Alzheimer's disease is a neuropsychological ailment characterized by progressive degeneration of neurons, which results in dementia and mental impairment.

The condition involves symptoms of mild cognitive impairment that eventually results in complete memory loss, confused mental state, impaired decision making, and increased dependency. The patients affected by the disease forget even the most routine activities in their lives.

The difficulty in carrying out any tasks increases as the disease progresses. Alzheimer's patients also develop behavioral symptoms of apathy and social withdrawal. They also suffer from depression and bipolar mood swings.

Alzheimer's disease is classified into several types - based on onset time (late-onset, early onset), severity (severe, moderate, mild), and inflammatory response (inflammatory, non-inflammatory, cortical).

The hallmarks of Alzheimer's disease include the formation of neurofibrillary tangles of a protein called ‘tau’ that is used in the normal functioning of the brain and the generation of plaques of beta-amyloid proteins in the brain. These changes result in loss of cell-to-cell communication and ultimately cell death. Alzheimer's disease mostly affects the brain’s Hippocampus region.

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Incidence and Distribution

In 2016, approximately 47 million people live with dementia across the globe. Alzheimer's is the single most common cause of dementia, comprising 70% of all cases. The majority of the patients with Alzheimer's have late-onset (around 65 years of age or later), and few have early-onset during 40’s or 50’s.

Geographical distribution of Alzheimer's is slightly skewed. The western European countries and North America has the highest prevalence of Alzheimer's, followed by China, Latin America, and Western-Pacific countries. The incidence rates also depict similar picture, except for the fact that Latin America has a relatively higher incidence of Alzheimer's compared to the western European countries.

In the United States, approximately 5.7 million people are living with Alzheimer's. It’s the 6th leading cause of death in the United States, and the number of deaths skyrocketed by 123% between 2000 and 2015.

Epidemiological Factors

Alzheimer’s is believed to be the culmination of several different types of risk factors:

Genetic Risk Factors

Most cases of early-onset Alzheimer's depict the mutations in three distinct genes – PSEN1, PSEN2, and APP. Late-onset Alzheimer's is largely associated with a mutation in Apolipoprotein E4 (ApoE4) gene, especially in non-Hispanic White individuals. The direct correlation between ApoE4 and Alzheimer's was inconsistent in people of other ethnicities. Potential association of many other genes with Alzheimer's has come into light lately, albeit lacking a generalizable conclusion.

Non-Genetic Factors

Age is a major risk factor for Alzheimer's. In fact, Alzheimer's disease is predominantly a disease of aging. Females are more likely to develop Alzheimer's compared to males, partially because they live longer.
 

Hypertension has been found to be concurrent with Alzheimer's in some of the studies. The common understanding is that the increased blood pressure may cause damage to the integrity of the blood-brain barrier, and hence the transfer of toxic substrates in the brain causing neuronal damage and cognitive impairment.

Cerebrovascular disease is also a risk factor for Alzheimer's. Ischemic infarcts and vasculopathy in the brain pose a great risk. These have been associated with increased chances of Alzheimer's. However, the mechanism remains unestablished.

Type 2 diabetes increases the Alzheimer's risk by two-fold. The mechanism is not clear, but it is believed to be due to glucose hypometabolism and resultant inflammation in the brain. Also, the increased levels of plasma lipids are associated with high risk of Alzheimer's. This risk is further confirmed by a genetic link with mutation of genes responsible for lipid metabolism.

A person’s body weight can also be a risk factor. A high, as well as a low body weight, are considered to heighten the risk of developing Alzheimer's in later life. Physical activity can influence the development of Alzheimer's disease. It is a well-known fact that physical exercise can upregulate several neurotransmitters in the brain, and can enhance cognitive as well as logical reasoning functions. Thus, being physically active may reduce the risk of the development and progression of the disease.

Some studies have linked metabolic syndrome with the symptoms of memory loss. On the other hand, historical data indicate that a past brain injury (traumatic brain injury) can increase the chances of Alzheimer's and dementia in general.

One’s diet may also contribute to the development of the disease. Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is recommended to substantially minimize the risk of developing Alzheimer's as well as for preventing further neural damage in patients with the condition. This includes consuming green leafy vegetables, whole grain carbohydrates, wine, nuts, beans, and berries, among others. On the other hand,  the diet recommends avoiding processed foods, cheese items, and desserts.

The exposure to pollution may also increase the risk of developing Alzheimer's. Particulate matter, such as magnetite and nickel, pose a great risk of Alzheimer's. Even though the role of air pollution as a direct causative agent is not proven, it definitely enhances the risk of Alzheimer's in conjugation with other risk factors.

The evidence of the link between smoking and the development of Alzheimer's is controversial, albeit smoking is largely considered harmful, and hence should be avoided. Lastly, behavioral and observational studies indicate a significant benefit against dementia in the individuals who get involved in learning new things, reading, and playing games, to name a few.

Biomarkers

The levels of plasma, as well as cerebrospinal fluid biomarkers, are affected by Alzheimer's disease. This fact makes them a helpful tool in the accurate diagnosis of Alzheimer's early on.

Major plasma biomarker that is involved in Alzheimer's pathophysiology is ‘Abeta’ (Aβ). Others are interleukin 1 beta (IL-1β), C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor (TNF).

CSF biomarkers investigated for Alzheimer's and dementia include, but are not limited to, angiotensinogen, 24S-hydroxycholesterol, apolipoprotein E, complement components C3a and C4a, thioredoxin, vascular growth factor, N-acetyllactosamine, cystatin C etc.

Structural and functional MRI techniques along with biomarker assessments are utilized to understand the anatomical and physiological changes in the brain for evaluation of Alzheimer's.

A great deal of information has become available through extensive research on Alzheimer's during past few decades. Further research is needed to understand the exact cause, and to develop precise management approaches for Alzheimer's.