# Alzheimer Syndrome or Age-Related Dementia—History, Therapy and Prevention

## TL;DR

This paper reviews the historical evolution of Alzheimer's disease concepts, therapies, and prevention strategies over the past century.

## Contribution

The paper provides a historical and critical analysis of how Alzheimer's disease has been redefined over time and its implications for research and treatment.

## Key findings

- Alzheimer's disease has undergone three major conceptual shifts over 100 years.
- The current biological definition of AD faces criticism due to mixed pathology and lack of curative therapies.
- Dementia prevention is highlighted as the best practical approach in the absence of effective treatments.

## Abstract

This narrative review of Alzheimer’s disease (AD) history, therapy and prevention shows that its conceptualization has changed three times over 100 years. First, AD was a normative creation by Kraepelin in 1910 of a rare presenile dementia characterized by specific histological features. Second, during the 1970s, American neurologists, driven by sociological changes, merged presenile and senile dementias into an Alzheimer-type dementia with the universally accepted clinicopathological diagnostic criteria of McKhann. By the end of the 20th century, AD was divided into early-onset genetic (1%) and late-onset sporadic (99%) forms. In the 21st century, AD was redefined as a biological entity, using biological and neuroimaging markers of amyloid, tau and neurodegeneration, to better address research and clinical trials. This new nosology has been widely criticized, given the absence of curative therapy, the evidence of mixed pathology in most cases and the decline in the dementia/AD incidence in high-income countries. However, there are currently many drugs against AD in the pipeline; prevention appears as medical and social therapy. In summary, the ancient concept of age-related dementia has evolved into AD normative disorders over 100 years. Nowadays, AD requires a conceptual reassessment, although its medical paradigm remains. Awaiting pharmacological breakthroughs, dementia prevention seems the best practical approach.