Molecular imaging of neuropsychiatric symptoms in Alzheimer's and Parkinson's disease

Abstract

Neuropsychiatric symptoms (NPS) are very common in neurodegenerative diseases and are a major contributor to disability and caregiver burden. There is accumulating evidence that NPS may be a prodrome of neurodegenerative diseases and are associated with functional decline. The medications used to treat these symptoms in younger patients are not very effective in patients with neurodegenerative disease and may have serious side effects. An understanding of the neurobiology of NPS is critical for the development of more effective intervention strategies. Targeting these symptoms may also have implications for prevention of cognitive or motor decline. Molecular brain imaging represents a bridge between basic and clinical observations and provides many opportunities for translation from animal models and human post-mortem studies to in vivo human studies. Molecular brain imaging studies in Alzheimer’s disease (AD) and Parkinson’s disease (PD) are reviewed with a primary focus on positron emission tomography studies of NPS. Future directions for the field of molecular imaging in AD and PD to understand the neurobiology of NPS will be discussed.

Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of Dementia

“…Hanfelt and colleagues (38) found that those MCI phenotypes that showed prominent functional and neuropsychiatric features were more likely to have cerebrovascular disease (CVD) suggesting a possible etiology for MCI with NPS. NPS are likely to be associated with great neurochemical deficits and neuropathology, as we have reviewed recently (39). We would hypothesize that greater severity of NPS and increased risk of cognitive decline are associated with greater monoaminergic and glutamatergic deficits, as well as AD pathology in cortical-limbic circuits implicated in mood and impulse control symptoms.…”

Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders

“…As indicated in Table 1, the artificial divide between neurological and psychiatric disorders is being progressively effaced with the recognition that, quite apart from co-morbidity and common risk factors, they share common domains of dysfunction in mood and cognition (Cunningham et al, 2006;Hirao et al, 2014;Millan et al, 2012;Norton et al, 2014;Sierskma et al, 2009). Likewise contributing to the erosion of this artificial divide is the realisation that psychiatric disorders are ENP25 SV CHAPTER TEXT AND CITATION TO SUBMIT AND SEND 14 12 14 24 24 characterised by structural changes in the brain -such as altered size of the hippocampus -involving disruption of both grey and white matter, neurones and glial cells (Arnone et al, 2013;Bartzokis, 2012;Brent et al, 2013;Burckholtz and Meyer-Lindenberg, 2012;Czeh and Di Benedetto, 2012;Kempton and McGuire, 2014;Smiałowska et al, 2013;Watkins et al, 2014;Zhang et al, 2014).…”

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

“…Clinical depression has been associated with AD, both as a symptom and as a risk factor (40,41), and despite current controversy as to the role of biogenic amines in AD-associated depression (42), both neuropathological and in vivo imaging studies demonstrated links between monoaminergic systems and AD (43)(44)(45).…”