Pharmacotherapy of Behavioral and Psychological Symptoms of Dementia: State of the Art and Future Progress

Magierski, Radosław; Sobów, Tomasz; Schwertner, Emilia; Religa, Dorota

doi:10.3389/fphar.2020.01168

Cited by 84 publications

(75 citation statements)

References 167 publications

(177 reference statements)

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“…Accumulating evidence has demonstrated sleep disorder as a clinical contributing factor in patients with mild-moderate Alzheimer's disease at both disease development and progression 12 . However, very few studies were reported about the correlation of sleep quality (PSQI score) with behavioral and neuropsychological symptoms that occur at any stage in Alzheimer's disease 38 . In this study, we assessed patient sleep quality with the PSQI score system in parallel with behavioral and neuropsychological symptoms using MoCA (cognition), CDR (dementia), GDS (global deterioration scale), HRSD-24 (depression) and HAMA (anxiety) scoring systems.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Sleep Treatment Improves Neuropsychological Symptoms and Reduces Blood Aβ42/pTau Protein in Alzheimer's Disease Patients: a Longitudinal Study

Li¹,

Huang²,

Li³

et al. 2021

Preprint

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Background: Amyloid β peptide-42 (Aβ42) and phosphorylated Tau on Threonine 181 (Tau-pT181) are the core biomarkers in Alzheimer’s disease. Accumulated evidence showed an aberrant elevation of these biomarkers due to sleep disturbance. However, it is not clear if improving sleep quality reduces Aβ42 and Tau-pT181 in Alzheimer’s disease patients.Methods: A longitudinal study was conducted on 126 patients with mild-moderate dementia due to Alzheimer’s disease. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Behavioral and neuropsychological assessment was conducted using multiple self-reporting questionnaire score systems. Aβ42 and Tau-pT181 levels in blood specimens were measured using an ELISA assay kit. All patients received Donepezil treatment for Alzheimer’s disease. Sleep disorders were individually managed with either medication or physical therapy according to their symptom categories.Results: Of the 126 cases, 93 (73.8%) patients were diagnosed with sleep disorders. The PSQI scores significantly correlated with depression and anxiety scores, as well as Aβ42 and Tau-pT181 levels. Also, a significant correlation was found among depression, anxiety, Aβ42 and Tau-pT181 in all patients. Sleep intervention drastically reduced PSQI score, as well as Aβ42 and Tau-pT181 levels, in parallel with improved cognition, deterioration and anxiety scores. Dementia and depression scores were improved only in patients who completely recovered (PSQI < 7) after sleep treatment. There was a 35.9% reduction of Aβ42 levels and a 32.8% reduction of Tau-pT181 levels in this subgroup of patients (56 cases). Conversely, the reduction extent was only 6.9% for Aβ42 and 12.2% for Tau-pT181 in patients who did not completely recover (PSQI ≥ 7 post treatment, 37 cases). Multiple logistic regression analysis revealed that Aβ42 level is the strongest risk factor for sleep disorder incidence and incomplete recovery after sleep treatment.Conclusion: Sleep quality score is associated with patient depression and anxiety status, as well as blood Aβ42 and Tau-pT181 levels. A complete recovery is critical for a full improvement of all behavioral and neuropsychological assessments, which is also associated with a deep reduction of Aβ42 and Tau-pT181 levels. Aβ42 level is a prognostic factor for a diagnosis of sleep disorder and treatment responsiveness.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Sleep Treatment Improves Neuropsychological Symptoms and Reduces Blood Aβ42/pTau Protein in Alzheimer's Disease Patients: a Longitudinal Study

Li¹,

Huang²,

Li³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Several experts have agreed that, to optimize the clinical response, patients with dementia should be treated with specific and novel medications interacting with pharmacologically relevant targets (209)(210)(211). Therefore, preclinical and clinical studies focused on novel biological targets are needed.…”

Section: Clinical Pharmacological Trials and Future Prospectsmentioning

confidence: 99%

Agitation and Dementia: Prevention and Treatment Strategies in Acute and Chronic Conditions

et al. 2021

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Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes. The pathophysiological mechanism underlying agitation is represented by a frontal lobe dysfunction, mostly involving the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC), respectively, meaningful in selecting the salient stimuli and subsequent decision-making and behavioral reactions. Furthermore, increased sensitivity to noradrenergic signaling has been observed, possibly due to a frontal lobe up-regulation of adrenergic receptors, as a reaction to the depletion of noradrenergic neurons within the locus coeruleus (LC). Indeed, LC neurons mainly project toward the OFC and ACC. These observations may explain the abnormal reactivity to weak stimuli and the global arousal found in many patients who have dementia. Furthermore, agitation can be precipitated by several factors, e.g., the sunset or low lighted environments as in the sundown syndrome, hospitalization, the admission to nursing residencies, or changes in pharmacological regimens. In recent days, the global pandemic has increased agitation incidence among dementia patients and generated higher distress levels in patients and caregivers. Hence, given the increasing presence of this condition and its related burden on society and the health system, the present point of view aims at providing an extensive guide to facilitate the identification, prevention, and management of acute and chronic agitation in dementia patients.

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“…In view of previous neuroanatomical studies ( 36 , 37 ) and results obtained in non-demented patients, pharmacological treatment enhancing serotoninergic, noradrenergic, and dopaminergic transmission is indicated in patients with dementia and severe depression, provided response and safety is monitored, although significant effect was not deffinitely demonstrated in randomized controlled trials ( 24 – 27 ), which might be due to the exclusion of severely depressed patients ( 42 ).…”

Section: Depressionmentioning

confidence: 99%

“…The high prevalence of anxiety in people with dementia, together with the widespread use of drugs for its relief, contrasts with the absence of scientific studies to support that practice ( 24 , 27 ). Moreover, current standards of treatment of geriatric anxiety involve more of non-pharmacological approaches, which are the first line of recommended treatment.…”

Section: Anxietymentioning

confidence: 99%

Syndrome-Based Prescription to Optimize Psychotropics: Are CHROME Criteria a Game Changer?

Múñiz¹,

López-Álvarez

Agüera-Ortíz

et al. 2021

Front. Psychiatry

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A variety of medical and social factors have contributed over the last decades to the overuse of psychotropic drugs in people with dementia. One social factor is probably the frequent failure to provide adequate person-centered care, be it in the community or in institutional settings. This unfortunate reality has been reacted upon with numerous guidelines to reduce prescriptions of the most dangerous drugs (e.g., neuroleptics). Each psychotropic drug prescription can in principle be assessed around three dimensions: (a) adequate, (b) inadequate, and (c) chemical restraint. The CHemical Restraints avOidance MEthodology (CHROME) defined chemical restraint as any prescription based on organizational convenience, rather than justified with medical diagnosis. Two validation studies revealed that one of the main medical reasons of over- and miss-prescriptions was symptom-based prescription. By switching to syndrome-based prescription, a large proportion of drugs could be de-prescribed and some re-adjusted or kept. Paucity of research and weakness of data are not conclusive about the adequacy of specific drugs for the myriad of cases presented by patients with dementia and comorbid conditions. Clinical practice, however, leads us to believe that even under optimal care conditions, psychotropics might still contribute to quality of life if based on an adequate diagnosis. This article explains the rationale that underlies a syndromic approach aimed at optimizing psychotropic treatment in people with dementia whose significant suffering derives from their thought, affective, or behavioral problems. The results of previous validation studies of this new methodology will be discussed and conclusions for future results will be drawn.

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Pharmacotherapy of Behavioral and Psychological Symptoms of Dementia: State of the Art and Future Progress

Cited by 84 publications

References 167 publications

WITHDRAWN: Sleep Treatment Improves Neuropsychological Symptoms and Reduces Blood Aβ42/pTau Protein in Alzheimer's Disease Patients: a Longitudinal Study

WITHDRAWN: Sleep Treatment Improves Neuropsychological Symptoms and Reduces Blood Aβ42/pTau Protein in Alzheimer's Disease Patients: a Longitudinal Study

Agitation and Dementia: Prevention and Treatment Strategies in Acute and Chronic Conditions

Syndrome-Based Prescription to Optimize Psychotropics: Are CHROME Criteria a Game Changer?

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