Like a tricky puzzle, Alzheimer’s disease presents itself in various forms and can be difficult to differentiate from other brain pathologies. In fact, it’s rare to see Alzheimer’s existing in isolation, as it often coexists with other primary brain diseases. The diagnosis of Alzheimer’s requires accurate biomarkers to unravel its complexities. Treatment response depends on a multitude of factors such as the specific brain regions affected, the presence of comorbidities, genetic risk factors, and an individual’s brain reserve and cognitive reserve. But fear not! A recent study provides a comprehensive guide to precision medicine for diagnosing and treating Alzheimer’s. The study includes real-life examples, highlighting the decision-making process and treatment responses. It emphasizes the importance of an individualized approach towards Alzheimer’s, combining clinical and biomarker strategies. So grab your thinking cap and delve into the fascinating realm of Alzheimer’s research!

Article purposeThe clinical approach to Alzheimer’s disease (AD) is challenging, particularly in high-functioning individuals. Accurate diagnosis is crucial, especially given the significant side effects, including brain hemorrhage, of newer monoclonal antibodies approved for treating earlier stages of Alzheimer’s. Although early treatment is more effective, early diagnosis is also more difficult. Several clinical mimickers of AD exist either separately, or in conjunction with AD pathology, adding to the diagnostic complexity. To illustrate the clinical decision-making process, this study includes de-identified cases and reviews of the underlying etiology and pathology of Alzheimer’s and available therapies to exemplify diagnostic and treatment subtleties.ProblemThe clinical presentation of Alzheimer’s is complex and varied. Multiple other primary brain pathologies present with clinical phenotypes that can be difficult to distinguish from AD. Furthermore, Alzheimer’s rarely exists in isolation, as almost all patients also show evidence of other primary brain pathologies, including Lewy body disease and argyrophilic grain disease. The phenotype and progression of AD can vary based on the brain regions affected by pathology, the coexistence and severity of other brain pathologies, the presence and severity of systemic comorbidities such as cardiac disease, the common co-occurrence with psychiatric diagnoses, and genetic risk factors. Additionally, symptoms and progression are influenced by an individual’s brain reserve and cognitive reserve, as well as the timing of the diagnosis, which depends on the demographics of both the patient and the diagnosing physician, as well as the availability of biomarkers.MethodsThe optimal clinical and biomarker strategy for accurately diagnosing AD, common neuropathologic co-morbidities and mimickers, and available medication and non-medication-based treatments are discussed. Real-life examples of cognitive loss illustrate the diagnostic and treatment decision-making process as well as illustrative treatment responses.ImplicationsAD is best considered a syndromic disorder, influenced by a multitude of patient and environmental characteristics. Additionally, AD existing alone is a unicorn, as there are nearly always coexisting other brain pathologies. Accurate diagnosis with biomarkers is essential. Treatment response is affected by the variables involved, and the effective treatment of Alzheimer’s disease, as well as its prevention, requires an individualized, precision medicine strategy.

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