Behavioral and psychological subsyndromes in Alzheimer's disease using the Neuropsychiatric Inventory

Canevelli, Marco; Adali, Nawal; Voisin, Thierry; Soto, María; Bruno, Giuseppe; Cesari, Matteo; Vellas, Bruno

doi:10.1002/gps.3904

Cited by 98 publications

(105 citation statements)

References 40 publications

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“…This NPS-class is similar to the symptom pattern commonly reported in studies of MCI samples [5,8,19,24,39,40], and also the 'affective' cluster reported in studies of dementia samples [18]. In our study, 28% of all those with dementia (n = 11) and 19% of those with MCI (n = 25) were classified as having an affective/low comorbidity NPS pattern.…”

Section: Clusters Of Neuropsychiatric Symptomssupporting

confidence: 88%

“…This syndrome included high prevalence of agitation, disinhibition and irritability-a cluster that has been reported in dementia samples, and in conjunction with aberrant motor behavior [18]. Its low prevalence in the sample is also consistent with the literature.…”

Section: Clusters Of Neuropsychiatric Symptomssupporting

confidence: 86%

“…In our study, 28% of all those with dementia (n = 11) and 19% of those with MCI (n = 25) were classified as having an affective/low comorbidity NPS pattern. This affective syndrome may be the predominant NPS pattern in MCI and AD [18]. For example, Lyketsos et al [41] reported 28% of participants with AD in the Cache County study demonstrated an NPS syndrome characterized by high NPS burden as well as high prevalence of apathy, irritability, depression, and aberrant motor behavior.…”

Section: Clusters Of Neuropsychiatric Symptomsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Commonly identified clusters in dementia include an affective syndrome and a psychotic syndrome, with frontal/hypomanic and hyperactivity syndromes being less consistently observed [18]. However, while a systematic review of NPS found low concordance of evidence for NPS clusters derived from the Neuropsychiatric Inventory (NPI) in dementia samples [18], some NPS may define potential sub-syndromes of AD. Interestingly, Forrester et al [19] recently linked patterns of NPS in incident MCI to an increased likelihood of progression to dementia, demonstrating the severe symptom class (consisting of agitation, anxiety, apathy, night-time behaviors, inhibition) to have a 2-fold higher risk of progressing to dementia (hazard ratio (HR) = 2.69, 95% confidence interval (CI): 1.12-2.70), while the affective class (consisting of depression, anxiety, irritability, night-time behaviors) had a one-point-five-times higher risk of progressing to dementia (HR = 1.70, 95% CI: 1.12-2.70) when compared to the asymptomatic class.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Neuropsychiatric Symptoms and Cognitive Impairment: Understanding the Importance of Co-Morbid Symptoms

Mortby

Burns

Eramudugolla

et al. 2017

JAD

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Abstract.Background: Neuropsychiatric symptoms (NPS) are common in older adults with cognitive impairment, yet little is known about population-based prevalence and clinical implications of co-morbid symptom presentation across the spectrum from normal cognition to dementia. Objective: To characterize the prevalence of NPS and explore the clinical implications of co-morbid symptom presentation. Methods: Cross-sectional study of 1,417 older adults (aged 73-79) with dementia (n = 40); with mild cognitive impairment (MCI; n = 133); who are 'cognitively normal, but-at-risk' (CN-AR; n = 397); and who are cognitively normal (n = 847). NPS were assessed by the Neuropsychiatric Inventory. Cluster analyses were conducted using a latent class analysis (LCA). Results: NPS are highly prevalent across the cognitive function spectrum (30.8%-80%). NPS were associated with a 3-fold increased risk of dementia, a 2-fold increased risk of MCI, and a 1.5-times increased risk of CN-AR. Each additional co-morbid symptom was associated with an additional 1.5-times increased risk of dementia, but not MCI or CN-AR. LCA revealed four distinctive sub-populations: 1) frontal/low comorbidity; 2) high prevalence/high comorbidity; 3) affective/low comorbidity; and 4) sleep/low comorbidity. Conclusion: Our findings confirm previous reports on the prevalence of NPS in community-based samples and are consistent with the profiles of NPS domain characteristics of MCI and dementia. Number of co-morbid NPS and not symptom clusters are associated with increased risk of dementia. Understanding such patterns will help inform our understanding of mild behavioral disorders and assist with clinical assessment.

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Section: Clusters Of Neuropsychiatric Symptomssupporting

confidence: 88%

Section: Clusters Of Neuropsychiatric Symptomssupporting

confidence: 86%

Section: Clusters Of Neuropsychiatric Symptomsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neuropsychiatric Symptoms and Cognitive Impairment: Understanding the Importance of Co-Morbid Symptoms

Mortby

Burns

Eramudugolla

et al. 2017

JAD

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Dementia Subtypes Defined Through Neuropsychiatric Symptom–Associated Brain Connectivity Patterns

Zhao,

Xie,

Fonzo

et al. 2024

JAMA Netw Open

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ImportanceUnderstanding the heterogeneity of neuropsychiatric symptoms (NPSs) and associated brain abnormalities is essential for effective management and treatment of dementia.ObjectiveTo identify dementia subtypes with distinct functional connectivity associated with neuropsychiatric subsyndromes.Design, Setting, and ParticipantsUsing data from the Open Access Series of Imaging Studies-3 (OASIS-3; recruitment began in 2005) and Alzheimer Disease Neuroimaging Initiative (ADNI; recruitment began in 2004) databases, this cross-sectional study analyzed resting-state functional magnetic resonance imaging (fMRI) scans, clinical assessments, and neuropsychological measures of participants aged 42 to 95 years. The fMRI data were processed from July 2022 to February 2024, with secondary analysis conducted from August 2022 to March 2024. Participants without medical conditions or medical contraindications for MRI were recruited.Main Outcomes and MeasuresA multivariate sparse canonical correlation analysis was conducted to identify functional connectivity–informed NPS subsyndromes, including behavioral and anxiety subsyndromes. Subsequently, a clustering analysis was performed on obtained latent connectivity profiles to reveal neurophysiological subtypes, and differences in abnormal connectivity and phenotypic profiles between subtypes were examined.ResultsAmong 1098 participants in OASIS-3, 177 individuals who had fMRI and at least 1 NPS at baseline were included (78 female [44.1%]; median [IQR] age, 72 [67-78] years) as a discovery dataset. There were 2 neuropsychiatric subsyndromes identified: behavioral (r = 0.22; P = .002; P for permutation = .007) and anxiety (r = 0.19; P = .01; P for permutation = .006) subsyndromes from connectivity NPS–associated latent features. The behavioral subsyndrome was characterized by connections predominantly involving the default mode (within-network contribution by summed correlation coefficients = 54) and somatomotor (within-network contribution = 58) networks and NPSs involving nighttime behavior disturbance (R = −0.29; P &lt; .001), agitation (R = −0.28; P = .001), and apathy (R = −0.23; P = .007). The anxiety subsyndrome mainly consisted of connections involving the visual network (within-network contribution = 53) and anxiety-related NPSs (R = 0.36; P &lt; .001). By clustering individuals along these 2 subsyndrome-associated connectivity latent features, 3 subtypes were found (subtype 1: 45 participants; subtype 2: 43 participants; subtype 3: 66 participants). Patients with dementia of subtype 3 exhibited similar brain connectivity and cognitive behavior patterns to those of healthy individuals. However, patients with dementia of subtypes 1 and 2 had different dysfunctional connectivity profiles involving the frontoparietal control network (FPC) and somatomotor network (the difference by summed z values was 230 within the SMN and 173 between the SMN and FPC for subtype 1 and 473 between the SMN and visual network for subtype 2) compared with those of healthy individuals. These dysfunctional connectivity patterns were associated with differences in baseline dementia severity (eg, the median [IQR] of the total score of NPSs was 2 [2-7] for subtype 3 vs 6 [3-8] for subtype 1; P = .04 and 5.5 [3-11] for subtype 2; P = .03) and longitudinal progression of cognitive impairment and behavioral dysfunction (eg, the overall interaction association between time and subtypes to orientation was F = 4.88; P = .008; using the time × subtype 3 interaction item as the reference level: β = 0.05; t = 2.6 for time × subtype 2; P = .01). These findings were further validated using a replication dataset of 193 participants (127 female [65.8%]; median [IQR] age, 74 [69-77] years) consisting of 154 newly released participants from OASIS-3 and 39 participants from ADNI.Conclusions and RelevanceThese findings may provide a novel framework to disentangle the neuropsychiatric and brain functional heterogeneity of dementia, offering a promising avenue to improve clinical management and facilitate the timely development of targeted interventions for patients with dementia.

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Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal‐Dominant Alzheimer's Disease Colombia Trial

Ríos‐Romenets

Lopera

Sink³

et al. 2020

Alzheimer's & Dementia

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Introduction The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo‐controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60‐year‐old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non‐carriers who receive placebo. Methods Of the 252 enrolled, we present data on a total of 242 mutation carriers and non‐carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. Results We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non‐carriers, 30 to 53 years of age. Carriers were significantly younger than non‐carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. Discussion Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non‐carriers. Their demographic characteristics are representative of the local population.

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Behavioral and psychological subsyndromes in Alzheimer's disease using the Neuropsychiatric Inventory

Cited by 98 publications

References 40 publications

Neuropsychiatric Symptoms and Cognitive Impairment: Understanding the Importance of Co-Morbid Symptoms

Neuropsychiatric Symptoms and Cognitive Impairment: Understanding the Importance of Co-Morbid Symptoms

Dementia Subtypes Defined Through Neuropsychiatric Symptom–Associated Brain Connectivity Patterns

Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal‐Dominant Alzheimer's Disease Colombia Trial

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