Apolipoprotein E and affective symptoms in mild cognitive impairment and Alzheimer’s disease dementia: A systematic review and meta-analysis

Banning, Leonie C.P.; Ramakers, Inez H.G.B.; Deckers, Kay; Verhey, Frans R.J.; Aalten, Pauline

doi:10.1016/j.neubiorev.2018.11.020

Cited by 21 publications

(22 citation statements)

References 86 publications

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“…Heritability of psychotic symptoms in AD is estimated to be up to 61% 34 , and, in fact, it has been postulated that AD with psychosis could be considered a specific phenotype with a genetic basis 35 . However, in cognitively impaired subjects, and as it was previously reported, associations between NPS and APOE ɛ4 are unclear 2 . Beyond APOE, although it has been demonstrated that that sortilin-related receptor 1 gene (SORL1) and the ATP-binding cassette, subfamily A, member 7 gene (ABCA7) are associated with AD, the connection of these high-risk genes with NPS occurrence has to be also considered inconclusive 36 .…”

Section: Discussionmentioning

confidence: 94%

“…Our data demonstrate a synergistic effect of depression, apathy, anxiety, agitation, appetite and irritability, and a positive ε4 carrier status. These significant results are particularly relevant because there is no previous evidence, according to meta-analytical approaches, that the APOE ɛ4 genotype and behavioral symptoms are associated in MCI patients, except in the case of anxiety, where a differential distribution of the symptom seems to be associated to the APOE ε4 condition 2 . Interestingly, all these observations are concordant with our study's conclusions.…”

Section: Discussionmentioning

confidence: 96%

“…As MCI is considered an intermediated diagnosis between normal cognition and dementia, much effort has been dedicated to the identification of those individuals with MCI with a higher vulnerability of conversion to dementia. The study of the simultaneous effect of neuropsychiatric symptoms and genes is increasing its interest in recent years 2 . Considering that a susceptibility condition can be better explained by the confluence of a behavioral status and the effect of one or more genes, the main idea is to highlight the relevance of gene–behavioral interactions.…”

Section: Introductionmentioning

confidence: 99%

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

Valero

Marquié

Rojas

et al. 2020

Sci Rep

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To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3–2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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

Valero

Marquié

Rojas

et al. 2020

Sci Rep

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“…Common and rare variants of L3MBTL2 are associated with AD. mRNA expression levels of SORCS3 and OAT are differentially expressed in AD brain tissues, and 13 MDD risk genes may interact with core AD genes such as HACE1, NEGR1, and SLC6A15 [223].…”

Section: Depressive Disordersmentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6–10 drugs/day with the consequent risk for drug–drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 geno-phenotypes are involved in the metabolism of over 90% of drugs currently used in patients with dementia, and only 20% of the population is an extensive metabolizer for this tetragenic cluster. ADRs associated with anti-dementia drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, and antiepileptic drugs can be minimized by means of pharmacogenetic screening prior to treatment. These drugs are substrates, inhibitors, or inducers of 58, 37, and 42 enzyme/protein gene products, respectively, and are transported by 40 different protein transporters. APOE is the reference gene in most pharmacogenetic studies. APOE-3 carriers are the best responders and APOE-4 carriers are the worst responders; likewise, CYP2D6-normal metabolizers are the best responders and CYP2D6-poor metabolizers are the worst responders. The incorporation of pharmacogenomic strategies for a personalized treatment in dementia is an effective option to optimize limited therapeutic resources and to reduce unwanted side-effects.

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“…AD is characterized by severe atrophy of the brain, resulting in a progressive loss of neurons, both in number and mass [ 3 ]. The inter-neuronal communication is hampered due to impaired and disrupted electric impulses in the brain, causing dementia and other behavioral alterations [ 5 , 6 ]. This progressive disorder is characterized by gradual elevation in the occurrence of signs and symptoms associated with it, when passing from the initial stage to the next [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-β Cascade in Alzheimer’s Disease

Behl

Kaur

Frățilă

et al. 2020

IJMS

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One of the most commonly occurring neurodegenerative disorders, Alzheimer’s disease (AD), encompasses the loss of cognitive and memory potential, impaired learning, dementia and behavioral defects, and has been prevalent since the 1900s. The accelerating occurrence of AD is expected to reach 65.7 million by 2030. The disease results in neural atrophy and disrupted inter-neuronal connections. Amongst multiple AD pathogenesis hypotheses, the amyloid beta (Aβ) cascade is the most relevant and accepted form of the hypothesis, which suggests that Aβ monomers are formed as a result of the cleavage of amyloid precursor protein (APP), followed by the conversion of these monomers to toxic oligomers, which in turn develop β-sheets, fibrils and plaques. The review targets the events in the amyloid hypothesis and elaborates suitable therapeutic agents that function by hindering the steps of plaque formation and lowering Aβ levels in the brain. The authors discuss treatment possibilities, including the inhibition of β- and γ-secretase-mediated enzymatic cleavage of APP, the immune response generating active immunotherapy and passive immunotherapeutic approaches targeting monoclonal antibodies towards Aβ aggregates, the removal of amyloid aggregates by the activation of enzymatic pathways or the regulation of Aβ circulation, glucagon-like peptide-1 (GLP-1)-mediated curbed accumulation and the neurotoxic potential of Aβ aggregates, bapineuzumab-mediated vascular permeability alterations, statin-mediated Aβ peptide degradation, the potential role of ibuprofen and the significance of natural drugs and dyes in hindering the amyloid cascade events. Thus, the authors aim to highlight the treatment perspective, targeting the amyloid hypothesis, while simultaneously emphasizing the need to conduct further investigations, in order to provide an opportunity to neurologists to develop novel and reliable treatment therapies for the retardation of AD progression.

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Apolipoprotein E and affective symptoms in mild cognitive impairment and Alzheimer’s disease dementia: A systematic review and meta-analysis

Cited by 21 publications

References 86 publications

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

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

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-β Cascade in Alzheimer’s Disease

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