%0 Journal Article %J J Alzheimers Dis %D 2022 %T Safety and Efficacy of Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Published and Unpublished Clinical Trials. %A Lacorte, Eleonora %A Ancidoni, Antonio %A Zaccaria, Valerio %A Remoli, Giulia %A Tariciotti, Leonardo %A Bellomo, Guido %A Sciancalepore, Francesco %A Corbo, Massimo %A Lombardo, Flavia L %A Bacigalupo, Ilaria %A Canevelli, Marco %A Piscopo, Paola %A Vanacore, Nicola %K Alzheimer Disease %K Amyloid %K Amyloidogenic Proteins %K Amyloidosis %K Antibodies, Monoclonal %K Cognitive Dysfunction %K Humans %X

BACKGROUND: Monoclonal antibodies (mAbs) are currently among the most investigated targets for potential disease-modifying therapies in Alzheimer's disease (AD).

OBJECTIVE: Our objectives were to identify all registered trials investigating mAbs in MCI due to AD or AD at any stage, retrieve available published and unpublished data from all registered trials, and analyze data on safety and efficacy outcomes.

METHODS: A systematic search of all registered trials on ClinicalTrials.gov and EUCT was performed. Available results were searched on both platforms and on PubMed, ISI Web of Knowledge, and The Cochrane Library.

RESULTS: Overall, 101 studies were identified on 27 mAbs. Results were available for 50 trials investigating 12 mAbs. For 18 trials, data were available from both published and unpublished sources, for 21 trials only from published sources, and for 11 trials only from unpublished sources. Meta-analyses of amyloid-related imaging abnormalities (ARIA) events showed overall risk ratios of 10.65 for ARIA-E and of 1.75 for ARIA-H. The meta-analysis of PET-SUVR showed an overall significant effect of mAbs in reducing amyloid (SMD -0.88), but when considering clinical efficacy, data on CDR-SB showed that treated patients had a statistically significant but clinically non-relevant lower worsening (MD -0.15).

CONCLUSION: Our results suggest that the risk-benefit profile of mAbs remains unclear. Research should focus on clarifying the effect of amyloid on cognitive decline, providing data on treatment response rate, and accounting for minimal clinically important difference. Research on mAbs should also investigate the possible long-term impact of ARIA events, including potential factors predicting their onset.

%B J Alzheimers Dis %V 87 %P 101-129 %8 2022 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/35275549?dopt=Abstract %R 10.3233/JAD-220046 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Reversible Mild Cognitive Impairment: The Role of Comorbidities at Baseline Evaluation. %A Grande, Giulia %A Cucumo, Valentina %A Cova, Ilaria %A Ghiretti, Roberta %A Maggiore, Laura %A Lacorte, Eleonora %A Galimberti, Daniela %A Scarpini, Elio %A Clerici, Francesca %A Pomati, Simone %A Vanacore, Nicola %A Mariani, Claudio %K Analysis of Variance %K Cognitive Dysfunction %K Cohort Studies %K Comorbidity %K Female %K Humans %K Male %K Memory %K Mental Status Schedule %K Neuropsychological Tests %K Reference Values %K Verbal Learning %X

The prognostic value of mild cognitive impairment (MCI) is being questioned, with some MCI subjects reverting to normal cognition (NC). The reversion rate varies mostly depending on the study design, the setting, and both MCI and NC definitions. Previous studies have focused on the profile of subjects who revert to NC, but the role of comorbidities has not been entirely investigated. We aimed to evaluate the proportion of MCI subjects who revert to NC in a memory clinic context, focusing on the role of comorbidities. Between 2004 and 2013, 374 MCI subjects were recruited. During a mean time of 32 ± 25.5 months, 21 subjects (5.6%) reverted to NC. Subjects who reverted to NC were younger (p = 0.0001), more educated (p = 0.0001), had a better global cognition (p = 0.0001), as assessed by the Mini-Mental State Examination (MMSE) and suffered from more comorbidities (p = 0.002), as assessed by Cumulative Illness Rating Scale (CIRS) than those who developed dementia. The Cox Regression Model, constructed to adjust for the confounders, showed that the higher were the MMSE (HR = 1.83, CI 95%: 1.07-3.11) and the CIRS score (HR = 1.3, CI 95% 0.88-1.92) at baseline, the higher was the probability of returning to NC than developing dementia, though the last association was not significant. Subjects who reverted to NC were more frequently affected by respiratory (p = 0.002), urologic (p = 0.012), and psychiatric (p = 0.012) diseases. The cognitive performance of subjects with medical comorbidities could benefit from preventive strategies aimed at treating the underlying diseases.

%B J Alzheimers Dis %V 51 %P 57-67 %8 2016 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26836169?dopt=Abstract %R 10.3233/JAD-150786