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Abstract
Objective To examine the effects of baseline Alzheimer disease and cerebrovascular disease markers on longitudinal default mode network (DMN) and executive control network (ECN) functional connectivity (FC) changes in mild cognitive impairment (MCI).
Methods We studied 30 patients with amnestic MCI (aMCI) and 55 patients with subcortical vascular MCI (svMCI) with baseline Pittsburgh Compound B (PiB)–PET scans and longitudinal MRI scans. Participants were followed up clinically with annual MRI for up to 4 years (aMCI: 26 with 2 timepoints, 4 with 3 timepoints; svMCI: 13 with 2 timepoints, 16 with 3 timepoints, 26 with 4 timepoints).
Results β-Amyloid (Aβ) burden was associated with longitudinal DMN FC declines, while cerebrovascular burden was associated with longitudinal ECN FC changes. When patients were divided into PiB+ and PiB− groups, PiB+ patients showed longitudinal DMN FC declines, while patients with svMCI showed longitudinal ECN FC increases. Direct comparisons between the 2 groups without mixed pathology (aMCI PiB+ and svMCI PiB−) recapitulated this divergent pattern: aMCI PiB+ patients showed steeper longitudinal DMN FC declines, while svMCI PiB− patients showed steeper longitudinal ECN FC increases. Finally, using baseline PiB uptake and lacune numbers as continuous variables, baseline PiB uptake showed inverse U-shape associations with longitudinal DMN FC changes in both MCI subtypes, while baseline lacune numbers showed mainly inverse U-shape relationships with longitudinal ECN FC changes in patients with svMCI.
Conclusions Our findings underscore the divergent effects of Aβ and cerebrovascular burden on longitudinal FC changes in the DMN and ECN in the predementia stage, which reflect the underlying pathology and may be used to track early changes in Alzheimer disease and cerebrovascular disease.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADL=
- activities of daily living;
- aMCI=
- amnestic mild cognitive impairment;
- DMN=
- default mode network;
- ECN=
- executive control network;
- FC=
- functional connectivity;
- FLAIR=
- fluid-attenuated inversion recovery;
- GMV=
- gray matter volume;
- MCI=
- mild cognitive impairment;
- MNI=
- Montreal Neurological Institute;
- PiB=
- Pittsburgh compound B;
- SNSB=
- Seoul Neuropsychological Screening Battery;
- SUVR=
- standardized uptake value ratio;
- svMCI=
- subcortical vascular mild cognitive impairment;
- VOI=
- volume of interest
Footnotes
↵* These authors contributed equally to this work as co–first authors.
↵‡ These authors contributed equally to this work as co–senior authors.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received November 26, 2018.
- Accepted in final form May 21, 2019.
- © 2019 American Academy of Neurology
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