Most people have learned that there are two types of Alzheimer’s disease, a progressive form of dementia. The rare, entirely genetic form of the disease affects only one to three percent of all diagnosed patients, and usually causes symptoms when patients are still relatively young. The more common late-onset form may also have a genetic basis, but researchers commonly believe it arises from a variety of environmental factors, as well. Now neuroscientists at Mayo Clinic in Florida, who have defined the symptoms of hippocampal-sparing Alzheimer’s disease, believe this variant of the disease may be widespread even though is not well recognized.
"What is tragic is that these patients are commonly misdiagnosed and we have new evidence that suggests drugs now on the market for [Alzheimer’s] could work best in these hippocampal sparing patients — possibly better than they work in the common form of the disease," said Dr. Melissa Murray, an assistant professor of neuroscience at Mayo Clinic in Florida.
According to Murray, hippocampal-sparing Alzheimer’s disease made up a full 11 percent of a total 1,821 cases confirmed by Mayo Clinic researchers. (Mayo possesses one of the largest brain banks in the nation, with more than 6,500 donations total.) These numbers suggest the hippocampal-sparing variant may affect over 600,000 of the 5.2 million American patients who are currently living with Alzheimer’s disease (AD). Importantly, scientists say this hippocampal sparing variant often strikes at a much younger age and produces symptoms that are substantially different from the most common form of AD, which harms the hippocampus, the center of memory, before moving onto other areas of the brain. The symptoms cause patients, mostly men, to exhibit bizarre behavior, including using profane language (when previously they never would), socially unacceptable conduct — such as taking food from other people’s plates, and even believing their limbs are being controlled by alien or unidentifiable forces. At the same time patients may experience visual problems or even find themselves unable to speak, though they do not lose actual vocal or hearing abilities.
Worst of all, hippocampal sparing AD also causes patients to decline at a much faster rate, with patients becoming demented within a year of the first sign of symptoms. And, despite the insane behavior and rapid decline, doctors often misdiagnose patients because their symptoms are uncharacteristic of the most typical form of Alzheimer’s. "Many of these patients … have memories that are near normal," explained Murray in a press statement.
Typically, then, doctors will diagnose a patient as having frontotemporal dementia or corticobasal syndrome, which causes movement problems and cognitive decline. Yet, hippocampal sparing AD shows the same effects in the brain — the signature beta-amyloid plaques and tau tangles — found in the other two variants of Alzheimer's. The single difference is that the tau tangles are found to damage and eventually destroy neurons in parts of the brain involved in behavior, motor awareness, and recognition — in patients with hippocampal sparing AD, then, the tangles cause atrophy in the cortex (the outer layer of the brain, which plays a role in memory, attention, thought, and language), while also harming the amygdala (deeper inside the brain, it is the seat of our primal emotions) and the entorhinal cortex (also deeper inside the brain, it helps us understand spatial relations and navigate).
"What is fascinating is that all the AD patient subtypes had the same amount of amyloid, but for some reason tau tangles were found in strategic cortical regions disproportionate to the hippocampus," said Murray, who recently delivered a presentation at the annual meeting of the American Academy of Neurology in Philadelphia and discusses the topic in this YouTube video: