amzica and Steriade, 1998, Steriade, 1999). The inter-relationship between spindle generation and K-complex (or delta) generation is not entirely clear. Early studies implied a reciprocal relationship, with data from benzodiazepine administration studies indicating increased spindle production and decreased K-complex production (Naitoh et al., 1982). In addition, the temporal distribution of spindles over the night is the inverse of the changes in delta activity, with spindles increasing and delta decreasing with successive changes (De Gennaro et al., 2000). However, other studies indicate that they may be independent of delta frequency EEG being enhanced by drugs, which are GABA agonists, with no necessary impact on spindles (Lancel et al., 2001). There are also reports of spindles and K-complexes varying together, for example in the case of dementia where both spindles and K-complexes are reduced (Reynolds et al., 1988). It is therefore of interest to assess the whether there is a relationship between K-complex and spindle density as a function of aging.

There have also been relatively few studies investigating sex differences in spindle or K-complex production (Wu et al., 1980, Gaillard and Blois, 1981, Bove et al., 1994). EEG activity within the sleep spindle frequency range has been shown to be susceptible to changes in the level of reproductive hormones and neurosteroids. For example, during pregnancy, a profound reduction in the power spectral density in the frequency range of 14.25–15 Hz has been reported (Brunner et al., 1994). Within the frequency range of sleep spindles, Driver et al. (1996) reported a large variation in power density across the menstrual cycle, with a maximum in the luteal phase. These results suggest a specific effect of cyclic hormone release, as reflected by the progesterone-mediated biphasic menstrual temperature.

We have presented elsewhere an argument for the utility of differentiating normal from pathological aging (Crowley and Colrain, 2000). Whether or not changes in the characteristics of these phasic events is an inevitable consequence of the aging process can be addressed by studying healthy older adults who provide an example of the effects of age independently of those of disease. In this context, the current study addresses the following questions: (1) do healthy older adults display the same phasic events as those seen in younger adults; (2) what are the characteristics of sleep spindles and K-complexes in older adults and (3) are there sex-differences in the frequency and characteristics of sleep spindles and K-complexes.

Section snippets

Subjects and procedure

Two groups of subjects were studied. Fourteen young subjects (6 females and 8 males) with a mean age of 21.4±2.4 years (range 18–25 years) and a body mass index (BMI) of 22.7±2.7 kg/m2 (range 19–28 kg/m2) participated in the study. All subjects were healthy and free from any physical illness and none were taking any medication at the time of the study. Other exclusion criteria included a personal or family history of a sleep disorder, respiratory or cardiovascular problems and heavy caffeine or

Results

There were no significant differences between first and second nights in the young group on any of the sleep parameters used. Data analysed were derived from the second night's recording for both the elderly and young groups. This was due to the existence of a first night effect in several of the polysomnographic variables in the elderly. As expected, the elderly and young subjects differed on most of the polysomnographic measures of sleep architecture. Table 1 summarises the sleep data for

Discussion

The aim of this experiment was to explore the nature and various aspects of the microstructure of sleep in older adults. The results indicated a number of age-related differences. There was a decrease in sleep spindle density, corroborating the findings of Gaillard and Blois, 1981, Principe and Smith, 1982, Landolt et al., 1996, Wei et al., 1999, Nicolas et al., 2001, although this result was not consistent with that of others who have variously reported increases (Smith et al., 1979; Bowersox

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