Alzheimer’s Disease Biomarkers Can Predict Cognitive Decline in People Over 80 as Well

Cognitive decline in very old adults has been considered for decades to be an almost inevitable consequence of aging. In clinical practice, this has contributed to many memory problems in patients over the age of 80 being interpreted as a normal age-related phenomenon, without further investigation into their underlying cause. However, this view is increasingly being challenged as knowledge of neurodegenerative diseases advances and more accurate tools become available for their detection.

A study led by researchers at the Sant Pau Research Institute (IR Sant Pau) and recently published in Neurology provides new evidence on the value of Alzheimer’s disease biomarkers in this age group. The study, which focused on people aged 80 and older with mild cognitive impairment, shows that the presence of Alzheimer’s disease biology—determined through biomarkers in cerebrospinal fluid and blood—is not only common but is also consistently associated with a higher risk of more rapid cognitive decline and progression to dementia.

These findings challenge the still-widespread assumption that biomarkers have limited value at very advanced ages because of the coexistence of multiple pathologies. On the contrary, the study demonstrates that, even in this context of greater clinical complexity, identifying the underlying pathology continues to provide relevant information about patient outcomes.

“Not every memory problem after the age of 80 is normal, and assuming that it is can lead to the underdiagnosis of diseases such as Alzheimer’s,” says Dr. Ignacio Illán-Gala, a researcher in the Neurobiology of Dementia Group at IR Sant Pau, a neurologist at Hospital de Sant Pau, and one of the study’s authors. “We need to overcome the influence of ageism in the assessment of these patients and move toward a more accurate diagnosis at older ages as well,” he adds.

Without Biomarkers, Clinical Diagnosis Is Particularly Inaccurate at Older Ages

One of the main challenges in assessing cognitive decline in very old adults is the limited accuracy of diagnoses based exclusively on clinical evaluation. In routine practice, many patients over the age of 80 are assessed without the use of biomarkers, introducing a high degree of uncertainty about the true cause of their symptoms. This approach, which is widespread among clinicians, is largely justified by the high frequency of coexisting pathologies at older ages. In this group, different neurodegenerative diseases, vascular abnormalities, and other aging-related processes commonly coexist and can simultaneously affect cognition, producing clinical presentations that are more heterogeneous and less specific than those observed at younger ages.

In addition, as age increases, differences in cognitive performance between people with and without Alzheimer’s disease tend to become less pronounced during the early stages. Although patients with Alzheimer’s disease biology perform worse, particularly on memory tests, these differences are relatively modest and overlap considerably with the results of patients without the disease. This limits the ability of clinical assessment to distinguish between the two groups, thereby contributing to diagnostic and therapeutic nihilism.

“Older patients often have multiple coexisting pathologies that can impact memory, and relying exclusively on clinical assessment can lead to inaccurate diagnoses,” explains Dr. Chiara Ceriello, a geriatrician at Hospital de Sant Pau and first author of the article. “In fact, approximately half of the cases are not pure Alzheimer’s disease, which means that without biomarkers, it is difficult to determine what lies behind the cognitive decline and accurately anticipate its progression.”

Confirming Alzheimer’s Disease Biology Reveals Differences in Patient Outcomes

The study analyzed 167 people over the age of 80 with mild cognitive impairment from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort, a leading clinical cohort in neurodegenerative diseases in which patients are systematically evaluated using biomarkers. Nearly 70% had biology consistent with Alzheimer’s disease, determined by analyzing characteristic proteins in cerebrospinal fluid—such as the ratio of p-Tau181 to β-amyloid—and their blood correlate, p-Tau217. Although the initial cognitive differences between patients with and without this biology were relatively small, their outcomes over the follow-up period were clearly different.

Specifically, patients with Alzheimer’s disease biology experienced more rapid cognitive decline than those without evidence of the disease, as measured using the Mini-Mental State Examination (MMSE), a widely used scale for assessing overall cognitive function. Patients with Alzheimer’s disease biology showed an average decline of 0.47 points per year, compared with 0.18 points per year among those without evidence of the disease. Although this difference is moderate on an annual basis, it becomes clinically relevant when considered cumulatively, as it translates into more rapid progression toward greater impairment and loss of independence. Similarly, the presence of these biomarkers was also associated with a higher risk of progression to dementia during follow-up.

The findings also suggest that blood biomarkers not only make it possible to identify the presence of the pathology, but also provide relevant information about its behavior over time. In particular, higher levels of p-Tau217 were associated with a greater risk of progression to dementia, with increases in risk approaching 50% depending on biomarker levels. This reinforces its potential value not only for diagnosis, but also for prognosis.

“As age increases, differences in memory performance between people with and without Alzheimer’s disease tend to become less pronounced, making it more difficult to identify the disease based solely on clinical assessment,” explains Dr. Illán-Gala. “However, what does change clearly is the disease course: people with this biology have a worse prognosis and more rapid progression of cognitive decline over the medium term.”

In this regard, the information provided by biomarkers is particularly relevant to clinical practice in older adults. “Knowing whether these patients have Alzheimer’s disease biology not only enables us to refine the diagnosis, but also to anticipate their disease course and better tailor clinical management and care planning,” says Dr. Chiara Ceriello.  Thus, even at older ages, the presence of Alzheimer’s disease biology is not an incidental finding, but rather a factor that significantly shapes a patient’s clinical trajectory and allows their progression to be anticipated more accurately.

A Blood Biomarker Facilitates Diagnosis and Clinical Implementation

Beyond its prognostic value, one of the most relevant aspects of the study is the possibility of translating these findings into clinical practice through the use of blood biomarkers such as p-Tau217. Unlike traditional techniques such as lumbar puncture or amyloid positron emission tomography (PET), measuring this biomarker through a blood test offers a much simpler and more broadly applicable approach.

This development is particularly relevant in geriatrics, where the systematic use of more complex procedures has historically been limited. The availability of a blood-based marker opens the door to incorporating the biological assessment of Alzheimer’s disease in a larger number of patients and across broader health care settings, facilitating a more consistent diagnostic approach.

“The availability of a blood biomarker makes it much easier to incorporate this type of testing into clinical practice, particularly in older patients,” says Dr. Chiara Ceriello. “It allows us to obtain relevant biological information in a simpler and more practical way, and this has a direct impact on how we assess and monitor these patients.” The researchers emphasize, however, that these biomarkers must always be interpreted within the patient’s clinical context, considering factors such as frailty, comorbidities, and baseline functional status to determine their true clinical utility.

A More Accurate Diagnosis Helps Anticipate Disease Progression and Improve Clinical Management

The study’s findings challenge the practice of excluding people over the age of 80 from biomarker-based diagnostic strategies and point to the need for a more individualized approach. The authors emphasize that chronological age alone does not reflect the heterogeneity of this population, which includes patients with good functional status and a long life expectancy for whom a more accurate diagnosis may have a significant impact.

“Precision medicine should not have an age limit,” says Dr. Chiara Ceriello. “In well-preserved patients with a good quality of life, knowing whether biomarkers are present can change clinical management, prognosis, and future planning.”

Beyond diagnosis, identifying Alzheimer’s disease biology in older adults has direct implications for clinical practice. Understanding the cause of cognitive decline makes it possible to anticipate its progression, adjust follow-up, and facilitate both medical and family planning, particularly at a stage of life when these issues become increasingly important.

In this context, the arrival of new drugs capable of modifying the course of the disease reinforces the need for a more accurate diagnosis during the early stages, including in older patients. These treatments have demonstrated the ability to slow the progression of cognitive decline, making it even more significant to identify patients who could benefit from them.

“We are seeing increasing numbers of older people seeking medical advice because they have noticed changes in their memory and want to understand what is happening to them and what they can expect,” says Dr. Illán-Gala. “Answering these questions is part of providing appropriate care.”

Overall, the study demonstrates that Alzheimer’s disease biomarkers retain clinically relevant value in people aged 80 and older, and that their use may help improve diagnosis and decision-making in a growing population that has so far been underrepresented in research.

Reference Article:

Ceriello C, Torres OH, Rubio-Guerra S, García-Castro J, Selma-Gonzalez J, Sala I, Sánchez-Saudinós MB, Videla L, Vera-Campuzano E, Arranz J, Rodríguez-Baz Í, Maure-Blesa L, Dols-Icardo O, Valldeneu S, Barroeta I, Santos-Santos M, Carmona-Iragui M, Vaqué-Alcázar L, Alvarez-Sanchez E, Lorente O, Carreras M, Bejanin A, Belbin O, Lleó A, Fortea J, Alcolea D, Illán-Gala I. Clinical Impact and Prognostic Value of Alzheimer Disease Biomarkers in the Very Old. Neurology. 2026;107. https://doi.org/10.1212/wnl.0000000000218180.