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Purpose <p>Here, we combined a longitudinal design to assess whole-brain hyper- and hypo-connectivity in the different clinical phases of Alzheimer’s disease (AD) with a multimodal approach to understand how such connectivity changes were related to glucose hypometabolism.</p> Methods <p>We selected a longitudinal cohort of <i>N =</i> 66 subjects with clinical, cerebrospinal fluid and FDG-PET assessments, from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. <i>N</i> = 31 AD individuals were assessed at three stages: mild cognitive impairment (AD-MCI, T0), early phase of dementia (mild-AD, T1) and dementia (AD-D, T2). We included <i>N</i> = 35 age/sex-matched healthy controls. We assessed longitudinal metabolic connectivity using Pearson’s correlation, clustering analysis and graph theory metrics.</p> Results <p>In the MCI-AD stages, hypo- and hyper-connectivity coexisted. Data-driven, longitudinal clustering analysis identified specific pathological clusters: a default mode network cluster, with prevalent hypo-connectivity and severe, persistent hypometabolism; a limbic cluster showing hyper-connectivity and steeper metabolic decline. Metabolism in hyper-connected limbic regions showed a mediation effect on worsening of AD-like parieto-temporal hypometabolism and predicted faster conversion to dementia.</p> Conclusion <p>Hypo- and hyper-connectivity, especially in early stages, may have different roles in AD neurodegenerative processes, with metabolism in hyper-connected regions acting as a mediator on the neurodegeneration of core regions of AD pathology.</p>

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Glucose metabolism in hyper-connected regions predicts neurodegeneration and speed of conversion in Alzheimer’s disease

  • 期刊论文

  • 发表日期：

    2025年6月5日

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  • Alice Galli,
  • Marianna Inglese,
  • Luca Presotto,
  • Rachele Malito,
  • Xin Di,
  • Nicola Toschi,
  • Andrea Pilotto,
  • Alessandro Padovani,
  • Cristina Tassorelli,
  • Daniela Perani,
  • Arianna Sala,
  • Silvia Paola Caminiti

摘要

Purpose

Here, we combined a longitudinal design to assess whole-brain hyper- and hypo-connectivity in the different clinical phases of Alzheimer’s disease (AD) with a multimodal approach to understand how such connectivity changes were related to glucose hypometabolism.

Methods

We selected a longitudinal cohort of N = 66 subjects with clinical, cerebrospinal fluid and FDG-PET assessments, from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. N = 31 AD individuals were assessed at three stages: mild cognitive impairment (AD-MCI, T0), early phase of dementia (mild-AD, T1) and dementia (AD-D, T2). We included N = 35 age/sex-matched healthy controls. We assessed longitudinal metabolic connectivity using Pearson’s correlation, clustering analysis and graph theory metrics.

Results

In the MCI-AD stages, hypo- and hyper-connectivity coexisted. Data-driven, longitudinal clustering analysis identified specific pathological clusters: a default mode network cluster, with prevalent hypo-connectivity and severe, persistent hypometabolism; a limbic cluster showing hyper-connectivity and steeper metabolic decline. Metabolism in hyper-connected limbic regions showed a mediation effect on worsening of AD-like parieto-temporal hypometabolism and predicted faster conversion to dementia.

Conclusion

Hypo- and hyper-connectivity, especially in early stages, may have different roles in AD neurodegenerative processes, with metabolism in hyper-connected regions acting as a mediator on the neurodegeneration of core regions of AD pathology.