scholarly journals Neurobiology of neuropsychiatric symptoms in Alzheimer's disease: A critical review with a focus on neuroimaging

2013 ◽  
Vol 7 (3) ◽  
pp. 236-243 ◽  
Author(s):  
Lyssandra dos Santos Tascone ◽  
Cássio Machado de Campos Bottino
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Critical Review ◽  
Neural Circuits ◽  
Motor Behavior ◽  
Neuropsychiatric Symptoms ◽  
Key Words Dementia ◽  
Time Period ◽  
Monoaminergic System ◽  
The Individual

ABSTRACT The objective of this critical review of the literature was to reveal the neural circuits involved in the occurrence of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) patients through the association of these symptoms with neuroimaging findings. The search for articles was performed on PUBMED from January 2000 to May 2013, using the key words: Dementia AND BPSD; Dementia AND Neuropsychiatric Symptoms; and Dementia AND Psychosis, Delusions, Hallucinations, Agitation, Depression, Anxiety, Apathy, Euphoria, Disinhibition, Irritability, Aberrant Motor Behavior, Sleep or Eating Disorders. Forty-six articles were reviewed and important contributions, especially regarding the psychopathological concepts discussed, were also considered even if not included in this time period. The available evidence suggests the three most relevant neurobiological models for neuropsychiatric symptoms in Alzheimer's disease are the frontal-subcortical circuits, the cortico-cortical networks, and the monoaminergic system. We discussed the association of the individual symptoms or syndromes with these models.

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.

scholarly journals Neuropsychiatric symptoms and severity of dementia

2013 ◽  
Vol 7 (2) ◽  
pp. 171-175
Author(s):  
Gustavo Henrique de Oliveira Caldas ◽  
Sueli Luciano Pires ◽  
Milton Luiz Gorzoni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Motor Behavior ◽  
Neuropsychiatric Symptoms ◽  
Prevalence Ratio ◽  
Cross Sectional Study ◽  
Clinical Dementia Rating ◽  
Cross Sectional ◽  
Specific Stage ◽  
Severity Of Dementia

ABSTRACT Neuropsychiatric symptoms (NPS) cause distress, disabilitiy and reduced quality of life for both the patient and their families Objective: To evaluate the prevalence of NPS as a specific stage of dementia status. Methods: A cross-sectional study in patients attending an outpatient clinic for dementia was performed. We applied the Neuropsychiatric Inventory and Clinical Dementia Rating (CDR) scale. Statistical analysis was carried out with SPSS 17 software. Results: The 124 subjects (mean age of 80.4±7.0 years), 88 women (70.9%) had average duration of dementia of 7.1±3.2 years, most common dementias of Alzheimer's disease (35.5%) and mixed (31.5%) and most prevalent NPS of apathy (75%) and irritability (66.9%). Correlation between apathy and a CDR 1 had a PR (prevalence ratio) = 0.289 and p<0.001 while between apathy and CDR 4-5 (PR=8.333, p<0.005). A similar result was found between aberrant motor behavior (AMB) and CDR 1 (PR=0.352, p<0.003) and between AMB and CDR4-5 (PR=2.929, p<0.006). Conclusion: Alzheimer's disease and mixed dementia were predominant, while apathy and AMB were detected in association with the progressive stages of dementia.

Patterns of neuropsychiatric sub-syndromes in Brazilian and Norwegian patients with dementia

2012 ◽  
Vol 25 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Annibal Truzzi ◽  
Ingun Ulstein ◽  
Letice Valente ◽  
Eliasz Engelhardt ◽  
Evandro Silva Freire Coutinho ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Factor Analysis ◽  
Motor Behavior ◽  
Neuropsychiatric Symptoms ◽  
Principal Component ◽  
Mixed Dementia ◽  
Cross Sectional ◽  
Brazilian Sample ◽  
Two Samples

ABSTRACTBackground: Neuropsychiatric symptoms (NPS) affect the majority of patients who have dementia. Neuropsychiatric sub-syndromes with symptoms that occur together and have common neurobiological correlates have been identified. There are scarce data regarding the comparison of the pattern of the neuropsychiatric sub-syndromes in distinct ethnical and cultural populations. We aim at comparing the pattern of the NPS, and the factor analysis of the Neuropsychiatric Inventory (NPI-10) in two samples of outpatients with dementia living in Brazil and Norway.Methods: This is a cross-sectional study. The sample consists of 168 Brazilian and 155 Norwegian demented patients from psychogeriatric facilities and community-based educational programs. Brazilian patients were diagnosed with Alzheimer's disease (63.7%), vascular dementia (15.5%), or mixed dementia (20.8%), whereas the diagnoses of Norwegian patients were Alzheimer's disease (97.4%) and mixed dementia (2.6%). Principal component analysis with the Varimax rotation was used for factor analysis of the NPI-10.Results: Apathy (80.4 %), agitation/aggression (45.8%), and aberrant motor behavior (45.8%) were the most common symptoms in the Brazilian sample. Apathy (72.3%), dysphoria (61.9%), and anxiety (52.3%) were the most frequent symptoms in the Norwegian sample. Factor analysis of the NPI-10 revealed three syndromes for the Brazilian (Psychosis, Mood, Psychomotor) and Norwegian (Psychosis, Mood, Frontal) groups.Conclusions: The frequency of individual NPS may differ among distinct populations. However, Psychosis and Depression are common sub-syndromes in diverse ethnical and cultural patients with dementia. Our findings support the syndromic approach for the clinical assessment of the patients with dementia.

scholarly journals Association of caregiver demographic variables with neuropsychiatric symptoms in Alzheimer's disease patients for distress on the Neuropsychiatric Inventory (NPI)

2008 ◽  
Vol 2 (3) ◽  
pp. 211-216 ◽  
Author(s):  
Cláudia Godinho ◽  
Analuiza Camozzato ◽  
Renata Kochhann ◽  
Márcia Lorena Fagundes Chaves
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Motor Behavior ◽  
Neuropsychiatric Symptoms ◽  
Demographic Data ◽  
Demographic Variables ◽  
Demographic Characteristics ◽  
Behavioral Symptoms ◽  
Neuropsychiatric Inventory ◽  
Distress Level

Abstract Behavioral symptoms are frequently observed in Alzheimer's disease patients and are associated to higher distress for patients and caregivers, early institutionalization, worst prognosis and increased care. Objectives: The objective of the present study was to evaluate the frequency of neuropsychiatric symptoms in a sample of Alzheimer's disease patients and to analyze association between caregiver demographic characteristics and patient symptoms. Methods: Sixty Alzheimer's disease patients (NINCDS-ADRDA) and their caregivers were consecutively included in the investigation by the Dementia Outpatient clinic of Hospital de Clínicas de Porto Alegre. The Neuropsychiatric Inventory (NPI) was applied to evaluate behavioral symptoms and their impact upon caregivers. Age, sex, educational attainment, relationship to the patient, and time as caregiver were obtained from all caregivers. Results: Apathy was the symptom responsible for the highest distress level, followed by agitation and aggression. A significant correlation between total severity NPI and distress NPI was observed. None of the caregiver demographic data showed association to distress. The most frequent symptoms were apathy and aberrant motor behavior. Patients' relatives also considered apathy as the most severe symptom, followed by depression and agitation. Conclusions: Apathy was the most frequent and severe neuropsychiatric symptom. No relationship between caregiver demographic characteristics and distress was observed.

Neuropsychiatric symptoms and activities of daily living in Alzheimer’s disease: ALSOVA 5-year follow-up study

2019 ◽  
Vol 32 (6) ◽  
pp. 741-751 ◽  
Author(s):  
Toni Saari ◽  
Ilona Hallikainen ◽  
Taina Hintsa ◽  
Anne M. Koivisto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Activities Of Daily Living ◽  
Daily Living ◽  
Motor Behavior ◽  
Neuropsychiatric Symptoms ◽  
Study Data ◽  
Follow Up Study ◽  
Basic Adls

ABSTRACTBackground:Neuropsychiatric symptoms (NPSs) in Alzheimer’s disease (AD) are related to activities of daily living (ADLs), but longitudinal studies are sparse.Objectives:We investigated which NPSs were related to decline in instrumental ADLs (IADLs) and basic ADLs (BADLs) in a 5-year follow-up of individuals with AD.Methods:ALSOVA 5-year follow-up study data of 236 individuals with very mild or mild AD at baseline and their caregiver were analyzed. IADLs and BADLs were assessed with Alzheimer’s Disease Cooperative Study ADL inventory, and NPSs with Neuropsychiatric Inventory at annual follow-up visits. Generalized estimating equations (GEEs) were used for longitudinal data analysis, and NPS–ADL networks were estimated to demonstrate symptom interactions.Results:Apathy [rate ratio (RR) 1.23, 95% CI 1.06–1.44, p = 0.007], aberrant motor behavior (RR 1.24, 95% CI 1.07–1.44, p = 0.005), and appetite disturbances (RR 1.22, 95% CI 1.06–1.41, p = 0.005) were related to impairment in BADLs, and the same symptoms (RR 1.13, 95% CI 1.07–1.21, p < 0.001; RR 1.13, 95% CI 1.07–1.20, p < 0.001; RR 1.14; 95% CI 1.08–1.21, p < 0.001, for apathy, aberrant motor behavior, and appetite disturbances, respectively), in addition to delusions (RR 1.09, 95% CI 1.03–1.15, p = 0.004), were related to IADL impairment. Symptom networks varied at different time points.Conclusion:As AD progresses, common (apathy) and uncommon NPSs (aberrant motor behavior, appetite disturbances, delusions) seem to be related to ADLs through various symptom interactions. Previous literature suggests that frontal pathology could underlie these relationships.

scholarly journals Association of brain amyloidosis with the incidence and frequency of neuropsychiatric symptoms in ADNI: a multisite observational cohort study

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e031947 ◽  
Author(s):  
Naira Goukasian ◽  
Kristy S. Hwang ◽  
Tamineh Romero ◽  
Jonathan Grotts ◽  
Triet M. Do ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Motor Behavior ◽  
Neuropsychiatric Symptoms ◽  
Amyloid Pet ◽  
Neuropsychiatric Inventory ◽  
Night Time ◽  
Survival Analyses ◽  
Exact Test ◽  
Amyloid Pathology

ObjectiveTo investigate the relationship between amyloid burden and frequency of existing and incidence of new neuropsychiatric symptoms (NPS) in elderly with and without cognitive decline.Methods275 cognitively normal controls (NC), 100 subjective memory complaint (SMC), 559 mild cognitive impairment (MCI) and 143 Alzheimer’s disease dementia subjects from the Alzheimer’s Disease Neuroimaging Initiative received (18F)-florbetapir positron emission tomography (PET) scans. Yearly neuropsychiatric inventory (Neuropsychiatric Inventory (NPI)/NPI-Questionnaire) data were collected from the study partners at each visit. Mean standard uptake volume ratios (SUVR) normalised to whole cerebellum were obtained. Positive amyloid PET scan was defined as mean SUVR ≥1.17. Fisher’s exact test was used to compare frequency and incidence between amyloid positive and amyloid negative subjects. Survival analyses were used to estimate of neuropsychiatric symptoms (NPS) between amyloid positive and amyloid negative subjects. Survival analyses were used to estimate hazard ratios for developing the most common NPS by amyloid status.ResultsNo differences in NPS frequency were seen between amyloid positive and amyloid negative NC, SMC, MCI or dementia groups. MCI subjects with amyloid pathology however tended to have greater frequency x severity (FxS) of anxiety, hallucinations, delusions, apathy, disinhibition, irritability, aberrant motor behavior, and appetite, but not agitation, depression, night-time disturbances, or elation. MCI subjects with amyloid pathology were at greater risk for developing apathy, anxiety and agitation over time. Baseline presence of agitation and apathy and new onset agitation, irritability and apathy predicted faster conversion to dementia among MCI subjects.ConclusionsAmyloid pathology is associated with greater rate of development of new NPS in MCI. Anxiety and delusions are significant predictors of amyloid pathology. Agitation, irritability and apathy are significant predictors for conversion from MCI to dementia.

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.

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