Anti-Amyloid Therapy for Alzheimer’s Disease: Early Local Experience and What General Practitioners Should Know

Clin Assoc Prof Adeline Ng
Deputy Head & Director, Research, SingHealth Duke-NUS Memory and Cognitive Disorder Centre;
Senior Consultant, Department of Neurology,
Head, Department of Psychology,
Clinical Programme Director, Dementia & Cognitive Neuroscience,
Director, Strategic Projects, Office of Academic Affairs, National Neuroscience Institute

For patients with early Alzheimer’s disease, anti-amyloid therapies offer the possibility of slowing cognitive decline. We share early experience from the National Neuroscience Institute with insights on how patients are selected, treatment workflow and outcomes, as well as the promise and limitations of these therapies.

INTRODUCTION

A Changing Treatment Landscape

The treatment landscape for Alzheimer’s disease (AD) has undergone a paradigm shift. For decades, physicians were limited to symptomatic therapies that provided modest benefits but did little to alter the course of the disease itself. Traditional treatment - including cholinesterase inhibitors and NMDA receptor antagonists - focus primarily on symptom management but do not directly address the underlying neuropathology of AD, which primarily involves amyloid plaques and tau neurofibrillary tangles.

Emergence of Anti-Amyloid Therapies

The emergence of anti-amyloid monoclonal antibody therapies (AAT), designed to remove amyloid plaques from the brain in mild cognitive impairment due to AD (MCI-AD) and mild dementia due to AD, has begun to change this paradigm.

Rationale for Anti-Amyloid Therapy

Anti-amyloid therapies target one of the central pathological hallmarks of Alzheimer’s disease: the accumulation of beta-amyloid plaques in the brain.

By binding to aggregated amyloid and facilitating its clearance, these therapies aim to slow the neurodegenerative process itself. Clinical trials over the past several years have demonstrated modest but measurable slowing of cognitive decline in patients with early AD, leading to increasing interest in their use in real-world clinical settings.

Despite the modest clinical efficacy outcomes shown in AAT clinical trials, there has been significant patient interest in being considered for AAT, or in speaking with a clinician familiar with AATs.

LOCAL EXPERIENCE AT NATIONAL NEUROSCIENCE INSTITUTE

Early Clinical Outcomes

To date, all sixteen patients who have been started on therapy have tolerated treatment well. While it remains too early to draw definitive conclusions about long-term cognitive outcomes, several patients have reported subjective stabilisation of symptoms. Caregivers have similarly noted relatively stable day-to-day functioning. Importantly, none of the patients in our cohort have experienced clinically significant adverse effects requiring discontinuation of therapy. From a safety perspective, the most closely monitored complication has been amyloid-related imaging abnormalities.

Setting and Patient Population

At the National Neuroscience Institute (NNI), we initiated AAT in sixteen carefully selected patients with early AD who were very keen to undergo AAT treatment.

Due to growing demand from patients and families, we began offering AAT to selected patients who met established criteria - typically individuals with mild cognitive impairment (MCI-AD) due to AD or early-stage AD dementia with biomarker confirmation of amyloid pathology, typically using amyloid PET-CT scans or cerebrospinal fluid (CSF) testing.

The process of introducing such therapies requires careful planning, multidisciplinary collaboration, and thorough patient counselling.

Counselling takes time and usually occurs in the specialist clinic and covers the modest clinical efficacy, risks of amyloid-related imaging abnormalities (ARIA), impact of APOE genotype on ARIA risk, costs and the logistics involved, e.g., repeated imaging for safety monitoring etc. Such discussions are usually initiated with the treating neurologist, and subsequent discussions on cost and logistics can be performed by the dementia specialist nurses.

Patient Selection and Pre-Treatment Evaluation

The sixteen patients we initiated on therapy mostly sought referrals to NNI to be evaluated for suitability for AAT.

Each patient underwent a detailed clinical assessment, cognitive testing to ensure they were at a mild disease stage (i.e. MMSE > 20 or clinician impression of MCI or mild dementia stage) and baseline neuroimaging.

The pre-AAT screening MRI brain scan is important to exclude contraindications to AAT and potential risk factors associated with treatment complications, such as extensive vascular white matter changes (Fazekas grade 3) or the presence of > 4 microbleeds/superficial siderosis that could be markers of underlying cerebral amyloid angiopathy (CAA). After ensuring there are no imaging or medical contraindications to AAT, biomarker confirmation of amyloid pathology, mainly through amyloid PET-CT imaging or CSF biomarkers, is a critical prerequisite for treatment eligibility.

Currently, we do not use blood-based biomarkers such as p-tau217 for initiation of AAT without amyloid PET or CSF confirmation, as they have not yet been approved in Singapore to be used solely for AAT initiation.

Genetic Counselling and Risk Stratification

Genetic counselling and APOE genotyping are also discussed with patients where appropriate, given the known association between certain APOE variants (particularly APOE4 homozygous carriers) and increased risk of amyloid-related imaging abnormalities (ARIA). These discussions are an important part of shared decision-making and help patients understand their individual risk profile.

Once eligibility is confirmed, expectations have to be clearly set: AATs are not cures, and their clinical benefits are generally modest.

However, even modest slowing of cognitive decline may translate into meaningful preservation of independence and quality of life for patients and their families.

This is often translated as being able to remain in their current functional state, obtaining an additional five to six months on average of being in their current functional ability over an 18-month treatment period, with potential for an additional 12 months on average of maintaining function over a four-year treatment period (including open-label extension treatment beyond the 18-month treatment period).

Our Clinical Workflow

An important aspect of implementing anti-amyloid therapy at NNI has been the development of a structured and streamlined clinical workflow.

As these treatments require careful monitoring and coordination among multiple services, a clear pathway has been essential for the safe and efficient delivery of care. After the extensive discussions above have taken place and the decision has been made to proceed with a specific therapy, the date of the first infusion is scheduled.

At the same time, the subsequent MRI monitoring scans required for safety surveillance are ordered and scheduled in advance. This ensures that imaging slots are secured early and that surveillance occurs at the recommended intervals. The infusion itself takes place in our infusion centre (TTSH MAC for NNI@TTSH), where nurses monitor patients during and after the administration of therapy, based on protocols developed by NNI.

The nursing team plays a critical role not only in infusion safety but also in longitudinal patient monitoring. Patients are reviewed by dementia nurses in the infusion centre at each visit, and global cognitive assessments are incorporated into routine follow-up.

Tools such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA) are performed approximately every six months. These assessments provide a standardised way to track cognitive trajectory over time and complement the clinical evaluations conducted during neurology visits.

MONITORING FOR ARIA

ARIA refers to MRI findings associated with antiamyloid therapies and is broadly categorised into two types: ARIA-E (oedema or effusion) and ARIA-H (haemorrhage), which includes microhaemorrhages and superficial siderosis.

These imaging abnormalities represent one of the most important safety considerations when prescribing anti-amyloid therapies.

Our experience

In our cohort of sixteen patients (as of March 2026), three individuals developed mild ARIA-H consisting of a small number of new microbleeds detected on surveillance MRI. Importantly, all three patients remained completely asymptomatic. None of the three experienced headaches, confusion, seizures or focal neurological symptoms.

The abnormalities were detected through routine MRI monitoring, which forms an integral component of treatment protocols. Follow-up imaging has not shown significant progression.

Two of the three cases with mild asymptomatic ARIA-H only developed microbleeds much later in their treatment course, with one patient showing two microbleeds at the 17-month time point, whilst another patient already in the AAT open-label extension period had one microbleed at the 36-month time point on routine MRI imaging.

The occurrence of mild ARIA-H in three out of sixteen patients is consistent with rates reported in clinical trials and highlights the importance of structured imaging surveillance. It also reinforces a key message frequently conveyed during patient counselling: while ARIA can occur, many cases - particularly small microhaemorrhages - may be clinically silent and manageable with appropriate monitoring.

CONCLUSION AND FUTURE DIRECTIONS

Our early clinical experience with anti-amyloid therapy at the National Neuroscience Institute has been encouraging. Future developments will include the use of blood-based biomarkers that will simplify diagnosis and monitoring, allowing for triaging of high-risk patients and making these therapies more accessible in routine clinical practice.

Advances in MRI may further refine our ability to identify patients most likely to benefit while minimising risk. While longer follow-up and larger patient cohorts will be necessary to fully understand the real-world impact of these therapies, the initial results demonstrate that AAT can be safely implemented within a structured clinical workflow.

Although the cohort remains small and the follow-up period relatively short, our early experience has been encouraging in terms of patient safety and acceptability and highlights the practical considerations of introducing these therapies into routine clinical practice.

Associate Professor Adeline Ng is a Senior Consultant Neurologist and Director, Strategic Projects, Office of Academic Affairs at the National Neuroscience Institute (NNI@TTSH). She has a keen interest in cognitive and behavioural neurology, and completed a one-year fellowship at the Memory and Aging Centre, University of California, San Francisco, focusing on Young-Onset Dementias (YODs). Her main interests in clinical research are in neurodegenerative diseases and cognitive neurology, with a focus on genetics and biomarkers.

GPs can call the SingHealth Duke-NUS Memory & Cognitive Disorder Centre for appointments at the following hotlines:

• Singapore General Hospital 6326 6060
• Changi General Hospital 6788 3003
• Sengkang General Hospital 6930 6000
• National Neuroscience Institute 6330 6363