Metabolic brain connectivity reorganization in Alzheimer's disease patients: a systematic review

Metabolic connectivity has been studied in various neurodegenerative diseases, particularly Alzheimer's disease (AD), but there is a wealth of accumulated evidence and sometimes conflicting results, depending on the methodology applied. Therefore, the aim of this systematic review was to summarize the results obtained regarding metabolic brain connectivity using [¹⁸F]-FDG-PET in AD patients compared to cognitively normal subjects.

A systematic and exhaustive search of data available in the literature was carried out by querying the PubMed and Web of Science databases. Studies had to meet the following criteria: 1) a metabolic connectivity study with [¹⁸F]-FDG-PET in AD patients; 2) the inclusion of a control group of healthy subjects or cognitively normal controls; and 3) use of seed-based, independent/principal component analyses or methods derived from graph theory. This systematic review followed the PRISMA method.

A total of 49 full-text publications were included, involving 3589 AD patients, 3272 prodromal AD patients and 3898 cognitively normal subjects. These results show that AD patients have a reorganization of metabolic connectivity on a global scale, with a decrease in or even the loss of networks seen in the healthy brain and an increase in more local, less efficient connectivity. This reorganization affects not only areas commonly affected in AD but also remote regions known to be usually spared in this pathology.

Changes in metabolic connectivity in AD patients do not simply constitute a decrease in global connectivity but rather more complex local and global changes ultimately affecting all brain regions.