Multimodal Preventive Trial for Alzheimer's Disease (MIND-ADmini)

This is an interventional prevention trial for Alzheimer Disease; Prodromal focused on measuring Lifestyle intervention, Medical food, Randomized controlled trial, Prodromal Alzheimer's disease, Prevention, Intervention, Multidomain, Multimodal Read More

Inclusion criteria:

A) Prodromal AD as defined as -1 SD on 2 out of 8 tests, at least 1 memory:

Memory FCSRT - delayed free recall* ≤ 8 FCSRT free recall - learning ≤ 22 WMS-R story delayed recall (%) ≤75% WMS-R delayed recall of figures (%) ≤ 75% *Free and Cued Selective reminding test

Non-memory TMT A ≥ 60 TMT B ≥ 150 Symbol Digit Substitution Test ≤ 35 (120 sec.) Category Fluency ≤ 16 (60 sec.)

• Evidence for underlying AD pathology within 2 year prior to screening by either:

  1. CSF beta amyloid 1-42/1-40x10 ratio<1 and/or elevated T-tau and/or elevated phospho-tau and/or low beta amyloid 42 based on local lab cut-offs OR
  2. MRI evidence for medial temporal lobe atrophy (MTA score 1 or higher) OR

  3. Abnormal FDG PET and/or PiB PET compatible with AD type change

     B) Potential for lifestyle improvement, defined according to a Lifestyle Index.

     Lifestyle index. Participants with a score of 3 or above are included in the study.

     The lifestyle index identifies individuals who do not already have very healthy lifestyles, and thus have a margin for improving their lifestyle based on the MIND-AD intervention. The score is calculated by adding 1 point for each of the following factors:

• Physical activity less than 2.5 hours a week (defined as physical activity intensive enough to lead to sweating and some breathlessness)
• Diet - less than 5 portions of fruits and vegetables per day
• Diet - less than 2 portions of fish per week
• Hypertension (diagnosed by physician or current antihypertensive treatment or
• SBP>140mmHg or DBP>90 mmHg)
• Diabetes (type 1 or 2 diagnosed by physician; or current diabetes medication; or recorded elevated fasting blood glucose or HbA1C as per local guidelines within the past 6 months)
• Ongoing symptoms of sleep problems, depressive symptoms or psychological stress symptoms for at least 1 month, judged by the clinician as having some impact on everyday life

C) Age 60-85 D) MMSE ≥ 24 E) Availability of a responsible study partner. F) Written informed consent from participant as well as study partner G) Putative prescription cognitive enhancers (e.g. ginkgo, cholinesterase inhibitors) and statins are not excluded but the dosage should be stable prior to randomization. Doses should be kept stable during the study if possible.

Exclusion criteria

• Dementia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
• Use of omega-3 preparations > 500mg EPA+DHA per day
• Alcohol or drug abuse
• A concomitant serious disease
• Major depressive disorder (DSM-IV)
• Regular intake of supplements for vitamin B6, B12, folic acid, vitamin C and/or E > 200% RDI, unless prescribed by physician
• Participation in any other clinical trial in the last 30 days
• Subjects with MRI (or CT) scan consistent with a diagnosis of stroke, intracranial bleeding, mass lesion or NPH. Those subjects with a MRI scan demonstrating minimal white matter changes (Fazekas scale for white matter lesions <=3) and up to 1-2 lacunar infarcts which are judged to be clinically insignificant are allowed
• Severe loss of vision or communicative ability
• Conditions preventing cooperation as judged by the study physician
• Concomitant participation in any intervention trial