The effects of sitagliptin, a DPP-4 inhibitor, on cognitive functions in elderly diabetic patients with or without Alzheimer’s disease

Işık, Ahmet Turan; Soysal, Pınar; Yay, Adnan; Usarel, Cansu

doi:10.1016/j.diabres.2016.12.010

Cited by 142 publications

(106 citation statements)

References 22 publications

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“…Similar results were found in a shorter study, where they followed patients for 6 months (Isik et al 2017). T2DM patients with AD and without AD treated with DPP-4I performed better on MMSE 6 months after they started with the treatment than patients taking metformin (Isik et al 2017). In addition, patients treated with insulin or DPP-4I also had better glucose control and lower HbA1c at the end visit.…”

Section: Treatment Of Diabetes-related Cognitive Impairmentsupporting

confidence: 72%

“…Rizzo et al demonstrated in a prospective 2-year study that patients treated with DPP4I and metformin had better cognitive functioning in comparison to patients treated only with sulphonyl urea and metformin (Rizzo et al 2014). Similar results were found in a shorter study, where they followed patients for 6 months (Isik et al 2017). T2DM patients with AD and without AD treated with DPP-4I performed better on MMSE 6 months after they started with the treatment than patients taking metformin (Isik et al 2017).…”

Section: Treatment Of Diabetes-related Cognitive Impairmentsupporting

confidence: 66%

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The diabetic brain and cognition

et al. 2017

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The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders

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Section: Treatment Of Diabetes-related Cognitive Impairmentsupporting

confidence: 72%

Section: Treatment Of Diabetes-related Cognitive Impairmentsupporting

confidence: 66%

The diabetic brain and cognition

et al. 2017

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“…In contrast, a systematic review performed by Areosa Sastre, Vernooij, González‐Colaço Harmand, and Martínez () did not find any evidence that treatment of type 2 diabetes delays or prevents cognitive impairment. The results of studies investigating the effect of antidiabetic drugs on cognition in AD or MCI patients showed that DPP4I, insulin, and thiazolidinediones (TZD) were effective in increasing cognition in patients with AD or MCI (cohort studies; Isik, Soysal, Yay, & Usarel, ; Plastino et al, ; Rizzo et al, ; RCT; Craft et al, ; systematic review; Cao et al, , and meta‐analysis; Liu, Wang, & Jia, ). Only one cohort study found that metformin use was associated with impaired cognitive performance in AD and MCI patients (Moore et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…Metformin could, among other effects, provide neuroprotection by inhibiting the opening of mitochondrial permeability transition pores (leading to neuronal cell death; Orkaby et al, 2017) and decreasing neuroinflammation (Orkaby et al, 2017). Vildagliptin, which is a DPP4I, showed anti-inflammatory, antioxidant effects and induced hippocampal neurogenesis (Isik et al, 2017). TZDs could inhibit the inflammatory response induced by amyloid peptides (Cheng et al, 2014).…”

Section: Antidiabeticsmentioning

confidence: 99%

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

Barus

Béné

Deguil

et al. 2019

British J Pharmacology

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Many risk factors are known to induce or precipitate dementia. Drugs acting via different mechanisms can modulate cognitive performance and exert either beneficial or deleterious effects on cognition through functional or neuropathological mechanisms. This review discusses the association between several classes of drugs and cognitive impairment and dementia risk. These drugs can be divided into drugs targeting CNS disorders (e.g., anticholinergic drugs, antiepileptics, antipsychotics, benzodiazepines, and opioids) and drugs targeting non‐CNS disorders (e.g., antidiabetics, antihypertensives, proton pump inhibitors, and statins). Furthermore, we sought to highlight the pharmacological mechanisms underlying their possible detrimental or beneficial effects on cognition. Anticholinergic and antiepileptic drugs were excluded from this review because their effects on cognition are well known. Studies investigating benzodiazepines have revealed an increased risk of dementia. Conclusions on dementia risk or cognitive impairment regarding opioids and antipsychotic drugs are difficult to draw. These different classes appear to impair cognition not by a single clear mechanism of action specific to each class but by several relatively interdependent and interconnected mechanisms (e.g., impaired neurotransmission, neuroinflammation, neuronal death, oxidative stress, or interactions with dementia‐related pathways). The dementia risk initially associated with the use of proton pump inhibitors might have been overestimated. In contrast, statins, antihypertensive medications, and antidiabetics could potentially decrease the risk of dementia and cognitive impairment by acting in ways opposite to the mechanisms cited above. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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“…Intranasal insulin administration seems to open the possibility for a safe, and at least in the short term, effective symptomatic intervention that delays loss of cognition in AD patients [70]. Another study involving individuals with AD or mild cognitive impairment found that 4 months of intranasal insulin (20 IU, 2x/day) preserved cognition as measured by ADAS-cog, improved delayed memory, and improved caregiver-rated functional ability [71].…”

Section: New Possibilities For Treatment Of Ad Using Intranasal Insulinmentioning

confidence: 99%

Does the Choice of Treatment of Diabetes Mellitus Change Natural Course of Alzheimer Disease?

Karahmet¹,

Prnjavorac²,

Sejranić³

et al. 2018

J Alzheimers Dis Parkinsonism

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IntroductionAlzheimer's disease characterized clinically by a progressive and gradual decline in cognitive function and neuropathologically, by the presence of neuronal threats, specific neuron loss, synapse loss and disturbance of cholinergic synapses. Most people with Alzheimer's have the late-onset form of the disease, in which the symptoms become apparent in their mid-60s. Genetic Basis of Metabolic Changes in Alzheimer's DiseasesThe apolipoprotein E (APOE) gene is involved in late-onset Alzheimer's. This gene has several forms. One of them, APOE ε4, increases a person's risk of developing AD and is associated with an earlier age onset. Around 0.1% of the cases are familial forms of autosomal dominant inheritance, which has an onset before age 65 [1]. This form of the disease is known as onset familial Alzheimer's disease. Most of the autosomal dominant familial AD can be attributed to mutations in one of three genes: those encoding amyloid precursor protein (APP) and presenilins1 and 2 [2]. Most of the mutations in the APP and presenilin genes increase the production of a small protein called Aβ42, which is the main component of senile plaques [3]. Some of the mutations merely alter the ratio between Aβ42 and the other major forms particularly Aβ40 without increasing Aβ42 levels [4,5]. The major hallmarks of AD pathology are masses of the extracellular β-amyloid peptide (Aβ) and neurofibrillary tangles of the microtubule binding protein tau [6,7]. Aβ has crucial importance in the relation of AD as well as the crucial role of its pathogenesis. The neurotoxic potential of the Aβ peptide results from its biochemical properties, favoring aggregation into insoluble oligomers and protofibrils [7]. Etiological treatment of AD is AbstractAlzheimer disease (AD) is common worldwide and almost every case has comorbidities. One of the most common comorbidities of AD is Diabetes mellitus (DM), with or without metabolic syndrome. Both diseases effect nerve tissue and successful treatment would improve the status of the patient. In patients with Alzheimer disease treatment of DM, the treatment could be harmful to the AD, because of that high insulin intake. This may lead to progression of AD. Insulin is considered the best treatment for DM, but insulin therapy could increase comorbidity with AD. No specific therapy for AD is known up to date, so because of that DM is one of the most important risk for AD, concomitant therapy for DM should be planned very carefully. All options of DM therapy should be considered, and different mechanisms of anti-diabetic drugs are preferable. Treatment of AD is more complex metabolic syndrome is present. Any inflammation causes local tissue damage, including brain tissue during AD. Release of interleukins, primarily TNF-α, IL-6, IL-1β in the presence of adipokine leptin, maintains chronic inflammatory status in local brain tissue. Thus, low doses of immunosuppressant therapy should be considered for treatment of AD in future. To delay apoptosis of nerve tissue cells, brain and nerve tissue...

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The effects of sitagliptin, a DPP-4 inhibitor, on cognitive functions in elderly diabetic patients with or without Alzheimer’s disease

Cited by 142 publications

References 22 publications

The diabetic brain and cognition

The diabetic brain and cognition

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

Does the Choice of Treatment of Diabetes Mellitus Change Natural Course of Alzheimer Disease?

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