OPINION STATEMENT: Behavioral and psychological symptoms of dementia (BPSD) are frequent amongst people with Alzheimer's disease (AD) and other dementias, commonly confer risk to that person and others, and present a significant management challenge for clinicians. There is increasing evidence to support the value of simple psychological interventions and the treatment of pain as a first-line management strategy prior to pharmacotherapy. The most widely prescribed pharmacological treatments-atypical antipsychotics-have a modest but significant beneficial effect in the short-term treatment of aggression (over 6-12 weeks) but limited benefits in longer-term therapy. In addition, there have been increasing concerns regarding the potential for serious adverse outcomes, including stroke and death. The potential pharmacologic alternatives to atypical antipsychotics with the most encouraging preliminary evidence include memantine, carbamazepine, citalopram, and prazosin. Large, prospective, randomized placebo-controlled trials are needed to establish the role of these agents as clinical therapies for the treatment of BPSD.
"therapeutic drugs consideration which might be probably continue to play a role in the management of these devastating disorders in the foreseeable future. Genetic polymorphism within apolipo protein (APOE) and butyrylcholinesterase (BCHE) has been shown to contribute to inter-individual variability in response to cholinesterase-inhibitors (ChEIs) in this neuropathological condition as well as the identification of phylogenetic susceptibility to used drug-related traits especially into accounted allele frequencies (Hendrie, 1998; Gooch and Stennett, 1996; Corbett et al., 2012). "
"Non-cognitive symptoms, such as agitation, aggression, depression and psychosis, are often observed in demented patients including those with AD, in addition to progressive cognitive deterioration. These symptoms, known as “behavioral and psychological symptoms of dementia” (BPSD), have been reported to occur in about 20% of AD patients (Lyketsos et al., 2000) and affect up to 80% of patients living in social care facilities and nursing homes (Margallo-Lana et al., 2001; Ryu et al., 2005), placing an extremely heavy burden on families and caregivers (Corbett et al., 2012; Ballard and Corbett, 2013). These neuropsychological symptoms often exhibit sudden onset and tend to fluctuate over time. "
[Show abstract][Hide abstract] ABSTRACT: The incidence of dementia is increasing at an alarming rate, and has become a major public health concern. Alzheimer disease (AD) is the most common form of dementia and is characterized by progressive cognitive impairment. In addition to classical neuropathological features such as amyloid plaques and neurofibrillary tangles (NFT), accumulation of activated immune cells has been documented in the AD brain, suggesting a contribution of neuroinflammation in the pathogenesis of AD. Besides cognitive deterioration, non-cognitive symptoms, such as agitation, aggression, depression and psychosis, are often observed in demented patients, including those with AD, and these neuropsychological symptoms place a heavy burden on caregivers. These symptoms often exhibit sudden onset and tend to fluctuate over time, and in many cases, they are triggered by an infection in peripheral organs, suggesting that inflammation plays an important role in the pathogenesis of these non-cognitive symptoms. However, there is no mechanistic explanation for the relationship between inflammation and neuropsychiatric symptoms. Observations from experimental mouse models indicate that alteration of brain blood vessels, especially blood-brain barrier (BBB) dysfunction, may contribute to the relationship. The current review summarizes the results from recent studies on the relationship between inflammation and AD, while focusing on cerebrovascular alterations, which might provide an insight into the pathogenesis of cognitive/non-cognitive symptoms in AD patients and suggest a basis for the development of new therapeutic treatments for these conditions.
"As for the non-pharmacological approach, all best practice guides still recommend the non-drug approach as the first-line treatment option for NPS in dementia. All simple or intensive psychosocial interventions are based on activities and interactions which can be personalized within the structured framework of a nursing home setting, such as reminiscence and music therapy or a structured social interaction . However, despite some positive outcomes regarding the non-pharmacological treatment of agitation in dementia in a larger, randomized controlled trial , the implementation of these individualized interventions in clinical and care home settings might be difficult due to the high level of competence which is required by nursing staff and caregivers. "
[Show abstract][Hide abstract] ABSTRACT: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are present during the disease course of nearly all AD patients and consist of psychosis, agitation/aggression, and depression, among others. Given their detrimental consequences regarding life expectancy, cognition, and socio-economic costs, it is essential to elucidate their neurochemical etiology to facilitate the development of novel and effective pharmacotherapeutics. This study attempted to identify brain region-specific monoaminergic correlates of NPS by measuring the levels of eight monoamines and metabolites in nine relevant postmortem brain regions of 40 behaviorally characterized AD patients, i.e., dopamine (DA), serotonin (5-HT), (nor)epinephrine and their respective metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid, 5-hydroxy-3-indoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), using RP-HPLC-ECD. Likewise, Mini-Mental State Examination (MMSE) score correlates of monoaminergic neurotransmitter alterations were calculated. As a result, MMSE scores, used as a measure of dementia severity, correlated positively with hippocampal 5-HIAA levels as well as with 5-HT levels of the superior temporal gyrus and cerebellar cortex. Furthermore, hippocampal 5-HIAA levels inversely correlated with agitation scores, whereas thalamic MHPG levels comparably did with the presence of hallucinations. Finally, in the cerebellar cortex, DOPAC/DA ratios, indicative of DA turnover, correlated with physically agitated behavior while MHPG levels correlated with affective disturbances. These findings support the assumption that specific NPS features in AD might be (in)directly related to brain region-specific monoaminergic neurotransmitter alterations. Additionally, the effect of AD pathology on neurochemical alterations in the cerebellum requires further examination due to its important but underestimated role in the neurochemical pathophysiology of NPS in AD.
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