Improved functional connectivity after a 6‐month ketogenic supplementation in mild cognitive impairment. (31st December 2021)

• Record Type: Journal Article
• Authors: Roy, Maggie; Edde, Manon; Fortier, Melanie; Croteau, Etienne; Castellano, Christian‐Alexandre; St. Pierre, Valerie; Vandenberghe, Camille; Morin, Marie‐Christine; Langlois, Francis; Bocti, Christian; Fulop, Tamas; Descoteaux, Maxime; Cunnane, Stephen
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 9
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-31
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.057660
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Ketones, the brain's alternative fuel to glucose, bypass the brain glucose deficit in mild cognitive impairment (MCI). The BENEFIC trial conducted in MCI showed improved measures of cognition in multiple domains after a 6‐month ketogenic intervention [Fortier et al . 2019]. Functional connectivity in the dorsal‐attention network (DAN) deteriorates early in MCI, and prior to changes in the ventral‐attention network [Zhang et al . 2015]. We aimed to assess whether improved cognitive outcomes in the BENEFIC Trial were linked to improved brain functional connectivity. Method: Participants in this 6‐month intervention were randomized to a placebo ( n = 15) or ketogenic medium chain triglyceride (kMCT; n = 17) drink. A neurocognitive battery and brain imaging were performed pre‐ and post‐intervention. Functional connectivity was computed from resting‐state functional magnetic resonance images. Independent component analysis (FSL Melodic) was used to segment seven major resting‐state networks (DAN, ventral‐attention, frontoparietal, limbic, somatomotor, default‐mode and visual) [Yeo et al . 2011]. Regional cortical ketone ( 11 C‐acetoacetate) and glucose ( 18 F‐fluorodeoxyglucose) metabolic rates were also quantified using positron emission tomography (PET). Result: Changes (post ‐ pre) in DAN functional connectivity was significantly higher in the kMCT group vs placebo ( P = 0.024). After correction for age, sex, education, ApoE status and intracranial volume, the significant difference between groups was still present, with a large effect size (partial h 2 = 0.16; P = 0.043; Figure 1). Connectivity in no other networks was significantly different between groups. Changes in attention and processing speed composite Z‐score ( r = 0.42; P = 0.021) and specific tests targeting attention (Trail Making visual scanning and number sequencing conditions) were significantly associated with the increased DAN functional connectivity. Change in ketone uptake specifically in DAN cortical regions (Figure 2C) was significantly higher in the kMCT vs placebo group ( P = 0.001) and was directly associated with the improved DAN functional connectivity, with a large effect size ( r = 0.69; P = 0.002; Figure 3). Conclusion: We show that a 6‐month ketogenic intervention improves DAN functional connectivity in MCI, an improvement that is directly linked to increased energy (ketone) supply to the DAN. The beneficial effect of ketones on cognition in MCI may be linked to improved DAN connectivity.