New Dementia Discovery: 6.5 Million at Risk Due to Misdiagnosis

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Understanding LATE: A New Challenge in Dementia Diagnosis

Doctors are increasingly concerned about a condition known as LATE (Limbic-predominant Age-related TDP-43 Encephalopathy), which is causing confusion and misdiagnosis among many elderly individuals. This age-related dementia affects a significant number of seniors, particularly those over 65 years old. With an estimated 6.5 million people in this age group, the impact of LATE is becoming more evident.

LATE is often mistaken for Alzheimer’s disease due to similar symptoms such as memory loss, language difficulties, and challenges with focus and complex thinking. However, the underlying causes differ significantly. While Alzheimer’s involves the buildup of amyloid plaques, LATE is associated with the accumulation of TDP-43 protein. This distinction is crucial because it affects treatment approaches and patient care.

The recognition of LATE has raised concerns that many individuals previously diagnosed with Alzheimer’s may actually have LATE or a combination of both conditions. Studies suggest that approximately 40% of people with dementia also have LATE, highlighting its prevalence. This overlap complicates diagnosis and treatment, as current medications like Leqembi target amyloid plaques specific to Alzheimer’s, not the TDP-43 protein found in LATE.

Research into LATE is ongoing, with scientists exploring potential treatments. One promising drug being tested is nicorandil, which has been approved in Europe and Asia for chest pain. Researchers believe that nicorandil may improve blood flow in the brain, potentially protecting key areas affected by LATE, such as the hippocampus.

LATE typically affects individuals aged 85 and older, with a slower progression compared to typical Alzheimer’s. Symptoms include gradual memory and thinking decline, making it challenging to distinguish from other forms of dementia. The condition can coexist with other brain pathologies, further complicating diagnosis.

A definitive diagnosis of LATE can only be made post-mortem through examination of brain tissue. However, during a patient's lifetime, doctors can use a comprehensive evaluation that includes reviewing medical history, cognitive tests, blood work, and imaging techniques like MRI. In some cases, PET scans or spinal fluid analysis may be used to rule out other causes of memory loss.

The discovery of LATE was prompted by researchers who noticed that many individuals with dementia symptoms did not show the typical markers of Alzheimer’s, such as amyloid plaques or tau tangles. This led to the identification of TDP-43 accumulation as a possible cause. In 2019, Dr. Peter Nelson and an international team formally defined LATE, marking a significant step in understanding this condition.

For patients like Ray Hester, a 79-year-old retired Air Force officer, the diagnosis of LATE provided some comfort. Initially thought to have Alzheimer’s, Hester’s tests revealed no amyloid plaques, leading to a LATE diagnosis. This change offered his wife, Sandy, a sense of relief, knowing that LATE may progress more slowly than Alzheimer’s.

Hester is now participating in a clinical trial at the University of Kentucky, taking either nicorandil or a placebo. His daily routine includes manageable tasks, but he still faces challenges with complex home repairs and word retrieval. For him, the specific name of his condition matters less than the reality of living with it.

The trial includes 64 participants with mild memory issues, each taking two pills daily. Dr. Greg Jicha, the study leader, emphasizes that nicorandil, a heart medication, shows promise in addressing genetic factors linked to LATE. The strongest genetic risk factor for LATE is the APOE4 variant, which also increases Alzheimer’s risk.

By improving blood flow in small vessels, nicorandil may help protect brain cells and slow the processes that lead to TDP-43 buildup and hippocampal shrinkage. As research continues, the hope is that new treatments will emerge, offering better care and management for those affected by LATE.

In conclusion, the growing awareness of LATE underscores the need for accurate diagnosis and tailored treatment approaches. As scientists continue to explore this condition, the goal remains to improve the quality of life for those living with dementia, whether it be LATE, Alzheimer’s, or a combination of both.