|
|
|
In this report
September brought a practical expansion in blood-based diagnosis, alongside mixed evidence on how treatment changes biomarkers and cognition. Trial activity remained active but uneven, with one psychosis programme moving toward Phase 3 after a narrowly missed primary endpoint and a new prevention study entering Phase 2b. The month also extended the field's prevention, care, mechanistic and infrastructure agendas.
- FDA cleared C2N's PrecivityAD2 for symptomatic adults aged 40 and older, with supporting evidence that it improved primary-care diagnostic accuracy from 65% to 93%:
- Acadia's remlifanserin Phase 2 RADIANT topline narrowly missed its primary endpoint, met a key secondary endpoint and leaves both Phase 3 studies continuing:
- A meta-analysis found modest lecanemab-related cognitive benefits alongside a substantially higher risk of ARIA-E, while a real-world cohort showed treatment-associated plasma proteins moving in four different directions:
|
|
Diagnosis and treatment biomarkers
|
FDA clears PrecivityAD2 for adults aged 40 and olderBiomarkers and diagnosis
The FDA cleared C2N Diagnostics' single-draw plasma test for symptomatic adults aged 40 and older, widening the clinical setting in which a blood biomarker can contribute to an Alzheimer's workup. The clearance supports use alongside history, examination, cognitive testing and, where needed, imaging or CSF, rather than as a stand-alone diagnosis.
- In an AAIC-reported study of 1,310 patients assessed by 165 physicians, primary-care diagnostic accuracy rose from 65% to 93% after clinicians reviewed PrecivityAD2 results.
- Among roughly 2,700 cognitively unimpaired adults, elevated plasma p-tau217 was associated with an estimated 78% ten-year risk of cognitive impairment; that is risk stratification, not diagnosis.
What this means for you Blood biomarkers now have a clearer place in real-world diagnostic workflows, but clinical interpretation still depends on the wider assessment and the test's cleared population. |
|
Plasma Aβ narrows p-tau217's MCI grey zoneBiomarkers and diagnosis
In 186 people with MCI, adding plasma Aβ40/Aβ42 to p-tau217 reduced the proportion left unclassified by dual diagnostic cutoffs. The result is a workflow refinement, not evidence that one biomarker platform is sufficient across settings.
- p-tau217 alone left 27.4% of participants in an indeterminate zone; the combined model reduced that to 12.3%, while a sequential strategy reached 13.4%.
- CSF Aβ42/Aβ40 defined amyloid status, and the study used mass-spectrometry Aβ measurement in a modest secondary-care cohort.
What this means for you Diagnostic studies can now assess blood panels by the size of the residual confirmatory-testing group, not only by a single biomarker's AUC. |
|
Lecanemab study finds four plasma-protein trajectoriesClinical trials and regulatory decisions
A Washington University-led observational cohort found that lecanemab-associated plasma changes did not form a single biological response pattern. Amyloid and tau markers partly moved toward cognitively unimpaired controls, while inflammatory and neurodegeneration-related markers were mixed or moved further away.
- The study followed 197 treated patients, compared with 1,312 untreated cognitively impaired controls and 458 Aβ-negative controls, measuring 130 proteins.
- Thirty-four markers fell into normalising, overcorrecting, opposite or unchanged trajectories; the real-world observational design cannot establish that lecanemab caused the changes.
What this means for you Amyloid clearance and downstream biological recovery remain separable questions, so treatment-response biomarker panels need more than amyloid and tau alone. |
|
Therapeutic programmes and safety |
Acadia advances remlifanserin after mixed RADIANT resultsClinical trials and regulatory decisions
Acadia's 60 mg remlifanserin arm narrowly missed the Phase 2 primary endpoint in Alzheimer's disease psychosis but met a key secondary endpoint, leaving a plausible signal with confirmatory uncertainty. The company is continuing both Phase 3 studies while removing the weaker 30 mg arm.
- At week six, SAPS H+D changed by −12.6 with 60 mg versus −10.4 with placebo, with effect size 0.26 and p=0.0603.
- The key CGI-S-ADP secondary endpoint favoured 60 mg, −1.3 versus −0.9, with effect size 0.37 and nominal p=0.0077; safety measures were similar to placebo.
What this means for you AD psychosis still has no approved therapy, and the programme's evidentiary weight now rests on whether Phase 3 reproduces the secondary-endpoint signal without the 30 mg arm. |
|
NewAmsterdam starts Phase 2b obicetrapib trialClinical trials and regulatory decisions
NewAmsterdam dosed the first participant in SPINOZA, a 400-person Phase 2b trial testing obicetrapib in biomarker-positive, cognitively unimpaired adults. Its design makes plasma p-tau217 the primary readout for a preclinical Alzheimer's intervention.
- Participants aged 55 to 85 will receive 10 mg obicetrapib or placebo for 52 weeks, followed by a 26-week open-label extension.
- The trial is restricted to ApoE4/E4, ApoE3/E4 and ApoE3/E3 genotypes, with secondary plasma, cognitive and disease-progression measures.
What this means for you Preclinical Alzheimer's trials are increasingly being structured around biomarker-defined populations and blood-based efficacy signals before clinical decline is measurable. |
|
Meta-analysis confirms lecanemab benefit with ARIA riskClinical trials and regulatory decisions
A pooled analysis found small but consistent cognitive advantages for lecanemab, paired with a much larger relative risk of ARIA-E. The result reinforces that efficacy and safety are inseparable parts of the treatment effect.
- Across five articles covering eight trials, effect sizes were −0.20 for ADCOMS, −0.19 for CDR-SB and −0.18 for ADAS-Cog.
- ARIA-E risk was nearly six times higher with lecanemab, RR 5.99, while PET amyloid results showed high heterogeneity, I²=96%.
What this means for you The treatment literature supports a modest cognitive effect, but trial interpretation and clinical development remain constrained by imaging-defined safety risk and heterogeneous biomarker outcomes. |
|
Prevention, care and disease biology |
WHO expands dementia risk-reduction frameworkRisk factors and prevention
WHO's second-edition guideline reframes dementia risk reduction across the life course, connecting clinical risk management with environmental exposures, equity and service design. The executive summary sets the framework; specific changes from 2019 require the full guideline text.
- The document covers healthy behaviours, associated health conditions, environmental risk factors and tailored multidomain interventions.
- It is aimed at providers, policymakers and other stakeholders, and explicitly identifies structural and sociocultural barriers and research gaps.
What this means for you Prevention evidence is being framed less as an individual risk checklist and more as a multisectoral, equity-sensitive research and service question. |
|
Network analysis ranks cognitive training for cognitionRisk factors and prevention
A network meta-analysis placed cognitive training highest for global cognition across non-drug interventions in AD and MCI, while different modalities led individual domains. The ranking is informative but rests on heterogeneous evidence of uneven quality.
- The analysis pooled 82 RCTs involving 6,457 participants; cognitive training's global-cognition estimate was SMD 0.81, 95% CI 0.46 to 1.17.
- rTMS ranked highest for executive function, exercise for language and tDCS for memory, while several modalities remain understudied.
What this means for you Care research now has comparative signals across several non-drug approaches, but the ranking does not remove the need to resolve modality-specific and trial-quality differences. |
|
Chlorhexidine reveals transcriptional BACE1 mechanismDisease mechanisms and genetics
Cell and mouse experiments identify chlorhexidine as a probe of partial BACE1 suppression through JAK1, STAT3 and SOCS3 signalling. The work adds a mechanistic route to the biology, not a therapeutic candidate ready for translation.
- In APP/PS1 mice, eight weeks of oral dosing reduced plaque burden and cortical BACE1 while improving behavioural measures.
- SOCS3 knockdown abolished the effect, and promoter editing removed the response; the study began with a screen of 1,200 clinically used molecules.
What this means for you BACE1 biology remains open at the level of transcriptional regulation, but the preclinical probe does not support assumptions about chlorhexidine as an Alzheimer's treatment. |
|
Research infrastructure |
ADNI4 receives $147 million to broaden recruitmentResearch funding
ADNI4 received a five-year $147 million grant, roughly twice the funding for its previous phase, with a larger and more representative participant target. Its recruitment model also links digital screening and remote blood sampling to site-based longitudinal research.
- The programme plans about 1,500 enrolled participants, at least half from underrepresented populations, and screening of up to 20,000 people through a web portal.
- It will use digital cognitive testing, a voice assessment and remote amyloid and tau blood sampling, with 60 sites across the US and Canada and at least 500 new in-clinic enrollees targeted.
What this means for you The next ADNI dataset is being designed to improve both longitudinal scale and demographic reach, which will affect how broadly its biomarker and progression findings can generalise. |
|
How Iris covered your topics this month Every topic you track was searched over the last month. | Topic | Sources found | In this briefing | | Clinical trials and regulatory decisions | 18 | 4 stories | | Biomarkers and diagnosis | 13 | 2 stories | | Disease mechanisms and genetics | 16 | 1 story | | Risk factors and prevention | 13 | 2 stories | | Care research | 8 | Nothing of notable significance | | Research funding | 8 | 1 story |
|
|
