Reversing cognitive impairments

The status quo

Cognitive decline is often listed as the major concern of older adults. Already, Alzheimer's disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it's estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer's disease is on the rise--recent estimates suggest that AD has become the third leading cause of death in the United States behind cardiovascular disease and cancer.

Imagine having a roof with 36 holes in it, and your drug patched one hole very well--the drug may have worked, a single 'hole' may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.

Outside the box

We think addressing multiple targets within the molecular network may be synergistic, and that such a combinatorial approach may enhance drug candidate performance, as well. We're entering a new era," said Bredesen. "The old advice was to avoid testing for APOE because there was nothing that could be done about it. Now we're recommending that people find out their genetic status as early as possible so they can go on prevention." Sixty-five percent of the Alzheimer's cases in this country involve APOE4; with seven million people carrying two copies of the ApoE4 allele.

Patient cases

"Follow up testing showed some of the patients going from abnormal to normal."

One of the more striking cases involved a 66-year old professional man whose neuropsychological testing was compatible with a diagnoses of MCI and whose PET scan showed reduced glucose utilization indicative of AD. An MRI showed hippocampal volume at only the 17th percentile for his age. After 10 months on the protocol a follow-up MRI showed a dramatic increase of his hippocampal volume to the 75th percentile, with an associated absolute increase in volume of nearly 12 percent.

In another instance, a 69-year old professional man and entrepreneur, who was in the process of shutting down his business, went on the protocol after 11 years of progressive memory loss. After six months, his wife, co-workers and he noted improvement in memory. A life-long ability to add columns of numbers rapidly in his head returned and he reported an ability to remember his schedule and recognize faces at work. After 22 months on the protocol he returned for follow-up quantitative neuropsychological testing; results showed marked improvements in all categories with his long-term recall increasing from the 3rd to 84th percentile. He is expanding his business.

Another patient, a 49-year old woman who noted progressive difficulty with word finding and facial recognition went on the protocol after undergoing quantitative neuropsychological testing at a major university. She had been told she was in the early stages of cognitive decline and was therefore ineligible for an Alzheimer's prevention program. After several months on the protocol she noted a clear improvement in recall, reading, navigating, vocabulary, mental clarity and facial recognition. Her foreign language ability had returned. Nine months after beginning the program she did a repeat of the neuropsychological testing at the same university site. She no longer showed evidence of cognitive decline.

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