An investigation into the utility of the Mini Addenbrooke's Cognitive Examination (M-ACE) for the early detection of dementia and mild cognitive impairment in people aged 75 and over

Background/Aims: The Mini Addenbrooke’s Cognitive Examination (M-ACE) is the abbreviated version of the widely-used Addenbrooke’s Cognitive Examination (ACE-III), a cognitive screening tool that is used internationally in the assessment of mild cognitive impairment (MCI) and dementia. The objectives of this study were to investigate the diagnostic accuracy of the M-ACE with individuals aged 75 and over to distinguish between those who do and do not have a dementia or MCI, and also to establish whether the cut-off scores recommended by Hsieh et al. (2014) [9] in the original validation study for the M-ACE are optimal for this age group. Methods: The M-ACE was administered to 58 participants (24 with a diagnosis of dementia, 17 with a diagnosis of MCI and 17 healthy controls). The extent to which scores distinguished between groups (dementia, MCI or no diagnosis) was explored using receiver operating characteristic curve analysis. Results: The optimal cut-off for detecting dementia was ≤ 21/30 (score ≤ 21/30 indicating dementia with a sensitivity of 0.95, a specificity of 1 and a positive predictive value of 1) compared to the original higher published cut-off of ≤ 25/30 (sensitivity of 0.95, specificity of 0.70 and a positive predictive value of 0.82 in this sample). Conclusions: The M-ACE has excellent diagnostic accuracy for the detection of dementia in a UK clinical sample. It may be necessary to consider lower cut-offs than those given in the original validation study.

The influence of actions on auditory perception: cognitive and neural mechanisms

It is well known that self-generated stimuli are processed differently from externally generated stimuli. For example, many people have noticed since childhood that it is very difficult to make a self-tickling. In the auditory domain, self-generated sounds elicit smaller brain responses as compared to externally generated sounds, known as the sensory attenuation (SA) effect. SA is manifested in reduced amplitudes of evoked responses as measured through MEEG, decreased firing rates of neurons and a lower level of perceived loudness for self-generated sounds. The predominant explanation for SA is based on the idea that self-generated stimuli are predicted (e.g., the forward model account). It is the nature of their predictability that is crucial for SA. On the contrary, the sensory gating account emphasizes a general suppressive effect of actions on sensory processing, regardless of the predictability of the stimuli. Both accounts have received empirical support, which suggests that both mechanisms may exist. In chapter 2, three behavioural studies concerning the influence of motor activation on auditory perception were presented. Study 1 compared the effect of SA and attention in an auditory detection task and showed that SA was present even when substantial attention was paid to unpredictable stimuli. Study 2 compared the loudness perception of tones generated by others between Chinese and British participants. Compared to externally generated tones, a decrease in perceived loudness for others generated tones was found among Chinese but not among the British. In study 3, partial evidence was found that even when reading words that are related to action, auditory detection performance was impaired. In chapter 3, the classic SA effect of M100 suppression was replicated with MEG in study 4. With time-frequency analysis, a potential neural information processing sequence was found in auditory cortex. Prior to the onset of self-generated tones, there was an increase of oscillatory power in the alpha band. After the stimulus onset, reduced gamma power and alpha/beta phase locking were found. The three temporally segregated oscillatory events correlated with each other and with SA effect, which may be the underlying neural implementation of SA. In chapter 4, a TMS-MEG study was presented investigating the role of the cerebellum in adapting to delayed presentation of self-generated tones (study 5). It demonstrated that in sham stimulation condition, the brain can adapt to the delay (about 100 ms) within 300 trials of learning by showing a significant increase of SA effect in the suppression of M100, but not M200 component. Whereas after stimulating the cerebellum with a suppressive TMS protocol, the adaptation in M100 suppression disappeared and the pattern of M200 suppression reversed to M200 enhancement. These data support the idea that the suppressive effect of actions on auditory processing is a consequence of both motor driven sensory predictions and general sensory gating. The results also demonstrate the importance of neural oscillations in implementing SA effect and the critical role of the cerebellum in learning sensory predictions under sensory perturbation.