The Truth behind the Zeros: A New Approach to Principal Component Analysis of the Neuropsychiatric Inventory

Hellton, Kristoffer H.; Cummings, Jeffrey L.; Vik‐Mo, Audun Osland; Nordrehaug, Jan Erik; Aarsland, Dag; Selbæk, Geir; Giil, Lasse Melvær

doi:10.1080/00273171.2020.1736976

Cited by 11 publications

(14 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…by multiplying the severity score of 0 to 3 by the frequency score of 0 to 4 so that the values 5, 7, 10 and 11 cannot be observed. 49, 50 Using symptom-specific instruments such as the Apathy Evaluation Scale (score range 18– 71), Cohen-Mansfield Agitation Inventory (score range 29–203), and Geriatric Depression Scale (score range 0–30) may not only help to fully characterize specific NPS, but also enables the use of statisical modelling due to a larger variation in potential scores compared to the NPI.…”

Section: Discussionmentioning

confidence: 99%

Neuropsychiatric and cognitive symptoms across the Alzheimer’s disease clinical spectrum: Cross-sectional and longitudinal associations

Eikelboom

Berg

Singleton

et al. 2021

Preprint

View full text Add to dashboard Cite

Objective: To investigate the prevalence and trajectories of neuropsychiatric symptoms (NPS) in relation to cognitive functioning in a cohort of amyloid-β positive individuals across the Alzheimer's disease (AD) clinical spectrum. Methods: We included 1,524 amyloid-β positive individuals from the Amsterdam Dementia Cohort with subjective cognitive decline (SCD, n=113), mild cognitive impairment (MCI, n=321), or dementia (n=1,090). We measured NPS with the neuropsychiatric inventory (NPI), examining total scores and the presence of specific NPI-items. Cognition was assessed across five cognitive domains and with the MMSE. We examined trajectories including model based trends for NPS and cognitive functioning over time. We used linear mixed models to relate baseline NPI scores to cognitive functioning at baseline (whole-sample) and longitudinal time-points (subsample n=520, Mean=1.8 [SD=0.7] years follow-up). Results: NPS were prevalent across all clinical AD stages (NPI total score ≥1 81.4% in SCD, 81.2% in MCI, 88.7% in dementia). Cognitive functioning showed an uniform gradual decline; while in contrast, large intra-individual heterogeneity of NPS was observed over time across all groups. At baseline, we found associations between NPS and cognition in dementia that were most pronounced for NPI total scores and MMSE (range β:-0.18—0.11, FDR-adjusted p<0.05), while there were no cross-sectional relationships in SCD and MCI (β:-0.32—0.36, FDR-adjusted p>0.05). There were no associations between baseline NPS and cognitive functioning over time in any clinical stage (β:-0.13—0.44, FDR-adjusted p>0.05). Conclusion: NPS and cognitive symptoms are both prevalent across the AD continuum, but show a different evolution during the course of the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuropsychiatric and cognitive symptoms across the Alzheimer’s disease clinical spectrum: Cross-sectional and longitudinal associations

Eikelboom

Berg

Singleton

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, a systemic review has found a relatively low concordance of the composition of NPI clusters among available evidence although some consistent associations of specific symptoms defining potential subsyndromes in AD across studies had been observed [56]. Acknowledging this limitation, a novel version of principal component analysis that mitigates excessive floor effects in NPI scores has been developed for more robust identification of neurobehavioral subsyndromes [57]. Therefore, future studies could use this approach to test the replicability of the associations between neurobehavioral subsyndromes and metabolic decline reported in this study.…”

Section: Discussionmentioning

confidence: 99%

Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer’s disease

Pascoal

Mathotaarachchi

et al. 2021

Transl Neurodegener

View full text Add to dashboard Cite

Background Neuropsychiatric 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. Methods We 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. Results A 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. Conclusions The 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.

show abstract

“…Furthermore, a systemic review found a relatively low concordance of the composition of NPI clusters among available evidence although some consistent associations of speci c symptoms de ning potential subsyndromes in AD across studies had been observed [57]. Acknowledging the limitations of studying NPI subsyndromes using principal component analysis (PCA), a novel version of PCA has been developed for a more robust factor analysis of the NPI [58]. Therefore, future studies will need to con rm these associations between the NPI-Q subsyndromes with metabolic decline in a separate cohort using a more robust factor analysis.…”

Section: Discussionmentioning

confidence: 99%

Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer’s disease

Pascoal

Mathotaarachchi

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Neuropsychiatric 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 aim to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation carriers. Methods We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer’s Network according to their mutation carrier status. Regression mixed effect models with family-level random effects evaluated the interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q), age and estimated years of onset (EYO) as a function of metabolism measured by [ 18 F]flurodeoxyglucose ([ 18 F]FDG) positron emission tomography in DIAD mutation and non-mutation carriers. An exploratory factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q sub-components. Regression mixed effect models then evaluated the interactions of specific neuropsychiatric subsyndromes with EYO on metabolism.Results 119 mutation and 102 non-mutation carriers were studied. The interaction of higher NPI-Q and shorter EYO was associated with more rapid global and regional [ 18 F]FDG uptake decline in the posterior cingulate and ventromedial prefrontal cortices, bilateral parietal lobes and right insula in DIAD mutation carriers. The neuropsychiatric subsyndrome of agitation, disinhibition, irritability and depression interacted with EYO to drive [ 18 F]FDG uptake decline in the DIAD mutation carriers. The interaction of NPI and EYO was not associated with [ 18 F]FDG uptake in DIAD non-mutation carriers. Conclusions NPS in cognitively intact DIAD mutation carriers may be clinical indicators of subsequent metabolic decline in brain networks vulnerable to AD, which support 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.

show abstract

The Truth behind the Zeros: A New Approach to Principal Component Analysis of the Neuropsychiatric Inventory

Cited by 11 publications

References 49 publications

Neuropsychiatric and cognitive symptoms across the Alzheimer’s disease clinical spectrum: Cross-sectional and longitudinal associations

Neuropsychiatric and cognitive symptoms across the Alzheimer’s disease clinical spectrum: Cross-sectional and longitudinal associations

Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer’s disease

Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer’s disease

Contact Info

Product

Resources

About