title: Combined omega-3 fatty acids, aerobic exercise and cognitive stimulation prevents decline in gray matter volume of the frontal, parietal and cingulate cortex in patients with mild cognitive impairment.
abstract: Previous studies in older adults suggested beneficial effects of omega-3 fatty acid (FA) supplementation, aerobic exercise, or cognitive stimulation on brain structure and function. However, combined effects of these interventions in patients suffering from mild cognitive impairment (MCI) are unknown. Using a randomized interventional design, we evaluated the effect of combined omega-3 FA supplementation, aerobic exercise and cognitive stimulation (target intervention) versus omega-3 FA supplementation and non-aerobic exercise (control intervention) on cognitive function and gray matter volume in patients with MCI. Moreover, we analyzed potential vascular, metabolic or inflammatory mechanisms underlying these effects. Twenty-two MCI patients (8 females; 60-80years) successfully completed six months of omega-3 FA intake, aerobic cycling training and cognitive stimulation (n=13) or omega-3 FA intake and non-aerobic stretching and toning (n=9). Before and after the interventions, cognitive performance, magnetic resonance imaging of the brain at 3T (n=20), intima-media thickness of the internal carotid artery and serum markers of glucose control, lipid and B-vitamin metabolism, and inflammation were assessed. Intervention-related changes in gray matter volume of Alzheimer's disease (AD)-related brain regions, i.e., frontal, parietal, temporal and cingulate cortex were examined using voxel-based morphometry of high resolution T1-weighted images. After the intervention period, significant differences emerged in brain structure between groups: Gray matter volume decreased in the frontal, parietal and cingulate cortex of patients in the control intervention, while gray matter volume in these areas was preserved or even increased after the target intervention. Decreases in homocysteine levels in the target intervention group were associated with increases in gray matter volume in the middle frontal cortex (p=0.010). No significant differences in cognitive performance or other vascular, metabolic and inflammatory parameters were observed between groups. This pilot study provides preliminary evidence that omega-3 FA intake combined with aerobic exercise and cognitive stimulation prevents atrophy in AD-related brain regions in MCI patients, compared to omega-3 FA intake plus the control condition of stretching and toning. These promising findings should now be validated in a larger interventional trial.
authors.affiliation: Department of Neurology, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: theresa.koebe@charite.de.
authors.forename: Theresa
authors.initials: T
authors.lastname: Köbe
authors.affiliation: Department of Neurology, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; Max Planck Institute of Human Cognitive and Brain Sciences, Department of Neurology, Stephanstraße 1, 04103 Leipzig, Germany; SFB 1052 Obesity Mechanism subproject A1, University of Leipzig, Germany.
authors.forename: A Veronica
authors.initials: AV
authors.lastname: Witte
authors.affiliation: Department of Neurology, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Schnelle
authors.affiliation: Department of Neurology, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Lesemann
authors.affiliation: Department of Neurology, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Fabian
authors.affiliation: Institute of General Practice, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Tesky
authors.affiliation: Institute of General Practice, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Pantel
authors.affiliation: Department of Neurology, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; Center for Stroke Research Berlin, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: agnes.floeel@charite.de.
authors.forename: Agnes
authors.initials: A
authors.lastname: Flöel
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D060825:Cognitive Dysfunction / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D004035:Diet Therapy / Q000379:methods; D019587:Dietary Supplements; D005081:Exercise Therapy / Q000379:methods*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D016896:Treatment Outcome
chemical_list: D015525:Fatty Acids, Omega-3
keywords: Cognition; Combined intervention; MCI; Voxel-based morphometry; randomized controlled trial