Loss of smell may be the earliest warning of Alzheimer's disease

An unexpected symptom has been identified as a potential early warning sign of Alzheimer’s disease: the loss of smell. Researchers at the University of Chicago observed that this surprising symptom was particularly prevalent among those individuals who carry a certain genetic predisposition to Alzheimer’s. 

The findings, published in the journal Neurology, signal a potential new path to early detection and understanding of this neurodegenerative disease.

Dr. Matthew S. GoodSmith, the lead author of the study, remarked on the significance of the discovery: “Testing a person’s ability to detect odors may be a useful way to predict future problems with cognition.”

Focus of the study

The research focused specifically on individuals carrying the APOE e4 gene variant. This genetic marker has been the subject of considerable attention in the Alzheimer’s research community due to its strong association with an increased risk of the disease. 

The APOE gene, or apolipoprotein E, has several different forms known as alleles, specifically APOE e2, APOE e3, and APOE e4. The gene’s primary function is to carry cholesterol and other fats through the bloodstream. 

Each person inherits one APOE gene from each biological parent. While some variants of this gene are not associated with dementia, the APOE e4 allele is most closely linked with an increased risk of Alzheimer’s disease. 

The risk multiplies for individuals who inherit two copies of the APOE e4 gene. Roughly two to three percent of the population has this condition. In comparison, one in four people carry a single copy of the APOE e4 gene.

What the researchers discovered 

Interestingly, the scientists noticed that carriers of the APOE e4 gene were more likely to suffer from a loss of smell and cognitive decline than those without the gene. 

Previous studies establishing a relationship between loss of smell and brain inflammation link to this unexpected revelation. Brain inflammation associates with cognitive decline.

The research strengthens our understanding of this correlation, and sheds new light on the complex and multi-dimensional development of Alzheimer’s disease.

Promising findings 

The study involved 865 participants who took part in an at-home survey, which assessed their ability to detect an odor and to accurately identify the scent.

Although this new connection between smell and Alzheimer’s disease may seem strange, the study’s findings are promising. 

The results suggest that screening individuals’ sense of smell could serve as a non-invasive, preliminary method of identifying those at high risk of developing Alzheimer’s, potentially opening up new avenues for early intervention and treatment.

More about loss of smell

Loss of smell, or anosmia, is a condition where the ability to detect odors is impaired or completely lost. A variety of causes, broadly categorized into two types, can trigger this condition.

Conductive (or obstructive) loss of smell

This happens when something physically obstructs the flow of air carrying the odor to the olfactory receptors in the nose. This could be due to causes such as nasal congestion from a common cold, sinus infection, allergies, nasal polyps, or other blockages in the nasal cavity.

Sensorineural (or central) loss of smell

This occurs when there’s damage to the olfactory system itself. The types of damage could include the olfactory nerves and the brain areas involved in processing smells. This could be due to many issues. They include aging, certain medications, exposure to toxic substances, neurological disorders like Parkinson’s or Alzheimer’s disease, or brain injuries.

COVID-19 has a notable link to loss of smell. Many patients with this disease experience anosmia. It often occurs without nasal obstruction or other nose-related symptoms, suggesting the virus may directly affect the olfactory system.

Anosmia can have a significant impact on quality of life. It may affect the sense of taste (as flavor is a combination of taste and smell) and may prevent a person from noticing harmful smells, like gas leaks or smoke.

More about Alzheimer’s disease 

Alzheimer’s disease is a progressive neurological disorder that results in severe cognitive impairment. It is the most common type of dementia, accounting for an estimated 60-80% of cases worldwide.

Etiology

Alzheimer’s disease often emerges as a result of complex genetic, environmental, and lifestyle factors. Age remains the most significant risk factor. The prevalence of the disease doubles approximately every five years after age 65.

Although no single gene directly causes the “late-onset” type, which begins after age 65, certain gene variants increase risk. The Apolipoprotein E-e4 (APOE-e4) variant, for instance, elevates the risk of developing Alzheimer’s. On the other hand, early-onset Alzheimer’s, which appears before age 65, is less common but tends to have a stronger genetic link. Mutations in three genes—amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2)—are known to cause early-onset Alzheimer’s.

Lifestyle and heart health factors linked to Alzheimer’s include smoking, obesity, diabetes, hypertension, and high cholesterol. Growing evidence also suggests that chronic exposure to stress and a lack of physical and cognitive activity may contribute to the disease’s onset.

Pathophysiology

The exact biological processes leading to Alzheimer’s disease are yet to be fully understood. The disease is characterized by the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain. Beta-amyloid is a fragment of the larger amyloid precursor protein. When these fragments clump together, they form hard plaques between neurons, disrupting cell function.

Neurofibrillary tangles are twisted strands of a protein called tau, which supports microtubules in neurons. In Alzheimer’s disease, tau undergoes chemical changes. These changes cause it to form tangles, which leads to the failure of the transportation system within neurons and their subsequent death.

Over time, the disease leads to widespread brain tissue loss. The hippocampus, a region of the brain crucial for forming memories, is usually the first to suffer damage. This leads to the characteristic memory problems in early Alzheimer’s.

Clinical presentation

Alzheimer’s disease typically starts with subtle memory loss, often mistaken for normal aging. As the disease progresses, memory impairments become more severe, interfering with daily life.

Difficulties with complex tasks, confusion about time and place, problems with speech and writing, loss of smell, poor judgment, mood and personality changes, and eventually severe disorientation and dependency on others for basic activities of daily living follow.

Diagnosis from loss of smell

The diagnosis of Alzheimer’s disease primarily relies on detailed clinical assessment, including medical history, cognitive testing, and brain imaging.

While definitive diagnosis can only be confirmed via postmortem examination of the brain, new diagnostic tools such as PET scans for amyloid plaques are offering more certainty during life.

Treatment and management

As of now, there is no cure for Alzheimer’s disease. Treatment aims to manage symptoms and improve quality of life. Medications such as cholinesterase inhibitors and memantine can help manage cognitive symptoms for a limited period. These include memory loss and confusion.

Behavioral interventions, occupational therapy, and lifestyle changes, such as regular physical activity, a healthy diet, and cognitive stimulation, can also play a significant role in managing the disease. Social engagement and support from family and community resources are also vital to help patients and caregivers cope with the disease.

Research and future directions

Research on Alzheimer’s disease is ongoing, with efforts to uncover its causes, improve early detection, and find potential treatments. Promising areas of research include studying the role of inflammation and immune response, the impact of lifestyle factors, and the development of new treatments aimed at the disease’s root causes.

In summary, Alzheimer’s disease represents a significant challenge for individuals, families, and healthcare systems worldwide. Understanding, diagnosing, and managing this disease are critical tasks for the global community as populations continue to age.

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