A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer’s Disease Risk in Older Men with Prostate Cancer

Abstract

Prostate cancer (PCa) is one of the most prevalent malignancies affecting males worldwide. Despite reductions in mortality rates due to advances in early identification and treatment methods, PCa remains a major health concern. Recent research has shed light on a possible link between PCa and Alzheimer’s disease (AD), which is a significant neurological ailment that affects older males all over the world. Androgen deprivation therapy (ADT), a cornerstone therapeutic method used in conjunction with radiation and palliative care in advanced metastatic PCa cases, is critical for disease management. Evidence reveals a relationship between ADT and cognitive impairment. Hormonal manipulation may cause long-term cognitive problems through processes such as amyloid beta (Aβ) aggregation and neurofibrillary tangles (NFTs). Fluctuations in basal androgen levels can upset the delicate balance of genes that are sensitive to androgen levels, contributing to cognitive impairment. This detailed review dives into the various aspects of PCa aetiology and its relationship with cognitive decline. It investigates the discovery of particular biomarkers, as well as microRNAs (miRNAs), which play important roles in pathogenic progression. The review attempts to identify potential biomarkers associated with ADT-induced cerebral changes, including Aβ oligomer buildup, NFT formation, and tauopathy, which can contribute to early-onset dementia and cognitive impairment. Besides it further aims to provide insights into innovative diagnostic and therapeutic avenues for alleviating PCa and ADT-related cognitive sequelae by unravelling these complicated pathways and molecular mechanisms.

Keywords:

• metastatic cancer
• dementia
• cognitive defects
• androgen
• testosterone

Abbreviations

Pca, Prostate Cancer; ADT, Androgen Deprived Therapy; AD, Alzheimer’s disease; NFT, Neurofibrillary Tangles; Aβ, Amyloid Beta; SNP, Single Nucleotide Polymorphism; ECM, Extra Cellular Matrix; GTPase, Guanosine Diphosphatase; VEGF, Vascular Endothelial, Growth Factor; FGF, Fibroblast Growth Factor; RP, Ribosomal Proteins; NRP, Non-Ribosomal Proteins; miRNA, Micro-RNA; Pri-miRNA, Primary miRNA; HSP, Heat Shock Protein; AR, Androgen Receptor; NEP, Neprilysin; APP, Amyloid Precursor Protein; ACID, Amyloid Precursor Protein Intracellular Domain.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

Sachchida Nand Rai would like to acknowledge ICMR (3/1/3/196/Neuro/2021-NCD-I) for providing fellowship assistance.