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“Where did I leave my keys?” It’s a question most of us have asked ourselves on more than one occasion, and the inquiry is more likely a symptom of our increasingly hectic lifestyles rather than a true failure of our memory.

But when are these seemingly innocent episodes of forgetfulness really the first sign of something much more significant? What are the earliest signs of the onset of dementia?

The most common form of dementia is Alzheimer’s disease, widely known for its damaging effects on an individual’s memory, language and other cognitive skills. Patients with advanced Alzheimer’s disease dementia are unable to carry out day-to-day activities, including caring for themselves, and often end up being unable to recognize even their own spouses or children.

This devastating disease clearly affects not only the afflicted patients but also their family members, especially those who become caregivers.

As Alzheimer’s disease can extend across a decade or longer, the healthcare costs resulting from care for these patients are significant and rapidly growing. In 2015 alone, the cost for healthcare and other care-related costs for all dementias was an estimated $226 billion, in addition to the roughly $18 billion of unpaid Alzheimer’s disease care provided by family members and other unpaid caregivers.

This cost to families and society is expected to grow significantly as baby boomers reach the age typical for the onset of Alzheimer’s disease dementia and other dementias.

Alzheimer’s disease results in the accumulation of a protein called beta-amyloid, which builds up to form “plaques” in the brain. Similarly, another protein called tau accumulates during the disease process to form “tangles,” which, together with plaques, eventually cause irreversible and widespread damage and death to brain cells.

Unfortunately, once a person reaches a diagnosis of Alzheimer’s dementia, options for treatment become limited as it is not possible to bring back neurons once they are lost.

Early changes may be reversible

Therefore, many studies of Alzheimer’s disease currently focus on a condition called amnestic mild cognitive impairment, or MCI, thought to be a precursor to or a very early stage of Alzheimer’s disease. A patient with MCI typically has mild forgetfulness, such as more difficulty than usual recalling recent events, or getting lost on his or her way to a familiar place.

In MCI, the cell death that is seen in Alzheimer’s is not nearly as widespread, making this condition a preferable target for treatment. Instead, studies of patients with MCI show changes in the brain associated with this mild forgetfulness that may be reversible.

At Johns Hopkins, the research of Dr. Arnold Bakker and colleagues has shown that hyperactivity in the cells of the hippocampus, a small area of the brain that is critically important for memory function, contributes to memory impairment in patients with MCI.

This hyperactivity can be reduced with certain medications, potentially providing an effective treatment for memory symptoms in this early stage of the disease.

In currently ongoing studies, Bakker’s group is trying to determine just how early in the disease these reversible brain changes can be detected.

To do this, the team is conducting cognitive testing and functional magnetic resonance imaging (fMRI) — a test that uses MRI technology to measure brain activity by detecting changes associated with blood flow.

The studies also collect spinal fluid via lumber puncture to measure changes in brain activity and levels of beta-amyloid and tau in groups of individuals with different levels of cognitive impairment.

Bakker hopes that results from these studies will provide further insight into possible treatments for this early stage of Alzheimer’s disease and determine who may benefit from such treatments before forgetfulness becomes a true symptom of failing memory.

Volunteer for a study

Johns Hopkins Hospital is currently recruiting participants for a study on memory impairment in adults ages 55 to 90. They will make two visits to Johns Hopkins Hospital, undertake paper and pencil cognitive tests, have an MRI scan and a lumbar puncture. Participants will be compensated for their time and travel expenses.

Although lapses in memory may seem innocuous and merely the result of advancing age, they could be among of the first signs of significant changes in memory function. In fact, noticing a change in your ability to remember things over the past few years may be an important symptom. Research is needed to help better understand the disease.

If you have any concerns about your memory or are interested in being part of a scientific research study, contact Carrie Speck at (410) 955-5057 or at cspeck1@jhmi.edu.