Metformin and Alzheimer's disease, dementia and cognitive impairment: a systematic review protocol

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...

Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...

Elderly individuals encompass a diverse population with varying degrees of age-related physiological changes. Defining the elderly presents challenges, as the geriatric population is often arbitrarily categorized as individuals older than 65. However, many individuals in this group lead active and healthy lives, with an increasing number surpassing 85 years and falling into the older elderly category. Physiological changes associated with aging impact performance capacity and homeostatic...

Dementia is a collective term for cognitive disorders primarily affecting memory, thinking, and reasoning. It is not a specific disease but a syndrome, with Alzheimer's disease being the most common cause, accounting for approximately 60-80% of cases. Other types include vascular dementia, Lewy body dementia, and frontotemporal dementia. Dementia affects millions worldwide, particularly older adults, though it is not a normal part of aging.
The progression of dementia is generally gradual....

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...

Geriatric patients show significant variation in how their bodies process medications, which can change how effective and safe treatments are. The liver is the primary organ where drug metabolism occurs, involving two main types of chemical reactions: phase I and II. Phase I metabolism is driven by the cytochrome P450 enzyme system, which includes key types such as CYP3A, CYP2D6, and CYP2C9. Research indicates that while aging doesn't notably alter the levels or activity of these enzymes, it...