RESUMO
Heterogeneity among Alzheimer's disease (AD) patients confounds clinical trial patient selection and therapeutic efficacy evaluation. This work defines separable AD clinical sub-populations using unsupervised machine learning. Clustering (t-SNE followed by k-means) of patient features and association rule mining (ARM) was performed on the ADNIMERGE dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Patient sociodemographics, brain imaging, biomarkers, cognitive tests, and medication usage were included for analysis. Four AD clinical sub-populations were identified using between-cluster mean fold changes [cognitive performance, brain volume]: cluster-1 represented least severe disease [+17.3, +13.3]; cluster-0 [-4.6, +3.8] and cluster-3 [+10.8, -4.9] represented mid-severity sub-populations; cluster-2 represented most severe disease [-18.4, -8.4]. ARM assessed frequently occurring pharmacologic substances within the 4 sub-populations. No drug class was associated with the least severe AD (cluster-1), likely due to lesser antecedent disease. Anti-hyperlipidemia drugs associated with cluster-0 (mid-severity, higher volume). Interestingly, antioxidants vitamin C and E associated with cluster-3 (mid-severity, higher cognition). Anti-depressants like Zoloft associated with most severe disease (cluster-2). Vitamin D is protective for AD, but ARM identified significant underutilization across all AD sub-populations. Identification and feature characterization of four distinct AD sub-population "clusters" using standard clinical features enhances future clinical trial selection criteria and cross-study comparative analysis.
RESUMO
When we do our best work as leaders, we don't imitate others. Rather, we draw on our own values and capabilities. We enter what author Robert Quinn calls the fundamental state of leadership. This is a frame of mind we tend to adopt when facing a significant challenge: a promotion opportunity, the risk of professional failure, a serious illness, a divorce, the death of a loved one, or any other major life jolt. Crisis calls, and we rise to the occasion. But we don't need to spend time in the dark night of the soul to reach this fundamental state. We can make the shift at any time by asking ourselves-and honestly answering--four transformative questions: Am I results centered? (Am I willing to leave my comfort zone to make things happen?) Am I internally directed? (Am I behaving according to my values rather than bending to social or political pressures?) Am I other focused? (Am I putting the collective good above my own needs?) Am I externally open? (Am I receptive to outside stimuli that may signal the need for change?) When we can answer these questions in the affirmative, we're prepared to lead in the truest sense. Of course, we can't sustain the fundamental state of leadership indefinitely. Fatigue and external resistance pull us out of it. But each time we reach it, we then return to our everyday selves a bit more capable, and we usually boost the performance of the people around us. Over time, we create a high-performance culture--and that can be sustained.
