Neuropsychiatric Symptoms in Alzheimer’s Disease Are the Main Determinants of Functional Impairment in Advanced Everyday Activities

2019 ◽  
Vol 67 (1) ◽  
pp. 381-392 ◽  
Author(s):  
Carolina Delgado ◽  
Rodrigo C. Vergara ◽  
Melissa Martínez ◽  
Gada Musa ◽  
Fernando Henríquez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Impairment ◽  
Neuropsychiatric Symptoms ◽  
Everyday Activities ◽  
Main Determinants

Predictors of Life Expectancy in Autopsy-Confirmed Alzheimer’s Disease

2022 ◽  
pp. 1-11
Author(s):  
Jeff Schaffert ◽  
Christian LoBue ◽  
Linda S. Hynan ◽  
John Hart ◽  
Heidi Rossetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Functional Impairment ◽  
Neuropsychiatric Symptoms ◽  
Primary Objective ◽  
Cognitive Predictors ◽  
Clinical Diagnoses ◽  
Neurological Exam ◽  
Univariate Analyses

Background: Life expectancy (LE) following Alzheimer’s disease (AD) is highly variable. The literature to date is limited by smaller sample sizes and clinical diagnoses. Objective: No study to date has evaluated predictors of AD LE in a retrospective large autopsy-confirmed sample, which was the primary objective of this study. Methods: Participants (≥50 years old) clinically and neuropathologically diagnosed with AD were evaluated using National Alzheimer’s Coordinating Center (N = 1,401) data. Analyses focused on 21 demographic, medical, neuropsychiatric, neurological, functional, and global cognitive predictors of LE at AD dementia diagnosis. These 21 predictors were evaluated in univariate analyses. Variables found to be significant were then entered into a forward multiple regression. LE was defined as months between AD diagnosis and death. Results: Fourteen predictors were significant in univariate analyses and entered into the regression. Seven predictors explained 27% of LE variance in 764 total participants. Mini-Mental State Examination (MMSE) score was the strongest predictor of LE, followed by sex, age, race/ethnicity, neuropsychiatric symptoms, abnormal neurological exam results, and functional impairment ratings. Post-hoc analyses revealed correlations of LE were strongest with MMSE ≤12. Conclusion: Global cognitive functioning was the strongest predictor of LE following diagnosis, and AD patients with severe impairment had the shortest LE. AD patients who are older, male, white, and have more motor symptoms, functional impairment, and neuropsychiatric symptoms were also more likely have shorter LE. While this model cannot provide individual prognoses, additional studies may focus on these variables to enhance predictions of LE in patients with AD.

Neuropsychiatric symptoms, functional impairment and executive ability in Thai patients with Alzheimer's Disease

2005 ◽  
Vol 17 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Vorapun Senanarong ◽  
Niphon Poungvarin ◽  
Piyanuj Jamjumras ◽  
Akanittha Sriboonroung ◽  
Chotipat Danchaivijit ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Impairment ◽  
Neuropsychiatric Symptoms ◽  
Executive Ability

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 Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

2021 ◽  
Author(s):  
Luis Enrique Arroyo-García ◽  
Arturo G. Isla ◽  
Yuniesky Andrade-Talavera ◽  
Hugo Balleza-Tapia ◽  
Raúl Loera-Valencia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Gamma Oscillations ◽  
Gamma Oscillation ◽  
Gamma Rhythm ◽  
Fast Spiking

AbstractIn Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

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 Trajectories of decline in cognitively complex everyday activities across the Alzheimer’s disease continuum

2020 ◽  
Vol 16 (S6) ◽  
Author(s):  
Mark A. Dubbelman ◽  
Roos J. Jutten ◽  
Sarah Tomaszewski Farias ◽  
Rebecca Amariglio ◽  
Rachel F. Buckley ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Everyday Activities
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