Neuropsychiatric Subsyndromes Research Articles

Dementia Subtypes Defined Through Neuropsychiatric Symptom–Associated Brain Connectivity Patterns

Understanding the heterogeneity of neuropsychiatric symptoms (NPSs) and associated brain abnormalities is essential for effective management and treatment of dementia. To identify dementia subtypes with distinct functional connectivity associated with neuropsychiatric subsyndromes. Using 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. A 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. Among 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 < .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 < .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. These 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.

White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases

BackgroundNeuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases.MethodsFive hundred thirteen participants with one of these conditions, i.e. Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory – Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss.ResultsAlthough NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson’s disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities.ConclusionsIn participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.

Association of Cerebral Small Vessel Disease Burden with Neuropsychiatric Symptoms in Non-Demented Elderly: A Longitudinal Study.

The links between cerebral small vessel disease (CSVD) burden and neuropsychiatric symptoms (NPS) have not been fully studied. We aimed to explore the associations of the CSVD burden with Neuropsychiatric Inventory (NPI) total scores and its subsyndromes in the elderly without dementia. We investigated 630 non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. All of them had NPI assessments and 3 Tesla MRI scans at baseline and 616 had longitudinal NPI assessments during the follow-up. Linear mixed-effects models were used to investigate the cross-sectional and longitudinal associations of CSVD burden with NPI total scores and its subsyndromes. Higher CSVD burden longitudinally predicted more serious neuropsychiatric symptoms, including NPS (p &amp;lt; 0.0001), hyperactivity (p = 0.0006), affective symptoms (p = 0.0091), and apathy (p &amp;lt; 0.0001) in the total participants. Lacunar infarcts (LIs), white matter hyperactivities (WMHs), and cerebral microbleeds (CMBs) might play important roles in the occurrence of NPS, since they were longitudinally associated with specific neuropsychiatric subsyndromes. LIs contributed to hyperactivity (p = 0.0092), psychosis (p = 0.0402), affective symptoms (p = 0.0156), and apathy (p &amp;lt; 0.0001). WMHs were associated with hyperactivity (p = 0.0377) and apathy (p = 0.0343). However, CMBs were only related to apathy (p = 0.0141). CSVD burden was associated with multiple neuropsychiatric symptoms, suggesting the importance of monitoring and controlling vascular risk factors. Different markers of CSVD were associated with specific subsyndromes of NPS, suggesting that different markers tended to occur in different encephalic regions.

Neuropsychiatric symptoms and subsyndromes in patients with different stages of dementia in primary care follow-up (NeDEM project): a cross-sectional study

BackgroundThe objective was to describe the prevalence and intensity of neuropsychiatric symptoms (NPSs) isolated and grouped into subsyndromes in patients with dementia in primary care (PC) to analyse their distribution based on stages of dementia and the relationship between them and the intensity of symptoms.MethodsDesign: Cross-sectional study. Setting and population: Patients with dementia, not institutionalized, in a PC follow-up. Variables: Sociodemographic and clinical variables. Assessment instruments: The frequency and intensity of NPSs were measured with the Neuropsychiatric Inventory (NPI), and the stages of dementia with the Global Deterioration Scale (GDS). Statistical analysis: The number of NPSs per patient, the mean NPI value, and the prevalence and intensity of NPSs isolated and grouped into subsyndromes were calculated, as were their 95% confidence intervals (CIs). The analyses were performed on an overall basis and by GDS scores. To analyse the association between the NPI and GDS scores, multivariate analysis was performed with a generalized linear model.ResultsOverall, 98.4% (95% CI 94.5;99.8) of the patients presented some type of NPS, with an average of five symptoms per patient. The most frequent symptoms were apathy [69.8% (95% CI 61.1;77.5)], agitation [55.8% (95% CI 46.8;64.5)] and irritability [48.8% (95% CI 39.9;57.8)]. The more intense NPSs were apathy [NPI 3.2 (95% CI 2.5;3.8)] and agitation [NPI 3.2 (95% CI 2.5;4.0)]. For subsyndromes, hyperactivity predominated [86.0% (95% CI 78.8;91.5)], followed by apathy [77.5% (95% CI 69.3;84.4]). By phase of dementia, the most common isolated symptom was apathy (60.7–75.0%). Affective symptoms and irritability predominated in the initial stages, and psychotic symptoms predominated in advanced stages. The mean NPI score was 24.9 (95% CI 21.5;28.4) and increased from 15.6 (95% CI 8.2;23.1) for GDS 3 to 28.9 (95% CI 12.6;45.1) for GDS 7. Patients with in the most advanced stages of dementia presented an NPI score 7.6 (95% CI 6.8;8.3) points higher than the score for mild dementia with adjustment for the other variables.ConclusionsA high prevalence of NPSs was found among patients with dementia treated in PC. Symptoms change and increase in intensity as the disease progresses. Scales such as the NPI allow these symptoms to be identified, which may facilitate more stage-appropriate management.

Interactions of comorbid neuropsychiatric subsyndromes with neurodegenerative and cerebrovascular pathologies on cognition

Comorbid neuropsychiatric symptoms are commonly found in individuals with dementia and is likely influenced by a combination of neurodegenerative and cerebrovascular pathophysiology. We evaluated the associations of a validated composite MRI-based quantitative measure of both neurodegeneration (hippocampus volume and cortical thickness of AD-specific regions) and cerebrovascular disease (CeVD; white matter hyperintensities and infarcts) with neuropsychiatric subsyndromes, and their interactions on cognition in a community-based sample across the disease spectrum (N = 773). Lower composite MRI scores corresponding to greater comorbid neurodegeneration and CeVD burden were associated with hyperactivity (OR = 1.48) and apathy (OR = 1.90) subsyndromes. Lower MRI scores with concomitant hyperactivity was associated with greater cognitive impairment, especially in patients who were at least moderately impaired, while the interaction with apathy was not dependent on disease stage. These MRI scores interaction models resulted in a better fit than models consisting of neurodegeneration or CeVD alone. Integrating multiple biomarkers with specific, disease stage-dependent neuropsychiatric subsyndromes may provide a more holistic risk profile to facilitate the identification of individuals at the highest risk of disease progression.

Interaction of caregiver-expressed emotions and neuropsychiatric symptoms in persons with dementia: a longitudinal cohort study

ObjectivesNeuropsychiatric symptoms (NPS) have a major impact in persons with dementia (PwD). The interaction between the caregiver and the person with dementia may be related to the emergence of NPS....

Long-term neurobehavioral correlates of brain cortical microinfarcts in a memory clinic cohort in Singapore.

Cortical cerebral microinfarcts are a small vessel disease biomarker underlying cognitive impairment and dementia. However, it is unknown whether cortical cerebral microinfarcts are associated with neuropsychiatric disturbances, and whether its effects are independent of conventional small vessel disease markers. We investigated the associations of cortical cerebral microinfarcts burden with incidence and progression of neuropsychiatric subsyndromes in a memory clinic cohort of elderly in Singapore. In this prospective cohort, 496 subjects underwent detailed neuropsychological and clinical assessments, 3T brain MRI, and Neuropsychiatric Inventory assessment at baseline and two years later. Cortical cerebral microinfarcts and other small vessel disease markers, including white matter hyperintensities, lacunes, and microbleeds, were graded according to established criteria. Neuropsychiatric symptoms (NPS) were clustered into subsyndromes of hyperactivity, psychosis, affective, and apathy following prior findings. Functional decline was determined using the clinical dementia rating (CDR) scale. The presence of multiple cortical cerebral microinfarcts (≥2) was associated with higher total NPS scores (β = 4.19, 95% CI = 2.81-5.58, p < 0.001), particularly hyperactivity (β = 2.01, 95% CI = 1.30-2.71, p < 0.01) and apathy (β = 1.42, 95% CI = 0.65-2.18, p < 0.01) at baseline. Between baseline and year-2, multiple cortical cerebral microinfarcts were associated with accelerated progression in total NPS scores (β = 0.29, 95% CI = 0.06-0.53, p = 0.015), driven by hyperactivity (β = 0.45, 95% CI = 0.17-0.72, p < 0.01). Subjects with multiple cortical cerebral microinfarcts also had a faster functional decline, as measured with the CDR-sum-of-boxes scores, when accompanied with progression (β = 0.31, 95% CI = 0.11-0.51, p < 0.01) or hyperactivity in total NPS (β = 0.34, 95% CI = 0.13-0.56, p < 0.01). Cortical cerebral microinfarcts are associated with incidence and progression of geriatric neurobehavioral disturbances, independent of conventional small vessel disease markers. The impact of incident cortical cerebral microinfarcts on neurocognitive and neuropsychiatric trajectories warrants further investigations.

Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer\u2019s disease

BackgroundNeuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer’s disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic mutation. Hence, the study of DIAD mutation carriers enables the evaluation of the associations between pure AD pathophysiology and metabolic correlates of NPS without the confounding effects of co-existing pathologies. In this longitudinal study, we aimed to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation carriers.MethodsWe stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer’s Network according to their mutation carrier status. The interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q), age, and estimated years to symptom onset (EYO) as a function of metabolism measured by [18F]flurodeoxyglucose ([18F]FDG) positron emission tomography, were evaluated by the mixed-effects regression model with family-level random effects in DIAD mutation carriers and non-carriers. Exploratory factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q sub-components. Then the effects of interactions between specific neuropsychiatric subsyndromes and EYO on metabolism were evaluated with the mixed-effects regression model.ResultsA total of 119 mutation carriers and 102 non-carriers were studied. The interaction of higher NPI-Q and shorter EYO was associated with more rapid declines of global and regional [18F]FDG uptake in the posterior cingulate and ventromedial prefrontal cortices, the bilateral parietal lobes and the right insula in DIAD mutation carriers. The neuropsychiatric subsyndromes of agitation, disinhibition, irritability and depression interacted with the EYO to drive the [18F]FDG uptake decline in the DIAD mutation carriers. The interaction of NPI and EYO was not associated with [18F]FDG uptake in DIAD mutation non-carriers.ConclusionsThe NPS in cognitively intact DIAD mutation carriers may be a clinical indicator of subsequent metabolic decline in brain networks vulnerable to AD, which supports the emerging conceptual framework that NPS represent early manifestations of neuronal injury in AD. Further studies using different methodological approaches to identify NPS in preclinical AD are needed to validate our findings.

Correction: The course of neuropsychiatric symptoms in nursing home residents from admission to 30-month follow-up.

[This corrects the article DOI: 10.1371/journal.pone.0206147.].

The course of neuropsychiatric symptoms in nursing home residents from admission to 30-month follow-up.

AimThe aim of this study was to describe the prevalence and persistence of clinically significant neuropsychiatric symptoms (NPS) in nursing home residents with dementia, and to study the association between severity of dementia and specific neuropsychiatric sub-syndromes over time.MethodsIn total, 583 residents with dementia were included at admission to a nursing home and followed with biannual assessments until death, or to 30-month follow-up. At the end of the 30-month follow-up, 305 participants had died and 57 had left the study for other reasons, leaving 221 residents in the study. We collected data on demographics, cognition, severity of dementia, NPS, personal activities of daily living (P-ADL), physical health, medication and type of nursing home unit. NPS was assessed using the Neuropsychiatric Inventory (NPI), the Nursing Home version.ResultsThe prevalence and persistence at two consecutive time-points of clinically significant NPS was high during the study period. The mean NPI agitation sub-syndrome score increased during the study period, while the NPI affective and psychosis sub-syndrome scores remained unchanged. More severe dementia was associated with higher NPI agitation, psychosis and affective sub-syndrome scores. The association remained unchanged over time for agitation and psychosis. For the NPI affective sub-syndrome, the association was stronger at the beginning, and declined towards the end of the study period.ConclusionThe findings of high prevalence and persistence at two consecutive time points of clinically significant NPS over time, and the associations between severity of dementia and NPI sub-syndromes shed light on the burden and care needs of nursing home residents with dementia after admission to nursing home care. This information is of interest to health care planners and providers to enable them to increase the quality of care for nursing home residents.

The stability of neuropsychiatric subsyndromes in Alzheimer's disease

IntroductionNeuropsychiatric symptoms are common in Alzheimer's disease. Previous research has attempted to identify subsyndromes—sets of symptoms related to one another—to clarify underlying mechanisms and treatment targets. We examined the stability of these subsyndromes over time. MethodsWe administered the Neuropsychiatric Inventory annually for 3 years to 447 patients with Alzheimer's disease recruited from memory clinics. We conducted principal component analyses at each time point and multiple-group confirmatory factor analyses across time. ResultsPrincipal component analyses showed that no two time points shared the same factor structure. Factor solutions did not exhibit strong simple structures and substantial cross-loadings were common. Confirmatory analysis revealed significant differences in factor loadings and model fit over time. DiscussionSymptoms cannot be neatly partitioned into discrete clusters that are stable over time. The findings highlight the significant challenges that clinicians and caregivers face and may help explain the lack of success in intervention studies.

Neuropsychiatric subsyndromes and brain metabolic network dysfunctions in early onset Alzheimer's disease.

Neuropsychiatric symptoms (NPSs) often occur in early-age-of-onset Alzheimer's disease (EOAD) and cluster into sub-syndromes (SSy). The aim of this study was to investigate the association between 18 F-FDG-PET regional and connectivity-based brain metabolic dysfunctions and neuropsychiatric SSy. NPSs were assessed in 27 EOAD using the Neuropsychiatric Inventory and further clustered into four SSy (apathetic, hyperactivity, affective, and psychotic SSy). Eighty-five percent of EOAD showed at least one NPS. Voxel-wise correlations between SSy scores and brain glucose metabolism (assessed with 18 F-FDG positron emission tomography) were studied. Interregional correlation analysis was used to explore metabolic connectivity in the salience (aSN) and default mode networks (DMN) in a larger sample of EOAD (N = 51) and Healthy Controls (N = 57). The apathetic, hyperactivity, and affective SSy were highly prevalent (>60%) as compared to the psychotic SSy (33%). The hyperactivity SSy scores were associated with increase of glucose metabolism in frontal and limbic structures, implicated in behavioral control. A comparable positive correlation with part of the same network was found for the affective SSy scores. On the other hand, the apathetic SSy scores were negatively correlated with metabolism in the bilateral orbitofrontal and dorsolateral frontal cortex known to be involved in motivation and decision-making processes. Consistent with these SSy regional correlations with brain metabolic dysfunction, the connectivity analysis showed increases in the aSN and decreases in the DMN. Behavioral abnormalities in EOAD are associated with specific dysfunctional changes in brain metabolic activity, in particular in the aSN that seems to play a crucial role in NPSs in EOAD. Hum Brain Mapp 37:4234-4247, 2016. © 2016 Wiley Periodicals, Inc.

Association of neuropsychiatric symptoms and sub-syndromes with cognitive impairment in community-dwelling Asian elderly.

To investigate the presence of neuropsychiatric symptoms (NPS) and sub-syndromes in elderly community-dwelling Asians with varying severity of cognitive impairment. Chinese and Malay participants (n = 613) from the Epidemiology of Dementia in Singapore (EDIS) Study aged ≥ 60 years underwent clinical examination, neuropsychological testing, and NPS assessment using the Neuropsychiatric Inventory (NPI). Diagnosis of no cognitive impairment (NCI), cognitive impairment-no dementia (CIND), including CIND-mild and CIND-moderate, and dementia were made using established criteria. A significant increase in the numbers of NPS was observed accompanying with increasing severity of cognitive impairment (p < 0.001). Compared to those with NCI/CIND-mild, participants with CIND-moderate [Odds ratio (OR): 4.2, 95% confidence interval (CI): 1.8-10.0] or dementia [OR: 9.2, 95% CI: 2.3-36.0] were more likely to have two or more neuropsychiatric sub-syndromes. Participants with CIND-moderate were more likely to have hyperactivity [OR: 2.0, 95% CI: 1.0-3.8] and apathy [OR: 2.9, 95% CI: 1.0-8.4] sub-syndromes, whereas patients with dementia were more likely to have psychosis [OR: 6.9, 95% CI: 2.4-20.1], affective (OR: 8.7, 95% CI: 1.8-42.9), and hyperactivity (OR: 5.4, 95% CI: 1.8-16.1). Furthermore, executive dysfunction and visual memory impairment were associated with the presence of three neuropsychiatric sub-syndromes; whist language and visuomotor speed impairment were related to the presence of two sub-syndromes. By contrast, impairment in attention, verbal memory, and visuoconstruction were not associated with any of the sub-syndromes. The presence of NPS and sub-syndromes increase with increasing severities of cognitive impairment, and different neuropsychiatric syndromes are associated with specific impairment on cognitive domains in community-dwelling Asian elderly.

Neuropsychiatric sub-syndromes over time: A three-year longitudinal study

Neuropsychiatric sub-syndromes over time: A three-year longitudinal study

Changes in neuropsychiatric subsyndromes in long-term care residents with dementia across the circadian cycle

Changes in neuropsychiatric subsyndromes in long-term care residents with dementia across the circadian cycle

Neuropsychiatric Symptoms in Elderly Inpatients: A Multicenter Cross-Sectional Study

Background/Aims: We determined the prevalence of neuropsychiatric symptoms in geriatric rehabilitation patients to compare neuropsychiatric symptoms between patients with and without dementia, and to evaluate associations linking severity of cognitive impairment and neuropsychiatric symptoms. Methods: In February 2009, we studied patients aged 75 years or older who had been admitted to four geriatric rehabilitation units in the Paris area. The twelve Neuropsychiatric Inventory items and four neuropsychiatric subsyndromes defined by the European Alzheimer's Disease Consortium were evaluated. Results: Of the 194 patients, 149 (76.8%) had dementia, and 154 (79.4%) had exhibited at least one neuropsychiatric symptom during the past week. Agitation was the most common neuropsychiatric symptom in the group with dementia (36.9%) and depression in the group without dementia (35.6%). The dementia group had significantly higher prevalences of hyperactivity (p < 0.001) and delusions (p = 0.01) than the non-dementia group. In the dementia group, severity of cognitive impairment was associated with hyperactivity (p = 0.01) and psychosis (p = 0.02). Conclusion: The prevalence of neuropsychiatric symptoms among geriatric rehabilitation patients was high but not higher than in elderly outpatients.

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

Behavioral and psychological symptoms of dementia represent common clinical features of dementias, contributing to the heterogeneous phenotypic expression of Alzheimer's disease (AD). During the last two decades, several studies explored the possible presence of neuropsychiatric subsyndromes in dementia by examining the internal structure of the Neuropsychiatric Inventory (NPI). The aim of the present review is to present available evidence coming from studies adopting factor analysis to explore the NPI and describe neuropsychiatric clusters of symptoms in AD. A systematic review of literature was performed concerning available studies describing neuropsychiatric subsyndromes in AD by adopting the NPI. Overall, our analysis showed a relatively low concordance among available evidence for what concerns the definition and composition of NPI clusters, possibly due (at least in part) to the heterogeneity of the sample populations recruited in the studies. However, we also observed some consistent associations of specific symptoms across studies, defining potential subsyndromes in AD. More consistent results were obtained by studies evaluating the 10-item version of the NPI rather than the more recent 12-item one. This review represents the first attempt to systematically evaluate evidence coming from factor analyses exploring the internal structure of the NPI in order to facilitate the identification of neuropsychiatric syndromes in AD patients. The NPI may support the definition of behavioral subsyndromes in AD. The evaluation of neuropsychiatric subsyndromes should always take into account the main potential confounders, such as age, severity of disease, and concomitant pharmacological treatment.

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

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. 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. 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. 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.

Investigating the stability of neuropsychiatric sub‐syndromes with progression of dementia: a 2‐year prospective study

Previous studies have identified sub-syndromes of behavioral and psychological symptoms of dementia. But because of their cross-sectional design, the stability of these sub-syndromes over time remains unknown. Behavioral and psychological symptoms of dementia of 84 participants (out of an original sample of 144 patients) with Alzheimer's disease and vascular dementia were assessed by using the Neuropsychiatric Inventory every six months for two years. Principal component factor analysis with Varimax rotation was used to detect neuropsychiatric sub-syndromes at each time point. The 12 symptoms were reduced to four factors at baseline, 12, 18, and 24 months and three factors at six months. None of the factor structures matched the four sub-syndromes previously identified by studies. The most stable group of symptoms were a combination of "psychosis" and "hyperactivity" symptoms (delusions, hallucinations, irritability, agitation), which became stable at 18 months. The pattern of behavioral and psychological symptoms of dementia sub-syndromes over time has not been studied before, and this research suggests that some stability is evident particularly during the later stages of the disease process. These findings have implications for patients and their caregiver.

Stability of the factor structure of the Neuropsychiatric Inventory in a 31-month follow-up study of a large sample of nursing-home patients with dementia

Neuropsychiatric symptoms (NPS) are highly prevalent among nursing home patients with dementia. Several studies have investigated subsyndromes of NPS but the stability of these subsyndromes over time has rarely been examined. We have examined the stability over time of the factor structure of the Neuropsychiatric Inventory-Nursing Home version (NPI-NH) in a large sample of nursing-home patients with dementia. Nursing-home patients with dementia were assessed with the NPI-NH at baseline (n = 895), and at 12-month (n = 592) and 31-month (n = 278) follow-up assessments, giving three partly overlapping samples. Exploratory factor analysis was done to investigate neuropsychiatric subsyndromes of the NPI-NH at each assessment in these samples. Three- or four-factor solutions were found, termed agitation, psychosis, apathy, and affective symptoms. Depression and anxiety (affective), delusion and hallucination (psychosis), and agitation and irritability (agitation) were the symptoms that most often co-occurred in the same factor. Apathy did not load together with affective symptoms at any of the assessments. Subsyndromes of the NPI-NH are relatively stable over 31-month follow-up assessments in nursing-home patients with dementia, indicating that these subsyndromes may be useful for following the natural course of symptoms as well as observing the effect of interventions. Our findings lend support to the distinction between apathy and affective symptoms, which may have important clinical implications.