Early Onset Alzheimer’s Risk Factors

How The Study Worked

The researchers analyzed the primary healthcare records of 20,214 people with Alzheimers disease in the United Kingdom and 19,458 people with Alzheimers in France.

They compared each persons medical records with a control matched for sex and age who had not received a diagnosis of a progressive brain disease during the 15-year study period.

Out of the 123 health conditions they investigated, 10 had a statistically significant association with a diagnosis of Alzheimers disease 210 years later in France and the U.K.

Some of the conditions, such as depression, hearing loss, and sleep disorders, are already known risk factors for Alzheimers.

However, this study was the first to identify constipation as a possible risk factor. The link between the two conditions became apparent 7 years before the diagnosis of Alzheimers.

Interestingly, constipation is also associated with depression and is an established early sign of other brain diseases, such as Lewy-body dementia and Parkinsons disease.

The connections made allowed us to confirm known associations, such as hearing problems or depression, and other less-known factors or early symptoms, such as cervical spondylosis or constipation, says Thomas Nedelec, Ph.D., the first author of the study.

The question remains as to whether the health problems encountered are risk factors, symptoms, or warning signs of the disease, he added.

In their paper, the authors conclude:

Common Risk Factors For Early Onset Dementia

Early onset dementia or young-onset dementia is dementia that absorbs the patient before the age of 65. Dementia affects about 35.6 million people all around the world, out of which an estimate of four to ten percent is YOD or early onset dementia. This type of dementia hits the person when they are young, approximately at the age as early as 30-35. Dementia is caused when there are plaques built around the brain, risk factors of early onset dementia gene mutations that affects the production and processing of this plaque. There are 8 risk factors for early onset dementia that account for about 68 percent of this condition, here are they in order of importance:

Apoe Genotyping And App Copy Number Analysis

APOE genotypes were determined by either clinical testing, sequencing data, or SNP arrays. Additionally, copy number variation of the APP gene was assessed in at least one member of the included families, either using a made-to-order TaqMan assay or by CNV analysis of SNP arrays using the PennCNV algorithm .

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Risk Factors For Alzheimer’s Disease

Early-onset AD is infrequent, making up approximately 10% of AD cases seen in clinical practice. Most cases of early-onset AD are familial they have been linked to specific identifiable mutations and have an autosomal-dominant pattern of inheritance with nearly full penetrance. Mutations in the Alzheimer precursor protein gene on chromosome 21, the Presenilin-1 gene on chromosome 14, and the Presenilin-2 gene on chromosome 1 have been identified, and they account for approximately 50% of all cases of early-onset familial AD. Also, most individuals who have trisomy-21 , and therefore three APP genes instead of two, develop AD at relatively early ages, supporting the theory that the overexpression of the APP protein may be involved in causing AD.

Jose A. Soria Lopez, … Gabriel C. Léger, in, 2019

Preparing For Early Onset Ad

Receiving an early onset AD diagnosis can be worrying. Now is the time to put together a plan so that you have peace of mind for the future when symptoms appear or intensify.

Try creating a plan together with your family, friends, and medical team. It can also be beneficial to meet with a financial planner and a lawyer.

Here are some key things to consider:

• Education. You may find it helpful to learn more about AD and how it progresses. Talk with your doctor and learn about what your care plan could look like in the future.
• Health insurance. Find out which medications and treatments are covered by your plan.
• Future care costs. What will your medical and care expenses be? This may include professional home care of safety equipment for the home.
• Disability insurance. What is covered by your employer? What documentation is needed?
• Loss of income. Will you be able to keep working? If so, for how long? Will someone in your family need to stop working in order to become a caregiver?
• Power of attorney. Who will have the authority to make health, financial, and legal decisions for you when you cant any more?
• Support. Try finding a support group specifically for people with early onset AD and their caregivers. Their life situations are likely to be more similar to yours.

Its important to have a detailed, realistic plan for your future care. This will allow you to be more confident as you navigate through the stages of AD.

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Difficulty Determining Time Or Place

Losing track of dates and misunderstanding the passage of time as it occurs are also two common symptoms. Planning for future events can become difficult because they arent immediately occurring.

As symptoms progress, people with AD can become increasingly forgetful about where they are, how they got there, or why theyre there.

Bgrowth Hormone Response To Growth Hormone

Results of several studies addressing this point show varied results: superimposable responses of GH to GHRH than responses of GH to GHRH in controls a blunted GH to GHRH response in AD patients higher GH concentrations in the morning and a greater increase of GH to GHRH in AD patients than in controls . More recent studies demonstrate the reduced release of GH to GHRH in AD patients . In general, investigations of GH-releasing stimulation tests, especially of GHRH in AD, are equivocal and, in some cases, contradictory. Factors that may contribute to the inconsistent findings include the variability of GHRH stimulated among control groups, the age and sex of patients, the lack of uniformity in test procedures, and the variability and the lack of reproducibility of the GHRH test either in controls or in AD patients .

Table II. Different Patterns of Response of GH to Its Stimuli in Alzheimer’s Disease Patients

Leon E. Rosenberg, Diane Drobnis Rosenberg, in, 2012

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Difficulty Completing Familiar Tasks

Some people may experience a greater problem with concentration. Routine day-to-day tasks requiring critical thought may take longer as the disease progresses.

The ability to drive safely may also be called into question. If you or a loved one gets lost while driving a commonly traveled route, this may be a symptom of AD.

Pathophysiology Of Alzheimers Disease

The presence of extracellular plaques of insoluble -amyloid peptide and neurofibrillary tangles of P-tau in neuronal cytoplasm is the hallmark of AD . Although the mechanisms by which these changes lead to cognitive decline are still debated, these deposits are believed to lead to atrophy and death of neurons resulting from excitotoxicity processes , collapse in calcium homeostasis, inflammation and depletion of energy and neuronal factors. As a result of this process, damage to neurons and synapses involved in memory processes, learning and other cognitive functions lead to the aforementioned cognitive decline .

According to amyloid cascade theory , the cerebral accumulation of A peptide, resulting from the imbalance between production and clearance of this protein, is the main event causing the disease, being other events observed resulting from this process .

The A peptide, which has 36 to 43 aminoacids, is derived from amyloid precursor protein enzymatic proteolysis, a physiologically produced protein that plays important roles in brain homeostasis . The APP gene is located on chromosome 21, which explains the higher incidence of early-onset AD in individuals with 21 trisomy and in individuals with APP gene locus duplication . It is believed that overexpression of APP results in an increase of cerebral A peptide, and consequently, in its deposition .

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Still In Early Stages

Previous studies have shown a growing link between symptoms such as depression, anxiety, and hearing loss, but Nedelec said there were others that surprised him.

He explainedthat spondylosis and constipation were unexpected, as there is not much research linking these two with Alzheimers.

However, none of the above symptoms will automatically lead to an Alzheimers diagnosis.

Theres a bunch of reasons to wonder why that happened in the analysis and it becomes a kind of chicken or egg type of question, Scott Kaiser, MD, a geriatrician and director of geriatric cognitive health for the Pacific Neuroscience Institute at Providence Saint Johns Health Center who was not involved in the study, told Verywell. Is this a symptom of Alzheimers or is this a risk factor that increases your chances of Alzheimers?

Its also hard to make any definitive conclusions when other factors such as your socioeconomic status, genetics, and body mass index carry their own risks for Alzheimers.

Family history is something that can increase your odds of Alzheimers but then there are a bunch of other things like how active you are, how much second smoke or air pollution youre exposed to, loneliness, and social isolation, Kaiser explains. Having this information could create a more complete picture of what leads to an Alzheimers diagnosis.

Clinical Demographics Of Included Families

With the pooled genetic data of 4840 patients, we constructed 36 families comprising at least two patients . Seven pedigrees were previously clinically established and used to validate our two methods for determining relatedness. Both approaches were able to define first- and second-degree relationships and were fully concordant.

For each family, clinical and genetic findings are summarized in Table . All included families consisted of at least one patient with AD before the age of 70. The average age at onset of all affected individuals was 63 years. A lumbar puncture was performed in 32/36 probands, confirming decreased concentrations of -amyloid in cerebrospinal fluid . Occasionally, relatives had been diagnosed with other phenotypes on the dementia spectrum . Four families included an unaffected relative aged > 75. Detailed information on the individual level is provided in Additional file .

Table 1 Summary of the clinical characteristics and genetic findings of the 36 families evaluated in this study

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Can Environmental Factors Alone Cause Alzheimers No Genetic Factors Involved

Its really hard to answer this question scientifically. The studies in humans needed that look entirely at environment would be unethical because one would have to control a persons environment for many years.

However, you can cause memory loss with only environmental factors. Many scientists have done exactly that in animal models by exposing them to toxins or other factors that are not genetic-related. So, it is possible but its not as likely that you can cause memory loss in humans with environmental factors only.

It is unlikely that late onset Alzheimers is all due to genetics. And its also as unlikely that its 100% due to environment factors.

But, and this is also very unlikely, there are cases where certain medicines can cause dementia. Sometimes medicines can mimic Alzheimers disease. Or you have memory loss on certain medications.

Usually the doctor can put you on a different drug and that effect will reverse. Your memory would go back to typical. Sometimes its more important to treat the disease the medication is used for because the known side effects are reversible or very rare.

Are You 99% Safe If There Is No History Of Alzheimers In Your Family

This is a very nuanced topic but its a very important one. Many people get Alzheimers disease in the absence of any family history. So, it isnt surprising to get Alzheimers disease with no history of it in your family.

But think about it this way. If I asked you if Alzheimers runs in your family, you would think back to your parents, to your grandparents, and you may or may not know about your great-grandparents. You might say you are fine because none of them had Alzheimers disease. And that probably means that your genes are good.

But you also have to consider how medicine has changed throughout the years. Maybe your great grandparents were at high risk for Alzheimers disease but they didnt live long enough. Or perhaps medicine didnt recognize it as Alzheimers disease that many generations ago.

Family history means you have to transport yourself back in time and think about how medicine worked two generations ago.

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Alcohol Use And 8 Other Risk Factors For Early Dementia Identified

New research shows nine risk factors trigger early onset dementia, many of which can be prevented beginning in adolescence.

Swedish researchers have found strong evidence that nine contributing factors for young-onset dementia can be traced back to early adulthood.

Young-onset dementia is dementia diagnosed before 65 years of age. Dementia affects an estimated 35.6 million people worldwide, and YOD accounts for four to 10 percent of all dementia cases.

Experts have been able to trace early-onset dementiasuch as Alzheimers disease beginning in a persons early 30sto gene mutations that affects how the body produces and processes a specific protein that causes plaques to build-up on the brain.

A new study published in the journal

The nine risk factors that accounted for 68 percent of YOD cases in the study population, in order of importance, are:

• low cognitive function at the time of enlistment
• low weight at enlistment
• high blood pressure at enlistment

Researchers say their results also showed that men in the lowest third of overall cognitive function with at least two of these risk factors had a 20-fold increased risk of young-onset dementia.

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The risk of someone taking their own life is almost seven times higher after diagnosis of young onset dementia, a new study suggests.

Researchers say their findings indicate clinics should target suicide risk assessment to patients who are diagnosed with the condition before the age of 65.

Early recognition and a timely accurate diagnosis of dementia, combined with specialist support, are important factors in reducing the distress caused by a young onset diagnosis, they add.

Queen Mary University of London and University of Nottingham scientists looked at medical records of some 594,674 people from 2001 to 2019 to determine if there was a link between dementia diagnosis and suicide risk.

They found that nearly 2% of patients with a dementia diagnosis died from suicide.

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What Is Early Onset Familial Alzheimer Disease

Definition: What Is eFAD?

Early onset familial Alzheimer disease is hereditary and marked by Alzheimer disease symptoms that appear at an unusually early age. Symptoms can start in a person’s thirties, forties, and fifties . Generally, if you are diagnosed with eFAD, then one of your parents will also have had it if he or she lived long enough, and your siblings and your children may have a 50-50 chance of having inherited it. Very rarely, eFAD can make a first-time appearance in a family through a new genetic mutation.

Genetics researchers studied eFAD families to discover the three known genes that cause familial AD: amyloid precursor protein , presenilin-1 , and presenilin-2 . Of these, PS1 mutations account for most eFAD, while APP and PS2 are more rare. Having a pathogenic mutation in one of these three genes virtually guarantees that one will develop early onset Alzheimer disease. Tests can determine which gene is at fauly . There are also cases of eFAD that cannot be linked to one of these three genes. There may be additional genes waiting to be discovered, if only researchers could connect with more eFAD families.

Prognosis: Is eFAD Different from LOAD?

How Common Is Early Onset Familial Alzheimer Disease?

For practical and research purposes, doctors and scientists need defined populations for study and the numbers change based on the definitions. The definition would seem to rest on two criteria:

Genetic Data Generation And Processing

For the majority of patients, single nucleotide polymorphism arrays were available as part of the European Alzheimers and Dementia Biobank . Details on data generation and processing have been described previously . Exome sequencing data were generated for all selected patients and eight unaffected relatives. Genomic DNA was extracted from whole blood or frozen post-mortem brain tissue using standard laboratory procedures. DNA samples were paired-end sequenced using Illumina sequencers, after capturing using either Nimblegen SeqCap EZ v3 or v2 capture kits. Raw sequencing data from all sites were collected on a single site and processed using a uniform pipeline as reported recently . In brief, sequenced reads were processed using the Burrows-Wheeler Aligner Tool, Picard, and Samtools, and GATK was used for variant calling and quality control according to best practices . All samples were jointly genotyped into a single dataset VCF file . Subsequently, a family-VCF was generated for each family. Population database frequencies and functional and impact scores were annotated to variants using ANNOVAR .

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Modest Contribution Of Prs In Familial Eoad

The overall impact of PRS in the current families was modest, similar to earlier findings in autosomal dominant AD . It should be pointed out that the PRS was constructed based on GWAS data of mostly LOAD patients, but was replicated in EOAD with similar effect estimates . Although an oversimplification of polygenic inheritance, we calculated a family-averaged PRS to represent the shared polygenic burden. This allowed us to compare the contribution of PRS across families, also in conjunction with other genetic factors.

Similar to APOE and rare VUS, a cumulative effect might apply to the risk conveyed by APOE and PRS, as we observed a positive correlation between the two. Future work is needed to clarify if a combined signal might be based on biological interactions, endorsed by a recent study demonstrating a disproportionally large effect of PRS among APOE-4 carriers with earlier disease onset .