Abstract
Highlights
Reliable functional brain network subtypes accompany cognitive impairment in AD
Symptom-related subtypes exist in the default-mode, limbic and salience networks
A limbic subtype is associated with a familial risk of AD in healthy older adults
Limbic subtypes also associate with beta amyloid deposition and ApoE4
In Brief We found reliable subtypes of functional brain connectivity networks in older adults, associated with AD-related clinical symptoms in patients as well as several AD risk factors/biomarkers in asymptomatic individuals.
Summary The heterogeneity of brain degeneration has not been investigated yet for functional brain network connectivity, a promising biomarker of Alzheimer’s disease. We coupled cluster analysis with resting-state functional magnetic resonance imaging to discover connectivity subtypes in healthy older adults and patients with cognitive disorders related to Alzheimer’s disease, noting associations between subtypes and cognitive symptoms in the default-mode, limbic and salience networks. In an independent asymptomatic cohort with a family history of Alzheimer’s dementia, the connectivity subtypes had good test-retest reliability across all tested networks. We found that a limbic subtype was overrepresented in these individuals, which was previously associated with symptoms. Other limbic subtypes showed associations with cerebrospinal fluid Aβ1-42 levels and ApoE4 genotype. Our results demonstrate the existence of reliable subtypes of functional brain networks in older adults and support future investigations in limbic connectivity subtypes as early biomarkers of Alzheimer’s degeneration.
Footnotes
↵* Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
↵** Data used in preparation of this article were obtained from the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENTAD) program (http://www.prevent-alzheimer.ca), data release 2.0 (November 30, 2015). As such, the investigators of the PREVENT-AD program contributed to the design and implementation of PREVENT-AD and/or provided data but did not participate in analysis or writing of this report. A complete listing of PREVENT-AD Research Group can be found in: https://preventad.loris.ca/acknowledgements/acknowledgements.php?date=[2015-11-30].
