Potentially modifiable factors associated with agitation and aggression in Alzheimer’s disease: results of the ICTUS study

2019 ◽  
Vol 31 (10) ◽  
pp. 1509-1516 ◽  
Author(s):  
Adelaide de Mauleon ◽  
Maria Soto ◽  
Pierre Jean Ousset ◽  
Fati Nourhashemi ◽  
Benoit Lepage ◽  
...  

ABSTRACTObjectives:To study potentially modifiable factors associated with the severity of agitation or aggression (A/A) symptoms among Alzheimer’s disease (AD) patients.Design:Data from the Impact of Cholinergic Treatment Use (ICTUS) study, European longitudinal prospective observational study.Setting:Community dwelling outpatients included in 29 European memory clinics.Participants:1375 participants with probable AD (Mini-Mental State Examination score of 10–26) with an informal caregiver.Measurements:At baseline and twice yearly over the two-year follow-up, patients underwent comprehensive clinical and neuropsychological assessments: sociodemographic data, cognitive status, functional impairment, and assessment of neuropsychiatric symptoms based on Neuro-Psychiatric Inventory (NPI). The ZARIT scale assessed the caregiver’s burden. The variable of interest was the severity of the item of A/A of the NPI. To study factors associated to the severity of A/A symptoms six months later, a multivariate mixed regression model was used.Results:Frequency of A/A symptom varied from 30% to 34% at each visit. Two factors were found to be independently associated with the severity of A/A: (1) the presence of affective disorder (anxiety, depression, and/or irritability) that increased the severity of the A/A by 0.89 point (coefficient:0.89; 95% Confidence Interval (CI) = [0.48,1.30], p < 0.001), and (2) a severe caregiver burden that increased the severity of the A/A by 1.08 point (coefficient:1.08; 95% CI = [0.69,1.47], p < 0.001).Conclusion:Research should evaluate whether the identification and treatment of an affective disorder along with the evaluation and optimal management of the caregiver would have a positive impact on the course of A/A in mild to moderate AD patients.

2021 ◽  
pp. 1-27
Author(s):  
David A. Loeffler

There is an extensive literature relating to factors associated with the development of Alzheimer’s disease (AD), but less is known about factors which may contribute to its progression. This review examined the literature with regard to 15 factors which were suggested by PubMed search to be positively associated with the cognitive and/or neuropathological progression of AD. The factors were grouped as potentially modifiable (vascular risk factors, comorbidities, malnutrition, educational level, inflammation, and oxidative stress), non-modifiable (age at clinical onset, family history of dementia, gender, Apolipoprotein E ɛ4, genetic variants, and altered gene regulation), and clinical (baseline cognitive level, neuropsychiatric symptoms, and extrapyramidal signs). Although conflicting results were found for the majority of factors, a positive association was found in nearly all studies which investigated the relationship of six factors to AD progression: malnutrition, genetic variants, altered gene regulation, baseline cognitive level, neuropsychiatric symptoms, and extrapyramidal signs. Whether these or other factors which have been suggested to be associated with AD progression actually influence the rate of decline of AD patients is unclear. Therapeutic approaches which include addressing of modifiable factors associated with AD progression should be considered.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S641-S641
Author(s):  
Shanna L Burke

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.


2013 ◽  
Vol 7 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Corina Satler ◽  
Carlos Tomaz

ABSTRACT Anosognosia, impairment insight and unawareness of deficits are used as equivalent terms in this study. Objective: To investigate the relationship between the presence of anosognosia symptoms and cognitive domains, functional abilities, and neuropsychiatric symptoms in patients with probable Alzheimer's disease (pAD) and elderly controls (EC). Methods: Twenty-one pAD (14 women) and twenty-two EC (16 women) were submitted to a neuropsychological battery of tests assessing global cognitive status, and specific cognitive functions: memory, executive and attention functions, verbal fluency and visuoconstructive abilities. Additionally, functional abilities (FAQ) and neuropsychiatric symptoms (NPI) were measured. Results: The linear regression statistical test found general anosognosia to be associated with subjective memory complaints, age and Arithmetic-DRS in the EC group. On the other hand, cognitive and functional abilities scores (Arithmetic- DRS, IQCODE and FAQ) were the best predictors in pAD patients, particularly for behavioral awareness. Conclusion: These results indicated that different variables are associated with self-awareness for pAD patients and EC, but for both groups executive functions appear to play an important role, contributing particularly to awareness of behavioral changes.


Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 380
Author(s):  
Seunghee Na ◽  
Hyeonseok Jeong ◽  
Jong-Sik Park ◽  
Yong-An Chung ◽  
In-Uk Song

The neuropathology of Parkinson’s disease dementia (PDD) is heterogenous, and the impacts of each pathophysiology and their synergistic effects are not fully understood. The aim of this study was to evaluate the frequency and impacts of co-existence with Alzheimer’s disease in patients with PDD by using 18F-florbetaben PET imaging. A total of 23 patients with PDD participated in the study. All participants underwent 18F-florbetaben PET and completed a standardized neuropsychological battery and assessment of motor symptoms. The results of cognitive tests, neuropsychiatric symptoms, and motor symptoms were analyzed between the positive and negative 18F-florbetaben PET groups. Four patients (17.4%) showed significant amyloid burden. Patients with amyloid-beta showed poorer performance in executive function and more severe neuropsychiatric symptoms than those without amyloid-beta. Motor symptoms assessed by UPDRS part III and the modified H&Y Scale were not different between the two groups. The amyloid PET scan of a patient with PDD can effectively reflect a co-existing Alzheimer’s disease pathology. Amyloid PET scans might be able to help physicians of PDD patients showing rapid progression or severe cognitive/behavioral features.


2011 ◽  
Vol 24 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Alessandro Sona ◽  
Ping Zhang ◽  
David Ames ◽  
Ashley I. Bush ◽  
Nicola T. Lautenschlager ◽  
...  

ABSTRACTBackground: The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients.Methods: We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as with and without subjects who had died or were too severely affected to be interviewed at 18 months and after, both including and excluding subjects whose AD diagnosis was “possible” AD. We sought correlations between rapid cognitive decline and demographic, clinical and biological variables.Results: Of the 211 AD patients recruited at baseline, we had available data for 156 (73.9%) patients at 18 months. Fifty-one patients were considered rapid cognitive decliners (32.7%). A higher Clinical Dementia Rating scale (CDR) and higher CDR “sum of boxes” score at baseline were the major predictors of rapid cognitive decline in this population. Furthermore, using logistic regression model analysis, patients treated with a cholinesterase inhibitor (CheI) had a higher risk of being rapid cognitive decliners, as did males and those of younger age.Conclusions: Almost one third of patients satisfying established research criteria for AD experienced rapid cognitive decline. Worse baseline functional and cognitive status and treatment with a CheI were the major factors associated with rapid cognitive decline over 18 months in this population.


2021 ◽  
Author(s):  
Yan Ai ◽  
Hamdi Ben Abdessalem ◽  
Claude Frasson

There is an increasing number of people with Alzheimer’s disease. Negative emotions are not only one of the symptoms of AD, but also the accelerator of the disease. Animal therapy can have a positive impact on the negative emotions of patients, but it has strict requirements for both environments and animals. In this study, we aim to explore the effectiveness of using virtual animals and their impact on the reduction of patients’ negative emotions to improve the user’s cognitive functions. This approach has been implemented in the Zoo Therapy project, which presents an immersive 3D virtual reality animal environment, where the impact on the patient’s emotion is measured in real-time by using electroencephalography (EEG). In addition to creating highly realistic virtual animals, the innovation of Zoo Therapy is also in its communication mechanism as it implements bidirectional human-computer interaction supported by 3 interaction methods: 3D buttons, speech instruction, and Neurofeedback. Patients can actively interact with virtual animals through 3D buttons or speech instructions. The Neurofeedback system will guide the animal to actively interact with the patients according to their real-time emotional changes to reduce their negative emotions. Experiments and preliminary results show that it is possible to interact with virtual animals in Zoo Therapy, and the Neurofeedback system can intervene in Zoo VR environment when the emotional value goes down and might reduce patients’ negative emotions.


2012 ◽  
Vol 27 (8) ◽  
pp. 579-583 ◽  
Author(s):  
Charles Van Liew ◽  
Terry A. Cronan

Objective: Alzheimer’s disease (AD) is associated with considerable caregiver and social burden. It is important to examine ways to minimize the negative effects of AD. Health care advocates (HCAs) may be one means of limiting the aversive effects of AD. Method: Participants completed a short survey that assessed their perceptions of the impact of comorbid AD on health status and their likelihood of hiring an HCA to assist in managing it. A mediational model was proposed: cognitive status (AD vs cognitively healthy) was the independent variable, perception of severity was the mediator, and the probability of hiring an HCA was the dependent variable. Results: The results indicated that the relationship between cognitive status and probability of hiring an HCA was fully mediated by perceptions of severity. Conclusion: This study demonstrated that participants appreciated the impact of AD on health status, and this translated into a greater probability of hiring an HCA.


2018 ◽  
Vol 52 (02) ◽  
pp. 84-91 ◽  
Author(s):  
Philipp Hessmann ◽  
Richard Dodel ◽  
Erika Baum ◽  
Matthias Müller ◽  
Greta Paschke ◽  
...  

Abstract Introduction Benzodiazepines and related drugs (BZDR) should be avoided in patients with cognitive impairment. We evaluated the relationship between a BZDR treatment and the health status of patients with Alzheimer’s disease (AD). Methods Cross-sectional study in 395 AD patients using bivariate and multiple logistic analyses to assess correlations between the prescription of BZDR and patients’ characteristics (cognitive and functional capacity, health-related quality of life (HrQoL), neuropsychiatric symptoms). Results BZDR were used in 12.4% (n=49) of all participants. In bivariate analyses, the prescription was associated with a lower HrQoL, a higher need of care, and the presence of anxiety. Multivariate models revealed a higher risk of BZDR treatment in patients with depression (OR 3.85, 95% CI: 1.45 – 10.27). Community-dwelling participants and those treated by neurologists/psychiatrists had a lower risk of receiving BZDR (OR 0.33, 95% CI: 0.12 – 0.89 and OR 0.16, 95% CI: 0.07 – 0.36). Discussion The inappropriate use of BZDR conflicts with national and international guidelines. We suggest evaluating indications and treatment duration and improving the knowledge of alternative therapies in healthcare institutions.


2020 ◽  
Vol 77 (3) ◽  
pp. 1195-1207
Author(s):  
Jung Yun Jang ◽  
Jean K. Ho ◽  
Anna E. Blanken ◽  
Shubir Dutt ◽  
Daniel A. Nation ◽  
...  

Background: Affective neuropsychiatric symptoms (aNPS: depression, anxiety, apathy, irritability) have been linked to increased dementia risk. However, less is known whether this association is independent of Alzheimer’s disease (AD) pathophysiology. Objective: To investigate the contribution of early aNPS to dementia risk in cognitively normal (CN) older adults and mild cognitive impairment (MCI) patients, with and without AD biomarker abnormality. Methods: Participants included 763 community-dwelling, stroke-free older adults identified as CN and 617 with MCI at baseline, drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Baseline assessments included a neuropsychological battery, the Neuropsychiatric Inventory (NPI), and apolipoprotein E ɛ4 (ApoE4) genotyping. A participant subset completed cerebrospinal fluid (CSF) AD biomarker assessment. Time to progression to dementia was measured based on months at follow-up when an individual was diagnosed with dementia, over the follow-up period of 48 months. Results: Latent class analysis identified 3 subgroups of older adults in CN and MCI, indicated by the baseline profiles of neuropsychiatric symptoms (NPS). Subgroups with higher aNPS were at increased risk of progression to dementia in both CN (HR = 3.65, 95% CI [1.80, 7.40]) and MCI (HR = 1.52, 95% CI [1.16, 2.00]; HR = 1.86 [1.05, 3.30]) groups, adjusting for age, sex, global cognition, and ApoE4, compared with their counterparts with minimal NPS. There was no difference between higher aNPS and minimal NPS subgroups in their CSF AD biomarker profiles. Conclusion: Findings suggest that aNPS may represent a neurobiological vulnerability that uniquely contribute to the dementia risk, independent of AD biomarker profiles.


2021 ◽  
Vol 36 (6) ◽  
pp. 1022-1022
Author(s):  
Jeff Schaffert ◽  
Will Goette ◽  
Anne Carlew ◽  
Allison Parker ◽  
Saranya Patel ◽  
...  

Abstract Objective Neuropsychiatric symptoms (NPS) are common in neurodegenerative disease, but longitudinal studies using large autopsy-confirmed samples are lacking. Our primary aim was to investigate progression of NPS over time in autopsy-confirmed Alzheimer’s disease (ad), Lewy body disease (LBD), and mixed (ad+LBD) cohorts. Methods Data on individuals (age &gt; =50) with autopsy-confirmed ad (N = 1568), ad+LBD (N = 349), and LBD (N = 142) was obtained from the National Alzheimer’s Coordinating Center (Mean visits = 2.61). Neuropsychiatric Inventory Questionnaire (NPI-Q) and 15-item Geriatric Depression Scale (GDS) scores were used to measure NPS. Multilevel zero-inflated binomial regression models were used to assess if NPI-Q and GDS scores differed among ad, ad+LBD, and LBD groups over time. Covariates included: years from baseline to final visit, cognitive status at baseline (i.e., normal, MCI, or dementia), demographic characteristics, MMSE, Functional Activities Questionnaire, and psychotropic treatment of psychiatric conditions. Results Higher NPI-Q and GDS scores were observed at baseline in the LBD group compared to ad (p’s &lt; 0.001). NPI-Q scores increased over time in the LBD group compared to ad+LBD and ad groups (90% CI). GDS scores differed among all groups at baseline (95% CI), with more rapid increase in the LBD group vs. ad and ad+LBD groups. Conclusions Overall, the course of NPS differs among disease pathologies. Those with pure LBD appear to have more severe NPS over time compared to those with ad and ad+LBD. Depressive symptoms increased more in LBD and ad+LBD compared to ad over time. Future research examining clinical outcomes related to NPS burden (care needs, caregiver burden, and life expectancy) is needed.


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