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Medical Treatments and Therapies for Cognitive Decline Prevention

Medical treatment and therapy for cognitive decline (2025):
From breakthrough drugs to digital brain training

A decade ago, doctors only had symptomatic drugs to treat dementia or attention deficit disorders. Rapid scientific progress has now offered disease-modifying antibodies, blood test-based diagnostics, non-invasive neuromodulation, and AI cognitive therapies. This review discusses the latest evidence on:

  • Pharmacological innovations – from classic cholinesterase inhibitors to new generation anti-amyloid and anti-tau biological drugs;
  • Non-pharmacological methods – cognitive training, psychotherapy, neuromodulation, and multimodal digital platforms;
  • How these methods work together, enhancing neuroplasticity and functional independence.

Contents

  1. Pharmacological landscape 2025
  2. 1. Traditional symptomatic treatments
  3. 2. Disease-modifying treatments (DMT)
  4. 3. Developing Drugs and Biomarker-Based Care
  5. Non-pharmacological Interventions
  6. 4. Cognitive Training and Digital Therapies
  7. 5. Psychosocial and reminiscence therapies
  8. 6. Neuromodulation (rTMS, tDCS)
  9. Integrated care and implementation advice
  10. Conclusion
  11. Sources

Pharmacological landscape 2025

Today's drug arsenal has three layers:

  1. Symptom-enhancing drugs – increase neurotransmitter (e.g., acetylcholine or glutamate) activity;
  2. Disease progression-slowing biological drugs – remove amyloid or target tau protein during Alzheimer's disease;
  3. Developing drugs and supportive biomarkers – blood tests, anti-tau vaccines, inflammation-suppressing modulators.

1. Traditional symptomatic treatments

Class Drugs Main action Use cases
Cholinesterase inhibitors Donepezil, rivastigmine, galantamine Increases acetylcholine levels Mild to moderate Alzheimer's disease; Parkinson's dementia
NMDA antagonist Memantine Regulates glutamate toxicity Moderate to severe AD; often combined with ChEIs
Cognitive stimulants* Methylphenidate, modafinil Enhances dopamine/noradrenaline activity ADHD, post-stroke apathy; unofficially – “chemo brain”

*Use only under specialist supervision.

Although these drugs do not cure the disease, meta-analyses confirm small to moderate improvements in cognitive tests and daily functioning – especially when combined with lifestyle and rehabilitation methods.

2. Disease-modifying treatments (DMT)

2.1 Anti-amyloid monoclonal antibodies

  • Lecanemab (Leqembi) – first antibody to receive full FDA approval (July 2023); phase 3 data showed 27% slower cognitive decline over 18 months in early Alzheimer's disease.1
  • Donanemab (Kisunla) – phase 3 TRAILBLAZER‑ALZ 2 study showed 35% slower cognitive-functional decline; approved in Australia in May 2025, FDA considering approval.2
  • Aducanemab – removed from the US market in early 2024 after CMS reimbursement barriers and questionable efficacy.4

Practical aspects

  • Patient selection: confirmed amyloid load, early symptoms, APOE genotyping for risk assessment.
  • Safety monitoring: MRI performed every 3 months for ARIA (amyloid-related imaging abnormalities).
  • Infrastructure: monthly infusions, specialized imaging, reimbursement challenges (cost ~26–44 thousand $/month).

2.2 Other Targets

  • Anti-tau antibodies (semorinemab, bepranemab) – in phase 2–3 trials, aiming to halt the spread of neurofibrillary tangles.
  • Neuroinflammation modulators (lenalidomide, masitinib) – act on microglia and mast cells.
  • Neurotrophic small molecules (buntanetap) – activate BDNF to rescue synapses.

3. Developing Drugs and Biomarker-Based Care

3.1 Blood-Based Diagnostics

In May 2025, the FDA approved the first plasma pTau217/β-amyloid ratio test for early Alzheimer's detection – reducing costs and opening the way to participate in clinical trials or access new drugs.5

3.2 Combined Studies

  • Anti-amyloid + anti-tau combinations already in phase 2 (AlkiliX-001), targeting both pathologies.
  • DMT + digital training coach (ACTIV‑ALZ) – lecanemab combined with a wearable device that promotes exercise and increases BDNF, improving circulation.

Non-pharmacological Interventions

DMT slows disease progression, but functional outcomes depend on brain plasticity – here non-pharmacological methods are especially effective. Three clinically important areas:

4. Cognitive Training and Digital Therapies

4.1 Computer Programs

Modern platforms (e.g., BrainHQ, EndeavorRx) adapt task difficulty in real time, training working memory, processing speed, and executive functions. A 2025 systematic review of digital interventions for mild cognitive impairment found small-to-moderate improvements (especially in speed modules).6

4.2 Virtual and Augmented Reality

Pilot AR training with motion sensors improved inhibition, flexibility, and reaction time in older adults after 18 sessions.7

4.3 Cognitive Rehabilitation (CR)

Initially used for schizophrenia, it now encompasses structured strategic training and tasks. A 2024 meta-analysis (56 studies) showed a moderate effect on attention, working memory, and real-life functions.8

5. Psychosocial and reminiscence therapies

  • Reminiscence and Life Review: guided recall of autobiographical memories improves mood, increases autobiographical accuracy; small cognitive benefit (meta-analysis of 27 studies).
  • Music Therapy: rhythmic or active music interventions improved overall cognitive function levels in individuals with dementia.9
  • Cognitive Behavioral Therapy (CBT): adapted for mild cognitive impairment reduces anxiety, depression, and indirectly improves cognitive functioning.

6. Neuromodulation (rTMS, tDCS)

Method Evidence base Typical protocol duration Outcome
High-frequency rTMS (10 Hz) 2024 meta-analysis, 33 studies in MCI and mild AD cases → significant MMSE increase (SMD 0.41).10 10 sessions, bilateral DLPFC Improved memory and executive functions
Intermittent theta-burst rTMS 2025 pilot double-blind RCT – better delayed recall results than placebo.11 600 pulses, 3 min, 5 times/week Sustained benefit after one month
tDCS Smaller but significant effects; safe, portable; studies ongoing. 2 mA, 20 min, 10 sessions Improved attention

Neuromodulation is applied as an adjunct; combining rTMS with physical or cognitive exercises produces an even stronger effect (e.g., tai chi + rTMS improved sleep and cognition in a 2025 JAMA Network Open study).12

Integrated care and implementation advice

  1. Key biomarkers: Use blood/CSF markers and cognitive tests to monitor and evaluate treatment effectiveness.
  2. Combine interventions: Combine DMT with lifestyle modification and digital training to enhance plasticity.
  3. Safety assurance: Patients using antibodies are regularly monitored by MRI; neuromodulation clients are assessed for mood and sleep changes.
  4. Team care: Neurologist, neuropsychologist, occupational therapist, and digital coach collaborate through a shared EHR.
  5. Outcome measurement: ADAS-Cog, MoCA, functional scales (ADL/IADL), and patient quality of life self-assessment.

Conclusion

The 2020s brought precision medicine for cognitive disorders: targeted antibodies slow the disease, blood tests speed diagnosis, digital therapy, neuromodulation, and active engagement turn remaining neuron connections into a resilient network. The optimal approach is hybrid: drugs affect biology, while training and therapy unlock neuroplasticity potential. For doctors, caregivers, and patients, the new principle is not “drugs or therapy,” but “drugs and therapy – personalized, measured, continuously updated.”

Sources

  1. FDA traditional Leqembi (lecanemab) approval — July 2023.
  2. Donanemab slowed decline in phase 3, received approval in Australia (May 2025).
  3. Lilly TRAILBLAZER-ALZ 2 results report.
  4. Public policy and reimbursement review of Aducanumab (Aduhelm) (2024).
  5. FDA approved the first plasma Alzheimer’s diagnostic test (May 2025).
  6. Studies of digital cognitive interventions in MCI (2024–2025).
  7. AR-based cognitive-physical training pilot study (2024).
  8. Meta-analysis of cognitive rehabilitation (2023).
  9. Meta-analysis of music therapy effects on dementia (2024).
  10. rTMS vs. tDCS meta-analysis in MCI cases (2024).
  11. Intermittent theta-burst rTMS pilot RCT (2025).
  12. JAMA Network Open: Tai chi + rTMS synergy (2025).

Limitation of liability: This article is for informational purposes only and does not replace professional medical consultation. Medications and neuromodulation carry risks and should only be applied under a doctor's supervision.

 

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