Cognitive Decline
Conditions
Keywords
cognitive decline, dementia, cerebrovascular disease, insulin resistance, neurodegeneration, inflammation, diabetes
Brief summary
A randomised control study of metformin in people with mild cognitive impairment and without diabetes mellitus to determine effects on cognitive decline and neuroimaging over 3 years.
Detailed description
A randomised placebo-control study of metformin in people with mild cognitive impairment and without diabetes mellitus to determine effects on cognitive decline, neuroimaging and biomarkers over 3 years.
Interventions
DRUGMetformin XR, 500-2000mg nocte
Metformin XR, 500-2000mg nocte
Sponsors
National Health and Medical Research Council, Australia
Garvan Institute of Medical Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
randomised placebo controlled trial
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* overweight or obese (body mass index \>25.0 kg/m2, waist: women\>80 cm, men\>94cm; * Mild cognitive impairment (Mild Neurocognitive Disorder), based on DSM-5 criteria; * Fasting blood glucose \<7.0 mmol/L and HbA1c \<6.5%; * Able to undertake neurocognitive testing in English. * Not participating in another trial of drugs or lifestyle modification to reduce cognitive decline.
Exclusion criteria
* Life-threatening illnesses to preclude participation in a 3-year study; * Contraindications to the use of metformin (severe heart failure or eGFR \<40).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| changes in memory Z-score | 3 years | memory domain Z-score, derived from the following neuropsychological tests: i. Rey Auditory Verbal Learning Test (RAVLT); ii. Total Learning and Delayed recall; iii. the Logical Memory Story A- Immediate Recall; and iv. Delayed Recall tests. |
| changes in executive function Z-score | 3 years | executive function domain Z-score, derived from the following neuropsychological tests: i. Alphabet test; ii. D-KEFS Stroop; iii. Trail Making Test Part B; iv. Weschler Adult Intelligence Scale-IV (WAIS-IV) Digit Span Backward test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| changes in language performance domain Z-score | 3 years | language performance domain measured by the Category Fluency (Animals) neuropsychological test |
| changes in attention performance domain Z-score | 3 years | attention performance domain Z-score, measured by the WAIS-IV Digit Span Forward neuropsychological test |
| changes in Cogstate brief battery performance Z-score | 3 years | computerised cognition testing using the on-line test, the Cogstate brief battery (CBB) |
| changes in hippocampal volume (cubic millimetres) | 3 years | volume of the right and left hippocampal regions of the brain |
| changes in parahippocampal volume (cubic millimetres) | 3 years | volume of the right and left parahippocampal regions of the brain |
| changes in total brain volume (cubic millimetres) | 3 years | total grey and white matter volume |
| changes in cerebral blood flow (mL / 100 g / min) | 3 years | Cerebral blood flow will be measured using arterial spin labelling |
| changes in cerebral amyloid tracer standardized uptake value ratio (SUVR) | 3 years | standardized uptake value ratio of amyloid tracer using positron emission tomography |
| changes in cognitive performance Z-score using the NIH tool box | 3 years | The NIH Toolbox currently contains the following cognitive tests: Flanker, Pattern Comparison, Picture Sequence Memory and Dimensional Change Card Sort. |
| change in BOLD (blood-oxygen-level-dependent) time-series signals measured by functional magnetic resonance imaging | 3 years | change blood oxygen-level-dependent time-series signals, measured by functional MRI |
| changes in biomarkers, including fasting glucose (mmol/L) and insulin (mIU/L), insulin resistance (HOMA-IR index) | 3 years | fasting glucose (mmol/L) and insulin (mIU/L), insulin resistance (HOMA-IR index) |
| changes in brain white matter hyperintensity number | 3 years | the number of white matter hyperintensities visualised in bain imaging by magnetic resonance imaging |
| changes in processing speed domain Z-score | 3 years | processing speed domain measured by the i. WAIS-IV Coding; and ii. Trail Making Test part B |
Countries
Australia
Outcome results
None listed