Alzheimer’s Disease: Symptoms, Risk Factors, Treatment, and Prevention Strategies

Comprehensive Overview of Alzheimer’s Disease

Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative disorder accounting for 60–80% of dementia cases. It impairs memory, cognition, behavior, and eventually basic functional abilities.

Clinical Stages and Symptoms

Stage	Key Features
Preclinical	Biomarker changes (amyloid PET, CSF Aβ42/tau) years before symptoms.
Mild Cognitive Impairment (MCI) due to AD	Noticeable memory lapses (recent events, conversations); independent in daily activities.
Mild Dementia	Difficulty with complex tasks (finances, planning), word-finding problems, getting lost in familiar places, personality changes.
Moderate Dementia	Increased memory loss/confusion, difficulty recognizing family, inability to learn new things, impulsive behavior, hallucinations/delusions possible.
Severe Dementia	Loss of speech, complete dependence for ADLs, motor dysfunction (rigidity, dysphagia), susceptibility to infections.

Risk Factors

• Non-modifiable: Age (greatest risk), family history, APOE ε4 allele, Down syndrome, female sex.
• Modifiable (Lancet Commission 2020): Low education, hypertension, hearing loss, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol, traumatic brain injury, air pollution. Addressing these could prevent/delay up to 40% of cases.

Treatment Landscape (2024)

• Symptomatic: Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) for mild–moderate; memantine (NMDA antagonist) for moderate–severe. Modest, temporary benefit.
• Disease-Modifying (Anti-amyloid mAbs): Lecanemab, donanemab—IV infusions that reduce amyloid plaques; modest slowing of decline in early symptomatic AD; require amyloid confirmation (PET/CSF); carry ARIA (amyloid-related imaging abnormalities) risk.
• Non-Pharmacologic: Cognitive stimulation, exercise, Mediterranean/MIND diet, social engagement, sleep optimization, management of vascular risk factors.

Diagnosis and Early Intervention

Timely diagnosis allows access to treatments, clinical trials, advance care planning, and support services. The diagnostic workup includes history, cognitive testing (MoCA, MMSE), labs (B12, TSH, metabolic), and structural/functional imaging (MRI, FDG-PET, amyloid PET).