The Diabetic Brain and Dementia

Alzheimer’s Disease (AD) and Diabetes Mellitus (DM) are the two most common and devastating health problems in the elderly. They share a number of common features among which are important impact on quality of life and substantial health care costs. Epidemiological and biological evidence support a pathophysiological link between Type 2 Diabetes Mellitus (DMT2) and cognitive impairment. A causative association between DM and Alzheimer’s disease has been suggested on the basis of clinical, epidemiological, genetic and experimental studies. Persons with DM have a higher incidence of cognitive decline and an increased risk of developing AD and other types of dementia, and comorbidity increases the risk. Insulin resistance predicts medial temporal hypermetabolism in Mild Cognitive Impairment (MCI) conversion to AD and glucose uptake changes in AD in medial temporal regions predicting worse memory performance. DM has been shown to influence the rate of functional decline among patients with mild AD dementia than in those without comorbid DM. However, the precise mechanisms involved in the development of AD in diabetics are not yet fully understood, and several pathogenic pathways have been discussed.

Autopsy studies stated that diabetic patients show significantly less AD pathology (senile plaques, neurofibrillary tangles, cerebral amyloid angiopathy, etc.) but more cerebrovascular lesions including microvascular lesions and white matter changes than subjects without DM. Vasculo-neural dysfunction has been suggested to represent a potential etiological linkage between DMT2 and AD, while others suggested that the association between DM and dementia is only partially mediated through cerebrovascular disease and that DM is associated independently with overal dementia among elderly, but not with AD or vascular dementia.

Transcranial Magnetic Stimulation in Alzheimers Disease and Cortical Dementias

Alzheimer’s disease (AD), Dementia with Lewy Bodies (DLB), Parkinson’s disease dementia (PDD) and frontotemporal lobar degeneration (FTLD), account for the predominant cause of dementia in the population aged ≥ 60 years, with an estimated prevalence of 5-7% in this age-group, escalating to about 30% in the people older than 85. With the progressive aging of the population, the prevalence of dementia is estimated to double every 20 years, thus becoming a health- and social-care priority for many high-income countries. Numerous studies have tried to addressthe challenge of identifying early biological or neuroimaging markers in order to unravel the physiopathological processes underlying these disorders and to correctly recognize the earliest stages of disease, when the neurodegenerative process is still limited and possibly reversible.

In this view, also neurophysiological techniques, particularly transcranial magnetic stimulation (TMS), have become promising tools to assess specific cortical circuits in the central nervous system. Since its introduction, the use of TMS in clinical neurophysiology, neurology, neuroscience, and psychiatry has spread widely, leading to important findings on cortical function in physiological and pathological conditions.Indeed, with the contribution of pharmacological studies, numerous TMS stimulation paradigms have been developed to assess,non-invasively and in-vivo, the function of GABAergic, glutamatergic and cholinergic cortical circuits [6]. Furthermore, specific paradigms of paired associative stimulation (PAS) or repetitive TMS (rTMS) have shown to increase or decrease the excitability of corticospinal projections of the primary motor cortex (M1), representing a form of long-term potentiation (LTP) or depression (LTD) and thus a method of assessing synaptic plasticity.