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narrative_review·neurology, geriatrics, internal medicine, psychiatry, clinical trial·PMC10469885

A how-to guide for a precision medicine approach to the diagnosis and treatment of Alzheimer's disease

Frontiers in Aging Neuroscience · 1 author, 3 centres

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The author discusses the complexity of AD clinical presentation, noting that AD rarely exists in isolation and frequently co-occurs with other brain pathologies such as Lewy body disease and argyrophilic grain disease. De-identified case examples illustrate diagnostic and treatment decision-making, including the importance of considering brain reserve, cognitive reserve, genetic risk factors, systemic comorbidities, and psychiatric diagnoses. The author concludes that given the vast heterogeneity of AD, an individualized, case-by-case approach to treatment and prognosis is essential.

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neurology

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ORIGINAL PAPER

PMC10469885

A how-to guide for a precision medicine approach to the diagnosis and treatment of Alzheimer's disease

Frontiers in Aging Neuroscience

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ABSTRACT

Abstract Article purpose The 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. Problem The 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. Methods The 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. Implications AD 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. Keywords: Alzheimer's disease, treatment and diagnosis, precision medicine, differential diagnosis, biomarkers, lecanemab, aducanumab, prognosis

CITATION EXPORT

Gayatri Devi. A how-to guide for a precision medicine approach to the diagnosis and treatment of Alzheimer's disease. Frontiers in Aging Neuroscience. (2023). https://doi.org/10.3389/fnagi.2023.1213968

AUTHORS

1 · 3 CENTRES

Gayatri Devi

1Neurology and Psychiatry, Zucker School of Medicine, Hempstead, NY, United States
2Neurology and Psychiatry, Lenox Hill Hospital, New York City, NY, United States
3Park Avenue Neurology, New York City, NY, United States