Alzheimer’s Disease: Symptoms, Causes and Treatment

Definition

Alzheimer’s disease is a progressive neurodegenerative disease. It is the most common cause of dementia in older adults, with an increasing incidence as a function of age.

It typically destroys neurons of the brain and their different connections in parts of the brain involved in memory power, including the hippocampus and entorhinal cortex.

What is Alzheimer's Disease (AD)

• AD is the most frequent cause of dementia. It's a deadly neurological illness that causes an increasing decrease in cognition and memory, and also progressive impairment in everyday tasks, and a variety of neuropsychiatric and behavioral changes.

Epidemiology

AD continues to be one of the leading causes of morbidity and fatality worldwide. The disease has a significant detrimental impact on families, communities, and healthcare providers.

• Currently, more than 55 million people live with dementia worldwide, and there are nearly 10 million new cases every year (WHO, 2021).
• Dementia is currently the seventh leading cause of death among all diseases and one of the major causes of disability and dependency among older people globally.
• In India, more than 4m people are estimated to be suffering from Alzheimer’s disease.

Causes

Traumatic brain injury

• Participants exposed to traumatic brain injury (TBI) had an elevated chance of acquiring Alzheimer's disease (AD) in the Danish study.
• A Swedish study, which may be enhanced by certain particular TBI discoveries such as severe and numerous TBIs,
• The first few months after the trauma occurs occurrence, younger persons with the injury, and TBI affect the skull or spine.
• According to their death certificates, athletes who had had several years of head injuries were more likely to die from Alzheimer's disease.

Obesity

• When obesity is factored into prediction models, the prevalence of Alzheimer's disease and other dementias rises dramatically.
• Longitudinal studies have found that the following AD risk variables had a 6-fold additive effect:

1. 1. Midlife obesity
   2. High total cholesterol
   3. High systolic blood pressure

• Cross-sectional research of more than 1100 healthy late-middle-aged people yielded three prediction models for cognitive performance regarding metabolic indicators.
• Excess body fat was linked to poor cognitive performance, while BMI and cognitive function were inversely connected.
• Furthermore, a meta-analysis of observational studies indicated that obesity in middle age raises the risk of dementia later in life.

Smoking

• According to several cross-sectional research backed by the tobacco industry, smokers had a decreased prevalence of Alzheimer's disease.
• However, when incident cases were examined and the tobacco industry connection was taken into account,
• It was discovered that smoking continually raised the likelihood of Alzheimer's disease and cognitive decline.
• Both APOE 4 allele carriers and non-carriers were shown to have elevated risk.
• Mid-life smoking, in particular, was linked to an elevated risk of Alzheimer's disease.
• Smoking has been shown to have negative impacts on cognition at several levels.
• Middle-aged, active smokers have worse neurocognitive performance in executive domains than non-smokers (processing speed, learning, and memory).
• Diminished volume and thickness in the hippocampus, cortical, and subcortical regions, reduced neuronal and BBB integrity, and neurobiological abnormalities similar to those seen in early-stage AD were all linked to cognitive dysfunctions, with a dose-dependent impact.
• When compared to non-smokers, elderly active smokers had inferior executive functioning, processing speed, learning, and memory, as well as more cortical atrophy and reduced grey matter density in certain brain locations.
• Former smokers had anomalies that were halfway between smokers and non-smokers.

High cholesterol

• High total blood cholesterol levels in middle age have been linked to the development of Alzheimer's disease later in life.
• High total cholesterol in middle age is a risk factor for the development of Alzheimer's disease and other dementias 20 years later, but decreasing serum cholesterol levels in late middle age could be due to ongoing disease processes and could be a marker for later Alzheimer's disease and other dementias.
• The usage of statins has been shown to reduce the prevalence of Alzheimer's disease in various cross-sectional and case-control studies.
• While one analytical analysis demonstrated that statin usage was linked to a lower risk of Alzheimer's disease, other prospective trials reported either no benefit or only a modest reduction in the risk of Alzheimer's disease.
• Statins have been shown to reduce beta-amyloid formation both in vitro and in vivo in animal experiments.
• Statins have several different actions that may be advantageous to the CNS and hence reduce the risk of Alzheimer's disease.

Alzheimer’s Disease Symptoms

• Memory loss which can interfere with daily activities
• Challenges in planning or solving problems
• Difficulty completing easy tasks
• Confusion about the time or the plane
• Trouble in understanding spatial relationships and visual images
• Difficulty with words in speaking or writing
• Losing the ability to retrace steps
• Misplacing things and forgetting to recognize
• Decreased or poor judgment
• Absenteeism from the workplace or social situations
• Mood and personality changes

Types of Alzheimer’s disease

Early-onset Alzheimer’s

• This kind of effects persons under the age of 65. They are usually in their 40s or 50s when they are diagnosed with the condition.
• It is uncommon; up to 5% of all Alzheimer's patients have early onset. People with Down syndrome are more likely to develop it.
• Scientists have discovered a few differences between early-onset Alzheimer's and other varieties of the illness.
• People who have it have more of the brain abnormalities associated with Alzheimer's.
• The early-onset type appears to be associated with a problem in a specific section of a person's DNA: chromosome 14.
• Myoclonus, a kind of muscular twitching and spasm, is also more frequent in early-onset Alzheimer's.

Late-onset Alzheimer's

• This is the most frequent type of disease, affecting adults aged 65 and up.
• It might run in families or not. So yet, researchers have not identified a specific gene that causes it.
• Nobody knows why some individuals get it and others don't.

Familial Alzheimer's disease (FAD)

• FAD is a kind of Alzheimer's disease connected to genes, according to physicians.
• Members of at least two generations have had the illness in afflicted households.
• FAD accounts for fewer than 1% of all Alzheimer's cases.
• The majority of persons with early-onset Alzheimer's have FAD.

Diagnosis of Alzheimer’s disease

• Doctors conduct tests to asses memory impairment and other thinking skills, judge functional abilities, and identify behavior changes.
• Computed tomography (CT)
• MRI
• Positron emission tomography

Treatment

1. Pharmacological (allopathic drugs)
2. Non-pharmacological (ayurvedic drug)

Pharmacological treatment

Choline Esterase Inhibitor

• The cholinergic hypothesis states that AD is caused by a decrease in acetylcholine (ACh) production.
• One of the therapy options for improving cognitive and neural cell performance is to enhance cholinergic levels by inhibiting acetylcholinesterase (AChE).
• AChEIs work by preventing acetylcholine breakdown in synapses, resulting in a buildup of acetylcholine and activation of cholinergic receptors.
• Tacrine (tetrahydroaminoacridine) was the first FDA-approved cholinesterase inhibitor drug for the treatment of Alzheimer's disease.
• Tacrine works by increasing ACh in muscarinic neurons, but it was quickly taken off the market due to a high rate of side effects such as hepatotoxicity and a lack of benefits, as seen in several trials.

1. 1. Donepezil
   2. Galantamine
   3. Tacrine
   4. Rivastigmine

NMDA Receptor Antagonist

• In illnesses like Alzheimer's disease, NMDA-receptor ion channels may thus have an advantage over high-affinity blockers.
• The fundamental explanation for this is that low-affinity drugs temporarily block activated NMDA receptors, limiting primarily their pathological effects while leaving physiological processes unaffected.
• The medicine has reignited interest in NMDA antagonists, which were previously deemed to be "too toxic to be employed therapeutically" in humans.
• Improved cellular energy status and membrane function should be the therapeutic aim in Alzheimer's disease.

1. 1. Ketamine
   2. Dextrometraphan
   3. Memantine
   4. Amantadine

Anti-depressants

• The morphological/biological features of the hippocampus have been known to change during stress, and this has been linked to the development of depression.
• Antidepressants are thought to play a role in the creation of neurons in the brain by controlling neural stem cells.
• Despite a proven link between the two diseases, the impact of antidepressant medication on AD remains unknown.
• Antidepressants, on the other hand, can postpone the onset of AD by affecting inflammatory pathways and neurotransmitter balance.
• Furthermore, a wide range of antidepressant medicines has the potential to treat depression in Alzheimer's disease.

1. 1. Sertraline
   2. Mitrazepam
   3. Escitalopram
   4. Trazodone

Non-pharmacological treatment

• Meditation
• Yoga
• Punch karma