What is Alzheimer’s Disease
Alzheimer’s Disease is a progressive neurodegenerative disease that is characterized by memory loss, cognitive impairment (aphasia, apraxia, agnosia or disturbance in executive functioning) and functional decline.
Some of the initial symptoms of Alzheimer’s Disease include forgetfulness (impaired ability to learn new information) or difficulty with recalling recent events. While memory changes are the most common symptoms of Alzheimer’s Disease, they are not the only reason why patients initially seek medical attention.
In addition to memory and cognitive dysfunction, decline in physical function, self-care, and level of independence are frequent characteristics of disease progression. Loss of independence in daily function is a key feature of Alzheimer’s Disease1. Other symptoms associated with mild Alzheimer’s Disease are changes in logic, reasoning, or thought, which may or may not be accompanied by behavior/mood changes2.
At advanced stages of the disease, patients with Alzheimer’s Disease require permanent care, either by a home care professional or a family member. The rapidly declining status of patients with Alzheimer’s Disease results in a drastic reduction in quality of life for both patients and their caregivers. People with severe Alzheimer’s cannot communicate and are completely dependent on others for their care. Near the end, the person may be bedridden most or all of the time. Symptoms at this stage often include: inability to communicate, weight loss, seizures, skin infections, difficulty swallowing, groaning, moaning, or grunting, increased sleeping and loss of bowel and bladder control2.
- Vidoni ED, et al. J Alzheimers Dis. 2010. 19(2):517-527
- National Institute on Aging. Symptoms and Diagnosis of Alzheimer’s Disease. https://www.nia.nih.gov/health/what-are-signs-alzheimers-disease. Last visited October 2018
The family of a patient with Alzheimer’s Disease should be involved as early and as often as possible following the diagnosis, as they will inevitably be responsible for decision-making on behalf of the patient as the condition worsens.
A diagnosis of Alzheimer’s Disease is devastating for both the patient and their family, and patients can experience anxiety, depression, hopelessness, and a lack of social support, which can be major detractors from their quality of life. In addition, communication, memory, and cognitive functions are often impaired in Alzheimer’s Disease patients, particularly when they are in the advanced stages of the disease. It is common for family members and caregivers to also experience depression and anger. Maintaining the quality of life of caregivers is of significant clinical interest, as the stress from providing care for an Alzheimer’s Disease patient may put them at risk for emotional disturbances, such as depression or anxiety, which can interfere with the level of care they are able to provide1.
- GlobalData PharmaPoint: Alzheimer’s Disease. September 2017
Etiology and pathophysiology
Alzheimer’s Disease is a form of dementia which is characterized by an accumulation of misfolded amyloid peptides and tau proteins in the aging brain. This results in oxidative and inflammatory damage, which in turn leads to energy failure and synaptic dysfunction1.
The amyloid cascade hypothesis2,3, wherein the accumulation of the amyloid-β peptide in the brain is the main cause of the condition, has dominated research on Alzheimer’s disease for more than 25 years. Other hypotheses have historically been neglected but increasingly being considered in light of recent phase III failures targeting amyloid production or accumulation4.
- Querfurth HW and LaFerla FM. N Engl J Med. 2010. 362(4):329-344
- Hardy J and Selkoe DJ. EMBO Mol Med. 2016. 8(6):595-608
- Hardy JA and Higgins GA. Science. 1992. 256(5054):184-185
- Makin S. Nature. 2018. 559(7715):S4-S7
Linking metabolic dysfunction and etiology of Alzheimer’s disease
Although the first successful Aβ immunotherapy in mice1 gave hope to the therapeutic approach of removing amyloid from the brain, a disease modifying treatment remains unrealized. Since Alzheimer’s Disease is a complex, multifactorial disease and has been suggested to be a metabolic disease2, attention has turned to altering the components of bioenergetic metabolism in Late Onset Alzheimer’s Disease.
Indeed, mitochondria (the cell’s energy engine) have been shown to play a role in the pathogenesis of Alzheimer’s Disease. Mitochondrial abnormalities in Alzheimer’s Disease include decreased mitochondrial respiration and activity, and alterations in mitochondrial morphology1.
Moreover, aging is associated with not only Alzheimer’s Disease but also two metabolic disorders: obesity and type 2 diabetes. Alzheimer’s Disease, obesity, and type 2 diabetes share demographic profiles, risk factors, and clinical and biochemical features in common. Numerous studies have also shown that brain glucose metabolism, insulin signaling, and lipid metabolism are altered in Alzheimer’s Disease. Other studies have begun to outline a potential connection between abnormal leptin, ghrelin and adiponectin levels and Alzheimer’s Disease3,4,5,6.
MedDay is examining the potential for therapies that may improve cerebral metabolism or use brain metabolism as an approach to support patients with Alzheimer’s Disease.
- Schenk D, et al. Nature. 1999. 400(6740):173-177
- Sonntag KC, et al. Sci Rep. 2017. 7(1):14038
- Craft S. Arch Neurol. 2009. 66(3):300-305
- Cai H, et al. Curr Alzheimer Res. 2012. 9(1):5-17
- de la Monte SM and Tong M. Biochem Pharmacol. 2014. 88(4):548-559
- Kang S, et al. Yonsei Med J. 2017. 58(3):479-488