scholarly journals Is bigger better? Towards a mechanistic understanding of neuropsychiatric symptoms in Alzheimer’s disease

2021 ◽  
pp. 1-11
Author(s):  
Milap A. Nowrangi ◽  
Paul B. Rosenberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuropsychiatric Symptoms ◽  
Mechanistic Understanding

scholarly journals Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

2021 ◽  
Vol 14 (5) ◽  
pp. 458
Author(s):  
Barbara Miziak ◽  
Barbara Błaszczyk ◽  
Stanisław J. Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Ischemia ◽  
Neurodegenerative Disorder ◽  
Neuropsychiatric Symptoms ◽  
Antidepressant Drugs ◽  
Cancer Drug ◽  
Novel Treatments ◽  
Close Relationship ◽  
Approved Drugs

Alzheimer’s disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements—curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.

scholarly journals Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Adeline Su Lyn Ng ◽  
Juan Wang ◽  
Kwun Kei Ng ◽  
Joanna Su Xian Chong ◽  
Xing Qian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Network Topology ◽  
Neuropsychiatric Symptoms ◽  
Brain Network ◽  
Salience Network ◽  
Behavioral Variant Frontotemporal Dementia ◽  
Control Networks ◽  
And Control

Abstract Background Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network relationships and whole-brain network topology are also altered and underpin cognitive and social–emotional functional deficits. Methods In total, 111 participants (50 AD, 14 bvFTD, and 47 age- and gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Functional connectivity was derived among 144 brain regions of interest. Graph theoretical analysis was applied to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in AD, bvFTD, and healthy participants. Group differences in graph theoretical measures and empirically derived network community structures, as well as the associations between these indices and cognitive performance and neuropsychiatric symptoms, were subject to general linear models, with age, gender, education, motion, and scanner type controlled. Results Our results suggested that AD had lower integration in the default and control networks, while bvFTD exhibited disrupted integration in the salience network. Interestingly, AD and bvFTD had the highest and lowest degree of integration in the thalamus, respectively. Such divergence in topological aberration was recapitulated in network segregation and module distinctiveness loss, with AD showing poorer modular structure between the default and control networks, and bvFTD having more fragmented modules in the salience network and subcortical regions. Importantly, aberrations in network topology were related to worse attention deficits and greater severity in neuropsychiatric symptoms across syndromes. Conclusions Our findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.

scholarly journals Perceived stress and depressive symptoms not neuropsychiatric symptoms predict caregiver burden in Alzheimer’s disease: a cross-sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Manee Pinyopornpanish ◽  
Kanokporn Pinyopornpanish ◽  
Atiwat Soontornpun ◽  
Surat Tanprawate ◽  
Angkana Nadsasarn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Caregiver Burden ◽  
Perceived Stress ◽  
Neuropsychiatric Symptoms ◽  
Cross Sectional Study ◽  
Assessment Tools ◽  
Sectional Study ◽  
Cross Sectional

Abstract Background Caregiver burden affects the caregiver’s health and is related to the quality of care received by patients. This study aimed to determine the extent to which caregivers feel burdened when caring for patients with Alzheimer’s Disease (AD) and to investigate the predictors for caregiving burden. Methods A cross-sectional study was conducted. One hundred two caregivers of patients with AD at Maharaj Nakorn Chiang Mai Hospital, a tertiary care hospital, were recruited. Assessment tools included the perceived stress scale (stress), PHQ-9 (depressive symptoms), Zarit Burden Interview-12 (burden), Clinical Dementia Rating (disease severity), Neuropsychiatric Inventory Questionnaires (neuropsychiatric symptoms), and Barthel Activities Daily Living Index (dependency). The mediation analysis model was used to determine any associations. Results A higher level of severity of neuropsychiatric symptoms (r = 0.37, p < 0.01), higher level of perceived stress (r = 0.57, p < 0.01), and higher level of depressive symptoms (r = 0.54, p < 0.01) were related to a higher level of caregiver burden. The direct effect of neuropsychiatric symptoms on caregiver burden was fully mediated by perceived stress and depressive symptoms (r = 0.13, p = 0.177), rendering an increase of 46% of variance in caregiver burden by this parallel mediation model. The significant indirect effect of neuropsychiatric symptoms by these two mediators was (r = 0.21, p = 0.001). Conclusion Caregiver burden is associated with patients’ neuropsychiatric symptoms indirectly through the caregiver’s depressive symptoms and perception of stress. Early detection and provision of appropriate interventions and skills to manage stress and depression could be useful in reducing and preventing caregiver burden.

scholarly journals Brain mechanisms underlying neuropsychiatric symptoms in Alzheimer’s disease: a systematic review of symptom-general and –specific lesion patterns

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yaojing Chen ◽  
Mingxi Dang ◽  
Zhanjun Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Neuropsychiatric Symptoms ◽  
Onset Time ◽  
Anterior Cingulate ◽  
Neural Basis ◽  
Preclinical Ad ◽  
Disease Stages ◽  
Mild Cognitive Impairment Stage

AbstractNeuropsychiatric symptoms (NPSs) are common in patients with Alzheimer’s disease (AD) and are associated with accelerated cognitive impairment and earlier deaths. This review aims to explore the neural pathogenesis of NPSs in AD and its association with the progression of AD. We first provide a literature overview on the onset times of NPSs. Different NPSs occur in different disease stages of AD, but most symptoms appear in the preclinical AD or mild cognitive impairment stage and develop progressively. Next, we describe symptom-general and -specific patterns of brain lesions. Generally, the anterior cingulate cortex is a commonly damaged region across all symptoms, and the prefrontal cortex, especially the orbitofrontal cortex, is also a critical region associated with most NPSs. In contrast, the anterior cingulate-subcortical circuit is specifically related to apathy in AD, the frontal-limbic circuit is related to depression, and the amygdala circuit is related to anxiety. Finally, we elucidate the associations between the NPSs and AD by combining the onset time with the neural basis of NPSs.

scholarly journals RESTING HEART RATE MODERATES THE RELATIONSHIP BETWEEN NEUROPSYCHIATRIC SYMPTOMS, MCI, AND ALZHEIMER’S DISEASE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S641-S641
Author(s):  
Shanna L Burke
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heart Rate ◽  
Relative Risk ◽  
Neuropsychiatric Symptoms ◽  
Cognitive Status ◽  
Resting Heart Rate ◽  
Data Set ◽  
Increased Risk ◽  
The Relationship

Abstract Little is known about how resting heart rate moderates the relationship between neuropsychiatric symptoms and cognitive status. This study examined the relative risk of NPS on increasingly severe cognitive statuses and examined the extent to which resting heart rate moderates this relationship. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform Data Set was undertaken, using observations from participants with normal cognition at baseline (13,470). The relative risk of diagnosis with a more severe cognitive status at a future visit was examined using log-binomial regression for each neuropsychiatric symptom. The moderating effect of resting heart rate among those who are later diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) was assessed. Delusions, hallucinations, agitation, depression, anxiety, elation, apathy, disinhibition, irritability, motor disturbance, nighttime behaviors, and appetite disturbance were all significantly associated (p&lt;.001) with an increased risk of AD, and a reduced risk of MCI. Resting heart rate increased the risk of AD but reduced the relative risk of MCI. Depression significantly interacted with resting heart rate to increase the relative risk of MCI (RR: 1.07 (95% CI: 1.00-1.01), p&lt;.001), but not AD. Neuropsychiatric symptoms increase the relative risk of AD but not MCI, which may mean that the deleterious effect of NPS is delayed until later and more severe stages of the disease course. Resting heart rate increases the relative risk of MCI among those with depression. Practitioners considering early intervention in neuropsychiatric symptomology may consider the downstream benefits of treatment considering the long-term effects of NPS.

scholarly journals The individual course of neuropsychiatric symptoms in people with Alzheimer's and Lewy body dementia: 12-year longitudinal cohort study

2019 ◽  
Vol 216 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Audun Osland Vik-Mo ◽  
Lasse Melvaer Giil ◽  
Miguel Germán Borda ◽  
Clive Ballard ◽  
Dag Aarsland
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuropsychiatric Symptoms ◽  
Personalised Medicine ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Psychotic Symptoms ◽  
Primary Inclusion ◽  
The Individual

IntroductionUnderstanding the natural course of neuropsychiatric symptoms (NPS) in dementia is important for planning patient care and trial design, but few studies have described the long-term course of NPS in individuals.MethodPrimary inclusion of 223 patients with suspected mild dementia from general practice were followed by annual assessment, including the Neuropsychiatric Inventory (NPI), for up to 12 years. Total and item NPI scores were classified as stable, relapsing, single episodic or not present based on 4.96 (s.d. 2.3) observations (98% completeness of longitudinal data) for 113 patients with Alzheimer's disease and 84 patients with LBD (68 dementia with Lewy bodies and 16 Parkinson's disease dementia).ResultsWe found that 80% had stable NPI total ≥1, 50% had stable modest NPI total ≥12 and 25% had stable NPI total ≥24 scores. Very severe NPS (≥48) were mostly single episodes, but 8% of patients with Alzheimer's disease had stable severe NPS. Patients with Alzheimer's disease and the highest 20% NPI total scores had a more stable or relapsing course of four key symptoms: aberrant motor behaviour, aggression/agitation, delusions and irritability (odds ratio 55, P < 0.001). This was not seen in LBD. Finally, 57% of patients with Alzheimer's disease and 84% of patients with LBD had reoccurring psychotic symptoms.ConclusionsWe observed a highly individual course of NPS, with most presenting as a single episode or relapsing; a stable course was less common, especially in LBD. These findings demonstrate the importance of an individualised approach (i.e. personalised medicine) in dementia care.

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