Longitudinal Association between Late-Life Depression (LLD) and Frailty: Findings from a Prospective Cohort Study (MiMiCS-FRAIL).

OBJECTIVES: The aim of the present study was to investigate whether late-life depression (LLD) is associated with incident frailty over time. DESIGN: Prospective cohort study, one-year follow-up. SETTING: Geriatric outpatient clinic, Southwestern of Brazil. PARTICIPANTS: 181 follow-up participants aged 60 years or over. MEASUREMENTS: Depressive disorders were classified as Major Depressive disorder (MDD) or Subthreshold Depression (STD) according to DSM-5 criteria. Depressive symptoms were assessed with validated versions of 15-item Geriatric Depression Scale (GDS-15) and 9-item Patient Health Questionnaire (PHQ-9). We performed binary logistic regressions to estimate the odds ratio (OR) for frailty in LLD adjusting for multiple confounders. Participants who were frail at baseline were excluded from the analyses according to measures of frailty (FRAIL questionnaire and 36-item Frailty Index, FI-36). We also estimated the risk ratio or relative risk (RR) and the risk difference (RD) for incident frailty. RESULTS: We observed a 2 to 4-fold increased risk for incident frailty among participants with LLD. The presence of a depressive disorder was significantly associated with the onset of frailty (adjusted OR for FRAIL and FI-36: 3.07 [95% CI = 1.03 - 9.17] and 3.76 [95% CI = 1.09 - 12.97], respectively. Notably, the risk for frailty due to LLD was significantly higher with the FI-36 compared to the FRAIL (RR: 3.03 versus 2.23). RD was of 17.3% and 12.7% with the FRAIL and the FI-36, respectively. CONCLUSION: Our data support the association between LLD and incident frailty over one year among geriatric outpatients, reinforcing longitudinal evidence from population-based studies.

Fast, slow, and steady-state effects of contralateral acoustic activation of the medial olivocochlear efferent system in awake guinea pigs: action of gentamicin.

The function of the medial olivocochlear efferent system was observed in awake guinea pigs by recording, in the absence of ipsilateral external acoustic stimulation, the ensemble background activity (EBA) of the VIIIth nerve from an electrode chronically implanted on the round window of one ear. The EBA was measured by calculating the power value of the round window signal in the 0.5- to 2.5-kHz band after digital or analog (active) filtering. This EBA was compared with and without the addition of a low-level broadband noise to the opposite ear. The contralateral broadband noise (CLBN, 55 dB SPL) induced, via the efferent system, a decrease (suppression) of this EBA. With the use of noise bursts of different durations, two components in this suppression could be observed. After the onset of a 1-s CLBN, the power value of the EBA decreased rapidly by 38.0 +/- 4.2% (mean +/- SD, n = 3), with a latency of <10 ms and a decay time constant of 13.1 +/- 1.0 ms (fast effect). At the offset of the 1-s CLBN, EBA came back to prestimulation values with a similar latency and a time constant of 15.5 +/- 2.9 ms. During longer CLBN stimulation (>/=1 min), EBA presented, after the fast decrease, an additional, slower decrease of 15.6 +/- 3.1%, with a delay of 9.8 +/- 1.3 s and a decay time constant of 16.1 +/- 5.0 s (n = 12, slow effect), and then remained remarkably constant for as long as observed, i.e., >2 h (steady state). The average global suppression was thus up to 47.8 +/- 5.8% of the basal, pre-CLBN-stimulation EBA value. At the offset of the CLBN, EBA returned to pre-CLBN level with fast and slow phases, with, for the slow phase, no delay and a time constant of 32.1 +/- 8.1 s. Fast and slow changes in EBA power values were observed after a single injection of gentamicin (GM) at different doses (150, 200, and 250 mg/kg). At 150 and 200 mg/kg, GM progressively and reversibly blocked the rapid effect, but the slow component of the efferent medial suppression remained remarkably unchanged. However, at higher doses both the fast and slow suppressions were totally yet still reversibly blocked. These observations indicate that the medial olivocochlear efferent system exerts sustained influences on outer hair cells and that this effect develops in two different steps that may have different basic cellular mechanisms.

Changes in CM and CAP with sedation and temperature in the guinea pig: facts and interpretation.

The influence of xylazine on the amplitude, latency and waveform of VIIIth nerve compound action potential (CAP) and cochlear microphonic (CM) in response to clicks at 95 dB SPL in normal awake preimplanted guinea pigs was investigated. The animals' temperature was monitored but no thermoregulation was exerted, except in one control experiment. Following a 0.2 ml injection of xylazine, CM showed minor variations while CAP audiograms for tone pips between 0.5 and 25 kHz remained normal. However, a progressive decrease in temperature and a strongly correlated increase in CAP amplitude and in N1 and N2 latencies were noticed. For peak N1 the changes were equivalent to linear amplitude and time expansions, and could be reproduced through CAP synthesis with convolution methods using time expanded unit response model and firing density functions. All changes were maximal after 2 h of sedation and recovered within approximately another 2 h. Whereas xylazine is known to induce hypothermia, all the changes disappeared if the animal was thermoregulated. Therefore the changes are interpreted as a result of hypothermia. The mechanism of N1 latency lengthening and increase in amplitude during hypothermia can be understood as a simultaneous increase in spike duration, hair cell/nerve synaptic delay and postsynaptic time constant. This hypothesis yielded a theoretical temperature coefficient for N1 latency (-52 microseconds/degree C) matching that measured experimentally (-55 microseconds/degree C). When compared with peak N1, peak N2 appeared relatively more expanded. Arguments about the origin of N2 are discussed.

The efferent-mediated suppression of otoacoustic emissions in awake guinea pigs and its reversible blockage by gentamicin.

The physiology of the medial efferent olivocochlear system involves suppressive interactions of contralateral sounds on ipsilateral sound-evoked responses, but its role is largely unknown to date. Medial efferents act at the level of cochlear outer hair cells via cholinergic synapses and might affect their mechanical activity, thereby modulating auditory sensitivity. The aim of the present work was to obtain noninvasive measurements of distortion-product otoacoustic emissions (DPOEs), which reflect outer hair cell function, in order to establish the characteristics of medial efferent-induced suppression in awake, restrained guinea pigs. A clear suppression of DPOEs was induced by continuous contralateral white noise presented at 20-70 dB SPL, in the absence of any confounding effect of anesthesia, middle-ear muscles, or acoustic cross talk. Recently, acute injection of a high dose of the aminoglycoside antibiotic gentamicin (150 mg/kg) was reported to alter the suppressive effect of contralateral noise on eighth nerve-compound action potentials, presumably by blocking efferent synapses to outer hair cells. This hypothesis was confirmed with DPOEs for which a single injection of gentamicin at the same dose abolished suppression after about 1-2 h, whereas no change in basal levels was observed. Complete recovery was obtained after 48 h. This experiment may provide an easy, noninvasive tool for studying auditory function with and without functioning efferents.