How to Detect Alzheimer’s Before Dementia Starts

TL;DR

Early detection is presented as the best opportunity to prevent cognitive decline from reaching dementia, because Alzheimer’s pathology can begin before symptoms appear. Dr. Dale Bredesen recommends periodic biomarker testing and attention to subjective cognitive changes, arguing that people treated during the asymptomatic or subjective impairment phases have better outcomes than those who wait until dementia develops.

Transcript

In your latest book, The Ageless Brain, you write something that I think some people will regard as a little bit provocative. Okay. You write this. I've often noted that everyone knows a cancer survivor, but no one knows an Alzheimer's one. But let me tell you a secret. I do. In fact, I know many of them. Yeah. Not only do I know many of them, they... Read More

Key Insights

• Alzheimer’s disease is described as a four-phase process that begins with asymptomatic pathology, advances through subjective and mild cognitive impairment, and ends with dementia. Waiting until the final phase makes improvement more difficult and potentially less complete.
• Subjective cognitive impairment is a stage in which people sense that something is wrong despite still performing normally on cognitive tests. According to Bredesen, this phase lasts an average of 10 years and provides a substantial window for early intervention.
• Mild cognitive impairment is defined by abnormal performance on cognitive testing while the person remains able to complete activities of daily living. Bredesen’s trial includes people in this stage as well as people experiencing early dementia.
• Blood-based biomarkers are presented as the easiest way to investigate early Alzheimer’s pathology. The markers named in the discussion are phosphotau, the beta 42 to 40 ratio, GFAP, and NFL, all obtainable through blood testing.
• Brain imaging can identify signs associated with Alzheimer’s pathology before advanced dementia. The options discussed include amyloid, FDG, and tau PET scans, plus arterial spin labeling MRI, which evaluates subtle blood-flow changes in specific brain regions.
• Early treatment is associated with better reported outcomes in Bredesen’s clinical experience. He says optimally treated asymptomatic patients have not progressed to dementia, while virtually all treated patients with subjective cognitive impairment improve and sustain that improvement.
• Genetic information becomes more useful when people believe risk can be modified. Bredesen recommends that everyone aged 35 or older know their genetics, rather than avoiding testing because of the assumption that nothing can be done.
• Bredesen’s randomized controlled trial is being conducted at six sites across the United States. With 95% of the data available, he reports a treatment effect 8.5 times that of the US POINTER trial, 6.5 times that of Lembi, and 3.5 times that of Cassunla.

Questions & Answers

Q: How can Alzheimer’s disease be detected before dementia begins?

Alzheimer’s pathology can be investigated before dementia through blood-based biomarkers, cognitive changes, and brain imaging. Bredesen identifies phosphotau, the beta 42 to 40 ratio, GFAP, and NFL as blood markers. He also mentions spinal fluid testing, amyloid, FDG, or tau PET scans, and arterial spin labeling MRI. Subjective cognitive impairment can also provide an early warning even when standard cognitive testing remains normal.

Q: What are the four phases of Alzheimer’s disease?

The four phases described are asymptomatic pathology, subjective cognitive impairment, mild cognitive impairment, and dementia. During the first phase, a person has no symptoms, but biochemical markers may already be detectable. In the second, the person notices cognitive changes but still passes testing. The third produces abnormal cognitive test results without preventing daily activities. Dementia is the fourth and final phase.

Q: What is subjective cognitive impairment in Alzheimer’s disease?

Subjective cognitive impairment means a person senses that something is not quite right cognitively, although standard cognitive tests still produce normal scores. Bredesen says this stage lasts an average of 10 years. He considers it an important opportunity for intervention because the person has noticed changes before measurable impairment or loss of independence has developed.

Q: What is the difference between mild cognitive impairment and dementia?

Mild cognitive impairment is present when a person scores abnormally on cognitive tests but can still perform activities of daily living. Dementia is the later stage in which the condition has progressed beyond that threshold. Bredesen argues that treatment should begin before dementia whenever possible because delayed intervention tends to produce more difficult and less complete outcomes.

Q: Which blood tests can identify early Alzheimer’s pathology?

The discussion identifies phosphotau, the beta 42 to 40 ratio, GFAP, and NFL as blood-based biomarkers that can help detect early Alzheimer’s pathology. Bredesen describes blood testing as the easiest available approach and notes that phosphotau testing is offered by many laboratories. These tests are presented as a way to identify changes while a person may still be asymptomatic.

Q: How often should people check Alzheimer’s biomarkers?

Bredesen recommends checking relevant Alzheimer’s markers every five years, comparing the approach with monitoring for insulin resistance before type 2 diabetes develops. His argument is that periodic testing can reveal pathology before dementia appears. Early knowledge may allow people to respond during the asymptomatic or subjective cognitive impairment phases instead of waiting until cognitive testing and daily functioning have deteriorated.

Q: Can cognitive decline improve when treated early?

Bredesen reports that early treatment has produced sustained improvement in his clinical experience. He says no optimally treated asymptomatic patient has progressed to dementia and that virtually all treated patients with subjective cognitive impairment improve and remain improved. He also describes an initial patient treated in 2012 who was still doing well after 13 and a half years, at age 81.

Q: Why does Bredesen recommend learning about genetic Alzheimer’s risk?

Bredesen argues that genetic information has practical value if people accept that cognitive decline can be addressed. The older view discouraged genetic testing because Alzheimer’s was considered inevitable and untreatable. He recommends that everyone aged 35 or older know their genetics, reasoning that awareness of increased risk can motivate earlier testing and lifestyle changes rather than waiting for dementia to appear.

Summary & Key Takeaways

• Alzheimer’s disease is described as progressing through four phases: asymptomatic pathology, subjective cognitive impairment, mild cognitive impairment, and dementia. Bredesen argues that medicine often intervenes during the final phase, although biochemical changes can be detected much earlier, creating an opportunity to address cognitive decline before daily functioning becomes impaired.

• The earliest stage can be investigated using blood-based biomarkers such as phosphotau, the beta 42 to 40 ratio, GFAP, and NFL. Other approaches mentioned include spinal fluid testing, amyloid, FDG, or tau PET scans, and arterial spin labeling MRI, which detects subtle changes in blood flow within relevant brain regions.

• Bredesen recommends checking relevant markers every five years and learning about genetic risk from age 35 onward. He reports that optimally treated asymptomatic patients have not progressed to dementia in his experience, while virtually all patients treated during subjective cognitive impairment improve and remain improved. Outcomes become harder and less complete with delay.