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Introduction: With the exception of the recent accelerated approval of aducanumab, in over 26 years of research and development (R&D) investment in Alzheimer's disease (AD), only five novel drugs-all for symptomatic treatment only-have reached FDA approval. Here, we estimate the costs of AD drug development during this period in the private sector., Methods: To estimate private R&D funding, we collected information on AD clinical trials (n = 1099; phases 1-4) conducted between January 1, 1995 and June 21, 2021 from various databases. Costs were derived using previously published methodologies and adjusted for inflation., Results: Since 1995, cumulative private expenditures on clinical stage AD R&D were estimated at $42.5 billion, with the greatest costs (57%; $24,065 million) incurred during phase 3; approximately 184,000 participants were registered or are currently enrolled in clinical trials., Discussion: Measures to reduce expenditures while moving toward disease-modifying therapies that alleviate the rising burden of AD require continued investment from industry, government, and academia., (© 2021 Biogen. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction : Previous studies have found that music paired with lyrics at encoding may improve the memory performance of patients with mild Alzheimer's disease (AD). To further explore memory for different types of musical stimuli, the current study examined both implicit and explicit memory for music with and without lyrics compared to spoken lyrics. Method : In this mixed design, patients with probable mild AD ( n  = 15) and healthy older adults ( n  = 13) listened to auditory clips (song, instrumental, or spoken lyrics varied across three sessions) and then had their memory tested. Implicit memory was measured by the mere exposure effect. Explicit recognition memory was measured using a confidence-judgment receiver operating characteristic (ROC) paradigm, which allowed examination of the separate contributions made by familiarity and recollection. Results : A significant implicit memory mere exposure effect was found for both groups in the instrumental and song but not the spoken condition. Both groups had the best explicit memory performance in the spoken condition, followed by song, and then instrumental conditions. Healthy older adults demonstrated more recollection than patients with AD in the song and spoken conditions, but both groups performed similarly in the instrumental condition. Patients with AD demonstrated more familiarity in the instrumental and song conditions than in the spoken condition. Conclusions : The results have implications for memory interventions for patients with mild AD. The implicit memory findings suggest that patients with AD may still show a preference for information familiar to them. The explicit memory results support prior findings that patients with AD rely heavily on familiarity, but also suggest that there may be limitations on the benefits that music can provide to recognition memory performance.

In a previous study (Simmons-Stern, Budson & Ally, 2010), we found that patients with Alzheimer's disease (AD) better recognized visually presented lyrics when the lyrics were also sung rather than spoken at encoding. The present study sought to further investigate the effects of music on memory in patients with AD by making the content of the song lyrics relevant for the daily life of an older adult and by examining how musical encoding alters several different aspects of episodic memory. Patients with AD and healthy older adults studied visually presented novel song lyrics related to instrumental activities of daily living (IADL) that were accompanied by either a sung or a spoken recording. Overall, participants performed better on a memory test of general lyric content for lyrics that were studied sung as compared to spoken. However, on a memory test of specific lyric content, participants performed equally well for sung and spoken lyrics. We interpret these results in terms of a dual-process model of recognition memory such that the general content questions represent a familiarity-based representation that is preferentially sensitive to enhancement via music, while the specific content questions represent a recollection-based representation unaided by musical encoding. Additionally, in a test of basic recognition memory for the audio stimuli, patients with AD demonstrated equal discrimination for sung and spoken stimuli. We propose that the perceptual distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients via a non-selective distinctiveness heuristic, thereby reducing false recognition while at the same time reducing true recognition and eliminating the mnemonic benefit of music. These results are discussed in the context of potential music-based memory enhancement interventions for the care of patients with AD., (Published by Elsevier Ltd.)

Musical mnemonics have a long and diverse history of popular use. In addition, music processing in general is often considered spared by the neurodegenerative effects of Alzheimer's disease (AD). Research examining these two phenomena is limited, and no work to our knowledge has explored the effectiveness of musical mnemonics in AD. The present study sought to investigate the effect of music at encoding on the subsequent recognition of associated verbal information. Lyrics of unfamiliar children's songs were presented bimodally at encoding, and visual stimuli were accompanied by either a sung or a spoken recording. Patients with AD demonstrated better recognition accuracy for the sung lyrics than the spoken lyrics, while healthy older adults showed no significant difference between the two conditions. We propose two possible explanations for these findings: first, that the brain areas subserving music processing may be preferentially spared by AD, allowing a more holistic encoding that facilitates recognition, and second, that music heightens arousal in patients with AD, allowing better attention and improved memory., (Published by Elsevier Ltd.)