Diagnosing and Treating Alzheimer Disease: August's Key Developments

Alzheimer disease research and care advanced on multiple fronts this August, from new blood-based and imaging diagnostics to early-phase therapeutic data and expert perspective on evolving clinical practice. This recap rounds up key developments, including FDA actions on diagnostic tools, emerging pipeline results, and clinical guidance on benzodiazepine use in older adults amid ongoing questions about dementia risk.

FDA Clears First and Only Single-Biomarker Blood Test for Alzheimer Disease Assessment

The US Food and Drug Administration has cleared Roche's Elecsys Phospho-Tau (217P) Plasma test, a single-biomarker blood assay developed with Eli Lilly and Company to aid identification of amyloid pathology in patients aged 55 years and older presenting with cognitive decline. It is the first cleared blood test to support both rule-in and rule-out assessment of amyloid pathology using the same validated cutoffs across primary and specialty care settings, stratifying results into negative, intermediate, and positive categories. The assay is intended for use alongside clinical judgment and other diagnostic findings rather than as a stand-alone test, and its performance for predicting dementia onset or monitoring treatment response has not been established. Designed for deployment across Roche's existing cobas laboratory infrastructure, the test aims to reduce reliance on costly, invasive positron emission tomography and cerebrospinal fluid testing and to extend amyloid assessment into primary care, where most patients with cognitive complaints first present.

FDA Approves Tauklarify (MK-6240) For Tau Pathology Detection in Alzheimer Disease

The FDA has approved Tauklarify (florquinitau F18 injection), a positron emission tomography imaging agent designed to bind aggregated tau protein and identify neurofibrillary tangle pathology in patients undergoing evaluation for Alzheimer disease. Approval was supported by two phase 3 blinded-read studies encompassing more than 500 patients across 3 clinical trials, spanning individuals with no cognitive impairment, mild cognitive impairment, and mild Alzheimer disease; positive percent agreement between independent readers ranged from 80% to 88% in one study and 68% to 82% in the other. Safety was assessed in more than 1700 participants, with headache (0.7%), nausea (0.2%), and injection site reactions (0.1%) among the most commonly reported adverse effects. Developers positioned Tauklarify as a complement to amyloid PET imaging and emerging blood-based biomarkers rather than a replacement, offering clinicians additional information on tau burden within the broader diagnostic workup.

Positive Safety and Biomarker Phase 1b Results for PMN310 in Mild Cognitive Impairment and Alzheimer Disease

ProMIS Neurosciences reported positive 6-month interim safety and biomarker data from the PRECISE-AD phase 1b trial of PMN310, a monoclonal antibody selectively targeting toxic amyloid-beta oligomers while sparing plaques and vascular deposits. Among 136 patients with mild cognitive impairment due to Alzheimer disease or mild Alzheimer disease, no cases of amyloid-related imaging abnormalities-edema occurred, including among APOE4 carriers, 11% of whom were homozygous. Overall amyloid-related imaging abnormality incidence was 4.4%, limited to mild, asymptomatic microhemorrhage. No serious treatment-related adverse events or drug-related discontinuations were reported. Exploratory biomarker findings showed reductions in plasma pTau217 in 68.5% of patients and in cerebrospinal fluid MTBR-tau243 in 62.5%, changes investigators characterized as consistent with, though not confirmatory of, a treatment effect given the trial's 3:1 active-to-placebo randomization.

Benzodiazepines in Older Adults: Alzheimer Risk, Memory, and Beers Criteria

In this installment of "Brain Trust: Conversations in Psychopharmacology," Joseph F. Goldberg, MD, continued his discussion with Carl Salzman, MD, on benzodiazepine use in geriatric patients. Salzman characterized the American Geriatrics Society's Beers Criteria, which flags benzodiazepines as potentially inappropriate past age 65, as reasonable in principle but overly categorical in practice; heightened sensitivity to sedative-hypnotic effects in older patients warrants dose reduction rather than blanket avoidance, since oversedation can itself mimic dementia symptoms. Addressing observational data linking benzodiazepine use to Alzheimer disease, Salzman attributed the association to protopathic bias—patients experiencing prodromal cognitive decline often begin taking benzodiazepines for resulting anxiety before diagnosis, reversing the presumed causal direction—and cited subsequent controlled studies refuting a causal link. Salzman advocated "mindful prescribing": low-dose, closely supervised use of short half-life agents such as lorazepam or oxazepam, paired with evaluation for depression and consideration of psychotherapy.

The State of Alzheimer Disease Care: An Update From Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP

In this interview, Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP, professor and chair of psychiatry at Creighton University School of Medicine, reviewed recent advances in Alzheimer disease care, citing the approvals of the anti-amyloid antibodies lecanemab and donanemab for mild cognitive impairment and mild Alzheimer disease dementia, FDA-cleared blood-based biomarkers, the revised 2024 National Institute on Aging–Alzheimer's Association diagnostic criteria, and the approvals of brexpiprazole and a dextromethorphan-bupropion combination for agitation associated with Alzheimer disease dementia as the most significant recent developments. Looking ahead, Tampi pointed to oral and subcutaneous formulations of newer medication classes, neuromodulation strategies, and prevention-focused research as key future directions. He identified persistent misinformation about the disease, a shortage of trained clinical workforce, and insufficient funding and policy support for prevention and treatment research as ongoing barriers to care.