What is the earliest sign of Alzheimer's (Alzheimer) disease?

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Last updated: March 24, 2025View editorial policy

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From the Guidelines

The earliest sign of Alzheimer's disease is subtle memory loss, particularly difficulty remembering recently learned information, as highlighted in a 2021 review of timely and accurate diagnosis of symptomatic Alzheimer's disease in primary care 1. This symptom is often characterized by forgetting important dates or events, asking the same questions repeatedly, or increasingly relying on memory aids like notes or electronic devices.

  • The disease first affects the hippocampus, the brain region responsible for forming new memories, leading to these early memory-related symptoms.
  • As the disease progresses, protein abnormalities (amyloid plaques and tau tangles) damage and kill nerve cells in this area before spreading to other brain regions.
  • It's essential to distinguish between occasional forgetfulness, which is normal with aging, and persistent and worsening memory problems that interfere with daily life, which warrant medical evaluation.
  • Early diagnosis is crucial as it allows for better planning, potential participation in clinical trials, and implementation of strategies to manage symptoms, as emphasized by recent analyses suggesting the use of objective cognition-screening tools and in-development blood-based biomarkers for efficient and cost-effective identification of incipient AD-related cognitive decline 1.
  • While there are no medications that can reverse early Alzheimer's, some drugs like cholinesterase inhibitors may temporarily slow symptom progression in some individuals, making timely detection and intervention critical for optimizing patient outcomes.

From the Research

Earliest Signs of Alzheimer's Disease

The earliest signs of Alzheimer's disease can be complex and varied. According to 2, the initial sign of change was not memory impairment in 53% of patients, but rather:

  • Psychiatric type in 32.5% of patients
  • Neurologic type in 10.9% of patients
  • Noncoping type in 9.6% of patients These nonmemory signs, as perceived by caregivers, preceded objective memory impairment by a mean of 1.8 years.

Memory Impairment as an Early Sign

However, memory impairment is still considered a key early sign of Alzheimer's disease. As noted in 3, memory impairment has been considered one of the earliest clinical hallmarks of Alzheimer's disease. Additionally, 4 states that difficulty recognizing previously encountered stimuli is one of the earliest signs of incipient Alzheimer's disease.

Other Possible Early Signs

Other studies suggest that Alzheimer's disease may start with a memory impairment due to neurophysiological insights, such as the formation of amyloid plaques and neurofibrillary tangles 5. The economic and social impact of Alzheimer's disease is significant, with an estimated 47 million people affected worldwide, and this number is expected to increase to over 130 million by 2050 6.

Variability in Early Signs

It's worth noting that the early signs of Alzheimer's disease can vary significantly from person to person. While some people may experience memory impairment as the first symptom, others may experience psychiatric, neurologic, or noncoping symptoms first 2.

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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