INTRODUCTION: Mid-life dietary patterns are associated with Alzheimers disease (AD) risk, although few controlled trials have been conducted. METHODS: Eighty-seven participants (age range: 45 to 65) with normal cognition (NC, n = 56) or mild cognitive impairment (MCI, n = 31) received isocaloric diets high or low in saturated fat, glycemic index, and sodium (Western-like/West-diet vs. Mediterranean-like/Med-diet) for 4 weeks. Diet effects on cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral perfusion were assessed to determine whether responses differed by cognitive status. RESULTS: CSF amyloid beta (Aβ)42/40 ratios increased following the Med-diet, and decreased after West-diet for NC adults, whereas the MCI group showed the reverse pattern. For the MCI group, the West-diet reduced and the Med-diet increased total tau (t-tau), whereas CSF Aβ42 /t-tau ratios increased following the West-diet and decreased following the Med-diet. For NC participants, the Med-diet increased and the West-diet decreased cerebral perfusion. DISCUSSION: Diet response during middle age may highlight early pathophysiological processes that increase AD risk.

There is currently no established therapy to treat or prevent Alzheimer's disease. The ketogenic diet supplies an alternative cerebral metabolic fuel, with potential neuroprotective effects. Our goal was to compare the effects of a modified Mediterranean-ketogenic diet (MMKD) and an American Heart Association Diet (AHAD) on cerebrospinal fluid Alzheimer's biomarkers, neuroimaging measures, peripheral metabolism, and cognition in older adults at risk for Alzheimer's. Twenty participants with subjective memory complaints (n = 11) or mild cognitive impairment (n = 9) completed both diets, with 3 participants discontinuing early. Mean compliance rates were 90% for MMKD and 95% for AHAD. All participants had improved metabolic indices following MMKD. MMKD was associated with increased cerebrospinal fluid Aβ42 and decreased tau. There was increased cerebral perfusion and increased cerebral ketone body uptake (¹¹C-acetoacetate PET, in subsample) following MMKD. Memory performance improved after both diets, which may be due to practice effects. Our results suggest that a ketogenic intervention targeted toward adults at risk for Alzheimer's may prove beneficial in the prevention of cognitive decline.