Globally, the incidence of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) epidemics is increasing rapidly and has huge financial and emotional costs. The purpose of the current review article is to discuss the shared pathophysiological connections between AD and T2DM. Research findings are presented to underline the vital role that insulin plays in the brain’s neurotransmitters, homeostasis of energy, as well as memory capacity. The findings of this review indicate the existence of a mechanistic interplay between AD pathogenesis with T2DM and, especially, disrupted insulin signaling. AD and T2DM are interlinked with insulin resistance, neuroinflammation, oxidative stress, advanced glycosylation end products (AGEs), mitochondrial dysfunction and metabolic syndrome. Beta-amyloid, tau protein and amylin can accumulate in T2DM and AD brains. Given that the T2DM patients are not routinely evaluated in terms of their cognitive status, they are rarely treated for cognitive impairment. Similarly, AD patients are not routinely evaluated for high levels of insulin or for T2DM. Studies suggesting AD as a metabolic disease caused by insulin resistance in the brain also offer strong support for the hypothesis that AD is a type 3 diabetes.

Alzheimer’s disease (AD) is a rapidly growing disease that affects millions of people worldwide, therefore there is an urgent need for its early diagnosis and treatment. A huge amount of research studies are performed on possible accurate and reliable diagnostic biomarkers of AD. Due to its direct contact with extracellular space of the brain, cerebrospinal fluid (CSF) is the most useful biological fluid reflecting molecular events in the brain. Proteins and molecules that reflect the pathogenesis of the disease, e.g., neurodegeneration, accumulation of Abeta, hyperphosphorylation of tau protein and apoptosis may be used as biomarkers. The aim of the current manuscript is to present the most commonly used CSF biomarkers for AD as well as novel biomarkers. Three CSF biomarkers, namely total tau, phospho-tau and Abeta42, are believed to have the highest diagnostic accuracy for early AD diagnosis and the ability to predict AD development in mild cognitive impairment (MCI) patients. Moreover, other biomarkers such as soluble amyloid precursor protein (APP), apoptotic proteins, secretases and inflammatory and oxidation markers are believed to have increased future prospects.

The public health burden of type 2 diabetes mellitus and Alzheimer’s disease is steadily increasing worldwide, especially in the population of older adults. Epidemiological and clinical studies suggest a possible shared pathophysiology between the two diseases and an increased risk of AD in patients with type 2 diabetes mellitus. Therefore, in recent years, there has been a substantial interest in identifying the mechanisms of action of antidiabetic drugs and their potential use in Alzheimer’s disease. Human studies in patients with mild cognitive impairment and Alzheimer’s disease have shown that administration of some antidiabetic medications, such as intranasal insulin, metformin, incretins, and thiazolidinediones, can improve cognition and memory. This review aims to examine the latest evidence on antidiabetic medications as a potential candidate for the treatment of Alzheimer’s disease.

Objective: The aim of the current study was to estimate the discriminant potential and validity of the Digit Symbol Substitution Test (DSST) of the WAIS-R in the Greek elderly population meeting criteria for subjective cognitive decline (SCD), mild cognitive impairment (aMCI; amnestic subtype), or Alzheimer’s disease dementia (ADD). Method: Four hundred eighty-eight community-dwelling older adults, visitors of the Day Center of Alzheimer Hellas, participated in the study. Two hundred forty-three of them met the criteria for ADD, one hundred eighty-two for aMCI and sixty-three for SCD. Results: Path analysis indicated that the DSST score is affected by age group, educational level, and diagnostic category, but is not affected by gender. The ROC curve analysis showed that the DSST sum score could perfectly differentiate SCD from ADD patients, whereas test’s discriminant potential between aMCI and dementia ADD’s subtype was satisfactory. However, DSST was unable to separate the SCD from the aMCI group. Conclusion: It appears that the DSST is unable to separate the SCD from aMCI population. Therefore, the test in question may be insensitive to incipient cognitive decline. On the contrary, the discriminant potential of the DSST as regards SCD and ADD is excellent, while discrimination between aMCI and ADD is good.

Recent studies have shown that patients diagnosed with Vascular Dementia (VaD) exhibit deficits in executive functions. According to “vascular hypothesis of cognitive aging,” community-dwelling older adults having risk factors for vascular disease development (RVD) may suffer from cognitive decline of the same type. The aim of the study was to assess the level of specific executive functions (EF) that have been revealed as most affected by vascular abnormalities, in older adults with incipient VaD and RVD. Subsequently specific ways of EF measuring could be suggested for more accurate diagnosis of early stage VaD. The study compared three adult groups (N = 60): (a) patients diagnosed with incipient VaD, according to DSM-5 criteria (n = 20); (b) community-dwelling older adults presenting cardiovascular risk factors (RVD; n = 20); (c) healthy young adult controls (n = 20). Three types of executive functions were examined: inhibitory control, cognitive flexibility as rule/task switching, and planning. The following D-KEFS subtests were administered for their evaluation: The ‘Color-Word Interference Test,’ the ‘Verbal Fluency Test,’ and the ‘Tower Test.’ Mixed-measures ANOVA, MANOVA, and one-way ANOVA as well as Scheffe post hoc test were applied to the data of the scores in each condition of each test. The results showed that VaD patients had significantly lower performance in test conditions requiring switching and planning, compared to RVD group and young controls. The specific deficits of VaD patients, compared to older adults presenting RVD according to multiple-group path analyses were: more uncorrected errors in inhibition, the use of semantic knowledge primarily instead of switching ability to switch between semantic categories, as well as a lower level of movement precision in planning.

Episodic memory is the type of memory that allows the recollection of personal experiences containing information on what has happened and, also, where and when it happened. Because of its sensitivity to neurodegenerative diseases and the aging of the brain, it is considered a hallmark of Alzheimer’s disease dementia (ADD). The objective of the present study was to examine episodic memory in amnestic mild cognitive impairment (aMCI) and ADD. Patients with the diagnosis of early aMCI, late aMCI, and mild ADD were evaluated using the Doors and People tool which consists of four subtests examining different aspects of episodic memory. The statistical analysis with receiver operating characteristic curves (ROC) showed the discriminant potential and the cutoffs of every subtest. Overall, the evaluation of episodic memory with the Doors and People tool can discriminate with great sensitivity between the different groups of people with AD and, especially, early aMCI, late aMCI, and mild ADD patients.