Neuropsychiatric symptoms in Alzheimer's disease: Past progress and anticipation of the future

Abstract

Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer’s first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer’s Association convened a Research Roundtable on the topic of NPS in AD. A major outcome of the Roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer’s Research and Treatment (ISTAART). The NPS-PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome specific synthetic reviews and recommendations prepared by NPS-PIA Workgroups on depression, apathy, sleep, agitation, and psychosis.

Protective effects of quercetin glycosides, rutin, and isoquercetrin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma (PC-12) cells

“…[2][3][4] As vast numbers of neurons undergo neuronal death, patients may experience symptoms that compromise the quality of life, including difficulty in movement, neuropsychiatric symptoms, as well as performing basic individual requirements such as eating, sleeping, and speaking. 5,6 Although several lines of evidence have suggested that neurodegenerative diseases such as Parkinson's disease can be caused by genetic predisposition, environmental exposure to pesticides and insecticides, the most accepted concepts of neuronal death, is free radical-induced oxidative stress. [7][8][9] Disruption in the antioxidant redox system in neuronal cells results in progressive accumulation of superoxide anions that is not downregulated by endogenous antioxidant enzymes (i.e.…”

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

“…Given the modest efficacy and adverse effect profile associated with antipsychotic use in AD (Schneider et al ., 2006), there is a compelling clinical need to elucidate the pathophysiology of psychotic symptoms and identify novel therapeutic targets (Geda et al ., 2013). There is clear evidence that the psychosis syndrome (delusions and/or hallucinations) (Jeste and Finkel, 2000) represents a distinct endophenotype of AD, with a heritability of around 60% (DeMichele‐Sweet and Sweet, 2010).…”

Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia

“…However, in the past, our team has proposed 4 possible theoretical explanations for the link between neuropsychiatric symptoms and dementia. 35 They are: (1) the etiologic pathway: a particular neuropsychiatric symptom such as depression may have a direct deleterious effect on the brain via the hypothalamus-pituitary axis and lead to incident dementia, in which case neuropsychiatric symptoms would represent "risk factors"; (2) shared risk factor or confounding pathway: a biological risk factor for dementia, for instance, b-amyloid, may be the cause of both cognitive outcome and neuropsychiatric symptoms, in which case neuropsychiatric symptoms might be better considered as "disease markers"; (3) a synergistic interaction: a neuropsychiatric symptom and a biological factor such as APOE e4 genotype may have a synergistic interaction to elevate the risk of incident dementia; and (4) reverse Table 3 Investigation of the interaction between neuropsychiatric symptoms and APOE e4 genotype and the outcome of incident dementia causality: when a person starts noticing cognitive decline then the individual may show reactive depression. In this scenario, it is the cognitive decline that led to the genesis of neuropsychiatric symptom.…”