Objective To evaluate a cognitive test, the TYM (“test your memory”), in the detection of Alzheimer’s disease.Design Cross sectional study.Setting Outpatient departments in three hospitals, including a memory clinic.Participants 540 control participants aged 18-95 and 139 patients attending a memory clinic with dementia/amnestic mild cognitive impairment.Intervention Cognitive test designed to use minimal operator time and to be suitable for non-specialist use.Main outcome measures Performance of normal controls on the TYM. Performance of patients with Alzheimer’s disease on the TYM compared with age matched controls. Validation of the TYM with two standard tests (the mini-mental state examination (MMSE) and the Addenbrooke’s cognitive examination-revised (ACE-R)). Sensitivity and specificity of the TYM in the detection of Alzheimer’s disease.Results Control participants completed the TYM with an average score of 47/50. Patients with Alzheimer’s disease scored an average of 33/50. The TYM score shows excellent correlation with the two standard tests. A score of ≤42/50 had a sensitivity of 93% and specificity of 86% in the diagnosis of Alzheimer’s disease. The TYM was more sensitive in detection of Alzheimer’s disease than the mini-mental examination, detecting 93% of patients compared with 52% for the mini-mental state exxamination. The negative and positive predictive values of the TYM with the cut off of ≤42 were 99% and 42% with a prevalence of Alzheimer’s disease of 10%. Thirty one patients with non-Alzheimer dementias scored an average of 39/50.Conclusions The TYM can be completed quickly and accurately by normal controls. It is a powerful and valid screening test for the detection of Alzheimer’s disease.

Previous data suggest that methylphenidate can have variable effects on different cognitive tasks both within and between individuals. This is thought to be underpinned by inverted U-shaped relationships between cognitive performance and dopaminergic activity in relatively separate fronto-striatal circuits and reflected by individual differences in trait impulsivity. Direct evidence for this is currently lacking. In this study, we demonstrate for the first time that therapeutic doses of oral methylphenidate administered to young healthy subjects result in different sized changes in D 2 /D 3 receptor availability in different regions of the human striatum and that the change in receptor availability within an individual subregion predicts cognitive performance on a particular task. Methylphenidate produced significantly different effects on reversal learning and spatial working memory tasks within individuals. Performance on the reversal learning task was predicted by the drug-induced change in D 2 /D 3 receptor availability in postcommissural caudate, measured using [ 11 C]-raclopride radioligand PET imaging, whereas performance on the spatial working memory task was predicted by changes in receptor availability in the ventral striatum. Reversal learning performance was also predicted by subjects' trait impulsivity, such that the most impulsive individuals benefited more from methylphenidate, consistent with this drug's beneficial effects on cognition in attention deficit hyperactivity disorder.

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UKbased ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053.

It is possible to discriminate between grating contrasts over a 300-fold contrast range, whereas V1 neurons have very limited dynamic ranges. Using populations of model neurons with contrast-response parameters taken from electrophysiological studies (cat and macaque), we investigated ways of combining responses to code contrast over the full range. One model implemented a pooling rule that retained information about individual response patterns. The second summed responses indiscriminately. We measured accuracy of contrast identification over a wide range of contrasts and found the first model to be more accurate; the mutual information between actual and estimated contrast was also greatest for this model. The accuracy peak for the population of cat neurons coincided with the peak of the distribution of contrasts in natural images, suggesting an ecological match. Macaque neurons seem better able to code contrasts that are slightly higher on average than those found in the natural environment.

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