Alzheimer's disease could be detected over 20 years before symptoms appear


Alzheimer's disease could be detected over 20 years before symptoms appear


Scientists have found signs of Alzheimer's disease more than two decades before the onset of symptoms, among patients with a rare, inherited form of the disease.

The researchers from Banner Alzheimer's Institute in Arizona, USA, Boston University, USA, and the University of Antioquia, Colombia, reported their findings on two studies in The Lancet Neurology, November 6th, 2012 issue.

The authors say that their findings may provide scientists with an insight into how and why Alzheimer's disease progresses. They add that this could lead to better and much earlier detection of the disease, as well as more relevant and targeted clinical trials which focus on preventative treatments.

This inherited form of the disease is very rare. However, patients have provided researchers with a unique opportunity to seek out early signs of Alzheimer's, very long before the disease becomes apparent.

The problem with current Alzheimer's drug trials is "timing"

Setting up clinical trials which test a new compound's efficacy is very difficult, because participants with Alzheimer's have already sustained extensive damage to the nervous system. A novel drug would need to be tested earlier on; however, there has been no way of knowing who is in the very early stages of the disease before serious damage has occurred. Drugs have their greatest impact when a disease is starting.

Scientists suggest that they may be able to detect Alzheimer's Disease twenty years before symptoms develop.

If participants could be recruited earlier on, ideally those found to be most likely to have Alzheimer's long before symptoms appeared, clinical trials would be much more effective, and result in huge advances in achieving preventive treatments and interventions.

There are drugs today which scientists believe could delay the onset of Alzheimer's. Rapamycin, a medication prescribed for transplant recipients, could delay the onset of Alzheimer's, Parkinson's, and other neurodegenerative diseases.

Comparing participants with and without the PSEN1 mutation

The first study

The scientists carried out blood tests, brain scans and analyzed the cerebrospinal fluid of 44 adults - 20 of them had the PSEN1 mutation and 24 did not. Those with the mutation will definitely develop Alzheimer's symptoms. When the study began, none of them had signs of cognitive impairment.

Below are some highlights of the findings:

  • The brain structure and function of those in the PSEN1 mutation group differed from those in the non-mutation group.
  • Participants in the PSEN 1 mutation group had greater activity in the hippocampus and the parahippocampus; these are regions in the brain.
  • There was less gray matter in certain brain areas among the people in the PSEN1 mutation group.
  • Amyloid beta, a protein, was detected at higher levels among those with the PSEN 1 mutation.
Amyloid beta is an early biomarker of Alzheimer's disease. It is involved in the deposition of amyloid plaques in the brain. Before this study, amyloid plaques could be detected about ten to fifteen years before clinical onset of Alzheimer's. This study identified high amyloid beta levels in the cerebrospinal fluid before the amyloid plaques were even deposited in the brain, and a very long time before the anticipated clinical onset of Alzheimer's.

They found that Alzheimer's biomarkers can be detected at least two decades before symptoms appear - this is earlier than any other study that focussed on families with the inherited form of the disease.

Leader of the first study, Dr Eric Reiman, said:

"These findings suggest that brain changes begin many years before the clinical onset of Alzheimer's disease, and even before the onset of amyloid plaque deposition. They raise new questions about the earliest brain changes involved in the predisposition to Alzheimer's and the extent to which they could be targeted by future prevention therapies."

The second study

The same researchers used a scanning technique called florbetapir PET to detect amyloid plaque deposition in the brain in the PSEN1 mutation group.

They found that for those in the PSEN 1 mutation group, amyloid plaques start building up when they were in their late twenties.

They recruited 50 participants, some with and some without the mutation, they were aged from 20 to 56.

The researchers say the findings will "help set the stage for the evaluation of treatments to prevent familial Alzheimer's disease, and hopefully aid our understanding of the early stages of late-onset Alzheimer's disease, which is more widespread."

Written Comment in Lancet Neurology

Professor Nick Fox of the Institute of Neurology, University College London, UK, wrote:

"These findings question our models of Alzheimer's disease on several fronts. They suggest that neurodegenerative changes occur over 20 years before symptom onset and somewhat earlier than was suggested by previous brain imaging studies of individuals at risk of inherited Alzheimer's disease.

Further research is needed, but one interpretation of these results might be that they add to the accumulating evidence that Alzheimer's disease is characterised by a long presymptomatic period of slowly progressive changes that can potentially be tracked, thereby opening up a therapeutic window for early intervention."

About Alzheimer's Disease

Alzheimer's disease, also known as Alzheimer's, is a neurologic disease of the brain that eventually leads to irreversible loss of intellectual abilities, including reasoning, memory, speech, and comprehension. Alzheimer is a progressive disease - symptoms worsen with time.

During the course of Alzheimer's, plaques and tangles develop within the brain, which cause brain cells to die. Plaques are extracellular deposits of amyloid in the gray matter of the brain.

Alzheimer's patients also have low levels of some essential neurotransmitters; brain chemicals which are involved in the transmission of messages within the brain.

There is no cure for Alzheimer's disease. Modern treatment may help slow down its progression, as well as dealing with some of the symptoms. Eli Lilly's experimental drug, Solanezumab, slowed the rate of memory loss and cognitive decline by about 30% among patients in the early stages of Alzheimer's.

Alzheimer's is also a terminal disease - it causes death.

The National Institute of Aging says there are probably between 2.4 million and 4.5 million Americans with Alzheimer's. The Alzheimer's Society estimates that there are about 417,000 people in the United Kingdom living with the disease today.

Experts say that Alzheimer's can be hard to diagnose at first, because each patient has unique initial signs and symptoms, many of which exist in other conditions and diseases. It is classified into several stages. Some doctors use a 7-stage framework, while others may use a 4 to 6 stage one.

Alzheimer's starts slowly, and progresses relentlessly

Initial symptoms may be very subtle, and are often seen as normal age-related changes. There may be occasional memory lapses, such as forgetting words, familiar names, where one left one's keys or glasses.

As the disease progresses there may be some slight difficulties which affect everyday function; the patient may try to conceal the problems. It becomes harder to recall words, things become mislaid, things learnt recently are forgotten, organizing and planning things become more burdensome. The patient becomes moody and anxious, and sometimes depressed.

As the disease gets worse the patient is unable to look after himself/herself. In the advanced stage, patients cannot respond to their environment, are unable to speak, and eventually cannot control movement, cognitive ability becomes extremely limited, they can no longer recognize speech and may utter short words or simply utter sounds to communicate.

The ability to walk unaided is lost, and then to sit unaided too. The ability to smile is lost, and eventually the ability to hold the head up. Body systems start to fail and general health deteriorates. Swallowing becomes harder and harder and the patient chokes when eating or drinking. Reflexes become abnormal, muscles grow rigid. The patient spends more and more time asleep and is generally bedridden and requires round-the-clock care.

Nobody knows why people develop Alzheimer's disease, expect in the very rare cases of an inherited genetic mutation. One study suggested that Alzheimer's might be the result of a natural anti-cancer mechanism.


Can we treat Alzheimers 20 years early? (Video Medical And Professional 2018).

Section Issues On Medicine: Disease