Heterogeneity and Factorial Structure in Alzheimer’s Disease: A Cognitive Perspective

2021 ◽  
pp. 1-11
Author(s):  
Andrea Zangrossi ◽  
Sonia Montemurro ◽  
Gianmarco Altoè ◽  
Sara Mondini

Background: Alzheimer’s disease (AD) patients show heterogeneous cognitive profiles which suggest the existence of cognitive subgroups. A deeper comprehension of this heterogeneity could contribute to move toward a precision medicine perspective. Objective: In this study, we aimed 1) to investigate AD cognitive heterogeneity as a product of the combination of within- (factors) and between-patients (sub-phenotypes) components, and 2) to promote its assessment in clinical practice by defining a small set of critical tests for this purpose. Methods: We performed factor mixture analysis (FMA) on neurocognitive assessment results of N = 230 patients with a clinical diagnosis of AD. This technique allowed to investigate the structure of cognitive heterogeneity in this sample and to characterize the core features of cognitive sub-phenotypes. Subsequently, we performed a tests selection based on logistic regression to highlight the best tests to detect AD patients in our sample. Finally, the accuracy of the same tests in the discrimination of sub-phenotypes was evaluated. Results: FMA revealed a structure characterized by five latent factors and four groups, which were identifiable by means of a few cognitive tests and were mainly characterized by memory deficits with visuospatial difficulties (“Visuospatial AD”), typical AD cognitive pattern (“Typical AD”), less impaired memory (“Mild AD”), and language/praxis deficits with relatively spared memory (“Nonamnestic AD”). Conclusion: The structure of cognitive heterogeneity in our sample of AD patients, as studied by FMA, could be summarized by four sub-phenotypes with distinct cognitive characteristics easily identifiable in clinical practice. Clinical implications under the precision medicine framework are discussed.

2018 ◽  
Vol 14 (12) ◽  
pp. 1663-1673 ◽  
Author(s):  
Richard S. Isaacson ◽  
Christine A. Ganzer ◽  
Hollie Hristov ◽  
Katherine Hackett ◽  
Emily Caesar ◽  
...  

2021 ◽  
Vol 22 (3) ◽  
pp. 1244
Author(s):  
Anna Yang ◽  
Boris Kantor ◽  
Ornit Chiba-Falek

Alzheimer’s disease (AD) has a critical unmet medical need. The consensus around the amyloid cascade hypothesis has been guiding pre-clinical and clinical research to focus mainly on targeting beta-amyloid for treating AD. Nevertheless, the vast majority of the clinical trials have repeatedly failed, prompting the urgent need to refocus on other targets and shifting the paradigm of AD drug development towards precision medicine. One such emerging target is apolipoprotein E (APOE), identified nearly 30 years ago as one of the strongest and most reproduceable genetic risk factor for late-onset Alzheimer’s disease (LOAD). An exploration of APOE as a new therapeutic culprit has produced some very encouraging results, proving that the protein holds promise in the context of LOAD therapies. Here, we review the strategies to target APOE based on state-of-the-art technologies such as antisense oligonucleotides, monoclonal antibodies, and gene/base editing. We discuss the potential of these initiatives in advancing the development of novel precision medicine therapies to LOAD.


2011 ◽  
Vol 31 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Lieke L. Smits ◽  
Maarten Liedorp ◽  
Teddy Koene ◽  
Ilona E.W. Roos-Reuling ◽  
Afina W. Lemstra ◽  
...  

2007 ◽  
Vol 17 (3) ◽  
pp. 203-212 ◽  
Author(s):  
Ilse A. D. A. van Halteren-van Tilborg ◽  
Erik J. A. Scherder ◽  
Wouter Hulstijn

1999 ◽  
Vol 14 (1) ◽  
pp. 50-50
Author(s):  
M. J. Finton ◽  
J. A. Lucas ◽  
J. D. Rippeth ◽  
G. E. Smith ◽  
R. J. Ivnik ◽  
...  

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