RECENT ADVANCES IN ALZHEIMER'S RESEARCH

[Guest guest]

A very good morning to all NETRUMIANS. I am Mrinmoy Chakrabarty, from Dept. of Pharmacology, Veer Chandra Singh Garhwali Govt. Medical College and Research Institute, Srinagar, Pauri Garhwal, Uttarakhand. I am commencing a discussion on " RECENT ADVANCES IN ALZHEIMER'S RESEARCH" today and look forward to interacting with you on this theme. I expect to be able to cast light/ views on some of your queries or opinions and at the same time get stumped by the sheer insight of others. But then, that is the factor that spurs us to e- network for discussion on a topic. I felt a better discussion on the main theme would be facilitated with some information on few topics surrounding it and hence, am taking it up in a step wise manner with appropriate peripheral content.

1. Premise

Decades of research have proved futile to rein in the relentless progression of Alzheimer's disease (AD). With some of the most promising forerunner therapeutic molecules failing in late phase clinical trials lately and the existing modern therapies yielding only modest, short term benefits at the cost of different side effects, the scenario as of now is grim and looms large with the world burden of Alzheimer's slated to touch 65.7 million mark by 2030 and 115.4 million by 2050.

The disease biology is still obscure with experts trying to have a better handle on the course of the disease progression. Every small detail is being re read, every single hypothesis scrutinized and every single notion re- considered to put together the pieces of the Alzheimer's puzzle.

2. A Brief History

AD was discovered in 1907 by Alois Alzheimer, but was not considered a major disease or disorder until the 1970s. Alzheimer documented a case of a woman in her fifties, August Deter who exhibited severe cognitive disorders pertaining to memory, language, and social interaction, according to Khachaturian and Radebaugh who have authored a book titled "Alzheimer's disease: Cause(s), Diagnosis, Treatment, and Care."After the patient's death, Alzheimer performed an autopsy on her brain, using a silver staining technique that allowed him to visualize the neurons. In the process he found unusual formations, now known as amyloid plaques and neurofibrillary tangles. Alzheimer hypothesized that these lesions might be the cause or effect of the as yet to be named AD, or possibly a combination of the two. The disorder was later named after Alzheimer as more people were found to have the symptoms associated with his findings. In retrospect, before Alzheimer's 1907 discovery, scientists, clinicians and laymen took dementia as a "natural" progression of age, and "senility was accepted as a part of aging."

Additionally, AD was not differentiated from other types of age-induced dementia or senility. AD did not suddenly "appear" in 1907, rather it was then that the disease was first recognized and named.

Even with Alzheimer's discovery, however, the disease was not one that was accepted as, well, a "disease." Senility and dementia were still considered part of the aging process. Whaley states that AD did not become a common term, or even a large concern, until neurobiological research exploded in the late 1970s.

3. Dementia:

With a greater degree of prosperity setting in, we have a bigger ageing population to deal with and increasing age goes hand in hand with many of its attendant risks.

Dementia is one such prominent one for which we do not have a prevention, leave alone cure. It is defined as a generalized loss of cognitive abilities, including impairment of learning-memory with one or more of aphasia (defect or loss of power of expression by speech, writing, signs), apraxia (loss of ability to carry out familiar, purposeful movements, esp. inability to use objects correctly), agnosia (inability to recognize the import of sensory impressions e.g. auditory, gustatory, olfactory, tactile, visual), disturbed planning, organizing, abstract thinking abilities.

To simplify it is the loss of thinking, memory, and reasoning — that is severe enough to interfere with a person's daily functioning. Dementia is not a disease itself, but rather a group of symptoms that might accompany certain diseases or conditions. Symptoms also might include changes in personality, mood, and behaviour. Dementia is irreversible when caused by disease or injury, but might be reversible when caused by drugs, alcohol, hormone or vitamin imbalances, or depression.

Dementia develops when the parts of the brain that are involved with learning, memory, decision-making, and language are affected by any of various infections or diseases. The most common cause of dementia is AD, but there are as many as 50 other known causes.

Some of the disorders that cause dementia might be reversible, although unfortunately most types of dementia do not respond to treatment.

There are many causes of dementia but the most common causes include:

Degenerative neurological diseases, such as Alzheimer's, dementia with Lewy bodies, Parkinson's, and Huntington's

Vascular disorders, such as multiple-infarct dementia, which is causes by multiple strokes in the brain

Infections that affect the central nervous system, such as HIV dementia complex and Creutzfeldt-Jakob disease

Chronic drug use

Depression

Certain types of hydrocephalus, an accumulation of fluid in the brain that can result from developmental abnormalities, infections, injury, or brain tumors

AD causes 50 percent to 70 percent of all dementia. However, researchers are finding that some of what was previously considered AD is really one of two other degenerative diseases: Lewy body disease and Pick's disease. There also are a number of other important disorders that can lead to dementia.

Dementia is considered a late-life disease because it tends to develop mostly in elderly people. About 5 percent to 8 percent of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. It is estimated that as many as half of people 85 or older suffer from dementia.

Dementia is not a disease; it is the clinical presentation or symptoms of a disease. In a nutshell, dementia is a symptom, and AD is the cause of the symptom.

4. Types of dementia

Although they are classified variedly based on different criteria, one of the broadest classifications based on the part of brain that is principally affected is

Cortical dementias arise from a disorder affecting the cerebral cortex, the outer layers of the brain that play a critical role in cognitive processes such as learning, memory and language. Alzheimer's and Creutzfeldt-Jakob disease are two forms of cortical dementia. Cortical dementia typically show severe memory impairment and aphasia.

Subcortical dementias result from dysfunction in the parts of the brain that are beneath the cortex. Usually, the memory loss and language difficulties that are characteristic of cortical dementias are not seen. Rather, people with subcortical dementias, such as Huntington's disease, Parkinson's Disease, and AIDS dementia complex, tend to show changes in their personality and attention span, stagnancy and slowing in thinking.

Treatable causes of dementia are reversible disorders that can be cured completely, or at least partially, by treating the underlying disorder. For example, dementia caused by any of the following are often at least partially treatable:

Chronic drug abuse

Tumours that can be removed

Subdural hematoma, an accumulation of blood beneath the outer covering of the brain that results from a broken blood vessel, usually as a result of a head injury (which can be minor and even unrecognized)

Normal pressure hydrocephalus

Metabolic disorders, such as a vitamin B12 deficiency

Hypothyroidism, a condition that results from low levels of thyroid secretion

Hypoglycemia, a condition that results from low blood sugar

Non-treatable causes of dementia include:

AD

Multi-infarct dementia

Dementias associated with Parkinson's disease and similar disorders

AIDS dementia complex

Creutzfeldt-Jakob disease (CJD), a quickly progressing and fatal disease that is characterized by dementia and myoclonus — muscle twitching and spasm

Since it is Day 1 of the discussion, we restrict ourselves to these generalized aspects and gradually move to the thick of Alzheimer's neurodegeneration in the days to come. Looking forward to your participation and Have A Great Day Ahead .