The exact neuronal mechanism underlying the cognitive decline associated with diabetes mellitus type 2 (DM2) still remains to be elucidated. Multi-parametric functional MRI can potentially provide functional, micro-structural, micro-vascular, and metabolic information on the affected brain at an earlier stage than does conventional structural MRI. The overall aim of the current proposal is to obtain a better understanding in the neuronal mechanisms that underlie cognitive decline in DM2 and the putative prediabetic condition the metabolic syndrome (MetS).

Diabetes mellitus type 2 (DM2) is a common chronic metabolic disorder that affects 4.1% of the Dutch population. In addition to vascular disease, DM2 is associated with structural brain changes visible on MRI, accelerated cognitive decline, and dementia in older individuals. The exact pathophysiological mechanisms underlying cognitive decrements in DM2 still remain to be elucidated. The 'metabolic syndrome' (MetS), defined as a cluster of cardiovascular risk factors (including obesity, hypertension, and dyslipidemia) is often considered a prediabetic condition. Individuals with MetS display similar cognitive decrements as do DM2 patients, but do not share the severity of brain injury. It has been indicated that in prediabetic MetS, cognitive problems precede structural brain changes, and that MetS and DM2 affect the brain through a shared mechanism in which vascular co-morbidity is essential.

The primary objectives are defined according to a hierarchical design: i) to tailor and apply multi-parametric, functional MRI techniques to identify cerebral abnormalities (cerebral biomarkers) in DM2 and MetS; ii) to investigate which cerebral biomarkers are shared and differ between DM2 and MetS; iii) to assess whether these cerebral biomarkers are associated with cognitive decrements.

Inclusion criteria:

• Subjects aged 40-75 years
• Subjects enrolled in the existing 'Maastricht Study' (M-Study)
• Subjects gave written consent to be approached for additional research
• Subjects belongs to the 20% of the worst and 20% of the best performing (as based on neuropsychological cognitive testing (Stroop color-word test, 15 word learning test, and Delayed recall and recognition 15 word learning test)

Individuals Diabetes type 2:

- Fasting blood glucose ≥ 7.0 mmol/l, after an oral glucose tolerance test (OGTT)blood glucose ≥ 11.1 mmol/l or used oral glucose-lowering medication or insulin

Metabolic syndrome:

• Participants should meet three out of 5 of the following criteria [8]:

  1. Waist circumference > 88 cm (women), > 102 cm (men)

  2. Triglycerides ≥ 1.7 mmol/l

  3. HDL cholesterol < 1.3 mmol/l (women), < 1.0 mmol/l (men)

  4. Blood pressure ≥ 130/85 mmHg (or medication)

  5. Fasting blood glucose ≥ 6.1 mmol/l, after an OGTT blood glucose ≥ 7.8 mmol/l

     Control participants:

• Those who fulfilled no more than 1 criterium of the metabolic syndrome, no DM2.

Exclusion criteria:

• Contra-indications for MRI examination (e.g. pacemaker; neurostimulator; medication pump; cochlear or hearing implant; tattoos or other items that cannot be removed and include metal parts (for instance from operations in the past); metal splinter in the eye; pregnancy and claustrophobia; brain vessel clamps; denture, which contains magnets).
• Psychiatric co-morbidity and inability to perform the functional MRI tests.
• Incomplete cognitive assessment data
• Diabetes mellitus type 1 (DM1)
• Subjects who are not belonging to the 20% of the worst and 20% of the best performing individuals (as based on neuropsychological cognitive testing (Stroop color-word test, 15 word learning test, and Delayed recall and recognition 15 word learning test).
• Last visit of the subjects to the M-Study should be less than one year

Matched subjects aged 40-75 years with Diabetes mellitus type 2, metabolic syndrome, and healthy controls