Could Temperamental Features Modulate Participation in Clinical Trials?

The prodromal stages of Alzheimer's disease (AD) are the primary focus of research aimed at slowing disease progression. This study explores the influence of affective temperament on the motivation of people with mild cognitive impairment (MCI) and subjective cognitive decline (SCD) to participate in clinical trials. One hundred four subjects with MCI and SCD were screened for participation in pharmacological and non-pharmacological trials. Affective temperament was assessed based on the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego (TEMPS) scale. Demographic variables and temperament subscales scores were compared between MCI and SCD patients and among patients participating in the pharmacological trial, the non-pharmacological trial and refusing participation. Twenty-one subjects consented to participate in the pharmacological trial, seventy consented to the non-pharmacological trial and thirteen refused to participate in any trial. Patients with SCD had greater education and more depressive temperamental traits than those with MCI. While older age, higher education and anxious temperament were negatively associated with participation in the pharmacological trial, irritable temperamental positively predicted pharmacological trial participation. In conclusion, temperamental features may affect the willingness of patients with MCI and SCD to take part in clinical trials and, especially, the choice to participate in pharmacological studies.

Mild Cognitive Impairment in de novo Parkinson's Disease: Selective Attention Deficit as Early Sign of Neurocognitive Decay.

Background: In the present study, we aimed to better investigate attention system profile of Parkinson's disease-Mild Cognitive Impairment (PD-MCI) patients and to determine if specific attentional deficits are associated with 123I-FP-CIT SPECT. Methods: A total of 44 de novo drug-naïve PD patients [(27) with normal cognition (PD-NC) and 17 with MCI (PD-MCI)], 23 MCI patients and 23 individuals with subjective cognitive impairment (SCI) were recruited at the Clinical Neurology Unit of Santa Chiara hospital (Pisa University Medical School, Italy). They were assessed by a wide neuropsychological battery, including Visual Search Test (VST) measuring selective attention. Performances among groups were compared by non-parametric tests (i.e., Kruskal-Wallis and Mann-Whitney, Bonferroni corrected). Further, Spearman's rank correlations were performed to explore the association between neuropsychological variables and 123I-FP-CIT SPECT data in PD subgroup. Results: PD-MCI patients performed worse on VST than patients with PD-NC (p = 0.002), patients with MCI and individuals with SCI (p < 0.001). The performance of PD-MCI patients on VST significantly correlated with caudate nucleus 123I-FP-CIT SPECT uptake (rho = 0.582, p < 0.05), whereas a negative correlation between such test and 123I-FP-CIT SPECT uptake in the left putamen (rho = -0.529, p < 0.05) was found in PD-NC patients. Conclusions: We suggest that selective attention deficit might be a trigger of cognitive decay in de novo PD-MCI patients. The VST should be routinely used to detect attentional deficits in hospital clinical practice, in the light of its closely association with dopamine depletion of basal ganglia in mildly impaired PD patients.

Confabulations in Cases of Dementia: Atypical Early Sign of Alzheimer's Disease or Misleading Feature in Dementia Diagnosis?

Confabulations, also known as false memories, have been associated with various diseases involving mainly the frontal areas, such as Wernicke-Korsakoff syndrome or frontal epilepsy. The neuropsychological dysfunctions underlying mechanisms of confabulation are not well known. We describe two patients with memory impairment and confabulations at the onset speculating about neuropsychological correlates of confabulations and self-awareness. Both patients, a 77-year-old woman and a 57-years-old man, exhibited confabulations as first symptom of cognitive decline. She later developed memory impairment without awareness of her memory deficits and her cognitive and imaging profile suggested an amnesic mild cognitive impairment due to Alzheimer's disease (AD). Unlike her, he developed a prevalent involvement of frontal functions despite a clear consciousness of his cognitive deficits. However, the clinical diagnostic hypothesis of behavioral variant of frontotemporal dementia was not supported by imaging findings, which suggested AD. Both patients underwent neuropsychological evaluation including the Confabulation Battery. Despite that the exact anatomical correlation of confabulations is still not defined, imaging data shown by our patients is consistent with recent theories according to which at the origin of confabulatory tendency in AD there is an impairment of the connections between crucial hubs in frontal and mediotemporal areas, mainly involving the right hemisphere. Besides, it would be reasonable to hypothesize that self-awareness and confabulations should not be considered as necessarily associated dimensions.

Treatment of amblyopia in the adult: insights from a new rodent model of visual perceptual learning.

Amblyopia is the most common form of impairment of visual function affecting one eye, with a prevalence of about 1-5% of the total world population. Amblyopia usually derives from conditions of early functional imbalance between the two eyes, owing to anisometropia, strabismus, or congenital cataract, and results in a pronounced reduction of visual acuity and severe deficits in contrast sensitivity and stereopsis. It is widely accepted that, due to a lack of sufficient plasticity in the adult brain, amblyopia becomes untreatable after the closure of the critical period in the primary visual cortex. However, recent results obtained both in animal models and in clinical trials have challenged this view, unmasking a previously unsuspected potential for promoting recovery even in adulthood. In this context, non invasive procedures based on visual perceptual learning, i.e., the improvement in visual performance on a variety of simple visual tasks following practice, emerge as particularly promising to rescue discrimination abilities in adult amblyopic subjects. This review will survey recent work regarding the impact of visual perceptual learning on amblyopia, with a special focus on a new experimental model of perceptual learning in the amblyopic rat.

System consolidation of spatial memories in mice: effects of enriched environment.

Environmental enrichment (EE) is known to enhance learning and memory. Declarative memories are thought to undergo a first rapid and local consolidation process, followed by a prolonged process of system consolidation, which consist in a time-dependent gradual reorganization of brain regions supporting remote memory storage and crucial for the formation of enduring memories. At present, it is not known whether EE can affect the process of declarative memory system consolidation. We characterized the time course of hippocampal and cortical activation following recall of progressively more remote spatial memories. Wild-type mice either exposed to EE for 40 days or left in standard environment were subjected to spatial learning in the Morris water maze and to the probe test 1, 10, 20, 30, and 50 days after learning. Following the probe test, regional expression of the inducible immediate early gene c-Fos was mapped by immunohistochemistry, as an indicator of neuronal activity. We found that activation of the medial prefrontal cortex (mPFC), suggested to have a privileged role in processing remote spatial memories, was evident at shorter time intervals after learning in EE mice; in addition, EE induced the progressive activation of a distributed cortical network not activated in non-EE mice. This suggests that EE not only accelerates the process of mPFC recruitment but also recruits additional cortical areas into the network supporting remote spatial memories.

Enriched experience and recovery from amblyopia in adult rats: impact of motor, social and sensory components.

Amblyopia is one of the most common forms of visual impairment, arising from an early functional imbalance between the two eyes. It is currently accepted that, due to a lack of neural plasticity,amblyopia is an untreatable pathology in adults. Environmental enrichment (EE) emerged as a strategy highly effective in restoring plasticity in adult animals, eliciting recovery from amblyopia through a reduction of intracortical inhibition. It is unknown whether single EE components are able to promote plasticity in the adult brain, crucial information for designing new protocols of environmental stimulation suitable for amblyopic human subjects. Here, we assessed the effects of enhanced physical exercise,increased social interaction, visual enrichment or perceptual learning on visual function recovery in adult amblyopic rats. We report a complete rescue of both visual acuity and ocular dominance in exercised rats, in animals exposed to visual enrichment and in animals engaged in perceptual learning.These effects were accompanied by a reduced inhibition/excitation balance in the visual cortex. In contrast, we did not detect any sign of recovery in socially enriched rats or in animals practicing a purely associative visual task. These findings could have a bearing in orienting clinical research in the field of amblyopia therapy.

Environmental enrichment promotes plasticity and visual acuity recovery in adult monocular amblyopic rats.

Loss of visual acuity caused by abnormal visual experience during development (amblyopia) is an untreatable pathology in adults. In some occasions, amblyopic patients loose vision in their better eye owing to accidents or illnesses. While this condition is relevant both for its clinical importance and because it represents a case in which binocular interactions in the visual cortex are suppressed, it has scarcely been studied in animal models. We investigated whether exposure to environmental enrichment (EE) is effective in triggering recovery of vision in adult amblyopic rats rendered monocular by optic nerve dissection in their normal eye. By employing both electrophysiological and behavioral assessments, we found a full recovery of visual acuity in enriched rats compared to controls reared in standard conditions. Moreover, we report that EE modulates the expression of GAD67 and BDNF. The non invasive nature of EE renders this paradigm promising for amblyopia therapy in adult monocular people.