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Mortality in dementia with Lewy bodies compared with Alzheimer's dementia: a retrospective naturalistic cohort study.
OBJECTIVES: To use routine clinical data to investigate survival in dementia with Lewy bodies (DLB) compared with Alzheimer's dementia (AD). DLB is the second most common dementia subtype after AD, accounting for around 7% of dementia diagnoses in secondary care, though studies suggest that it is underdiagnosed by up to 50%. Most previous studies of DLB have been based on select research cohorts, so little is known about the outcome of the disease in routine healthcare settings. SETTING: Cambridgeshire & Peterborough NHS Foundation Trust, a mental health trust providing secondary mental health care in England. SAMPLE: 251 DLB and 222 AD identified from an anonymised database derived from electronic clinical case records across an 8-year period (2005-2012), with mortality data updated to May 2015. RESULTS: Raw (uncorrected) median survival was 3.72 years for DLB (95% CI 3.33 to 4.14) and 6.95 years for AD (95% CI 5.78 to 8.12). Controlling for age at diagnosis, comorbidity and antipsychotic prescribing the model predicted median survival for DLB was 3.3 years (95% CI 2.88 to 3.83) for males and 4.0 years (95% CI 3.55 to 5.00) for females, while median survival for AD was 6.7 years (95% CI 5.27 to 8.51) for males and 7.0 years (95% CI 5.92 to 8.73) for females. CONCLUSION: Survival from first presentation with cognitive impairment was markedly shorter in DLB compared with AD, independent of age, sex, physical comorbidity or antipsychotic prescribing. This finding, in one of the largest clinical cohorts of DLB cases assembled to date, adds to existing evidence for poorer survival for DLB versus AD. There is an urgent need for further research to understand possible mechanisms accounting for this finding
No evidence for ITD-specific adaptation in the frequency following response
Neurons sensitive to interaural time differences (ITDs) in the fine structure of low-frequency signals have been found in binaurally responsive auditory nuclei in a wide range of species. The present study investigated whether the frequency following response (FFR) would show evidence for neurons “tuned” to ITD in humans. The FFR is a scalp-recorded measure of sustained phase-locked brainstem activity that has been shown to follow the frequency of low-frequency tones. The magnitude of the FFR often decreases over time for tones of long duration. The present study investigated whether this adaptation effect is ITD specific.The FFR to a 100-ms, 80-dB SPL, 504-Hz target tone was measured for ten subjects. The target was preceded by a 200-ms, 80-dB SPL, 504-Hz adaptor. The target always led by 0.5 ms in the left ear. The adaptor led either in the left ear or in the right ear by 0.5 ms. Stimuli (adaptor + target = pair) were presented in alternating polarity at a rate of 1.81 Hz. We used a “vertical” montage (+Fz, – C7, ground = Fpz) for which the FFR is assumed to reflect phase-locked neural activity from rostral generators in the brainstem. The averaged FFR waveforms for each polarity were subtracted, to enhance temporal fine structure responses. The results showed significant adaptation effects in the spectral magnitude of the FFR. However, adaptation was not larger when the adaptor had the same ITD as the target than when the ITD of the adaptor differed from that of the target. Thus, the current data provide no evidence that the spectral magnitude of the scalp-recorded FFR provides a non-invasive indicator of ITD-specific neural activation
Differences between psychoacoustic and frequency following response measures of distortion tone level and masking
The scalp-recorded frequency following response (FFR) in humans was measured for a 244-Hz pure tone at a range of input levels and for complex tones containing harmonics 2-4 of a 300-Hz fundamental, but shifted by +/- 56 Hz. The effective magnitude of the cubic difference tone (CDT) and the quadratic difference tone (QDT, at F-2-F-1) in the FFR for the complex was estimated by comparing the magnitude spectrum of the FFR at the distortion product (DP) frequency with that for the pure tone. The effective DP levels in the FFR were higher than those commonly estimated in psychophysical experiments, indicating contributions to the DP in the FFR in addition to the audible propagated component. A low-frequency narrowband noise masker reduced the magnitude of FFR responses to the CDT but also to primary components over a wide range of frequencies. The results indicate that audible DPs may contribute very little to the DPs observed in the FFR and that using a narrowband noise for the purpose of masking audible DPs can have undesired effects on the FFR over a wide frequency range. The results are consistent with the notion that broadly tuned mechanisms central to the auditory nerve strongly influence the FFR