Change in cognitive function determined by a composite Z-score from 4 neuropsychological tests (see description) at 0, 6 and 12 months
The composite score combines the scores of the following neuropsychological tests: FCSRT score as the sum of free recall (sum of the three learning tests) and of cued recall (sum of free recall and indexed recall), Orientation score (10 items) from MMSE, Number of symbols reported during 90 sec (Digit symbol Substitution test) and the Number of words reported during 2-minutes (Category naming test)
Changes in cognitive function assessed by the FCSRT (Free and Cued Selective Reminding Test) at 0, 6 and 12 months
FCSRT score as the sum of free recall (sum of the three learning tests) and of cued recall (sum of free recall and indexed recall)
Changes in cognitive function assessed by the Orientation score from the Mini Mental Scale Examination (MMSE) at 0, 6 and 12 months
Orientation score: Subcale of MMSE (see outcome 8); score from 0 to 10.
Changes in cognitive function assessed by the WAIS-IV coding test at 0, 6 and 12 months
Number of symbols reported during 90 seconds
Changes in cognitive function assessed by the Category Naming Test (CNT) at 0, 6 and 12 months
Number of words reported during 2 minutes
Cognitive function assessed by the (Mini Mental Scale Examination) MMSE total score at 6 and 12 months
Total score of the MMSE from 0 to 30. Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.
Cognitive status changes assessed by the Trail Making Test parts A and B at 0, 6 and 12 months
Time in sec to complete Trail Making Test parts A and B
Cognitive status changes assessed by the Logical Memory subtest of the WMS-R Test at 0, 6 and 12 months
Number of correct story elements recalled
Cognitive status changes assessed by the Letter Fluency Test at 0, 6 and 12 months
Number of correct words reported in 2 minutes
Cognitive status changes assessed by the Stroop Color Word Test (SCWT) at 0, 6 and 12 months
Time required to complete each sub-test and interference measure
Cognitive status changes assessed by the Digit Span (DS) at 0, 6 and 12 months
Number of digits recalled for forwards and backward sequences
Change in cognitive impairment assessed by the Clinical Dementia Rating - Sum of Boxes (CDR-SOB) at 0 and 12 months
CDR-SOB score ranging from 0 to 18 (0: Normal ; 0.5-4: Questionable cognitive impairment ; 4.5-9: Mild dementia ; 9.5-15.5: Moderate dementia ; 16-18: Severe dementia)
Change in clinical status assessed by Clinical Dementia Rating (CDR) at 0 and 12 months
Conversion rates to Mild cognitive impairment (MCI) and to dementia (0 = Normal, 0.5= very mild dementia, 1= mild dementia, 2 = moderate dementia, 3= severe dementia)
Subjective change in cognitive function assessed by the PROMIS Applied Cognition - Abilities instrument, Cognitive Function Instrument at 0, 1 and 12 months
PROMIS score: 33 items noted from 0 to 5 (Min score= 0, Max score =165) not used as diagnosis score but to assess the performance from baseline
Subjective change in quality of life and health status assessed by the EQ-5D-5L questionnaire at 0 and 12 months
EQ-5D-5L score: EQ-5D-5L, 5 item questionnaire and a visual analogue scale ranging from 0-100 to describe health status
Changes in depression status assessed by the Geriatric depression scale (GDS) at 0 and 12 months
GDS score ranging from 0 to 15: 0-9: Normal ; 10-19: Mild depression ; 20-30 : Severe depression.
Changes in depression, anxiety and psychiatric symptoms assessed by the Neuropsychiatric Inventory Questionnaire (NPI-Q) at 0 and 12 months
Change in the presence (yes-no) and severity score (1: mild; 2: moderate; 3: severe) of 12 neuropsychiatric symptoms related to dementia, as well as informant distress score for each of the present symptoms (from 0: 'No distress' to 5: 'Extreme distress') measured at 0 and 12 months.
Changes in physical functions assessed by the Short Physical Performance Battery (SPPB) at 0, 6 and 12 months
SPPB score ranging from 0 to 12. Assessment of score's evolution from baseline to 12 months.
Changes in frailty syndromes assessed by the Fried Frailty Criteria at 0 and 12 months
Grip strength, timed walking, involuntary weight loss, fatigue and physical activity (categories: robust, pre-frail, frail)
Changes in brain structure assessed by Magnetic Resonance Imaging (MRI) in a subset of the study population at 0 and 12 months
Regional tissue volume, Regional tissue thickness, Regional surface area, Intracranial volume (total, regional), Total brain volume, Regional volume (eg hippocampus)
Changes in brain structure assessed by fluid-attenuated inversion recovery (FLAIR) MRI and diffusion tensor imaging (DTI) in a subset of the study population at 0 and 12 months
Total white matter lesion volume
Changes in brain function assessed by Arterial spin label (ASL) perfusion MRI in a subset of the study population at 0 and 12 months
Cerebral blood flow
Changes in brain function assessed by resting State fMRI in a subset of the study population at 0 and 12 months
Brain connectivity
Changes in brain structure assessed by MRI diffusion tensor imaging (DTI) in a subset of the study population at 0 and 12 months
White matter integrity
Changes in brain function assessed by Amyloid Florbetapir Positron Emission Tomography (PET) in a subset of the study population at baseline
Amyloid load
Changes in levels of biomarkers associated with cognitive decline: BDNF levels at 0, 6 and 12 months
Brain-Derived Neurotrophic Factor (BDNF) plasma levels
Changes in levels of biomarkers associated with cognitive decline: Aβ40 levels at 0, 6 and 12 months
Aβ40 plasma levels
Changes in levels of biomarkers associated with cognitive decline: Aβ42 levels at 0, 6 and 12 months
Aβ42 plasma levels
Changes in levels of biomarkers associated with cognitive decline: Tau protein levels at 0, 6 and 12 months
Tau protein plasma levels
Changes in levels of biomarkers associated with cognitive decline: Asymmetric dimethylarginine levels at 0, 6 and 12 months
Asymmetric dimethylarginine plasma levels
Changes in levels of biomarkers associated with cognitive decline: Homocysteine levels at 0, 6 and 12 months
Homocysteine plasma levels
Changes in levels of blood plasma inflammatory markers 0, 6 and 12 months
Inflammatory markers (sCAMs, E-Selectin, TNF-alpha, IL1, IL6, IL10, CRP, neopterin)
Changes in levels of blood plasma markers of oxidative stress at 0, 6 and 12 months
Markers of oxidative stress (Oxidized Low-density lipoprotein (oxLDL), F2-isoprostane)
Changes in levels of plasma nutrient levels at 0, 6 and 12 months
e.g.vitamins, minerals, lipids, amino acids, erythrocyte omega-3 index
Treatment effects in a subgroup population defined by the below described subject characteristic:
Clinical Dementia Rating (CDR) of 0.5 at baseline
Treatment effects in a subgroup population defined by the below described subject characteristic:
Low DHA status (erythrocyte omega 3 index in the lower quartile) at baseline
Treatment effects in a subgroup population defined by the below described subject characteristic:
High plasma homocysteine levels (plasma homocysteine ≥ 12 µmol/L) at baseline
Treatment effects in a subgroup population defined by the below described subject characteristic:
CAIDE (Cardiovascular Risk Factors, Aging and Dementia) risk score at baseline
Treatment effects in a subgroup population defined by the below described subject characteristic:
Genotype