We’ve all had those days: forgetting the keys, misplacing the wallet. But have you ever forgotten the face of a loved one? Or the location of your home? That is the reality for patients living with Alzheimer’s Disease, which is the leading cause of dementia.
AD is a progressive neurodegenerative disorder composed of three main characteristics: declining memory, impaired cognition, and behavioural changes. It shows a complicated mix of genetic predisposition, abnormal protein accumulation, and neuro-inflammatory cascades that gradually erode neural networks’ performance.1
Essentially, AD is defined by two hallmark pathologies:
- Amyloid-beta (Aβ) plaques block the extracellular spaces, and
- Neurofibrillary tangles (NFTs, and not the Bored Ape kind) of hyperphosphorylated tau within neurons.
All around the world, over 55 million people suffer from dementia, and of that count, Alzheimer’s accounts for nearly 70% of these cases. By 2050, that number will increase way beyond 130 million.3
In Sri Lanka, recent estimates suggest around 200,000–250,000 individuals live with Alzheimer’s or related dementias. This figure is expected to triple by 2050 as the aging population rises.4
Pathophysiology: The Science Behind Alzheimer’s Disease
It’s a complex process, but let’s go over it step by step.
1. Amyloid-Beta Plaque Formation
The amyloid cascade hypothesis states that Alzheimer’s disease (AD) starts when amyloid-beta (Aβ) peptides are produced. These peptides originate from the amyloid precursor protein (APP) and accumulate in brain tissue. The formation of Aβ plaques and fibrils outside cells results in synaptic dysfunction. This dysfunction activates both inflammatory processes and oxidative stress.
2. Neurofibrillary Tangles and Tauopathy
The tau protein inside neurons holds excessive amounts of these phosphates, which normally act to stabilize microtubules. This results in the formation of neurofibrillary tangles (NFTs) that disrupt the neuron’s delivery system and ultimately cause the cell to die.
3. Neuroinflammation and Neuronal Loss
The activation of microglia and astrocytes leads to increased production of inflammatory cytokines, which results in extra harm to neurons. Neural death causes the brain to shrink, primarily in the hippocampus region, which functions as the memory creation centre.
Clinical Features and Diagnosis
Cognitive symptoms include
- Gradual short-term and long-term memory loss
- Impaired language and comprehension
- Disorientation in time and place
- Reduced executive function and judgment
Non-cognitive symptoms include
- Personality and behavioural changes
- Depression, anxiety, or apathy
- Sleep disturbances and agitation in later stages
Diagnosis is clinical, supported by:
- History and cognitive assessment (MMSE, MoCA)
- Neuroimaging: MRI for cortical atrophy, PET for amyloid/tau deposition ● Biomarkers: ↓CSF Aβ42, ↑phosphorylated tau
The NIA-AA 2021 criteria integrate clinical findings, imaging, and biomarkers to enhance diagnostic accuracy.
How Alzheimer’s Affects People Worldwide
Dementia impacts 55 million people worldwide, according to the World Health Organization (2024). Alzheimer’s disease makes up 66% of all dementia cases. The worldwide increase in life expectancy has resulted in a significant growth in the number of affected individuals. Scientists forecast that the number will surpass 139 million by 2050. The annual cost of dementia care now exceeds 1.3 trillion US dollars, and if current trends continue, this amount is predicted to triple in the next ten years. The financial impact is equally astounding.
How do we treat Alzheimer’s?
1) Pharmacological Interventions
Presently available drugs do not cure AD but help manage symptoms:
- Cholinesterase inhibitors: Donepezil, Rivastigmine, Galantamine
- NMDA antagonists: Memantine (for moderate–severe AD)
Recent FDA approvals, like lecanemab (anti-Aβ monoclonal antibody), show promise in slowing early disease progression.2
2) Non-Pharmacological Strategies
- Cognitive training and memory exercises
- Routine physical activity and social engagement
- Nutritional support: Mediterranean or MIND diet
- Family counseling and caregiver support
Emerging Therapies and Research
Scientists now direct their Alzheimer’s disease research toward developing treatments that can alter disease progression, instead of focusing on symptom relief. They are working on three promising approaches, which include substances that stop tau proteins from aggregating, agents that break down existing tangles, treatments that control brain immune cell activity to decrease chronic inflammation, and gene or stem cell therapies for neuron replacement or genetic defect correction. The development of new detection techniques includes artificial intelligence systems that use speech patterns, eye health, and brain imaging to detect Alzheimer’s disease before patients show any symptoms. Researchers and scientists foster optimism about future success in controlling or stopping neuronal degeneration. This will lead to significant breakthroughs in disease treatment.
What Happens Over Time: Alzheimer’s Prognosis
Stages of Alzheimer’s Disease
- Pre-clinical stage: Pathological changes occur years before symptoms.
- Mild cognitive impairment (MCI): Subtle memory lapses, daily activities intact.
- Mild–Moderate AD: Worsening confusion, word-finding difficulty, and mood changes.
- Severe AD: Dependence in all ADLs, incontinence, loss of speech, and mobility.
Factors Influencing Prognosis
- Age at onset
- Genetic profile (ApoE ε4)
- Comorbidities
- Early diagnosis and intervention
Median survival after diagnosis: 8–10 years.
The scientific battle against Alzheimer’s disease stands as the fundamental human problem. The actual effects of new treatments emerge through the daily experiences of patients and their relatives who face the challenges of memory loss and their attempts to preserve their relationships.
The process of learning about Alzheimer’s disease extends past the simple act of memorizing medical information or brain pathways. The story reveals medical diagnosis through human experiences as it follows the battle to protect both personal identity and memory. Discoveries allow us to move closer to protecting family relationships, which define our identity.
References
1. Abhayasinghe, K., Dissanayake, L., Saunders, B., Campbell, P., & Sumathipala, A. (2020). Dementia research activity in Sri Lanka: A review. Journal of
Neurodegenerative Disorders, 3, Article 603. https://doi.org/10.36959/459/603
2. Alkhalifa, A. E., Al Mokhlf, A., Ali, H., Al-Ghraiybah, N. F., & Syropoulou, V. (2025). Anti-Amyloid Monoclonal Antibodies for Alzheimer’s Disease: Evidence, ARIA Risk, and Precision Patient Selection. Journal of personalized medicine, 15(9), 437. https://doi.org/10.3390/jpm15090437
3. Alzheimer’s Disease Central (n.d.). Dementia statistics.
https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/
4. The Lanka Alzheimer’s Foundation (LAF) (n.d.). Sri Lanka statistics. Lanka Alzheimer’s Foundation (LAF). https://alzlanka.org/srilanka-statistics
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