Falls in older people with diabetes: Identification of simple screening measures and explanatory risk factors.

AIMS: To identify risk factors for falls in older people with diabetes mellitus (DM) and to develop a low-cost fall risk screening tool. METHODS: Older adults with DM (n = 103; age = 61.6 + 6.0 years) were recruited from diabetic clinics. Demographic, DM specific factors, lower limb strength and sensation, cognition, fear of falling, hand reaction time, balance, mobility and gait parameters were assessed using validated methods. Falls were prospectively recorded over six months. RESULTS: Past falls and female gender were identified as significant predictors of falls: history of falls and female gender increased fall rates by 4.62 (95% CI = 2.31-9.27) and 2.40 (95% CI = 1.04-5.54) respectively. Fall rates were significantly associated with Diabetic Neuropathy scores, HbA1c level, contrast sensitivity, quadriceps strength, postural sway, tandem balance, stride length and Timed Up and Go Test times. A multi-variable fall risk tool derived using five measures, revealed that absolute risk for multiple falls increased from 0% in participants with zero or one factor to 83% in participants with all five risk factors. CONCLUSIONS: Simple screening items for fall risk in people with DM were identified, with parsimonious explanatory risk factors. These findings help guide tailored interventions for preventing falls in DM.

Sensory gating, cannabinoids and schizophrenia.

Sensory gating, a mandatory process in early information processing, has been found to be defective in neuropsychiatric diseases such as schizophrenia. Understanding the neurobiology of sensory gating may provide insight into unravelling the neurobiology of information processing and to yet unanswered queries on the pathophysiology of disabling neuropsychiatric diseases. The endocannabinoid system has been linked to the pathophysiology of schizophrenia. Furthermore, cannabinoids disrupt sensory gating in animals and humans which supports the hypothesis that the disruption of sensory gating by alterations in the endocannabinoid system is a significant factor in the etiology of schizophrenia. Based on the above hypothesis this article reviews the sensory gating process in relation to the auditory conditioning-test paradigm with an emphasis on its association with the endocannabinoid system and schizophrenia.

Effects of phencyclidine on auditory gating in the rat hippocampus and the medial prefrontal cortex.

Sensory gating can be assessed using an auditory conditioning (C)-test (T) paradigm which measures the reduction in the auditory-evoked response produced by a test stimulus following a conditioning stimulus. Schizophrenic patients demonstrate absence of gating while dysfunction in glutamatergic neurotransmission is implicated in the pathophysiology of schizophrenia. This study examined the effect of the glutamate receptor antagonist, phencyclidine (PCP) on auditory gating in the CA3 region and dentate gyrus (DG) of rat hippocampus and medial prefrontal cortex (mPFC). Local field potential (LFP) activity was recorded simultaneously from CA3, DG and mPFC in isoflurane anaesthetised Lister hooded rats using in vivo electrophysiology. Paired auditory stimuli were presented binaurally over 128 trials. The effect of PCP (1 mg/kg, i.p.) on gating of the N2 LFP wave was assessed as the test:conditioning response amplitude ratio (T/C ratio); a value of < or =50% was indicative of gating. Auditory gating of the N2 wave was observed in the CA3, DG and mPFC. PCP disrupted gating in all three areas with significant increases in test amplitudes (P<0.001). Clozapine (5 mg/kg i.p) prevented the auditory gating deficits induced by PCP in the CA3, DG and mPFC. This study shows that PCP disrupts sensory gating in the CA3, DG and mPFC in the isoflurane anaesthetised rat. Similar deficits are observed in schizophrenic patients and the current method may provide an animal model with good predictive validity, a view substantiated by the fact that clozapine prevented the sensory gating deficits induced by PCP.

Sensory gating and its modulation by cannabinoids: electrophysiological, computational and mathematical analysis.

Gating of sensory information can be assessed using an auditory conditioning-test paradigm which measures the reduction in the auditory evoked response to a test stimulus following an initial conditioning stimulus. Recording brainwaves from specific areas of the brain using multiple electrodes is helpful in the study of the neurobiology of sensory gating. In this paper, we use such technology to investigate the role of cannabinoids in sensory gating in the CA3 region of the rat hippocampus. Our experimental results show that application of the exogenous cannabinoid agonist WIN55,212-2 can abolish sensory gating. We have developed a phenomenological model of cannabinoid dynamics incorporated within a spiking neural network model of CA3 with synaptically interacting pyramidal and basket cells. Direct numerical simulations of this model suggest that the basic mechanism for this effect can be traced to the suppression of inhibition of slow GABA(B) synapses. Furthermore, by working with a simpler mathematical firing rate model we are able to show the robustness of this mechanism for the abolition of sensory gating.

Auditory gating in rat hippocampus and medial prefrontal cortex: effect of the cannabinoid agonist WIN55,212-2.

Sensory gating can be assessed in rodents and humans using an auditory conditioning (C)-test (T) paradigm, with schizophrenic patients exhibiting a loss of gating. Dysregulation of the endocannabinoid system has been proposed to be involved in the pathogenesis of schizophrenia. We studied auditory gating and the effects of the cannabinoid agonist WIN55,212-22 on gating in CA3 and dentate gyrus (DG) of the hippocampus and medial prefrontal cortex (mPFC) in male Lister hooded rats using in vivo electrophysiology. The effects of a single dose of WIN55,212-2 on the N2 local field potential (LFP) test/conditioning amplitude ratios (T/C ratio) and response latencies were examined. In rats that demonstrated gating of N2, mPFC showed higher T/C ratios and shorter conditioning response latencies compared to DG and CA3. WIN55,212-2 disrupted auditory gating in all three areas with a significant increase in test amplitudes in the gating rats. A group of non-gating rats demonstrated higher test amplitudes and higher T/C ratios compared to gating rats. WIN55,212-2 had no effect on T/C ratios in the non-gating rats. The cannabinoid receptor (CB1) antagonist SR141716A prevented WIN55,212-2 induced disruption of gating. This study demonstrates gated auditory-evoked responses in CA3, DG and mPFC. The mPFC showed an early phase of gating which may later be modulated by CA3 and DG activity. Furthermore, cannabinoid receptor activation disrupted auditory gating in CA3, DG and mPFC, an effect which was prevented by CB1 receptor antagonism. The results further demonstrate the presence of a non-gating rat population which responded differently to cannabinoid agonists.