Alzheimer’s disease

Alzheimer’s disease

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Alzheimer’s disease is a neurodegenerative disorder that presents with gradual cognitive and functional abnormalities, together with behavioral deficits (Calderon-Garcidueñas & Duyckaerts, 2018). The persons become socially and occupationally dysfunctional. The disease is incurable and is characterized by a long preclinical period. Often when the disease presents itself, it is already too late. The plaques accumulate in the hippocampus region associated with memory. The pathophysiology is not entirely clear on whether the plaques cause AD or if the plaques are a by-product of the disease. AD is the most prevalent form of dementia. The paper will focus on the pathophysiology, etiology, epidemiology, and management of the condition.

In 2017, there were approximately 6.08 million Americans with clinical AD. The number is projected to grow to about 15 million people by 2060 as the general population grows older. AD is a major public health problem (Brookmeyer & Abdalla, 2019). Since AD is incurable, many patients spend their time in long term care facilities and symptomatic therapy. In 2017, the estimated cost of treatment for AD was $259 billion (Calderon-Garcidueñas & Duyckaerts, 2018). The American life expectancy is expected to get even older with better healthcare systems. Hence, this number can be expected to grow. Most of the patients are over 65 years old. There are approximately more than 200,000 patients below 65 years old (Weller & Budson, 2018). Also, most of them present with only mild symptoms of the disease, though it later escalates to the more advanced form. In 2017, Alzheimer’s disease was the sixth prominent cause of death. Other industrialized nations have a similar prevalence to that of the USA. Countries with a high proportion of the older population have a higher or similar prevalence. Some studies show that women are more predisposed to AD than men. In the US, close to two-thirds of the cases are in women. The disease is more prevalent in African-Americans. They are more than twice likely to get AD, especially among persons over 71 years (Calderon-Garcidueñas & Duyckaerts, 2018). The name “Alzheimer” is derived from the first person to characterize the condition. In 1901, Dr. Alois Alzheimer, a German psychiatrist, observed symptoms of short-term memory loss in his patient. At the time, no one knew much about the clinical condition; and Alzheimer took the initiative to investigate further. He sent brain samples and clinical data to a lab in Munich. The lab report indicated the presence of amyloid plaques and neurofibrillary tangles in the brain images.

The pathophysiology of the disease is a continuum with the normal aging process. Before, discussing the pathology of the disease, it is fundamental to understand the normal physiology of the neurons. The neurons are supported by internal structures called microtubules that form a track-like process that guides the delivery of nutrients from the cell body to the axon terminals. The process occurs rapidly. The tau protein stabilizes microtubules ensuring efficient functioning. In AD, the tau protein undergoes chemical changes and instead of binding with microtubules, it binds to other tau portions causing the microtubules to disintegrate, collectively impairing the transport system (Braak & Del Tredici, 2015). This results in the apoptosis of neurons causing symptoms of memory lapse, behavioral changes, and social impairment. Senile plaques precede the clinical presentation of the disease. There has been a widespread emphasis to study the composition of senile plaques and neurofibrillary tangles. SPs contain the amyloid substance. Studies indicate the synthesis of the protein is dictated by the genes on chromosome 21 (Weller & Budson, 2018). The plaques are dense and almost insoluble. The SPs begin to deposit in the fifth decade of human life in the hippocampal region. It is crucial to know that the presence of SPs and NFTs is not enough confirmation of AD since they can be found in other neurodegenerative diseases.

Scientists studies have tried to link the pathogenesis of AD to the presence of amyloid and NFTs. The link is still unsatisfactory. However, an abnormal amyloid substance is central to the development of the disease. Amyloid material is neurotoxic to cultured neurons. The Ab material causes phosphorylation of tau proteins. The APOE4 gene variant is a predisposing risk factor in the development of sporadic AD. A single copy increases the risk of developing AD by three-fold, while the presence of two copies increases it by fifteen-fold (Calderon-Garcidueñas & Duyckaerts, 2018). Another hypothesis alludes to the role of the cholinergic system in the pathogenesis of AD. The cholinergic system plays an essential role in memory function in healthy brains. In AD, the cholinergic system is somewhat deficient in performing its function. Studies on cadaver brains of patients with AD, demonstrate decreased functionality of the enzymes choline acetyltransferase and acetylcholinesterase in several brain regions such as the hippocampus, amygdala, and cerebral cortex (Kumar & Singh, 2015). Oxidative stress causes neuronal damage in several regions involved in cognition. Reactive radicals such as free carbonyls and thiobarbituric acid damage proteins like the tau. Oxidative stress also causes Parkinson’s disease and ALS. ROS chemical substances cause lipid peroxidation, DNA, and protein destruction. Another hypothesis links the role of the immune system in the pathology of the disease. Studies show that transforming growth factor-beta 1 is an anti-inflammatory cytokine that enhances the deposition of amyloid. Some researchers report that estrogen loss in post-menopausal women leads to cognitive decline and neuronal degeneration. Studies show that estrogen has protective effects in human neuroblastoma cultures. This may partly elaborate on why the condition manifests more in women than men.

The exact etiology of AD is unknown. Several factors coalesce to trigger its pathogenesis in susceptible persons. Generally, environmental and genetic factors are the main culprits. They include the following old age, family history, APOE genotype, obesity, insulin resistance, hypertension, Down syndrome, inflammatory factors, and dyslipidemia. The AD cases are sporadic; few cases are familial. Mutations in the APP gene, PSI-1 on chromosome 14, and PSI-2 on chromosome 1 lead to the early manifestations of the disease. Depression exacerbates the symptoms of AD (Kumar & Singh, 2015).

Generally, AD presents with symptoms of cognitive decline, behavioral changes, and functional deficit (Calderon-Garcidueñas & Duyckaerts, 2018). Cognitive decline is the most prevalent manifestation feature. Initially, the patient retains distant memories but has short-term memory lapses. Working and semantic memory are only affected in persons with the most advanced forms of AD. Hence, the patient may present with aphasia, language disturbance, apathy, and behavioral changes. Neuropsychiatric symptoms such as apathy, anxiety, and irritability begin to occur at the early stages of the disease. The aforementioned symptoms are problematic to the immediate family members and caregivers. Other psychiatric symptoms include anorexia, insomnia, hallucinations, delusions, mood and personality changes, compromised judgment, short attention span, compromised ability to organize thoughts, inability to learn new stuff, restlessness, agitation, and paranoia. Severe AD patients present with weight loss, seizures, increased sleep, loss of voluntary bladder and bowel control, and difficulty in swallowing. End-stage patients are mostly bed-ridden, and death is frequently the outcome. Bed-ridden patients die due to aspiration pneumonia due to lack of movement (Masters et al., 2015).

The current guidelines utilize the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). According to the DSM-5, there are two main cognitive syndromes: major neurocognitive and mild cognitive impairment. From the naming, the distinguishing factor is the severity of the cognitive decline. The major change in this edition excludes the necessity of the presence of memory loss for a diagnosis of dementia to be made. Biomarkers are useful in making a clinical diagnosis. The American Academy of Neurology (AAN) recommends that physicians should ensure they obtain a structural brain imaging scan in instances of objective cognitive decline. This is because 5% of the patients with symptoms of cognitive decline have a causative non-degenerative lesion. Clinicians need to rule this out before commencing treatment. MRI and CT scans are essential in identifying potentially treatable causative factors. SPECT and PET are indicated for the identification of AD-specific patterns. Amyloid-PET is a recent technology that allows the detection of moderate to severe amyloid deposits in the brain (Jack et al., 2018). The technology is highly sensitive and specific. However, its use is limited by economical factors. CSF Ab and tau protein levels are important AD biomarkers.

The aims of therapy include: to improve the patient’s quality of life and to delay the progression of the disease. Clinicians recognize the importance of psychosocial support in the management of AD. Medication alone is insufficient in improving the quality of the life of the patient. The patient often struggles to adapt to the new society and, therefore, it is essential to add the patient to support groups and also to encourage the family to show care and compassion. The hospital staff should work in harmony to ensure that the patient’s needs are met. The patient should participate in social activities to avoid cases of social withdrawal and suicide. Acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine act by increasing acetylcholine levels in cholinergic neurons in the hippocampal and cerebral cortex regions involved in memory (Weller & Budson, 2018). The N-methyl-D-aspartate (NMDA) receptor antagonist, memantine, is a useful adjunct in the management of AD. The ACEIs have clinically important side effects that should be monitored. GIT adverse effects are dose-dependent. The physician should rule out the presence of cardiac conditions since ACEIs cause heart block and bradycardia.

Behavioral symptoms can be managed by non-pharmacological methods. Non-pharmacological techniques like staying in a quiet, familiar room with sufficient lighting and positive reassurance talks stabilize most patients. Depressive symptoms require the utilization of SSRIs. Besides, the SSRIs ease symptoms of anxiety, irritability, and agitation. The prognosis is worse for patients with early-onset AD. Generally, most patients die in 3-10 years due to aspiration pneumonia (Brookmeyer & Abdalla, 2019). Current studies are focused on clearing the amyloid deposits. Studies in patients have shown that these deposits can be cleared. Other researches are dedicated to passive immunization and modification of beta-amyloid plaques and tau synthesis.

There is more knowledge now about AD than ever before but there is still a deficiency in the know-how of preventing and treating the condition. AD is detrimental not only to the affected family but also to the general population that has to bear with the economic losses. There is no effective method of preventing AD but people can be sensitized to embrace healthy lifestyles like regular exercise, physical activities, and proper nutrition. The sensitization should also discourage the stigmatization of persons with AD. AD is here to stay. Better treatment techniques can help improve Americans’ quality of life.

References

Braak, H., & Del Tredici, K. (2015). The preclinical phase of the pathological process underlying sporadic Alzheimer’s disease. Brain, 138(10), 2814-2833.

Brookmeyer, R., & Abdalla, N. (2019). Multistate models and lifetime risk estimation: Application to Alzheimer’s disease. Statistics in medicine, 38(9), 1558-1565.

Calderon-Garcidueñas, A. L., & Duyckaerts, C. (2018). Alzheimer disease. In Handbook of clinical neurology (Vol. 145, pp. 325-337). Elsevier.

Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., … & Broich, K. (2016). Preclinical Alzheimer’s disease: definition, natural history, and diagnostic criteria. Alzheimer’s & Dementia, 12(3), 292-323.

Jack Jr, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., … & Liu, E. (2018). NIA‐AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia, 14(4), 535-562.

Kumar, A., & Singh, A. (2015). A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacological reports, 67(2), 195-203.

Masters, C. L., Bateman, R., Blennow, K., Rowe, C. C., Sperling, R. A., & Cummings, J. L. (2015). Alzheimer’s disease. Nature reviews. Disease primers, 1, 15056-15056.

Vinters, H. V. (2015). Emerging concepts in Alzheimer’s disease. Annual Review of Pathology: Mechanisms of Disease, 10, 291-319.

Weller, J., & Budson, A. (2018). Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research, 7.