Researchers in the Netherlands discovered a subset of people in a national brain bank whose brains showed indicators of Alzheimer's but never exhibited symptoms while living. Although some experts claim this is an uncommon event, it is possible because the disease's hallmark amyloid deposits can occur decades before symptoms manifest.

Researchers in the Netherlands have uncovered an astounding discovery while reviewing data from over 2,000 brains at the Netherlands Brain Bank.

They discovered that a subset of individuals exhibited distinct signs of Alzheimer's in their brain tissue but did not exhibit any symptoms while they were living. Acta Neuropathologica Communications published the study [1].

They only identified 12 of these people from the available brain tissue and recorded the essential clinical data. However, it prompted several questions concerning the disease and the factors that contribute to an individual's resilience.

How Might Alzheimer's Progress Without Symptoms?

The phenomenon of Alzheimer's without symptoms is known as "resilience."

In the resilient group, researchers discovered that astrocytes, or "garbage collectors" that help protect the brain [2], appeared to produce more of an antioxidant known as metallothionein.

Astrocytes can cause inflammation in the brain when they interact with microglia. However, the pathways linked to Alzheimer's appeared less active in the resilient group.

Additionally, researchers discovered that the resilient group's brain cell response— meant to eliminate any hazardous misfolded proteins—was relatively normal. 

This so-called "unfolded protein response" is commonly impaired in Alzheimer's patients. There were also indicators that resilient individuals' brain cells contained more mitochondria than those of other Alzheimer's patients, implying that energy generation must be stronger in this group.

Cognitive Reserve and “Resilience”

According to David Merrill, MD, PhD, a geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in Santa Monica, CA, genetics and lifestyle influence this type of resilience [3].

Cognitive reserve [4], the brain’s resilience to damage, is critical. Furthermore, genetic, behavioral, and environmental elements can all influence the onset and severity of symptoms, regardless of the underlying pathology.

Cognitive reserve is the brain's ability to withstand the impacts of age-related changes or disease-related pathology, such as beta-amyloid, which normally causes a loss in cognitive function. It suggests that people's lifetime experiences and knowledge help them better manage pathologies like beta-amyloid and sustain cognitive function for longer.

You can read books, pick up a new language, learn to play an instrument, enroll in a class to learn something new or engage in other stimulating and challenging activities to build up your cognitive reserve.

Is Alzheimer's Without Symptoms Common?

According to Merrill, adult children or spouses of individuals with Alzheimer's may visit the clinic for testing even in the absence of symptoms. However, most patients at the clinic seek treatment after symptoms manifest.

Patients without symptoms are uncommon, whether they have Alzheimer's or not. Since the initial signs of the disease might resemble those of normal aging, many people wonder if what they are experiencing is normal or the start of the disease.

He further stated that In clinical practice, asymptomatic people can have Alzheimer's pathology, although this is the exception rather than the rule. It is consistent with recent findings—reported in the study—that Alzheimer's may exist in the absence of obvious cognitive symptoms, presumably as a result of cognitive reserve or compensatory mechanisms in the brain.

Yuko Hara, PhD, director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation (ADDF), who was not involved in the study, stated that Alzheimer's markers can appear early in life, even without the existence of usual symptoms [3].

Many people have pathological markers, beta-amyloid, for the disease but do not exhibit symptoms. Beta-amyloid can begin to build up in the brain as early as the 20s [5].

Amyloid deposition in the brain begins decades before the appearance of Alzheimer's symptoms. According to one study, amyloid pathology was present in 44% of 90-year-olds with normal cognitive function [6].

She further added that there are also genetic mutations that provide protection against a genetic variant of Alzheimer's. She did point out that these seem to be uncommon occurrences. 

A 2019 study found that a lady with the presenilin 1 (PSEN1) mutation, which causes early-onset Alzheimer's disease, did not acquire dementia in her 40s like others with the mutation. Instead, in her 70s, she experienced very slight memory deterioration. Despite having excessively high amounts of beta-amyloid in her brain, researchers discovered that the woman has two copies of an uncommon mutation known as the APOE3 Christchurch mutation, which may have made her resistant to the development of Alzheimer's symptoms by 30 years [7].

Genetics and lifestyle choices can contribute to the development of so-called resilience to Alzheimer's symptoms. However, engaging in cognitively stimulating activities can help counteract these symptoms.

Alzheimer’s Research Association is a non-profit organization dedicated to helping caregivers of Alzheimer’s disease and dementia. We provide the latest information and news about the illness and helpful tips to help caregivers cope with their daily caregiving challenges. We realize the most important thing that a caregiver needs is financial assistance. Therefore, we provide grants to caregivers to ease their financial burden. Caregivers can apply for grants here: Alzheimer's Grant Application. 

You can also help caregivers in their endeavor by donating as much as possible: Donation To Alzheimer's Research Associations.