Month: November 2022

One of the most investigated questions in Alzheimer’s research is its cause. The accepted theory for more than a century was that amyloid plaque formation in the brain resulted in the disease. However, a recent study has challenged this prevailing hypothesis, claiming that the disease results due to a decline in levels of a specific protein.

The Prevailing Theory: Amyloid Beta Plaques Cause Alzheimer’s

In 1906, Alois Alzheimer, a neuroanatomist and psychiatrist, reported a severe disease process of the cerebral cortex. The case subject was a 50-year-old woman who suffered from delusions, memory loss, aggression, hallucinations, and confusion some of the symptoms of Alzheimer’s. After her death, an autopsy showed distinctive plaques on her brain. These plaques were clumps of amyloid-beta protein, which is still considered the cause of Alzheimer’s disease.

The amyloid beta peptide is a naturally occurring protein derived from amyloid precursor protein (APP) in our brains that forms throughout life. According to the widely-accepted theory, it accumulates as amyloid plaques in the brain that are the markers of Alzheimer’s and the culprit involved in initiating the pathological cascade of the disease.

The basement membranes of the artery and capillary walls along the interstitial fluid drainage pathway are the routes for the elimination of Aβ. It is considered the perivascular lymphatic drainage pathway for the brain. However, as arteries in the brain age, they become stiff, thus, failing the perivascular elimination of Aβ. As a result, the protein accumulates in blood vessel walls as brain parenchymal plaques.

The Recent Research Findings: What Might Cause Alzheimer’s

The researchers have highlighted two main issues in the commonly accepted theory. First, it does not explain why the subjects have developed plaques in their brain without showing any neurological symptoms, such as memory loss. Second, it does not explain the reason for the failure of clinical trials for drugs that reduce these plaques (with one exception).

The initial soluble form of the protein responsible for carrying out crucial tasks in the brain degrades and is lost when amyloid-beta starts to build up as insoluble clumps (plaques). Research has revealed that decreased levels of this soluble protein called amyloid-beta 42 result in causing patients having worse clinical outcomes.

In the recent research published in the Journal of Alzheimer’s Disease, the question for investigation is whether it is the remaining amount of amyloid-beta 42 or the number of plaques in the brain which has a more significant role in Alzheimer’s disease progression.

The researchers hypothesized that plaques are simply the result of lower quantities of soluble amyloid-beta in the brain. These levels decline due to normal protein transforming into aberrant amyloid plaques in the presence of biological, metabolic, or viral stress.

The study team looked at the amyloid-beta levels in a group of people with rare inherited gene mutations that foretold an overabundance of amyloid plaques in the brain, thought to increase their risk of Alzheimer’s.

After an average of three years of follow-up, the researchers discovered that participants with high amyloid-beta 42 levels in their cerebrospinal fluid were protected and retained their cognitive abilities throughout the study regardless of the number of plaques in their brains.

It is also worth noting that in some uncommon, inherited forms of Alzheimer’s, such as those caused by the Osaka gene mutation or the Arctic mutation, people can acquire dementia with low levels of amyloid-beta 42 and no apparent plaques. It shows that low amyloid-beta 42 levels may be the source of their dementia rather than plaques.

Lecanemab – A Drug That Increases The Amyloid-beta 42 Levels

Based on the belief that Alzheimer’s patients will form fewer plaques if the protein levels decline, some researchers created medications to reduce the amount of amyloid-beta 42. Unfortunately, these drugs frequently made the patient’s condition worse.

A recent trial has reported an antibody drug, lecanemab, to have a significant effect in decreasing cognitive decline. The drug has exhibited an increase in the levels of amyloid-beta 42 in the CSF. This research also supports the hypothesis that a rise in the normal amyloid protein can be helpful.

However, further research in this field will bring more to light. The researchers believe that future trials should focus on amyloid-beta 42 levels and if it is helpful to boost and restore them to normal levels rather than targeting them for eradication. “Protein analogs” or proteins that resemble amyloid-beta 42 but do not clump together as much as their natural counterparts can help achieve this goal.

Research is still underway to clearly understand the cause of Alzheimer’s. However, if future trials focus on the active protein replacement approach, they might uncover a promising new treatment for protein aggregation diseases, such as Alzheimer’s, motor neuron disease, and Parkinson’s.

The holiday season can be a difficult time for families with Alzheimer’s. Even though it is typically a time for celebration, they may feel a sense of loss for how things used to be.

The holidays may also mean more responsibility and work for caregivers. They will have to consider the needs of their loved one with Alzheimer’s when decorating for the holidays and hosting gatherings.

Caregivers can discover meaningful ways to enjoy holidays by adapting their expectations and changing some traditions. The following tips may help them make the holiday season enjoyable for their loved ones.

Create a peaceful and safe environment

It is crucial to make preparations to ensure a calm and safe space for the person with Alzheimer’s. The following tips can help in this regard:

• Avoid potential hazards. Replace burning candles with electric candles. Do not let candles burn unattended if you light them. Avoid delicate ornaments or ornaments that could be mistaken for food, like fake fruit. Fix the Christmas tree to a wall if you have one.
• Avoid using blinking lights or huge decorative displays, which can be confusing. Also, avoid decorations that create clutter or necessitate rearranging a room familiar to the person.
• Play the person’s favorite music. Consider holiday music that is familiar or enjoyable for them. Adjust the volume to be calming rather than distressing.

Adapt holiday activities

The following tips can help you make the holidays for your loved one with Alzheimer’s more enjoyable:

• Make holiday preparations together, such as baking cookies, opening holiday cards, and making simple decorations. Concentrate on the task at hand rather than the consequence.
• Organize a small gathering and keep the celebrations calm and relaxed.
• Arrange a gathering at the optimal time of day for the person with Alzheimer’s. Maintain daily routines as much as feasible to avoid disturbances.
• If you have guests, ensure a quiet area where the person with Alzheimer’s may spend some time alone and relax.
• Make plans for meaningful holiday activities. You may read a favorite holiday story, browse through photo albums, watch a movie, or sing songs.
• Make your excursions brief. If you are going to a Christmas party, make your visit brief and be ready to depart early if necessary. Be sure there is a place for the person with Alzheimer’s to take a break and rest.

Preparing Visitors

It is crucial to let the guests know about the person’s behavioral changes before their visit. The following tips can help:

• Update and inform visitors beforehand of any modifications to behavior or memory from their previous visit. People may be better prepared for changes in appearance if you provide a recent photo.
• Offer communication tips to the guests and suggest that they listen patiently to the person. Ask them to refrain from correcting mistakes, criticizing repetitive comments, and interrupting.
• Inform your guests in advance of the activities you have planned or suggest something they might bring, for instance, a photo album.

Celebrating the holiday at a care facility

If a member of your family is in a nursing home or other type of care facility, consider the following:

• Try celebrating in the most familiar environment. Holding a little family celebration within the facility could be a good idea because a change in the atmosphere might be upsetting. You could participate in the festivities scheduled for the residents of the facility.
• Minimize the number of visitors. Make arrangements for a few family members to visit on different days. A large group could be intimidating for a person with Alzheimer’s.

Caregivers, remember! Simplifying celebrations, planning ahead of time, and establishing boundaries can help reduce stress and create an enjoyable holiday experience for you and the person with Alzheimer’s.

Depression can affect people at any age, whereas dementia often affects older people. Depressive symptoms, particularly clinical depression, are a chief symptom of dementia, but they may also be a significant predictor of dementia later in life.

With depression, the time course also varies significantly, with some people having only brief depression with complete recovery, while others experience remitting and relapsing depression over many years. Chronic depression can occur in certain persons; however, it is uncommon. All of these diverse categories may have varied long-term health outcomes.

The current research indicates the association of depression with increased dementia risk. However, it is still ongoing and needs further investigation.

What does the Research Say?

Scientists have conducted a lot of research to establish a connection between dementia and depression. Although some studies suggest a relationship between Alzheimer’s and depression, it is uncertain if it is a risk factor for the disease, an early sign of neurodegeneration, or a reaction to early cognitive abnormalities. Similarly, some studies have reported that depression symptoms occur soon after the onset of AD rather than before it. Furthermore, some others have indicated that depression has only a mild effect on dementia and does not increase the likelihood of Alzheimer’s.

There is also emerging evidence that depression is associated with cognitive decline. According to a meta-analysis of behavioral and psychological symptoms in cognitively normal middle-aged or older adults, depression was the most consistently related risk factor with behavioral or psychological symptoms and cognitive deterioration in Alzheimer’s patients.

In a study published in the Lancet Psychiatry, the researchers reported that those with growing depression symptoms were consistently associated with a higher probability of getting dementia. On the other hand, those who suffered from depression with less severe but persistent symptoms did not exhibit an elevated risk of acquiring the disease. However, another large-cohort study (with 10,000 participants) has concluded that early-life depressive symptoms did not increase dementia risk.

Both the above investigations discovered that extended depressed symptoms in later life (during the decade preceding dementia onset rather than earlier) are good predictors of increased dementia risk. Other studies have discovered similar links, such as the fact that having depression later in life doubles the risk of acquiring dementia. Furthermore, multiple studies have established that late-life depression might increase the risk of all-cause dementia, vascular dementia, and Alzheimer’s.

Researchers in San Francisco recently tried to investigate the possibility of early adulthood depression as a potential risk factor for dementia. They reported in the published study that depressive symptoms in young adulthood are associated with a 59% higher dementia risk.

A Swedish study evaluated the risk of dementia in individuals with and without depression. The researchers found that those with a depression diagnosis were more likely to develop dementia. The risk of dementia seemed to be the most significant in the first year following a diagnosis of depression. After that, it declined substantially over time but remained elevated for more than 20 years after the diagnosis.

Brain Changes in Dementia and Depression

Some previous studies suggest plausible mechanisms that make depressed people more prone to dementia.

Depressed individuals exhibit hyperactivity in the adrenal gland-stimulating area of the brain. As a result, these glands produce more glucocorticoids (such as the stress hormone cortisol). Higher cortisol levels can cause the impairment of the hippocampus, an area of the brain crucial for memory and cognitive function. Research has also revealed that people with Alzheimer’s may experience hippocampus atrophy.

According to research, other factors contributing to cognitive decline may also be at work. Vascular disease, changes in glucocorticoid steroid levels, hippocampus shrinkage, increased amyloid plaque deposition, inflammatory changes, and nerve growth factor abnormalities are among the possible molecular processes linking depression to dementia.