Metabolic correlates of reserve and resilience in MCI due to Alzheimer

Alzheimer's Research & Therapy, Apr 2018

Matteo Bauckneht, Andrea Chincarini, Roberta Piva, Dario Arnaldi, Nicola Girtler, Federico Massa, Matteo Pardini, Matteo Grazzini, Hulya Efeturk, Marco Pagani, et al.

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Metabolic correlates of reserve and resilience in MCI due to Alzheimer

Bauckneht et al. Alzheimer's Research & Therapy Metabolic correlates of reserve and resilience in MCI due to Alzheimer's Disease (AD) Matteo Bauckneht 0 1 Andrea Chincarini Roberta Piva 0 1 Dario Arnaldi Nicola Girtler Federico Massa Matteo Pardini Matteo Grazzini Hulya Efeturk 0 1 Marco Pagani Gianmario Sambuceti 0 1 Flavio Nobili Silvia Morbelli 0 1 0 Nuclear Medicine Unit, Polyclinic San Martino Hospital , Genoa , Italy 1 Department of Health Sciences (DISSAL), University of Genoa , Genoa , Italy Background: We explored the presence of both reserve and resilience in late-converter mild cognitive impairment due to Alzheimer's disease (MCI-AD) and in patients with slowly progressing amyloid-positive MCI by assessing the topography and extent of neurodegeneration with respect to both “aggressive” and typically progressing phenotypes and in the whole group of patients with MCI, grounding the stratification on education level. Methods: We analyzed 94 patients with MCI-AD followed until conversion to dementia and 39 patients with MCI who had brain amyloidosis (AMY+ MCI), all with available baseline 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) results. Using a data-driven approach based on conversion time, patients with MCI-AD were divided into typical AD and late-converter subgroups. Similarly, on the basis of annual rate of Mini Mental State Examination score reduction, AMY+ MCI group was divided, obtaining smoldering (first tertile) and aggressive (third tertile) subgroups. Finally, we divided the whole group (MCI-AD and AMY+ MCI) according to years of schooling, obtaining four subgroups: poorly educated (Low-EDUC; first quartile), patients with average education (Average-EDUC; second quartile), highly educated (High-EDUC; third quartile), and exceptionally educated (Except-EDUC; fourth quartile). FDG-PET of typical AD, late converters, and aggressive and smoldering AMY+ MCI subgroups, as well as education level-based subgroups, were compared with healthy volunteer control subjects (CTR) and within each group using a two-samples t test design (SPM8; p < 0.05 family-wise error-corrected). Results: Late converters were characterized by relatively preserved metabolism in the right middle temporal gyrus (Brodmann area [BA] 21) and in the left orbitofrontal cortex (BA 47) with respect to typical AD. When compared with CTR, the High-EDUC subgroup demonstrated a more extended bilateral hypometabolism in the posterior parietal cortex, posterior cingulate cortex, and precuneus than the Low- and Average-EDUC subgroups expressing the same level of cognitive impairment. The Except-EDUC subgroup showed a cluster of significant hypometabolism including only the left posterior parietal cortex (larger than the Low- and Average-EDUC subgroups but not further extended with respect to the High-EDUC subgroup). Conclusions: Middle and inferior temporal gyri may represent sites of resilience rather than a hallmark of a more aggressive pattern (when hypometabolic). These findings thus support the existence of a relatively homogeneous AD progression pattern of hypometabolism despite AD heterogeneity and interference of cognitive reserve. In fact, cortical regions whose “metabolic resistance” was associated with slower clinical progression had different localization with respect to the regions affected by education-related reserve. 18F-FDG PET; Alzheimer's disease; Mild cognitive impairment; Cognitive Reserve; Resilience - Background 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (MRI) have been demonstrated to reflect cognitive function and are considered progression biomarkers in patients with Alzheimer’s disease (AD) [ 1 ]. Moreover, given their capability to demonstrate neurodegeneration in vivo, both FDG-PET and MRI have significantly contributed to the understanding of cognitive reserverelated adaptive mechanisms [ 2–4 ]. In fact, given a particular level of imaging-assessed brain damage, cognitive reserve could hypothetically be defined as the difference between an individual’s expected and actual cognitive performance [ 5 ]. However, the concept of cognitive reserve and the capability of FDG-PET and MRI to capture reserve mechanisms are somehow in contrast to the emerging role and value of these techniques as predictors of clinical disease milestones, such as time to conversion from the mild cognitive impairment (MCI) to the dementia stage. Moreover, whereas a large body of literature has been devoted to assessment of the value of FDG-PET in the prediction of further cognitive decline in MCI for diagnostic purposes, only the identification and localization of regions whose metabolism is able to predict the speed of progression in patients with mild cognitive impairment due to Alzheimer’s disease (MCIAD) may allow researchers to further address the existence of a specific interference due to cognitive reserve [ 6–9 ]. We recently demonstra (...truncated)


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Matteo Bauckneht, Andrea Chincarini, Roberta Piva, Dario Arnaldi, Nicola Girtler, Federico Massa, Matteo Pardini, Matteo Grazzini, Hulya Efeturk, Marco Pagani, Gianmario Sambuceti, Flavio Nobili, Silvia Morbelli. Metabolic correlates of reserve and resilience in MCI due to Alzheimer, Alzheimer's Research & Therapy, 2018, pp. 35, Volume 10, Issue 1, DOI: 10.1186/s13195-018-0366-y