Improving risk indexes for Alzheimer's disease and related dementias for use in midlife.

Knowledge of a person's risk for Alzheimer's disease and related dementias (ADRDs) is required to triage candidates for preventive interventions, surveillance, and treatment trials. ADRD risk indexes exist for this purpose, but each includes only a subset of known risk factors. Information missing from published indexes could improve risk prediction. In the Dunedin Study of a population-representative New Zealand-based birth cohort followed to midlife (N = 938, 49.5% female), we compared associations of four leading risk indexes with midlife antecedents of ADRD against a novel benchmark index comprised of nearly all known ADRD risk factors, the Dunedin ADRD Risk Benchmark (DunedinARB). Existing indexes included the Cardiovascular Risk Factors, Aging, and Dementia index (CAIDE), LIfestyle for BRAin health index (LIBRA), Australian National University Alzheimer's Disease Risk Index (ANU-ADRI), and risks selected by the Lancet Commission on Dementia. The Dunedin benchmark was comprised of 48 separate indicators of risk organized into 10 conceptually distinct risk domains. Midlife antecedents of ADRD treated as outcome measures included age-45 measures of brain structural integrity [magnetic resonance imaging-assessed: (i) machine-learning-algorithm-estimated brain age, (ii) log-transformed volume of white matter hyperintensities, and (iii) mean grey matter volume of the hippocampus] and measures of brain functional integrity [(i) objective cognitive function assessed via the Wechsler Adult Intelligence Scale-IV, (ii) subjective problems in everyday cognitive function, and (iii) objective cognitive decline measured as residualized change in cognitive scores from childhood to midlife on matched Weschler Intelligence scales]. All indexes were quantitatively distributed and proved informative about midlife antecedents of ADRD, including algorithm-estimated brain age (ß's from 0.16 to 0.22), white matter hyperintensities volume (ß's from 0.16 to 0.19), hippocampal volume (ß's from -0.08 to -0.11), tested cognitive deficits (ß's from -0.36 to -0.49), everyday cognitive problems (ß's from 0.14 to 0.38), and longitudinal cognitive decline (ß's from -0.18 to -0.26). Existing indexes compared favourably to the comprehensive benchmark in their association with the brain structural integrity measures but were outperformed in their association with the functional integrity measures, particularly subjective cognitive problems and tested cognitive decline. Results indicated that existing indexes could be improved with targeted additions, particularly of measures assessing socioeconomic status, physical and sensory function, epigenetic aging, and subjective overall health. Existing premorbid ADRD risk indexes perform well in identifying linear gradients of risk among members of the general population at midlife, even when they include only a small subset of potential risk factors. They could be improved, however, with targeted additions to more holistically capture the different facets of risk for this multiply determined, age-related disease.

Assessment of the efferent auditory system in children with suspected auditory processing disorder: the Middle ear muscle reflex and contralateral inhibition of OAEs.

OBJECTIVE: To determine whether children aged 7 to 12 years with listening difficulties show objective evidence for efferent auditory function based on measurements of medial olivo-cochlear and middle ear muscle reflexes. DESIGN: Click-evoked otoacoustic emissions recorded with and without contralateral broadband noise and ipsilateral and contralateral tonal (1000, 2000 Hz) middle ear muscle reflex thresholds were examined. STUDY SAMPLE: 29 children diagnosed with suspected auditory processing disorder (APD) and a control group of 34 typically developing children participated in this study. RESULTS: Children with suspected APD had poorer performance on auditory processing tests than the control group. Middle ear muscle reflex thresholds were significantly higher at 2000 Hz in the suspected APD group for contralateral stimulation. MOC inhibition effects did not differ between APD and control groups. CONCLUSIONS: This research supports earlier studies showing altered acoustic reflexes in children with APD. No group differences were found for the MOC reflex measures, consistent with some earlier studies in children with APD.

Electrophysiological and behavioural processing of complex acoustic cues.

OBJECTIVES: To examine behavioural and neural processing of pitch cues in adults with normal hearing (NH) and adults with sensorineural hearing loss (SNHL). METHODS: All participants completed a test of behavioural sensitivity to pitch cues using the TFS1 test (Moore and Sek, 2009a). Cortical potentials (N1, P2 and acoustic change complex) were recorded in response to frequency shifted (deltaF) tone complexes in an 'ABA' pattern. RESULTS: The SNHL group performed more poorly than the NH group for the TFS1 test. P2 was more reflective of pitch differences between the complexes than N1. The presence of acoustic change complex in response to the TFS transitions in the ABA stimulus varied with deltaF. Acoustic change complex amplitudes were reduced for the group with SNHL compared to controls. CONCLUSION: Behavioural performance and cortical responses reflect pitch processing depending on the salience of pitch cues. SIGNIFICANCE: These data support the use of cortical potentials and behavioural sensitivity tests to measure processing of complex acoustic cues in people with hearing loss. This approach has potential for evaluation of benefit from auditory training and hearing instrument digital signal processing strategies.

Choral singing therapy following stroke or Parkinson's disease: an exploration of participants' experiences.

PURPOSE: People with stroke or Parkinson's disease (PD) live with reduced mood, social participation and quality of life (QOL). Communication difficulties affect 90% of people with PD (dysarthria) and over 33% of people with stroke (aphasia). These consequences are disabling in many ways. However, as singing is typically still possible, its therapeutic use is of increasing interest. This article explores the experiences of and factors influencing participation in choral singing therapy (CST) by people with stroke or PD and their significant others. METHOD: Participants (eight people with stroke, six with PD) were recruited from a community music therapy choir running CST. Significant others (seven for stroke, two for PD) were also recruited. Supported communication methods were used as needed to undertake semi-structured interviews (total N = 23). RESULTS: Thematic analysis indicated participants had many unmet needs associated with their condition, which motivated them to explore self-management options. CST participation was described as an enjoyable social activity, and participation was perceived as improving mood, language, breathing and voice. CONCLUSIONS: Choral singing was perceived by people with stroke and PD to help them self-manage some of the consequences of their condition, including social isolation, low mood and communication difficulties. IMPLICATIONS FOR REHABILITATION: Choral singing therapy (CST) is sought out by people with stroke and PD to help self-manage symptoms of their condition. Participation is perceived as an enjoyable activity which improves mood, voice and language symptoms. CST may enable access to specialist music therapy and speech language therapy protocols within community frameworks.

Oscillatory decoupling differentiates auditory encoding deficits in children with listening problems.

OBJECTIVE: We sought to examine whether oscillatory EEG responses to a speech stimulus in both quiet and noise were different in children with listening problems than in children with normal hearing. METHODS: We employed a high-resolution spectral-temporal analysis of the cortical auditory evoked potential in response to a 150 ms speech sound /da/ in quiet and 3 dB SNR in 21 typically developing children (mean age=10.7 years, standard deviation=1.7) and 44 children with reported listening problems (LP) with absence of hearing loss (mean age=10.3 years, standard deviation=1.6). Children with LP were assessed for auditory processing disorder (APD) by which 24 children had APD, and 20 children did not. Peak latencies, magnitudes, and frequencies were compared between these groups. RESULTS: Children with LP had frequency shifts in the theta, and alpha bands (p<0.05), and children with LP+APD had additional frequency (p<0.01) and latency shifts (p<0.05) in the upper beta and in the lower gamma bands. CONCLUSIONS: These results provide evidence for differences in higher level modulatory processing in children with LP, and that APD is driven by differences in early auditory encoding. SIGNIFICANCE: These findings may better guide future research toward improving the differential diagnosis and treatment of listening problems in this population of children.

Assessing spectral and temporal processing in children and adults using temporal modulation transfer function (TMTF), Iterated Ripple Noise (IRN) perception, and spectral ripple discrimination (SRD).

BACKGROUND: There are many clinically available tests for the assessment of auditory processing skills in children and adults. However, there is limited data available on the maturational effects on the performance on these tests. PURPOSE: The current study investigated maturational effects on auditory processing abilities using three psychophysical measures: temporal modulation transfer function (TMTF), iterated ripple noise (IRN) perception, and spectral ripple discrimination (SRD). RESEARCH DESIGN: A cross-sectional study. Three groups of subjects were tested: 10 adults (18-30 yr), 10 older children (12-18 yr), and 10 young children (8-11 yr) DATA COLLECTION AND ANALYSIS: Temporal envelope processing was measured by obtaining thresholds for amplitude modulation detection as a function of modulation frequency (TMTF; 4, 8, 16, 32, 64, and 128 Hz). Temporal fine structure processing was measured using IRN, and spectral processing was measured using SRD. RESULTS: The results showed that young children had significantly higher modulation thresholds at 4 Hz (TMTF) compared to the other two groups and poorer SRD scores compared to adults. The results on IRN did not differ across groups. CONCLUSIONS: The results suggest that different aspects of auditory processing mature at different age periods and these maturational effects need to be considered while assessing auditory processing in children.

Effects of broadband noise on cortical evoked auditory responses at different loudness levels in young adults.

Young adults with no history of hearing concerns were tested to investigate their /da/-evoked cortical auditory evoked potentials (P1-N1-P2) recorded from 32 scalp electrodes in the presence and absence of noise at three different loudness levels (soft, comfortable, and loud), at a fixed signal-to-noise ratio (+3 dB). P1 peak latency significantly increased at soft and loud levels, and N1 and P2 latencies increased at all three levels in the presence of noise, compared with the quiet condition. P1 amplitude was significantly larger in quiet than in noise conditions at the loudest level. N1 amplitude was larger in quiet than in noise for the soft level only. P2 amplitude was reduced in the presence of noise to a similar degree at all loudness levels. The differential effects of noise on P1, N1, and P2 suggest differences in auditory processes underlying these peaks. The combination of level and signal-to-noise ratio should be considered when using cortical auditory evoked potentials as an electrophysiological indicator of degraded speech processing.

Effect of interstimulus interval and age on cortical auditory evoked potentials in 10-22-week-old infants.

This study compares cortical auditory evoked potentials (CAEPs) at different interstimulus intervals (ISIs) in infants to determine the impact of stimulus rate on wave morphology. Infant CAEPs are dominated by a positive peak P1. We hypothesized that infant CAEPs would be more adult-like at longer ISI with P1, followed by negativity (labelled N450). Participants were 10 typically developing infants aged 10-13 weeks (N=4) and 20-22 weeks (N=6). CAEPs were measured in one recording session for /da/ in quiet at 55 dB SPL for ISIs of 910, 1820, 3640 and 4550 ms in a randomized order. Recordings were complete at each ISI for 7-10 infants. Seven infants who completed all testing in quiet were also tested in continuous white noise (+5 dB signal-to-noise ratio) for the shortest ISI. P1 was observable in all infants; N450 was only present in the older infants. There appeared to be no ISI effect for younger or older infants, which is not consistent with ISI findings for adults and older children. The presence of N450 in the older infants only suggests that cortical maturational differences are evident in speech-evoked CAEPs in young infants. There were minimal effects of noise on P1 latency and amplitude. Results suggest different effects of ISI for very young infants than those observed in older infants and children. CAEPs are being used to measure hearing aid effectiveness in young infants and hence it is imperative that the effects of factors such as ISI are better understood.

Bilateral cochlear implants in long-term and short-term deafness.

This case is of a 70-year-old man with single-sided deafness (SSD) in the right ear since childhood, who developed a sudden severe hearing loss in the left ear at the age of 63. Eventually, after he received cochlear implants in both ears, he started to present behavioural auditory processing skills associated with binaural hearing, such as improved ability to understand speech in the presence of background noise, and sound localization. Outcomes were measured using cortical auditory evoked potentials, speech perception in noise, sound localization tests, and a self-rating questionnaire. The results suggest that even after more than 50 years of unilateral deafness it was possible to develop binaural interaction and sound localization as a result of electric auditory stimulation.

Duration-sensitive neurons in the auditory cortex.

The aim of this study was to determine whether there is a difference in the neural encoding of tones and complex sounds. Obligatory cortical auditory evoked potentials were obtained from normal hearing adults using tones and complex sounds with two stimulus durations and two inter-stimulus intervals. The response was smaller in amplitude for all of the long duration stimuli when using a short inter-stimulus interval. The difference in amplitude between the short and long duration tones disappeared when using the longer inter-stimulus interval but persisted for the complex sounds. The results provide evidence for duration-sensitive neurons in the auditory cortex as well as evidence for differences in the neural encoding of tones and complex sounds.

Evidence for adaptive plasticity in elderly monaural hearing aid users.

Hearing aids can induce perceptual changes in some elderly listeners but few studies have investigated physiological changes in this population. Loudness discomfort levels and acoustic reflex thresholds were measured in long-term users of a single hearing aid. The results show an asymmetry of +2 to +9 dB between ears in the sound level that (i) causes loudness discomfort and (ii) elicits a reflex contraction of the middle ear muscles. The elevation of the acoustic reflex threshold occurs in the ear with hearing aid experience, irrespective of the ear of stimulation. Therefore, there is evidence of adaptive plasticity and this can be measured at the level of the auditory brainstem.

Rising-frequency chirps and earphones with an extended high-frequency response enhance the post-auricular muscle response.

The purpose of this study was to determine whether rising-frequency chirps presented via earphones with an extended high-frequency response would optimize the post-auricular muscle response (PAMR). The PAMR was recorded in adults using three different stimuli (a click, a rising-frequency chirp, and a truncated speech stimulus, /t/). Conventional ER-3A insert earphones were compared to ER-2 insert earphones to determine whether the PAMR is enhanced by the ER-2's extended highfrequency response. There were significant stimulus and earphone effects on PAMR amplitudes. The PAMR was largest for the chirp stimulus and the ER-2 earphones. The poorest responses were obtained using the /t/ stimulus and conventional ER-3A earphones. The results support previous ABR studies that have demonstrated a significant advantage of chirps over clicks for evoked response audiometry, and indicate that the PAMR is enhanced by inclusion of additional high-frequency stimulus energy.

Electrophysiological and speech perception measures of auditory processing in experienced adult cochlear implant users.

OBJECTIVE: This study determined the relationship between auditory evoked potential measures and speech perception in experienced adult cochlear implant (CI) users and compared the CI evoked potential results to those of a group of age- and sex-matched control subjects. METHODS: CI subjects all used the Nucleus CI-22 implant. Middle latency response (MLR), obligatory cortical potentials (CAEP), mismatch negativity (MMN) and P3a auditory evoked potentials were recorded. Speech perception was evaluated using word and sentence tests. RESULTS: Duration of deafness correlated with speech scores with poor scores reflecting greater years of deafness. Na amplitude correlated negatively with duration of deafness, with small amplitudes reflecting greater duration of deafness. Overall, N1 amplitude was smaller in CI than control subjects. Earlier P2 latencies were associated with shorter durations of deafness and higher speech scores. In general, MMN was absent or degraded in CI subjects with poor speech scores. CONCLUSIONS: Auditory evoked potentials are related to speech perception ability and provide objective evidence of central auditory processing differences across experienced CI users. SIGNIFICANCE: Since auditory evoked potentials relate to CI performance, they may be a useful tool for objectively evaluating the efficacy of speech processing strategies and/or auditory training approaches in both adults and children with cochlear implants.

ABR thresholds to tonebursts gated with Blackman and linear windows in adults with high-frequency sensorineural hearing loss.

OBJECTIVE: The goal of this study was to determine whether tonebursts gated on and off using a nonlinear, exact-Blackman-gating function would be a more frequency-specific stimulus for auditory brain stem response audiometry than the more traditional 2-1-2 cycle linearly gated toneburst. DESIGN: Toneburst ABRs were recorded in 10 adults with normal hearing and in 18 adults with sloping high-frequency sensorineural hearing loss. It was hypothesized that any advantage of the Blackman stimuli for frequency-specific threshold assessment should be evident in hearing-impaired subjects with hearing loss confined to the 2000 to 4000 Hz frequency region since spectral splatter in the toneburst stimuli could lead to an underestimation of hearing loss based on the ABR thresholds. ABR stimuli consisted of 2000- and 4000-Hz 2-1-2 (rise-plateau-fall) cycle linearly gated tonebursts and 1-0-1 msec exact-Blackman-gated tonebursts. An additional 0.5-0-0.5 msec 4000-Hz Blackman-gated toneburst was used to investigate whether the difference in rise/fall characteristics of the linearly and Blackman-gated tonebursts could account for any differences in ABR results at 4000 Hz. The ABR toneburst stimuli were calibrated behaviorally in 15 adults with normal hearing. RESULTS: In the normal-hearing listeners toneburst-ABR thresholds generally exceeded behavioral thresholds by 10 to 13 dB for all stimuli. Correlations of 0.85 to 0.96 were obtained between 2000 and 4000 Hz toneburst ABR thresholds and pure-tone audiometric thresholds in the hearing-impaired listeners. Results were similar for Blackman- and linearly gated stimuli. CONCLUSIONS: There were no clear differences between Blackman- and linearly gated tonebursts in terms of how well ABR thresholds predicted pure-tone thresholds at 2000 and 4000 Hz. In general audiometric thresholds were predicted with good accuracy (+/-15 dB) by the toneburst ABR thresholds. The 4000-Hz audiometric threshold was underestimated in one subject with a very steeply sloping hearing loss by both Blackman- and linearly gated toneburst ABR thresholds, indicating that ipsilateral masking such as notched noise would be needed to ensure frequency specificity in this and similar cases.