Alzheimer's disease
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Metabolic testing of 50 test subjects over 2 years revealed not one but three disease subtypes for Alzheimer’s Disease: inflammatory; non-inflammatory; and cortical. The findings may help optimize treatments for people with this serious neurological condition.

“Because the presentation varies from person to person, there has been suspicion for years that Alzheimer’s represents more than one illness. When laboratory tests go beyond the usual tests, we find these three distinct subtypes,” said Dale Bredesen, MD, the study’s author and a professor of neurology at University of California, Los Angeles (UCLA), in a statement issued by the university. Results appeared in the journal Aging.

“The important implications of this are that the optimal treatment may be different for each group, there may be different causes, and, for future clinical trials, it may be helpful to study specific groups separately,” Bredesen explained.

While all three subtypes are distinct, the cortical subtype differs from the other two in that it tends to affect younger people without an Alzheimer’s-related gene. Initially it is more likely to affect language skills than memory loss.

As Bredesen explained, “In this subtype there is an initial loss of long-term memory maintenance, resulting in problems such as dyscalculia and aphasia, with an initial retention of new memory formation and retrieval.”

There’s often a link to zinc deficiency with this subtype, which as the study points out, may contribute to decline in cognitive ability. To describe how the cortical subtype could manifest in a patient, the study mentions the case of a 52-year-old scientist who over a 2-year period began struggling with simple cognitive tasks such as paying bills, and eventually needed assistance with writing a grant proposal. “She declined rapidly and developed a simple, childlike affect,” the study’s authors wrote in the article.

C-reactive protein elevations and increased serum albumin-to-globulin ratio characterize the markers for the inflammatory subtype. The study highlights the case of a 65-year-old man who previously had excellent memory recall, but over the last 4 years had been experiencing progressive memory loss and so-called “senior moments.” Both of his parents suffered from dementia. His situation illustrates the manifestation of inflammatory Alzheimer’s. The non-inflammatory subtype is distinguished by other metabolic abnormalities such as insulin resistance, hormonal loss associated with early oophorectomy, hypovitaminosis D, and hyperhomocysteinemia. This subtype may explain why a 75-year-old woman experienced rapid memory loss over the course of 1 year, in a fashion similar to her mother’s.

The findings could benefit future research on therapeutic options for Alzheimer’s disease, Bredesen concluded.

“Since increasing evidence supports an important role for metabolic abnormalities such as insulin resistance in Alzheimer’s disease pathophysiology, it is of interest to determine whether metabolic profiling may be useful clinically, both in classification and, ultimately, in therapeutic trials,” he suggested.