Held July 22 to 28 in Toronto, the Alzheimer’s Association International Conference showcased a field in transformation. At the clinical level, groups from Europe, North America, and Japan are attempting to coalesce around new ways to recruit preclinical populations for large observational and trial platforms for late-onset AD, while the smaller but more established DIAN initiative is growing into a worldwide movement. At the biological level, research is set to expand thanks to funding increasing in response to national plans. Health economics research is pressing in. Topically, tau ruled the roost, though genetics, vascular contributions to dementia, and efforts to define ever-earlier stages of the decades-long disease continuum advanced, as well. On the clinical trials front, the only Phase 3 study appears to have been largely a bust, while some Phase 1 presentations of new antibodies, BACE inhibitors, and a small-molecule tau modifier drew quiet praise.
Claims of a positive effect in a small subgroup of patients are statistically meaningless, experts say.
At AAIC, researchers suggested splitting out the markers in a new staging scheme. Called ATN, it aims to clarify underlying causes of atypical dementias and suspected non-Alzheimer’s pathology (SNAP).
This past year, the Global Alzheimer’s Platform and the European Prevention of Alzheimer’s Dementia have moved quickly, and jointly, to pave the way toward more, faster, cheaper trials. Will they be better, too?
Alarmed by crushing screen failure rates of the first prodromal Alzheimer’s trials, EPAD and GAP are chasing new ways to reach people who don’t know they really should be in a secondary prevention trial.
Clinical trial centers are preparing to position themselves as standing networks, with standardized paperwork, clinical rater systems, and a central IRB, for trials anticipated to start late next year.
Dementia incidence in intervention group was no different from control, though targeting hypertension may protect, researchers say.
At AAIC, 28 scientific presentations and five attendant meetings of the Dominantly Inherited Alzheimer’s Network showed how data is rolling in while the platform expands to more countries and a second therapeutic trial.
Serial measurements on hundreds of people in the Dominantly Inherited Alzheimer’s Network put proposed staging diagrams on an empirical footing. CSF markers sTREM2 and VILIP-1 track tau.
At AAIC, updated imaging data in autosomal-dominant AD shows that longitudinal MRI in large numbers of people confirms atrophy patterns. Tau PET is more variable in DIAN participants than in the Colombian families.
Armed with what they consider comprehensive data sets from the DIAN initiative, researchers are beginning a quest to settle an old question that may become key to drug approvals for late-onset AD.
As data pours in, DIAN leaders strive to share and publish it without accidentally disclosing mutation status. The more is learned about preclinical AD, the harder this may get.
Researchers at AAIC presented congruent data on the place tau tangles take in AD progression, and their close correlation with cognitive decline.
Researchers at AAIC discussed technical limitations of current tracers and ways to improve the signal. A new ligand debuted that may be more specific for tangles.
BACE inhibitors are shaping up; pyroglutamate Aβ antibody clears plaques without ARIA, but immune reaction raises a flag.
Clinical trial design could benefit from new estimates of how slowly amyloid accumulates and how best to detect it at various disease stages.
Researchers at AAIC proposed several different measures of brain connectivity that may predict progression to AD.
Different genetic factors underlie amyloid accumulation and atrophy, researchers at AAIC reported.
Increasingly, people must learn of their amyloid status and/or ApoE genotype in order to enter secondary prevention trials. At AAIC, researchers laid out their procedures to ethically break the news.