Aging and the Alzheimer’s brain: what we know in 2020

The best known and most common type of dementia is Alzheimer’s dementia (commonly known as Alzheimer’s disease). It alone accounts for around 60% to 65% of dementia cases. The Alzheimer’s brain affects only the thin outer layer of grey matter, the cortex.

Because it begins in a progressively old region of the cortex involved in memory, the hippocampus and the cortex entorhinal, the first observable deficits of this type of dementia are therefore memory disorders. The best known and most common type of dementia is Alzheimer’s dementia (commonly known as Alzheimer’s disease). It alone accounts for around 60% to 65% of dementia cases.

Alzheimer’s dementia affects only the brain. And in the brain, it’s only the thin outer layer of grey matter, the cortex, that is affected. Because it begins in a progressively old region of the cortex involved in memory, the hippocampus and the cortex entorhinal, the first observable deficits of this type of dementia are therefore memory disorders.

Our brain, like the rest of our body, is transformed throughout our lives. After the rapid and spectacular development of the first years, brain plasticity slows down but persists throughout adult life. As we age, however, it’s not unusual to see a gradual decline in our intellectual faculties, including our memory.

After death, a patient’s brain may show cortical atrophy in the presence of both types of lesions characteristic of Alzheimer’s, and amyloid plaques and neurofibrillary tangles will confirm the suspicions.

Scans of alzheimers brain compared to normal brain
Brain with amyloid plaques


This is a natural phenomenon associated with normal ageing. Sometimes this decline is much faster for some, and there are disastrous consequences for their lives and those of their loved ones.

The general term dementia, which appeared at the beginning of the 19th century, is then used to describe this phenomenon. Dementia was then part of what was then called “insanity,” which also included schizophrenia and mood swings. And since it is elderly people who most often have the most serious symptoms, there was the talk of “senile” dementia, an expression that is less and less used.

Drug Failures and Lifestyle Changes

After the latest drug trial for aducanumab was halted in March for its observable risks, many Alzheimer’s patients and their loved ones were understandably disappointed. With a long string of consecutive drug failures, Alzheimer’s is increasingly perceived as impossible to cure. However, some studies show that we may be looking in the wrong places for viable methods to reduce and improve the symptoms of Alzheimer’s disease.

The Finnish Geriatric Intervention Study To Prevent Cognitive Impairment and Disability (popularly known as the FINGER study) was a two-year European study observing the effects of a number of lifestyle choices on influencing risk factors for Alzheimer’s. It demonstrated considerable benefits to a healthy diet, sufficient sleep and exercise in a control group of over a thousand adults in the 60-77 age range. This has lead researchers to speculate that lifestyle intervention and counselling may be a more viable controller of Alzheimer’s risk factors than any of the drugs in the clinical trial today.

New Findings Show Numerous Brain Abnormalities Are Associated With Alzheimer’s

A recent systematic review compiles findings that show the vast majority of Alzheimer’s cases are not isolated from brain anomalies. Factors such as chemical imbalances, abnormal protein syntheses and past strokes were observed to play a consistent role in the emergence of dementia symptoms in at-risk adults.

Possible Links Between Brain Abnormalities, Alzheimer’s and Viable Medication

In light of the July 2018 review, researchers are increasingly convinced that the diagnosis of Alzheimer’s is most likely linked to other conditions in patients suffering from the disease. If this assertion can be substantiated in future studies, it could redefine the current-day approach to treating Alzheimer’s with prescription drugs. By eliminating concurrent disorders, it may be possible to significantly reduce, improve or even eliminate symptoms of Alzheimer’s disease.

Understanding a Rare Genetic Mutation Which Could Hold the Key

A case study in the journal Nature Medicine studied a woman whose genetic profile showed that she would begin to suffer from Alzheimer’s disease by her 50th birthday. She was born with a heredity gene mutation that had affected many of her relatives, going back generations, causing the onset of rapid cognitive deterioration from the age of 40. Surprisingly, by the time of her 70th birthday, she was yet to suffer any decline in cognitive ability.

The woman had an extremely rare brain mutation which helped to fight the onset of Alzheimer’s by minimizing the binding of a sugar compound to a gene known to be important in the development of the disease. The researchers involved are positive that treatments could be developed in order to induce these same protective measures in other patients.

Dementia and Language

At the language level, the Alzheimer’s brain tends to compensate for the forgetting of specific terms by boilerplate words like “thing,” etc. Memory problems can extend to important dates like birthdays, names of famous people. Motor skills with familiar household appliances can also be affected.

At the emotional level, the person can become sad, unstable, and even verbally or physically aggressive. He or she will sometimes have social disinhibition with excessive familiarity, sometimes fearful behavior or suspicion. Episodes of euphoria, depression or anxiety may occur.

Alzheimer’s  Behavior

At the behavioral level, there is a decline in interest for others, a loss of contact with friends, a gradual abandonment of leisure. There is often a slowdown in the speed of movement, causing difficulties with driving a car, for example.

Other functions will then be altered, such as language, orientation in time and space, action planning, recognition of faces or objects, and so on. The person can also have mood swings or become apathetic or depressed. At an advanced stage, the confusion and laborious movements make the patient lose the autonomy necessary for everyday life (washing, dressing, eating).

Although it isn’t yet known how to stop the progression or even cure Alzheimer’s dementia, different medications and therapeutic approaches can relieve some symptoms and improve the quality of life of patients.

Research on Aging and Neuronal Deterioration

This is another area where a lot of research is done. There are two major degenerative processes recently brought to light which are associated with neuronal death. They were markings outside and inside the neurons first described by the German doctor Alois Alzheimer in 1906. We speak of neurodegenerative diseases to designate various pathologies leading progressively to the death of the neurons and to the destruction of the nervous system.

While some of these diseases affect children or young adults, the majority occur after age 65. The attacks can be predominantly cognitive, as in the case of Alzheimer’s dementia, predominantly motor-related, as in Parkinson’s disease, or the combination of both, as in Huntington’s chorea or Creutzfeldt-Jakob disease.

There are some similarities between different neurodegenerative diseases. For the most part, genetic factors causing a hereditary form of the disease are known, but the disease also occurs in a form called “sporadic,” in people who have no family history, and it does not exclude the implication of genetic factors.

Different Neurons, Different Neurodegenerative Diseases

The types of neurons, as well as the affected brain areas, vary greatly depending on the different neurodegenerative diseases. Pyramidal neurons of the temporal cortex are severely affected by Alzheimer’s dementia. With Parkinson’s disease, it’s the neurons of the substance that secrete dopamine that degenerates. In patients with Huntington’s disease, atrophy occurs in the striatum, caudate and putamen, in those with amyotrophic lateral sclerosis, motor neurons in the cerebral cortex, and motoneurons in the spinal cord. For those with multiple sclerosis, the myelin sheath surrounding the central nervous system axons is affected.

Amyloid-beta is found in healthy cells but builds up in brains of individuals with Alzheimer’s disease. Studies have found a connection between this peptide, autism, and related disorders.

Biological Markers for Alzheimer’s

Researchers have been trying for decades to discover a biological marker that would distinguish Alzheimer’s from normal ageing and other neurodegenerative diseases. The simplicity of a blood test where one would detect certain molecules revealing the presence of Alzheimer’s type dementia, however, is still awaited.

This diagnosis remains difficult to establish, often because the symptoms of Alzheimer’s can be like mild memory loss or symptoms of other diseases such as depression. Moreover, it’s still only a “probable” diagnosis that is done by eliminating other possible causes (the so-called “differential diagnosis” approach). As a first step, the doctor will interview the patient and try to see if he or she is suffering from dementia by eliminating other conditions that cause similar symptoms (reaction to certain drugs, brain tumor, stroke). Due to the heterogeneity of the symptoms of Alzheimer’s, the doctor also questions the patient’s relatives to try to better understand the evolution of memory loss and other difficulties experienced daily.

The Link Between Financial Scams, Victimhood and Alzheimer’s Disease

A small US study reports that not only are cognitively impaired adults more likely to fall victim to financial scamming; victims of scans are more likely to develop Alzheimer’s, as well. There is some valid criticism of the study, citing its limitations in methodology (namely the use of questionnaires) and ability to follow up with subjects several years after the first questionnaires.

These limitations somewhat hamper the validity of the assertion that low scam awareness can be a very early sign of Alzheimer’s disease.

Standardized Tests Imaging For The Alzheimer’s Brain

An Alzheimer’s brain next to a larger normal brain
The Alzheimer’s brain is smaller than a normal individual’s

Standardized tests, such as the MMS (for “Mini-Mental Status”, in English), then make it possible to evaluate the severity of the attacks on various cognitive abilities of the patient (location in time and space, memorization, attention, calculation, etc.). If necessary, the doctor can also advise the patient to have a brain imaging test to increase the likelihood of diagnosis. These techniques are unfortunately not always accessible because of their high cost. But they can allow a doctor to evaluate, for example, the cortical atrophy in various brain regions, the increase in the size of the cerebral ventricles, and the decline in the metabolism of regions involved in the memory. They also eliminate other causes such as brain tumors, meningiomas, multiple ACVs, etc.

Risk Factors and Prevention

The precise cause of many diseases is known. Measles, for example, are due to a virus, tuberculosis to a bacterium and malaria to a protozoan. But as is the case for many chronic diseases, there is no clearly identifiable cause for Alzheimer’s. It’s generally agreed that this type of dementia develops under the influence of several factors. These risk factors can combine and override the natural mechanisms of brain self-repair. Then cascades of biochemical reactions will lead, years later, to the appearance of the first symptoms of Alzheimer’s. These risk factors, specific to each individual, can be grouped into three broad areas.

Nature vs. Nurture
First of all, the family antecedents, that is to say the genes that we inherit from our parents. These hereditary factors may predispose to developing Alzheimer’s in some families. In the rare “familial” form of Alzheimer’s, these genetic factors will have an even more direct effect.

Environmental Factors
For several decades, it was believed that it was from environmental factors that Alzheimer’s was developing. But the viral, bacterial or toxic tracks of these so-called purely environmental hypotheses have fallen one after the other. Nevertheless, we know today that the wider environment (diet, stress level, intellectual stimulation or physical exercise, etc) has an influence on the development of Alzheimer’s. And for those affected, a healthy and stimulating lifestyle puts the odds on their side.

Physiological Disturbances
Finally, as we grow older, the interaction between our genetics and the environment in which we evolve is at the origin of concrete disturbances in our body. This means chemical imbalances, immune deficiency, excess of toxic free radicals, or malformed proteins that disrupt the inner workings of neurons or become toxic by accumulating around them. Without being the ultimate cause of Alzheimer’s, each of these physiological disturbances contributes to aggravate it by way of the problems they generate in the neuronal communication.

What are The Mechanisms Behind Alzheimer’s?

As is often the case in science, different hypotheses still exist, but most have taken as a central point one or the other of these dysfunctions. Thus, the cholinergic hypothesis is one of the oldest and from which most drugs to treat Alzheimer’s have been created. The amyloid hypothesis put forward in the early 1990s, assumes that it is the deposition of amyloid plaques between neurons that is the primary cause of Alzheimer’s disease. It is based on the fact that the form 4 of the apolipoprotein E gene, which is a recognized risk factor for Alzheimer’s disease, leads to an overproduction of the amyloid fragment at the origin of the plaques. As research continues, this hypothesis continues to dominate despite growing criticism of it.

The tau hypothesis, meanwhile, gained momentum, particularly following a 2004 study showing that there is no clear correlation between amyloid plaque deposition and neuronal loss. The name of this hypothesis refers to that of a protein located in the axon of neurons. It takes abnormal forms in Alzheimer’s, rendering the axon transport system non-functional, its communication functions deficient, and possibly the death of the neuron. And it is this cascade of events that would be, according to this hypothesis, the origin of Alzheimer’s.