What, If, and When to Move: Basal Ganglia Circuits and Self-Paced Action Initiation.

Deciding what to do and when to move is vital to our survival. Clinical and fundamental studies have identified basal ganglia circuits as critical for this process. The main input nucleus of the basal ganglia, the striatum, receives inputs from frontal, sensory, and motor cortices and interconnected thalamic areas that provide information about potential goals, context, and actions and directly or indirectly modulates basal ganglia outputs. The striatum also receives dopaminergic inputs that can signal reward prediction errors and also behavioral transitions and movement initiation. Here we review studies and models of how direct and indirect pathways can modulate basal ganglia outputs to facilitate movement initiation, and we discuss the role of cortical and dopaminergic inputs to the striatum in determining what to do and if and when to do it. Complex but exciting scenarios emerge that shed new light on how basal ganglia circuits modulate self-paced movement initiation.

The prevalence of dementia in a Portuguese community sample: a 10/66 Dementia Research Group study.

BACKGROUND: Dementia imposes a high burden of disease worldwide. Recent epidemiological studies in European community samples are scarce. In Portugal, community prevalence data is very limited. The 10/66 Dementia Research Group (DRG) population-based research programmes are focused in low and middle income countries, where the assessments proved to be culture and education fair. We applied the 10/66 DRG prevalence survey methodology in Portugal, where levels of illiteracy in older populations are still high. METHODS: A cross-sectional comprehensive one-phase survey was conducted of all residents aged 65 and over of two geographically defined catchment areas in Southern Portugal (one urban and one rural site). Nursing home residents were not included in the present study. Standardized 10/66 DRG assessments include a cognitive module, an informant interview and the Geriatric Mental State-AGECAT, providing data on dementia diagnosis and subtypes, mental disorders including depression, physical health, anthropometry, demographics, disability/functioning, health service utilization, care arrangements and caregiver strain. RESULTS: We interviewed 1405 old age participants (mean age 74.9, SD = 6.7 years; 55.5% women) after 313 (18.2%) refusals to participate. The prevalence rate for dementia in community-dwellers was 9.23% (95% CI 7.80-10.90) using the 10/66 DRG algorithm and 3.65% (95% CI 2.97-4.97) using DSM-IV criteria. Pure Alzheimer's disease was the most prevalent dementia subtype (41.9%). The prevalence of dementia was strongly age-dependent for both criteria, but there was no association with sex. CONCLUSIONS: Dementia prevalence was higher than previously reported in Portugal. The discrepancy between prevalence according to the 10/66 DRG algorithm and the DSM-IV criteria is consistent with that observed in less developed countries; this suggests potential underestimation using the latter approach, although relative validity of these two approaches remains to be confirmed in the European context. We improved the evidence base to raise awareness and empower advocacy about dementia in Portugal, so that the complex needs of frail older people may be met in better ways.

Plasma and platelet clusterin ratio is altered in Alzheimer's disease patients with distinct neuropsychiatric symptoms: findings from a pilot study.

BACKGROUND: Clusterin protein in plasma has been found to differentiate between people with and without cognitive changes. However, these findings are not conclusive, despite the clusterin gene variations repeatedly being linked to increased risk for dementia, in particular Alzheimer's disease (AD). METHOD: We analysed the level of clusterin in platelet and plasma in 25 subjects with a clinical diagnosis of AD and 26 subjects with no cognitive impairment. RESULTS: In the current study, we report that the levels of both plasma and platelet clusterin are similar between AD and cognitively intact individuals. Clusterin plasma and platelet levels, as well as the plasma/platelet clusterin ratio, were not affected by age, gender, cognitive impairment and/or overt behavioural symptomatology, including presence of hallucinations and delusions, as well as depression. However, the plasma/platelet clusterin ratio was positively associated in with the Neuropsychiatric Inventory measures of agitation, apathy, irritability and motor aberrant behaviour in AD subjects. CONCLUSION: Previous inconsistencies in reported blood clusterin levels may be a result of underlying non-cognitive symptoms in people with AD. Our findings need now to be replicated in larger group of dementia subjects.

Platelet immunoglobulin and amyloid precursor protein as potential peripheral biomarkers for Alzheimer's disease: findings from a pilot study.

BACKGROUND: the diagnosis of dementia, in particular Alzheimer's disease (AD), is enhanced with the use of molecular biomarkers. Since cerebrospinal fluid analysis and molecular neuroimaging are not routinely used in many countries, blood biomarker molecules may be more readily applicable in a routine clinical setting. METHODS: twenty-five subjects with a clinical diagnosis of AD and 26 control participants were assessed for cognitive and behavioural functioning. Platelet measures of amyloid protein precursor (APP), tau protein, clusterin, α-synuclein and immunoglobulin (Ig) were measured. Linear regression analysis for platelet proteins and cognitive and behavioural status were determined, and receiver operating characteristic (ROC) curves created to assess the discriminating power of each biochemical parameter between AD and control groups. RESULTS: both AD and control subjects had similar platelet levels of measures platelet proteins, with the exception of slightly elevated Ig levels in AD subjects (P = 0.052). The latter were not related to increasing age, or extent of cognitive impairment. APP-N measures were negatively correlated with cognitive scores. CONCLUSION: these preliminary findings suggest that platelet measures of the traditional biomarkers for AD are feasible in the periphery. The measures of platelet APP-N and Ig, in particular, merit further study in a larger cohort of AD and control subjects.

A comparison of primary and secondary caregivers of persons with dementia.

Having 2 or more relatives involved in the informal care of people with dementia is frequent worldwide. There are, however, few comparisons of primary and secondary caregivers and even fewer of those who are caring for the same person. Our study aimed to contrast these 2 experiences of caregiving. We compared 2 related samples of 61 primary and 61 secondary family caregivers of the same persons with dementia in a nonrandomized cross-sectional study. Caregivers' main outcome assessments were the Zarit Burden Interview (for subjective burden), the General Health Questionnaire (for psychological distress), and the Positive Aspects of Caregiving scale. We controlled for caregiver variables (e.g., demographics, caregiving arrangements, social support, sense of coherence) and the neuropsychiatric symptoms of dementia. Subjective burden was higher in primary than secondary caregivers (p = .013), but positive aspects of caregiving did not differ (p = .150). Psychological distress was high at clinically relevant levels in primary and secondary caregivers, without statistically significant differences between groups (p = .456). The findings demonstrate that notwithstanding the difficulties faced by primary caregivers, secondary caregivers may also experience clinically significant distress. Therefore, their needs for assistance and support should be addressed more systematically. These findings call for systemic family-focused interventions in dementia that address the support each person provides or might provide, as well as the psychological distress each person may feel. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Postingestive Modulation of Food Seeking Depends on Vagus-Mediated Dopamine Neuron Activity.

Postingestive nutrient sensing can induce food preferences. However, much less is known about the ability of postingestive signals to modulate food-seeking behaviors. Here we report a causal connection between postingestive sucrose sensing and vagus-mediated dopamine neuron activity in the ventral tegmental area (VTA), supporting food seeking. The activity of VTA dopamine neurons increases significantly after administration of intragastric sucrose, and deletion of the NMDA receptor in these neurons, which affects bursting and plasticity, abolishes lever pressing for postingestive sucrose delivery. Furthermore, lesions of the hepatic branch of the vagus nerve significantly impair postingestive-dependent VTA dopamine neuron activity and food seeking, whereas optogenetic stimulation of left vagus nerve neurons significantly increases VTA dopamine neuron activity. These data establish a necessary role of vagus-mediated dopamine neuron activity in postingestive-dependent food seeking, which is independent of taste signaling.