The Ketogenic Diet In Alzheimer's

INTERVENTION: We aim to recruit 60 to 80 volunteers from the Waikato and Bay of Plenty regions via presentations at Dementia Waikato meetings in Hamilton and at similar meetings in Rotorua and Tauranga, as well as via Waikato and Bay of Plenty geriatric services and letters of invite to GPs. This will be a single‐phase (all at once), parallel‐group (1:1 randomization), 12‐week study in patients with mild AD. Patients will be randomized using an online randomization generator, stratified by recommended calorie intake (<2,000, 2,000‐2,500, and >2,500 kcal per day) as well as APO‐E4 status (noncarriers, heterozygotes, homozygotes). There will be five visits at Waikato Hospital: 1 screening visit, 1 training visit, 1 baseline assessment visit, 1 assessment visit at week 6 after commencing the diet intervention, and 1 assessment visit at week 12 after commencing the diet intervention. The 2‐hour screening visit will include (1) a presentation of the study and diet plans, (2) relevant demographic, medical, and social history, (3) Montreal Cognitive Assessment (MoCA), (4) Geriatric Depression score (short form), (5) body mass index (BMI) calculations, and (6) written informed consent from both the patient and their study partner (and enduring power of attorney, if not the study partner). The screening visit will occur 1‐2 months before the start of the diet interventions. Patients will continue their usual, nonmodified diets as well as their usual medications from the screening visit to the start of the diet intervention. The 45‐minute training visit will include recommended calorie intake calculations, blood tests for APO‐E4 status, training on how to use the blood glucose and ketone monitors, and a detailed explanation of how to use the diet plans. Patients will be given a blood glucose and ketone monitor at this visit, with which they will record their own levels every second night (at bedtime); this will not only demonstrate whether a patient is in physiological ketosis or not, it will also provide instant feedback to the patient as to how “well” they are doing. The 45‐minute baseline assessment visit, as well as those at weeks 6 and 12, will consist of: (1) A cognitive assessment using the Addenbrookes Cognitive Examination (ACE‐III) scale (New Zealand version A at baseline, version B at week 6, and version C at week 12). (2) A functional assessment using the AD Cooperative Study ‐ Activities of Daily Living (ADCS‐ADL) inventory. (3) A quality of life assessment using the Quality of Life in AD (QOL‐AD) questionnaire. (4) Body weight measurements. (5) Blood tests for glycosylated haemoglobin (HbA1C), triglycerides, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), and total cholesterol. For each assessment visit, each scale (ACE‐III, ADCS‐ADL, and QOL‐AD) will be performed by the same diet‐blinded clinician, on the same weekday, at the same time of day. It will be strictly forbidden for either patient or clinician to discuss any aspect of diet during the assessments. Patients will receive their randomized diet plan at the end of the baseline assessment visit. Regular support and education sessions will be provided via emails and videos ‐ the lead investigator and nutrition specialist will send global e‐mails to all patients every second day and film and post 10‐minute videos on the study’s website every weekend for the 12 weeks of the study. Both diets will be equally presented as potentially conferring health benefits, and both groups will be consistently reminded to eat until satiated. Primary outcomes will be within‐ and between‐group changes in the ACE‐III, ADCS‐ADL, and QOL‐AD scales CONDITION: Alzheimer's disease PRIMARY OUTCOME: Change in cognition (points). ; ‐ Assessment (study partner only) using the AD Cooperative Study ‐ Activities of Daily Living (ADCS‐ADL) inventory. Change in quality of life (points). Both diet plans will consist of 6‐week low‐fat and ketogenic diet plans. We will incorporate food from multiple ethnicities into each diet, including several traditional Maori meals (certain traditional Maori recipes are suitable for each diet, such as rewena flat bread, pork and puha for the low‐fat diet and kawakawa aioli, kutai in coconut cream for the ketogenic diet). Each plan will include weekly shopping lists containing ingredients available at local supermarkets, daily set menus with space to tick the completion of each meal as well as record daily (bedtime) blood glucose and ketone levels, and simple recipes. The low‐fat plan will provide 1,750 kcal per day composed of 42 g of fat (10 g saturated), 75 g of protein, 246 g net carbohydrate, and 33 g of fiber, and for those with higher energy needs, ad libitum “calorie‐booster” recipes each providing on average 500 extra kcal composed of 4 g of fat (1 g saturated), 6 g of protein, 102 g net carbohydrate, and 13 g of fiber. The ketogenic plan provides 1,750 kcal per day composed of 152 g of fat (67 g saturated), 75 g of protein, 16 g net carbohydrate, and 11 g of fiber, with each calorie‐booster recipe providing on average 500 extra kcal composed of 50 g of fat (22 g saturated), 6 g of protein, 5 g net carbohydrate, and 4 g of fiber. ; ‐ Assessment (patient) using the Addenbrookes Cognitive Examination (ACE‐III) scale (New Zealand version A at baseline, version B at week 6, and version C at week 12). Change in function (points). ; ‐ Assessment (study partner only) using the Quality of Life in AD (QOL‐AD) questionnaire. SECONDARY OUTCOME: Blood beta‐hydroxybutyrate (ketone) level (mmol/L) via serum assay. Blood glucose level (mmol/L) via serum assay. Change in body mass index (BMI) using a standard scale to check weight (same scale every visit) and a tape measure to check height (in cm) and then BMI will be calculated using an online BMI calculator. Change in glycosylated hemoglobin (HbA1C) (mmol/mol) via serum assay. Change in high‐density lipoprotein (HDL) (mmol/L) via serum assay. Change in low‐density lipoprotein (LDL) (mmol/L) via serum assay. Change in total cholesterol (mmol/L) via serum assay. Change in triglycerides (mmol/L) via serum assay. Change in weight (kg), shoes off, using a standard scale (same scale every visit). INCLUSION CRITERIA: Inclusion criteria will be: (1) Aged 50 to 80 years. (2) Mild (MoCA 16 to 26) probable AD (NINCDS‐ADRDA criteria). (3) BMI >18.5. (4) An active study partner able and willing to follow either diet plan.