Metabolic correlates of reserve and resilience in MCI due to Alzheimer's Disease (AD) Rik Ossenkoppele

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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- A nd 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- A nd 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.

Original languageEnglish
Article number35
JournalAlzheimer's Research and Therapy
Volume10
Issue number1
DOIs
Publication statusPublished - Apr 3 2018

Fingerprint

Alzheimer Disease
Parietal Lobe
Education
Temporal Lobe
Positron-Emission Tomography
Cognitive Reserve
Gyrus Cinguli
Fluorodeoxyglucose F18
Amyloidosis
Prefrontal Cortex
Amyloid
Dementia
Disease Progression
Healthy Volunteers
Cognitive Dysfunction
Phenotype
Brain

Keywords

  • F-FDG PET
  • Alzheimer's disease
  • Cognitive Reserve
  • Mild cognitive impairment
  • Resilience

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Metabolic correlates of reserve and resilience in MCI due to Alzheimer's Disease (AD) Rik Ossenkoppele. / Bauckneht, Matteo; Chincarini, Andrea; Piva, Roberta; Arnaldi, Dario; Girtler, Nicola; Massa, Federico; Pardini, Matteo; Grazzini, Matteo; Efeturk, Hulya; Pagani, Marco; Sambuceti, Gianmario; Nobili, Flavio; Morbelli, Silvia.

In: Alzheimer's Research and Therapy, Vol. 10, No. 1, 35, 03.04.2018.

Research output: Contribution to journalArticle

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T1 - Metabolic correlates of reserve and resilience in MCI due to Alzheimer's Disease (AD) Rik Ossenkoppele

AU - Bauckneht, Matteo

AU - Chincarini, Andrea

AU - Piva, Roberta

AU - Arnaldi, Dario

AU - Girtler, Nicola

AU - Massa, Federico

AU - Pardini, Matteo

AU - Grazzini, Matteo

AU - Efeturk, Hulya

AU - Pagani, Marco

AU - Sambuceti, Gianmario

AU - Nobili, Flavio

AU - Morbelli, Silvia

PY - 2018/4/3

Y1 - 2018/4/3

N2 - 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- A nd 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- A nd 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.

AB - 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- A nd 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- A nd 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.

KW - F-FDG PET

KW - Alzheimer's disease

KW - Cognitive Reserve

KW - Mild cognitive impairment

KW - Resilience

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