Alzheimer's disease can be definitively diagnosed only through an autopsy after death by identifying characteristic brain changes such as abundant neuritic plaques and neurofibrillary tangles. During life, a clinical diagnosis of Alzheimer's is based on medical history, cognitive testing, physical and neurological examinations, brain imaging, and biomarker tests, but this diagnosis is considered "possible" or "probable," not definitive.

Definitive Diagnosis

• The definitive diagnosis requires histopathological confirmation at autopsy, showing abundant neuritic plaques and neurofibrillary tangles in brain regions like the neocortex, entorhinal cortex, and hippocampus.

Clinical Diagnosis During Life

• Clinicians gather detailed medical history and assess cognitive function (memory, language, executive function) through neuropsychological tests.
• Physical and neurological exams evaluate reflexes, muscle tone, coordination, and balance.
• Brain imaging like CT, MRI, and PET scans help support the diagnosis and exclude other causes.
• Biomarkers in cerebrospinal fluid or blood, detecting amyloid and tau proteins linked to Alzheimer's, help improve diagnostic certainty.
• Diagnosis of probable or possible Alzheimer's disease is made based on standardized criteria (DSM-5, NIA-AA) which incorporate cognitive decline patterns and biomarker evidence.

Thus, the only definitive confirmation occurs postmortem by microscopic brain examination, while living diagnosis is based on a comprehensive clinical and diagnostic evaluation.