Memory, Age-Related Changes, and Dementia Risk: The Role of Genetics

Cognitive functions change with age, but the nature and degree of that change differ from person to person. It is shaped by a combination of factors, including genetic variants. For cognitive functions, as for the risk of neurodegenerative diseases, what matters is their combined effect.

Age-related decline in memory is not, in itself, a sign of developing dementia. Dementia is a clinical syndrome, while genetic markers reflect a statistical association with particular features of cognitive function or with the likelihood (not the certainty) of disease.

How to tell age-related memory changes from dementia

Age-related memory changes and dementia are distinguished by their impact on a person's everyday functioning. Dementia is characterized by a persistent, progressive loss of cognitive abilities severe enough to interfere with independence in daily life. Age-related fluctuations in memory, by contrast, do not lead to such consequences on their own (NIA, What Is Dementia? Symptoms, Types, and Diagnosis, 2026).

Slower recall of names or facts and occasional lapses in memory for everyday details are common signs of age-related brain changes, in which a person continues to manage daily life, work, and make decisions independently. Dementia, on the other hand, gradually begins to interfere with carrying out a range of activities on one's own.

Alzheimer's disease is the most common cause of dementia, but not the only one: vascular disorders, dementia with Lewy bodies, and other conditions also lead to the clinical syndrome of dementia, with different biological underpinnings (NIA, What Is Dementia? Symptoms, Types, and Diagnosis, 2026). Under current criteria, Alzheimer's disease is diagnosed on the basis of biomarkers, in particular signs of amyloid and tau protein accumulation detected by neuroimaging or cerebrospinal fluid analysis, regardless of whether clinical symptoms are already present (Jack et al., Alzheimer's Dement., 2024).

Memory is shaped by many genetic variants

Memory does not depend on a single gene — it is a quantitative trait influenced by many genetic variants. At the same time, environmental factors play no less a role in shaping it.

Genetic variants are identified through genome-wide association studies (GWAS) — a method that compares individual variants in the genome, single-nucleotide polymorphisms (SNPs), with a specific trait across large samples. A family-based study that analyzed the genetics of memory and executive function (the cognitive processes of planning, control, and attention switching) in people with an elevated familial risk of Alzheimer's disease identified numerous loci linked to individual cognitive domains — episodic memory, working memory, and verbal recall speed. The architecture of these traits proved to be polygenic: the genes involved are related to synaptic function and neuronal signaling (Wang et al., Curr. Issues Mol. Biol., 2026).

This means that individual differences in memory are not explained by any single “memory gene” but are made up of a large number of variants spread across different regions of the genome and across different cognitive domains.

Which genetic variants are linked to the risk of Alzheimer's disease

The role of APOE ε4 in Alzheimer's disease risk

The APOE gene (apolipoprotein E) encodes a protein involved in transporting cholesterol and other lipids in the blood. Disruption of this process is considered one of the factors in the development of Alzheimer's disease (NIA, Alzheimer's Disease Genetics Fact Sheet, 2025).

The gene exists in several forms — the ε2, ε3, and ε4 alleles:

• The ε4 allele raises the likelihood of Alzheimer's disease and is associated with an earlier age of symptom onset in some populations

• The ε3 allele is the most common variant, with a neutral effect

• The ε2 allele is associated with a lower likelihood of the disease (NIA, Alzheimer's Disease Genetics Fact Sheet, 2025).

Each person inherits one allele from each parent, so six combinations are possible. Having two copies of ε4 is associated with a higher likelihood of the disease than having one, but even with this genotype, not everyone develops the disease (NIA, Alzheimer's Disease Genetics Fact Sheet, 2025).

Alzheimer's disease risk loci beyond APOE

A large-scale genome-wide study in 2022 identified 75 loci associated with Alzheimer's disease and related dementias (Bellenguez et al., Nature Genetics, 2022). An updated consensus meta-analysis in 2026, which combined data from several large consortia, expanded this list to 91 loci; 56 of them are specifically linked to clinically diagnosed Alzheimer's disease, while the rest reflect the broader category of related dementias (EADB et al., Nature Genetics, 2026).

Each individual locus is typically associated with a small increase in likelihood, unlike APOE ε4, whose contribution to risk assessment remains the largest among the variants known to date (Bellenguez et al., Nature Genetics, 2022).

A polygenic risk score summarizes the contribution of many variants

Alzheimer's disease is influenced by numerous genetic variants, each with a small effect. A polygenic risk score (PRS) summarizes their combined contribution and shows a person's position relative to a reference population. GWAS studies, in particular Bellenguez et al. (2022) and the EADB consensus meta-analysis (2026), are examples of how the individual associations that make up such a score are identified.

A multiethnic PRS model for Alzheimer's disease, which does not rely solely on the APOE region, showed an association not only with the disease itself but also with poorer results on cognitive tests — of memory, executive function, and language. The same model is also linked to reduced hippocampal volume and to neurodegeneration biomarkers in cerebrospinal fluid (Kurniansyah et al., Nature Genetics, 2026).

Genetic risk and the development of dementia

Genetic predisposition is an important layer among the factors that influence the risk of developing dementia. At the same time, age, vascular health, and other lifestyle factors have no less of an effect, regardless of a person's genetic profile.
The current Lancet Commission report identifies 14 modifiable risk factors that together account for a significant share of dementia cases worldwide; new factors in the 2024 report include high LDL cholesterol in midlife and untreated vision loss, alongside previously known factors: low education, hearing loss, arterial hypertension, smoking, obesity, depression, social isolation, and others (Livingston et al., Lancet, 2024). The preventive potential of these factors does not depend on APOE status: a person with elevated genetic risk benefits from controlling blood pressure or hearing just as much as a person with lower genetic risk.

How a genetic test expands the understanding of cognitive health

Apixmed Prism DNA tests analyze indicators related to memory, cognitive function, and neurodegenerative risks, including Alzheimer's disease — these are related but distinct genetic dimensions. A genetic result is meaningful only alongside other data about how the body works.

Genetic data show hereditary predisposition — a stable layer of information that does not change over a lifetime. Cognitive tests and observation of everyday functioning make it possible to assess the current functional state. Laboratory and instrumental examinations, when there are clinical indications for them, provide information about the biological processes in the brain here and now. Age, medical history, and lifestyle factors add clinical context, without which none of the preceding layers gives a complete picture of a person's condition.

A DNA test result should be read as a relative genetic predisposition and, if needed, discussed with a doctor who will weigh the genetic context against the clinical picture and decide whether additional examinations are needed.

Learn more about the genetic features of your memory with the Apixmed Prism genetic test.

Genetic test results are not a diagnosis and not a substitute for a doctor's consultation. The Apixmed Prism report provides genetic context that complements the results of examinations and helps in making decisions together with your doctor.

Sources

1. Bellenguez, C., Küçükali, F., Jansen, I. E. et al. (2022). New insights into the genetic etiology of Alzheimer's disease and related dementias. Nature Genetics, 54(4), 412–436. https://doi.org/10.1038/s41588-022-01024-z

2. EADB, EADI, Bonn, ADGC, CHARGE, FinnGen, GERAD, GR@ACE/DEGESCO, PGC-ALZ (Bellenguez, C., Castillo Morales, A., Amin, N. et al.). (2026). Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementias. Nature Genetics, 58(6), 1214–1225. https://doi.org/10.1038/s41588-026-02583-1

3. Wang, K., Yang, X., Magwood, G. et al. (2026). Family-Based GWAS of Cognitive Endophenotypes Reveals Genetic Architecture of Memory and Executive Function in Alzheimer's Disease. Current Issues in Molecular Biology, 48(5), 442. https://doi.org/10.3390/cimb48050442

4. Kurniansyah, N., Tasaki, S., Rehman, H. et al. (2026). A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations. Nature Genetics. Published online ahead of print 27.08.2026. https://doi.org/10.1038/s41588-026-02722-8

5. Livingston, G., Huntley, J., Liu, K. Y. et al. (2024). Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. The Lancet, 404(10452), 572–628. https://doi.org/10.1016/S0140-6736(24)01296-001296-0)

6. Jack, C. R., Andrews, J. S., Beach, T. G. et al. (2024). Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimer's & Dementia, 20(8), 5143–5169. https://doi.org/10.1002/alz.13859

7. National Institute on Aging. (2023). Alzheimer's Disease Genetics Fact Sheet. NIA. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/alzheimers-disease-genetics-fact-sheet

8. National Institute on Aging. (2026). What Is Dementia? Symptoms, Types, and Diagnosis. NIA. https://www.nia.nih.gov/health/alzheimers-and-dementia/what-dementia-symptoms-types-and-diagnosis