Alzheimers Disease

What is Alzheimers Disease?

Alzheimers Disease is an age-related degenerative brain disorder

characterized by the abnormal accumulation of extracellular deposits called

Amyloid Plaques and intra-neuronal tangles of fibrils in the brain. These

changes lead to neuronal atrophy and synapse loss in the medial temporal

lobe limbic structures that are critical for short term memory and extend to

the association cortices of the frontal, temporal, and parietal lobes as the

disease progresses. (Braak and Braak, 1991). It is the leading cause of

dementia, a pattern mental decline characterized by impairment in memory

and at least one other cognitive function such as language or executive

functions, thus impacting upon behavior and interfering with social or

occupational functioning (American Psychiatric Association, 2000).

Diagnosis:

Until Recently, most of our understanding of the physiological pathology

surrounding the terrifying decline of the patients mental faculties, their loss

of memory, loss of language, loss of social connections of a whole lifetime,

came from information gleaned from post mortem autopsies, way too late to

do anything for hapless patients who eventually succumb to the disease

after years and years of decline. The clear presenting common factor in all

cases has been two identifiable abnormalities of structure, the first being the

accumulation of plaques called Beta Amyloid Plaques.These plaques are

caused by the bundling of protein fragments called amyloid precursor protein

whichcollect in the spaces between neurons in the brain. The second

abnormal factor occurs within the Neurons themselves, a series

neurofibrillary tangles of abnormal, insoluble clumps of a protein called tau.

Normally these neurofibrils form part of the transport system within the

neuron itself, for if you picture a neuron, it is incredibly long in comparison to

the cell body size, with dendritic branches receiving neural impulses from the

thousands of connected neurons, as well as the axon, which is the afferent

branch carrying each neurons impulses to its connected neurons. The

neurofibrils, together with the microtubules, can be visualized as a railway

track with the track itself and the sleepers securing the track in position. It

seems that the sleepers come loose and the line falls apart, and the train

transporting nutrients and materials to the far reaches of the neuron

becomes derailed.

The two above mentioned anomalies lead to the functional decline of the

neuron, as the cell thrives on synaptic connections with other cells, and this

function is seen as the Raison Detre of neurons, and form the billions of

trillions of possible connection combinations which allow our brains, in the

words of Dr VS Ramachandran, to contemplate the universe, to contemplate

the concept of infinity, and to contemplate itself contemplating infinity!! The

net effect results in a generalized atrophy of the brain which manifests in the

ongoing deterioration of short term memory, loss of speech and other

executive functions and deepening dementia as the disease progresses.

More recently, however, brain imaging techniques have been developed,

which for the first time allow doctors to see and measure the presence and

development of Beta Amyloid Plaques and Neurofibrillary tangles in live

patients. This has opened the possibility of studying the correlation

between the plaques and tangles to the progress of the disease in real time,

and studies conducted at the University of Kentucky that there is a

correlation. In addition, they have discovered that many people develop the

amyloid plaques and the neurofibrillary tangles at an early age, but are

asymptomatic, until it reaches a point where the levels of plaque begin to

present with signs of degeneration.

This means is that we now have access to technology which gives us early

warning, a bit like RADAR allowed us to see approaching bombers hours

before we could actually see them, giving a window of opportunity to do

something about the condition while still asymptomatic.

This has been referred to as risk markers or risk assessment, and recent

studies at the said Kentucky University are being conducted into ways to

forestall or avert the development of the disease.

One of the exciting observations is that lifestyle plays an important part in

the way that the disease progresses, and that even where the risk markers

have become present, that lifestyle changes such as exercise and diet

positively impact the progression of the disease.

The Kentucky University is currently conducting trials to assess different

types of exercise, different amounts of exercise and optimal regimens of

exercise, with the view that exercise may be prescribed almost in the same

way that drugs are deployed to treat other diseases.

Additional risk factors which have been identified are levels of cortisol, linked

to our levels of stress, which increases our risk of developing Alzheimers

Disease (AD).

Tools for diagnosing probable Alzheimers disease include a medical history,

a physical exam, and testspreferably over timethat measure memory,

language skills, and other abilities related to brain functioning. Information

provided by family members or other caregivers about changes in a persons

day-to-day function and behavior also help in diagnosis. Currently, a

definitive diagnosis of Alzheimers can be made only after a brain is

autopsied after death. However, in specialized research facilities such as the

NIAs network of 29 Alzheimers Disease Centers, clinicians may also use

brain scans and biomarkers in blood and cerebrospinal fluid to help diagnose

Alzheimers dementia in people who may or may not be participating in a

clinical trial.

In other research it has been shown that Insulin resistance in peripheral

tissue , a hallmark of type 2 diabetes, also develops in Alzheimers disease

(AD) brains (Beeri MS, Middleton L). This means that by being physically

active, maintaining good body mass index and a healthy diet, we can
ameliorate our risk of developing AD. (Neurology 2012;78: 1290 1291.)

Brain levels of insulin and insulin receptor (IR) are lower in AD, and insulin

signaling impairments have been documented in both postmortem analysis

and in animal models of AD (e la Monte SM. Insulin resistance and

Alzheimers disease. BMB Rep. 2009;42(8):475481). Brain insulin signaling

is particularly important for learning and memory (Chiu SL, Chen CM, Cline

HT. Insulin receptor signaling regulates synapse number, dendritic plasticity,

and circuit function in vivo. Neuron. 2008; 58(5):708719.), suggesting that

insulin resistance may contribute to cognitive deficits in AD.