The neurochemistry of agitation in Alzheimer's disease: a systematic review.

Objective: To provide an up-to-date systematic review of the characteristics, methodology and findings of studies that have investigated the neurochemistry of agitation in Alzheimer's disease (AD).

Methods: Electronic databases were searched for published peer-reviewed articles which provided data on any neurotransmitter system in relation to agitation in AD. Screening of titles and abstracts and data extraction from full texts were conducted in duplicate.

Service and treatment engagement of people with very late-onset schizophrenia-like psychosis.

Aims and method Electronic patient records were used to investigate the level of engagement and treatment that patients with very late-onset schizophrenia-like psychosis (VLOSLP) had with mental health services. Results Of 131 patients assessed and diagnosed, 63 (48%) were taking antipsychotic treatment at 3 months, 46 (35%) at 6 months and 36 (27%) at 12 months. At discharge from mental health services, 54% of patients had failed to engage with services or became lost to follow-up, 18% had engaged with services but were not taking antipsychotic medication and only 28% were taking treatment.

Cognitive phenotype of psychotic symptoms in Alzheimer's disease: evidence for impaired visuoperceptual function in the misidentification subtype.

Background: Establishing the cognitive phenotype of psychotic symptoms in Alzheimer's disease (AD) could localise discrete pathology and target symptomatic treatment. This study aimed to establish whether psychotic symptoms would be associated with poorer performance on neuropsychological tests known to correlate with striatal dopaminergic function and to investigate whether these differences would be attributed to the paranoid (persecutory delusions) or misidentification (misidentification phenomena +/- hallucinations) subtype.

Methods: Seventy patients with probable AD (34 psychotic and 36 nonpsychotic) were recruited to the study.

Does human presynaptic striatal dopamine function predict social conformity?

Socially desirable responding (SDR) is a personality trait which reflects either a tendency to present oneself in an overly positive manner to others, consistent with social conformity (impression management (IM)), or the tendency to view one's own behaviour in an overly positive light (self-deceptive enhancement (SDE)). Neurochemical imaging studies report an inverse relationship between SDR and dorsal striatal dopamine D₂/₃ receptor availability. This may reflect an association between SDR and D₂/₃ receptor expression, synaptic dopamine levels or a combination of the two.

Establishing test-retest reliability of an adapted [(18)F]fallypride imaging protocol in older people.

[(18)F]fallypride is a high-affinity dopamine D2/3 receptor tracer with the ability to reliably quantify D2/3 receptor sites in both striatal and corticolimbic regions. The translational potential of [(18)F]fallypride imaging is, however, limited by the lengthy scanning sessions (60-80 minutes duration over a total of 3-4 hours) required by current protocols. The aims of our study were to adapt [(18)F]fallypride imaging for use in clinical populations with neurological and neuropsychiatric disorders, by reducing the duration of individual scanning sessions; and to establish the reproducibility and reliability of our adapted protocol in healthy older people.

Origins of delusions in Alzheimer's disease.

Research over the past two decades supports a shared aetiology for delusions in Alzheimer's disease (AD) and schizophrenia. Functional networks involved in salience attribution and belief evaluation have been implicated in the two conditions, and striatal D2/3 receptors are increased to a comparable extent. Executive/frontal deficits are common to both disorders and predict emergent symptoms.

Limbic striatal dopamine D2/3 receptor availability is associated with non-planning impulsivity in healthy adults after exclusion of potential dissimulators.

Positron emission tomography (PET) studies have reported an association between reduced striatal dopamine D2/3 receptor availability and higher scores on self-report measures of trait impulsivity in healthy adults. However, impulsivity is a multi-faceted construct, and it is unclear which aspect(s) of impulsivity might be driving these associations. The current study aimed to investigate the relationship between limbic (ventral) striatal D2/3 receptor availability and individual components of impulsivity (attentional, motor and non-planning) using the Barratt Impulsiveness Scale (BIS-11) and [(11)C]raclopride PET in 23 healthy volunteers.

Association of serotonin and dopamine gene pathways with behavioral subphenotypes in dementia.

Genetic association studies investigating the association between genes of serotonergic and dopaminergic systems and behavioral and psychological symptoms in dementia (BPSD) are contradictory. We have utilized 1008 probable Alzheimer's disease (AD) patients from the UK and used the 12-item Neuropsychiatric Inventory. We applied a multiple indicators-multiple causes (MIMIC) approach to investigate the effect of 11 polymorphisms on the 4 behavioral subphenotypes "psychosis", "moods", "agitation", and "behavioural dyscontrol".

Truth, lies or self-deception? Striatal D(2/3) receptor availability predicts individual differences in social conformity.

Previous positron emission tomography (PET) studies have consistently shown a negative association between striatal D(2/3) receptor availability and socially desirable responding (SDR). However, as SDR is a complex personality trait, the functional significance of this relationship is unclear. The aim of the present study was to determine whether the relationship between D(2/3) receptor availability and SDR reflects a tendency to present oneself positively to others, consistent with social conformity (impression management, IM), or the tendency to view one's own behavior positively (self-deceptive enhancement, SDE).

Acute effect of the anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: an [11C]raclopride PET study.

Bupropion is an effective medication in treating addiction and is widely used as an aid to smoking cessation. Bupropion inhibits striatal dopamine reuptake via dopamine transporter blockade, but it is unknown whether this leads to increased extracellular dopamine levels at clinical doses in man. The effects of bupropion on extracellular dopamine levels in the striatum were investigated using [(11)C]raclopride positron emission tomography (PET) imaging in rats administered saline, 11 or 25 mg/kg bupropion i.

The dopaminergic basis of human behaviors: A review of molecular imaging studies.

This systematic review describes human molecular imaging studies which have investigated alterations in extracellular DA levels during performance of behavioral tasks. Whilst heterogeneity in experimental methods limits meta-analysis, we describe the advantages and limitations of different methodological approaches. Interpretation of experimental results may be limited by regional cerebral blood flow (rCBF) changes, head movement and choice of control conditions.

Dopamine release in the human striatum: motor and cognitive tasks revisited.

Striatal dopamine (DA) release has been shown during behavioural tasks, but the relative contribution of motor, reward, and cognitive components is unclear. Dopamine release was quantified using [(11)C]-raclopride in two studies using a triple-scan approach, comprising active task, motor control, and rest. In the first, bolus radiotracer was delivered during a sequential motor learning paradigm; in the second, a spatial planning task, bolus plus constant infusion was applied.

Premorbid personality and behavioral and psychological symptoms in probable Alzheimer disease.

Objectives: Previous research investigating the influence of premorbid personality on behavioral and psychological symptoms in dementia (BPSD) has produced mixed findings. Addressing some limitations of previous studies, the authors aimed to investigate whether some of the common individual symptoms of BPSD (depression, anxiety, irritability, and aggression) were associated with key aspects of previous personality (neuroticism and agreeableness); and also to perform an exploratory investigation into the broader influence of personality factors on behavioral and psychological syndromes.

Methods: Two hundred eight patients with a diagnosis of probable Alzheimer disease were assessed for the presence of BPSD over the disease course using the caregiver-rated Neuropsychiatric Inventory (NPI).

Striatal dopamine (D2) receptor availability predicts socially desirable responding.

Research in non-human primates has implicated striatal dopamine (D2) receptor function in the expression of social dominance--a fundamental component of social extraversion. We predicted that trait extraversion - indexed by the revised Eysenck Personality Questionnaire (EPQ-R) - would correlate with striatal DA (D2) receptor measures - indexed by [(11)C]-Raclopride binding potential (BP) - in 28 healthy post-menopausal females (mean age=75 years; range=58-91 years). Region of interest (ROI) and voxel-based statistical parametric mapping (SPM) analyses were performed, using a reference tissue model for [(11)C]-Raclopride.

A diffusion tensor magnetic resonance imaging study of frontal cortex connections in very-late-onset schizophrenia-like psychosis.

Objective: Onset of psychosis after the age of 60 may be associated with structural abnormalities within cerebral white matter. The authors looked within white-matter tracts, which mediate connectivity of the frontal lobes, in psychotic patients for evidence of loss of fiber integrity consistent with degenerative damage.

Methods: Fourteen patients with very-late-onset schizophrenia-like psychosis and an age-matched control group underwent diffusion tensor magnetic resonance imaging.

Age effects on diffusion tensor magnetic resonance imaging tractography measures of frontal cortex connections in schizophrenia.

Diffusion tensor magnetic resonance imaging (DT-MRI) has previously been used to investigate white matter tracts in schizophrenia, with inconsistent results. The aim of the study was to use a novel method for tract-specific measurements of fronto-temporal fasciculi in early-onset schizophrenia. We hypothesized that by making tract-specific measurements, clear diffusion abnormalities would be revealed in specific fasciculi in schizophrenia.

A positron emission tomography (PET) investigation of the role of striatal dopamine (D2) receptor availability in spatial cognition.

The functional significance of age-related changes in regional brain dopamine (DA) function is poorly understood in health. Two recent studies have reported positive linear associations between measures of striatal DA (D2) receptor availability (binding potential) and specific aspects of motor and cognitive performance, after controlling for the effects of age [(Volkow, N.D.