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Concept: Apathy

28

Animals housed in impoverished cages are often labelled ‘bored’. They have also been called ‘apathetic’ or ‘depressed’, particularly when profoundly inactive. However, these terms are rarely operationally defined and validated. As a negative state caused by under-stimulation, boredom should increase interest in stimuli of all kinds. Apathy (lack of interest), by contrast, should manifest as decreased interest in all stimuli, while anhedonia (loss of pleasure, a depressive symptom) should specifically decrease interest in normally rewarding stimuli. We tested the hypotheses that mink, a model carnivore, experience more boredom, depression-like apathy, or anhedonia in non-enriched (NE) cages than in complex, enriched (E) cages. We exposed 29 subjects (13 E, 16 NE) to ten stimuli categorized a priori as aversive (e.g. air puffs), rewarding (e.g. evoking chasing) or ambiguous/neutral (e.g. candles). Interest in stimuli was assessed via latencies to contact, contact durations, and durations oriented to stimuli. NE mink contacted all stimuli faster (P = 0.003) than E mink, and spent longer oriented to/in contact with them, albeit only significantly so for ambiguous ones (treatment*type P<0.013). With stimulus category removed from statistical models, interest in all stimuli was consistently higher among NE mink (P<0.0001 for all measures). NE mink also consumed more food rewards (P = 0.037). Finally, we investigated whether lying down while awake and stereotypic behaviour (both increased by NE housing) predicted these responses. Lying awake positively co-varied with certain measures of increased exploration. In contrast, stereotypic 'scrabbling' or locomotion (e.g. pacing) did not. Overall, NE mink showed no evidence of apathy or depression, but instead a heightened investigation of diverse stimuli consistent with boredom. This state was potentially indicated by spending much time lying still but awake (although this result requires replication). Boredom can thus be operationalized and assessed empirically in non-human animals. It can also be reduced by environmental enrichment.

Concepts: Scientific method, A priori, Apathy, A priori and a posteriori, Flow, Boredom, Stereotypy

24

Cognitive and functional compromise, as frequently observed in Alzheimer’s disease (AD), hinders communication and social interactions. One consequence of this hindrance may be a feeling of loneliness. Moreover, emptiness and boredom, as observed in social isolation and loneliness, may thus be compensated for by creating imagined stimuli. Conditions of loneliness may be viewed as potentially generating hallucinatory experiences. To assess this assumption, the present study explored the relationship between social isolation, loneliness, and hallucinations in a sample of 22 mild AD participants and 24 elderly, healthy controls.

Concepts: Time, Sociology, Knowledge, Apathy, Hallucinations in the sane

4

Depression remains an important risk factor for Alzheimer’s disease, yet few neuroimaging biomarkers are available to identify treatment response in depression.

Concepts: Alzheimer's disease, Positron emission tomography, Neuroimaging, Neurology, Hematology, Dementia, Apathy, Treatment-resistant depression

3

Parkinson’s disease (PD) is traditionally conceptualised as a disorder of movement, but recent data suggest that motivational deficits may be more pervasive than previously thought. Here, we ask whether subclinical deficits in incentivised decision-making are present in PD and, if so, whether dopaminergic therapy ameliorates such deficits. We devised a novel paradigm in which participants decided whether they were willing to squeeze a hand-held dynamometer at varying levels of force for different magnitudes of reward. For each participant, we estimated the effort level at which the probability of accepting a reward was 50% - the effort ‘indifference point’. Patients with PD (N = 26) were tested ON and OFF their usual dopaminergic medication, and their performance compared to those of age-matched controls (N = 26). No participant was clinically apathetic as defined by the Lille Apathy Rating Scale (LARS). Our data show that, regardless of medication status, patients with PD chose to engage less effort than controls for the lowest reward. Overall, however, dopamine had a motivating effect on participants' choice behaviour - patients with PD chose to invest more effort for a given reward when they were in the ON relative to OFF dopamine state. Importantly, this effect could not be attributed to motor facilitation. We conclude that deficits in incentivised decision-making are present in PD even in the absence of a clinical syndrome of apathy when rewards are low, but that dopamine acts to eliminate motivational deficits by promoting the allocation of effort.

Concepts: Alzheimer's disease, Parkinson's disease, Substantia nigra, Motivation, Dopamine, Reward system, Apathy, Flow

2

The tau tracer [(18)F]AV1451, also known as flortaucipir, is a promising ligand for imaging tau accumulation in Alzheimer’s disease (AD). Most of the previous studies have quantified tau load using standardized uptake value ratios (SUVr) derived from a static [(18)F]AV1451 scan. SUVr may, however, be flow dependent and, especially for longitudinal studies, should be validated against a fully quantitative approach. The objective of this study was to identify the optimal tracer kinetic model for measuring tau load using [(18)F]AV1451.

Concepts: Alzheimer's disease, Scientific method, Longitudinal study, Epidemiology, Positron emission tomography, Sociology, Apathy, Proteopathy

2

In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer’s disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published in BMJ Open (2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers.

Concepts: Alzheimer's disease, Clinical trial, Neurology, Hematology, Apolipoprotein E, Placebo, Cerebrospinal fluid, Apathy

2

To determine whether lower cerebral blood flow (CBF) is associated with faster cognitive decline in patients with Alzheimer’s disease (AD).

Concepts: Alzheimer's disease, Neurology, Hematology, Memory, Apathy

2

To investigate arterial spin-labelling (ASL) cerebral blood flow (CBF) changes in predementia stages of Alzheimer’s disease (AD).

Concepts: Alzheimer's disease, Blood, Neurology, Hematology, Artery, Apathy, Cerebral perfusion pressure, Cerebral blood flow

2

The present study explored whether the optic flow deficit in Alzheimer’s disease (AD) reported in the literature transfers to different types of optic flow, in particular, one that specifies collision impacts with upcoming surfaces, with a special focus on the effect of retinal eccentricity. Displays simulated observer movement over a ground plane toward obstacles lying in the observer’s path. Optical expansion was modulated by varying [Formula: see text]. The visual field was masked either centrally (peripheral vision) or peripherally (central vision) using masks ranging from 10° to 30° in diameter in steps of 10°. Participants were asked to indicate whether their approach would result in “collision” or “no collision” with the obstacles. Results showed that AD patients' sensitivity to [Formula: see text] was severely compromised, not only for central vision but also for peripheral vision, compared to age- and education-matched elderly controls. The results demonstrated that AD patients' optic flow deficit is not limited to radial optic flow but includes also the optical pattern engendered by [Formula: see text]. Further deterioration in the capacity to extract [Formula: see text] to determine potential collisions in conjunction with the inability to extract heading information from radial optic flow would exacerbate AD patients' difficulties in navigation and visuospatial orientation.

Concepts: Photon, Optics, Vision, Visual perception, Visual system, Book of Optics, Apathy, Andrew Jaspan

1

To analyze voxel-wise correlation between cerebral blood flow (CBF) measured using ASL-MRI and cognition in patients with Alzheimer’s disease (AD).

Concepts: Blood, Neurology, Hematology, Perfusion, Apathy