Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic

Valero, Sergi; Marquié, Marta; Rojas, Itziar de; Espinosa, Ana; Moreno‐Grau, Sonia; Orellana, Adelina; Montrreal, Laura; Hernández, Isabel; Mauleón, Ana; Rosende-Roca, Maiteé; Alegret, Montserrat; Pérez‐Cordón, Alba; Ortega, Gemma; Roberto, Natalia; Sanabria, Ángela; Abdelnour, Carla; Gil, Silvia; Tartari, Juan Pablo; Vargas, Liliana; Antonio, Ester Esteban‐De; Benaque, Alba; Tárraga, Lluís; Boada, Merçé; Ruiz, Agustín

doi:10.1038/s41598-020-77023-z

Cited by 14 publications

(24 citation statements)

References 38 publications

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“…In a search of profiles of clustered symptoms that could serve as markers of disease progression in early stages, NPS would act as early clinical manifestations of an emergent process of neurodegeneration ( Gallagher et al, 2017 ). In particular, affective NPS (depression, apathy, anxiety and irritability) were associated with a more rapid progression to AD in older adults with MCI ( Jang et al, 2020 ), and those have also even shown synergic effects with the APOE ε4-allele ( Valero et al, 2020 ). Recently, some attempts have been made to investigate grouped NPS as possible predictors of cognitive decline along the progression of MCI toward dementia ( Palmer et al, 2007 ; Edwards et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment

Roberto¹,

Portella²,

Marquié³

et al. 2021

Front. Aging Neurosci.

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Introduction: Mild cognitive impairment is often associated with affective and other neuropsychiatric symptoms (NPS). This co-occurrence might have a relevant impact on disease progression, from MCI to dementia.Objective: The aim of this study was to explore the trajectories of cognitive decline in an MCI sample from a memory clinic, taking into consideration a perspective of isolated cognitive functions and based on NPS clusters, accounting for the different comorbid symptoms collected at their baseline visit.Methods: A total of 2,137 MCI patients were monitored over a 2.4-year period. Four clusters of NPS (i.e., Irritability, Apathy, Anxiety/Depression and Asymptomatic) were used to run linear mixed models to explore the interaction of cluster with time on cognitive trajectories using a comprehensive neuropsychological battery (NBACE) administered at baseline and at the three subsequent follow-ups.Results: A significant interaction between cluster and time in cognitive decline was found when verbal learning and cued-recall were explored (p = 0.002 for both memory functions). For verbal learning, the Irritability cluster had the largest effect size (0.69), whereas the Asymptomatic cluster showed the smallest effect size (0.22). For cued-recall, the Irritability cluster had the largest effect size among groups (0.64), and Anxiety/Depression had the smallest effect size (0.21).Conclusions: In MCI patients, the Irritability and Apathy NPS clusters shared similar patterns of worsening in memory functioning, which could point to these NPS as risk factors of a faster cognitive decline, acting as early prognostic markers and helping in the diagnostic process.

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Section: Introductionmentioning

confidence: 99%

Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment

Roberto¹,

Portella²,

Marquié³

et al. 2021

Front. Aging Neurosci.

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“…Studies in MCI have examined such interactions, finding that co‐occurrence of APOE ɛ4 and apathy posed the greatest risk for incident dementia. 29 , 30 While concomitance of the aforementioned risk marker is associated with greater dementia risk, a systematic review and meta‐analysis investigating the relationship between APOE and affective symptoms in MCI and AD dementia found no evidence that APOE ɛ4 carriership is associated with the presence of apathy. 31 The lack of an association may be the result of capturing apathy with more liberal conventional approaches versus the more conservative MBI approach used for our study.…”

Section: Discussionmentioning

confidence: 99%

“…Until present, little was known about the interaction between APOE genotype and NPS in determining risk, especially in NC. Studies in MCI have examined such interactions, finding that co‐occurrence of APOE ɛ4 and apathy posed the greatest risk for incident dementia 29,30 . While concomitance of the aforementioned risk marker is associated with greater dementia risk, a systematic review and meta‐analysis investigating the relationship between APOE and affective symptoms in MCI and AD dementia found no evidence that APOE ɛ4 carriership is associated with the presence of apathy 31 .…”

Section: Discussionmentioning

confidence: 99%

Apathy and APOE in mild behavioral impairment, and risk for incident dementia

Vellone

Ghahremani

Goodarzi

et al. 2022

A&D Transl Res & Clin Interv

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Introduction Mild behavioral impairment (MBI) is a high‐risk state for incident dementia and comprises five core domains including affective dysregulation, impulse dyscontrol, social inappropriateness, psychotic symptoms, and apathy. Apathy is among the most common neuropsychiatric symptoms (NPS) in dementia but can also develop in persons with normal cognition (NC) or mild cognitive impairment (MCI). The later‐life emergence and persistence of apathy as part of the MBI syndrome may be a driving factor for dementia risk. Therefore, we investigated MBI‐apathy–associated progression to dementia, and effect modification by sex, race, cognitive diagnosis, and apolipoprotein E ( APOE ) genotype. Methods Dementia‐free National Alzheimer's Coordinating Center participants were stratified by persistent apathy status, based on Neuropsychiatric Inventory (NPI)–Questionnaire scores at two consecutive visits. Hazard ratios (HRs) for incident dementia for MBI‐apathy and NPI‐apathy relative to no NPS, and MBI‐apathy relative to no apathy, were determined using Cox proportional hazards regressions, adjusted for baseline age, sex, years of education, race, cognitive diagnosis, and APOE genotype. Interactions with relevant model covariates were explored. Results Of the 3932 participants (3247 with NC), 354 had MBI‐apathy. Of all analytic groups, MBI‐apathy had the greatest dementia incidence (HR = 2.69, 95% confidence interval [CI]: 2.15–3.36, P < 0.001). Interaction effects were observed between cognitive diagnosis and APOE genotype with the NPS group. The contribution of apathy to dementia risk was greater in NC (HR = 5.91, 95% CI: 3.91–8.93) than in MCI (HR = 2.16, 95% CI: 1.69–2.77, interaction P < 0.001) and in all APOE genotypes, was greatest in APOE ɛ3 (HR = 4.25, 95% CI: 3.1–5.82, interaction P < 0.001). Discussion Individuals with MBI‐apathy have a markedly elevated risk for future dementia, especially when symptoms emerge in those with NC. Both cognitive status and APOE genotype are important moderators in the relationship between MBI‐apathy and incident dementia. MBI‐apathy may represent a group in whom apathy is a preclinical or prodromal manifestation of dementia and identify a precision medicine target for preventative interventions.

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“…Additive interactions were obtained for depression, apathy, anxiety, agitation, appetite, or irritability and positive ε4 carrier status, which significantly increased the risk ratio for dementia. A combination of behavioral status and genetic trait could be considered to identify subjects with MCI most likely to progress to dementia [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Positive Effect of Cognitive Training in Older Adults with Different APOE Genotypes and COVID-19 History: A 1-Year Follow-Up Cohort Study

et al. 2022

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(1) Background: Older people suffer from cognitive decline; several risk factors contribute to greater cognitive decline. We used acquired (COVID-19 infection) and non-modifiable (presence of APOE rs429358 and rs7412 polymorphisms) factors to study the progression of subjective cognitive impairment while observing patients for one year. Cognitive training was used as a protective factor. (2) Methods: Two groups of subjects over the age of 65 participated in the study: group with subjective cognitive decline receiving cognitive training and individuals who did not complain of cognitive decline without receiving cognitive training (comparison group). On the first visit, the concentration of antibodies to COVID-19 and APOE genotype was measured. At the first and last point (1 year later) the Mini-Mental State Examination scale and the Hospital Anxiety and Depression Scale were performed. (3) Results: COVID-19 infection did not affect cognitive function. A significant role of cognitive training in improving cognitive functions was revealed. Older adults with APOE-ε4 genotype showed no positive effect of cognitive training. (4) Conclusions: Future research should focus on cognitive dysfunction after COVID-19 in long-term follow-up. Attention to the factors discussed in our article, but not limited to them, are useful for a personalized approach to maintaining the cognitive health of older adults.

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Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic

Cited by 14 publications

References 38 publications

Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment

Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment

Apathy and APOE in mild behavioral impairment, and risk for incident dementia

Positive Effect of Cognitive Training in Older Adults with Different APOE Genotypes and COVID-19 History: A 1-Year Follow-Up Cohort Study

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