Mr. Morris, 76, has experienced progressive memory loss over two years; it is now interfering with daily activities. His daughter asks about next steps for diagnosis and management.

Geriatric psychiatry has many emerging developments beyond usual medications. Anti-amyloid antibodies are a new option for Alzheimer’s disease (AD), neuromodulation expands options for treatment-­resistant depression (TRD), and blood biomarkers and digital therapeutics are advancing rapidly. We’ll review these treatment options below.

Dementia 

Anti-amyloid monoclonal antibodies
Lecanemab (Leqembi) and donanemab (Kisunla) have drawn attention as treatments for early symptomatic Alzheimer’s dementia, including mild cognitive impairment due to AD. Lecanemab is now also available as an FDA-approved auto-injector for maintenance dosing.

How they work: These drugs target ­beta-amyloid plaques in the brain at different stages of formation, helping the brain clear them. 

Efficacy: Clinical trials demonstrate a modest but meaningful slowing of clinical progression, on average around 25% less decline over 18 months compared with placebo (van Dyck CH et al, N Engl J Med 2023;388(1):9–21). Set realistic expectations with patients: These treatments may slow progression, but they do not improve, halt, or reverse symptoms. 

Clinical considerations:

• Before starting, confirm amyloid pathology via cerebrospinal fluid (CSF) lumbar puncture or amyloid positron emission tomography (PET) scan. 
• These medications require IV infusions every two to four weeks and regular MRIs to monitor for amyloid-related imaging abnormalities (ARIA): edema (ARIA-E) or hemorrhage (ARIA-H). Most episodes are self-limited and resolve without intervention, so patients can be reassured. 
• Discuss cost and insurance barriers upfront and review existing medical conditions and concurrent medications to assess eligibility. 
• Access remains limited to specialized medical centers certified to administer these treatments; clinicians can locate participating sites through manufacturer websites (www.leqembi.com; https://infusionlocator.kisunla.com) or via Alzheimer’s Association referral ­resources.

p-tau217/beta-amyloid 1-42 plasma ratio
The FDA recently approved the p-tau217/beta-amyloid 1-42 plasma ratio for detecting amyloid plaques in patients aged 55 and older. This blood test offers a less invasive alternative to CSF or PET scans for detecting and monitoring Alzheimer’s ­dementia.

How it works: The patient receives a standard blood draw, with plasma analyzed for p-tau217 and beta-amyloid 1-42 levels. The ratio indicates amyloid plaque presence, enabling earlier detection and monitoring.

Efficacy: Diagnostic metrics match gold-standard CSF and PET methods, with robust performance across diverse populations (Wang J et al, Alzheimers Dement 2025;21(3):e70038).

Clinical considerations:

• Interpret results within clinical context. Confirmatory CSF or PET remains necessary for ambiguous cases or trial enrollment.
• Real-world availability is limited. The test is primarily available in research or specialized centers, and most clinicians have not yet used it in routine practice. Access typically requires referral through academic memory clinics or participation in research protocols.

tDCS, VNS, and CES
Neuromodulation tools like transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and cranial electrotherapy stimulation (CES) are under investigation for mood and cognitive disorders. These techniques deliver ­low-intensity electrical stimulation with minimal systemic effects.

Efficacy:

• tDCS delivers low-voltage currents through scalp electrodes to enhance synaptic plasticity. It is less effective than ECT or transcranial magnetic stimulation for late-life depression.
• Early RESTORE-LIFE study data suggest older adults respond better to VNS, showing greater drops in depression scores than younger patients (Kavakbasi E et al, J Affect Disord 2025;378:39–46).
• CES devices (eg, Alpha-Stim) are marketed for anxiety and depression. Their evidence is mixed and largely limited to open-label or small trials. One recent trial in older adults found benefits for generalized anxiety disorder as add-on treatment (Chu CS et al, J Formos Med Assoc 2024;123(7):781–787).

Clinical considerations:

• tDCS, VNS, and CES may be options for patients who have exhausted many pharmacologic or neuromodulation treatments.
• VNS is FDA approved for TRD and other neuropsychiatric conditions. Surgical requirements limit its appeal in frail patients.
• More research is needed for CES devices to be recommended in practice.

Newer medications 

Esketamine
Esketamine (Spravato) is a rapid-acting N-methyl-D-aspartate receptor antagonist, one of the first antidepressants with this mechanism. The intranasal spray is FDA approved for TRD and depression with suicidality in adults, including those 65+, and is typically given with an oral ­antidepressant.

Efficacy: Esketamine has a mixed track ­record in older adults. In the ­TRANSFORM-3 RCT, esketamine plus an oral antidepressant did not meet the primary endpoint in patients over 65, though subgroup analyses suggested benefit in those aged 65–74 and with ­earlier-onset depression (Ochs-Ross R et al, Am J Geriatr Psychiatry 2020;28(2):121–141). Long-term open-label data (SUSTAIN-2) and real-world studies suggest late-life response and remission rates can match those in younger adults (d’Andrea G et al, Am J Geriatr Psychiatry 2023;31(12):1032–1041).

Clinical considerations:

• If your patient is not an ECT candidate or has significant suicidality, esketamine may be a reasonable next step.
• Esketamine can be prescribed with or without antidepressants.
• Each treatment requires three hours of observation in a certified setting, which could make it preferable for patients at risk for medication nonadherence.
• Common side effects include dissociation, dizziness, confusion, and transient hypertension.

Pimavanserin (Nuplazid)
Pimavanserin is FDA approved for Parkinson’s disease psychosis; it functions as a selective serotonin 5-HT2A receptor inverse agonist without dopaminergic activity.

Efficacy: Off-label data suggest pimavanserin may reduce psychosis relapse risk in dementia, regardless of subtype, though trials for negative symptoms in schizophrenia have failed.

Clinical considerations: For dementia-related psychosis, pimavanserin is used off-label. Start at 34 mg daily (the same dose for Parkinson’s disease psychosis); no titration needed. It costs about $6000 monthly, so confirm insurance coverage until generics become available.

Brexpiprazole (Rexulti)
A partial dopamine D2 receptor agonist, brexpiprazole is the first FDA-approved medication for agitation in AD.

Efficacy: Brexpiprazole 2–3 mg/day modestly reduces agitation in AD with a small effect size; this can be clinically meaningful for severe symptoms (da Silva AMB et al, CNS Drugs 2025; Epub ahead of print).

Clinical considerations: Typically reserved for agitation when nonpharmacologic strategies and off-label medications (selective serotonin reuptake inhibitors or other antipsychotics) have failed. Start at 0.5 mg daily; increase to 1 mg after 1 week and 2 mg after 2 weeks, with a maximum of 3 mg daily.

Xanomeline-trospium (Cobenfy, KarXT)
The combination of xanomeline, a muscarinic M1/M4 receptor agonist, with trospium, a peripheral muscarinic antagonist, is FDA approved for schizophrenia. It is also  under study for cognitive and behavioral symptoms in Alzheimer’s dementia.

Efficacy: While xanomeline/trospium shows promise for agitation and psychosis in AD, cognitive benefits are uncertain. Patients with schizophrenia and baseline cognitive impairment showed notable gains in one trial, suggesting a possible procognitive effect (Horan WP et al, Am J Psychiatry 2025;182(3):297–306).

Clinical considerations: Early data are promising, but evidence is limited. Use is restricted to research settings.

Digital health 
Technology isn’t just for the young. Today’s older adults are logging on, signing up, and benefiting from tech-based care like cognitive training apps and wearables.

Efficacy:

• Cognitive training apps (eg, Peak, ­BrainHQ) may improve processing speed, working memory, executive function, and verbal memory in older adults without cognitive impairment (Bonnechère B et al, Sci Rep 2020;10(1):15276). Improvements on other apps, like Lumosity, tend to be task-specific with limited real-world ­generalization.
• Early studies of wearables tracking sleep, mood, or activity as digital biomarkers of dementia link wearable data to mental health rating scales and ­real-time detection of behavioral patterns (Iaboni A et al, Alzheimers Dement (Amsterdam) 2022;14(1):e12305).

Clinical considerations:

• Consider cognitive training apps when older adults ask how to maintain or boost cognitive function.
• Wearables (eg, Empatica E4, ­EmbracePlus) can track activity, sleep, and stress signals in patients with dementia, alerting clinicians or caregivers to agitation or mood changes. They are currently mostly useful for research, not standard care.
• Take patient motivation, technological savvy, and access into account when choosing among digital health tools.

Carlat Verdict: Blood-based biomarkers are moving Alzheimer’s diagnosis earlier, while lecanemab and donanemab show promise for slowing progression. A growing range of brain-training apps and wearables is adding new tools for late-life care.