This review will compare longitudinally the cognitive deficits and associated metabolic and structural abnormalities in two
models with spontaneous onset of type 1 and type 2 diabetes, respectively. From these studies it is becoming increasingly
evident that the cerebral dysmetabolism differs in many respects as to underlying mechanisms leading up to progressive cognitive
dysfunction, although mechanistic overlaps exist between the two models. In the type 1 model, insulin deficiency appears to
play a prominent role in degenerative and apoptotic phenomena of neuronal populations and white matter constituents. In these
processes, undoubtedly, hyperglycemia and its downstream metabolic aberrations are also active participants.
In the type 2 model, which reflects closely the situation in human type 2 diabetes, the underlying mechanisms appear more
complex and are likely to include components of the metabolic syndrome such as hypercholesterolemia and hypertension. This
model displays increased activity of the amyloidogenic processing of APP with subsequent accumulation of A(amyloid)β products.
This together with central insulin resistance is likely to be responsible for increased presence of hyperphosphorylated tau.
Hence, in this model similarities with factors responsible for the progressive degenerative changes characterizing Alzheimer’s
disease are obvious. Although information to date is rather limited in genetically unmanipulated models of diabetes, available
information stresses differences in the pathogeneses responsible for diabetic encephalopathy in the two types of diabetes
will be reviewed.
Key words Diabetic encephalopathy – Type 1 diabetes – Type 2 diabetes – Morris water maze – Neuronal apoptosis – Amyloidogenesis – BB/Wor-rat – BBZDR/Wor-rat