Primary progressive dementia in 2026: beyond amyloid, towards biomarker-guided and equitable care. A viewpoint from Croatia and resource-constrained health systems

Dementia caused by primary neurodegenerative disease, traditionally termed “primary progressive dementia” in our region, affected an estimated 57 million people worldwide in 2019, a figure projected to approach 153 million by 2050, with the steepest increases in low- and middle-income countries (LMICs). Recent years have transformed the field. Alzheimer disease is now defined biologically; plasma phosphorylated tau 217 approaches the diagnostic accuracy of cerebrospinal fluid and positron emission tomography; and two anti-amyloid monoclonal antibodies, lecanemab and donanemab, have shown that removing amyloid modestly slows decline in early disease, at the price of amyloid-related imaging abnormalities, intensive monitoring and high cost. At the same time, the failure of semaglutide in two large phase 3 trials, the high frequency of mixed pathologies, and the frequent dissociation between amyloid burden and clinical state remind us that amyloid is a necessary but insufficient part of the story. In this viewpoint we argue that neurodegeneration is better understood as a progressive failure of neuronal networks, in which collapse of intracellular transport, impaired clearance and regulated cell death converge, than as a single-protein disease. We then consider what the new diagnostic and therapeutic tools mean for health systems with limited resources, drawing on Croatian experience: a strong research tradition, scarce imaging capacity, care that rests largely on families, and a national dementia plan still under development. We propose that blood biomarkers, task-sharing with primary care and population-wide risk-factor reduction, rather than costly infusions, should be the first priorities for LMICs and resource-constrained European systems.