Jun 5, 2019
By Jacqueline Posada, MD, 4th-year resident in the department of
psychiatry & behavioral sciences at George Washington
George T. Grossberg, MD:
Samuel W. Fordyce Professor; director, geriatric psychiatry at
Saint Louis University.
Dr. Grossberg spoke at the American Academy of Clinical
Psychiatrists 2019 annual meeting in Chicago, sponsored by
Global Academy for Medical Education (GAME). GAME and the MDedge
Psychcast are owned by the same company.
New developments in Alzheimer’s research
- The Systolic Blood Pressure Intervention Trial, also known as
the SPRINT MIND Study, showed
that tightly controlled systolic blood pressure (SBP) of 120 mm Hg,
compared with an SBP of 140 mm Hg, resulted in a 20% reduced risk
of developing mild cognitive impairment.
- The SPRINT study was terminated early at the median follow-up
of 3.26 years as its results showed that tightly controlled SBP
significantly reduces the risk of stroke and heart disease.
- The Alzheimer’s Association has agreed to fund an additional 2
years of the SPRINT MIND Study to evaluate whether tightly
controlled BP is effective in reducing the risk of Alzheimer’s
- In the brain, the glymphatic
system was discovered in 2012 and is similar to the lymphatic
system in its role as a drainage system for removing toxins.
- Glial cells mediate toxin removal, and the glymphatic system
removes toxins that eventually can cause cell death in the
- Because the glymphatic system is involved in removing the
beta-amyloid plaques that contribute to cell death in AD, the
glymphatic system is another area of investigation in the
pathogenesis of AD.
- Novel treatment of moderate to advanced AD involves using
- Infusion of plasma products from healthy, nonimmunocompromised
18-year-old individuals into older patients with AD is a potential
treatment for AD.
- Precedent for this intervention comes from animal studies
investigating parabiosis, a
procedure in which two animals are connected so that they share
each other’s blood stream.
- When such a circulatory exchange occurs between a younger mouse
and an older mouse with AD, the older AD model mouse regains
cognitive abilities and is able to complete mazes that it was
unable to complete before.
- How can this model be adapted to humans? One possibility might
involve infusing plasma from young healthy individuals into older
adults with advanced AD.
- A safety proof-of-concept study, published recently, found that
plasma products can be safely infused. The next step is an efficacy
- A relationship has been found between AD and periodontal
- The primary bacteria related to periodontal disease,
Porphyromonas gingivalis, is found in close
proximity in the brain to the plaques and tangles of AD.
- One theory posits that the presence of this bacteria is related
to inflammation that may contribute to the causality of AD.
- Could AD be treated with the antibiotics used to treat
periodontal disease? The answers remain unclear.
- Aducanumab, a monoclonal antibody targeting the
beta-amyloid plaques of AD, initially showed favorable changes in
imaging studies of the brains of people with AD.
- In March 2019, the study was halted because of futility.
- An independent data-monitoring committee determined that the
early results seen on imaging did not result in clinically
meaningful changes, compared with placebo.
- Some AD researchers consider this drug failure the “final nail
in the coffin” of the amyloid hypothesis, and the pathogenesis of
AD is most likely related to tau neurofibrillary tangles and other
mediators, such as the immune system and inflammation.
SPRINT Research Group. A randomized trial of intensive versus
standard blood-pressure control. N
Engl J Med. 26 Nov 2015;373:2103-16.
Jessen NA et al. The glymphatic system: A beginner’s guide.
Neurochem Res. 2015
Dominy SS et al. Porphyromonas gingivalis in
Alzheimer’s disease brains: Evidence for disease causation and
treatment with small-molecule inhibitors. Science Advances. 23 Jan
Conese M et al. The fountain of youth: A tale of parabiosis,
stem cells, and rejuvenation.
Open Med (Wars).
Phase 3 study of aducanumab in early Alzheimer’s disease.
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