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Variable Selection Before EDA

After a thorough literature review, potential diagnostic and non-diagnostic predictors of MCI reversion to CN were chosen a priori for preliminary EDA and prediction modeling for MCI reversion at two years from baseline. These factors have previously been implicated in either MCI reversion or conversion, and include the following:

  1. Demographic characteristics: age, gender, ethnicity, race, education and marital status;
  2. Lifestyle factors: baseline smoking and alcohol abuse;
  3. Neurocognitive/neuropsychological assessments: baseline Mini-Mental State Examination (MMSE) score, Rey Auditory Verbal Learning Test (RAVLT) scores (including RAVLT Learning, Immediate Recall, and Percent Forgetting), Auditory Verbal Learning Test (AVLT) Delayed Recognition score, AVLT Delayed Recall score, Alzheimer’s disease assessment scale-cognitive (ADAS) 11-item/13-item progression model, Trail Making Tests A and B, Animal Fluency Test, Clinical Dementia Rating score (CDR-SB), Functional Activities Questionnaire (FAQ) (Ewer, 2012; Sachdev, 2013; Park, 2015). These tests assess different facets of cognitive performance, including daily functional ability, severity of cognitive impairment, verbal learning and fluency, and memory;
  4. Neuroimaging data: baseline WholeBrain_bl, MidTemp_bl, Hippocampus_bl, Entorhinal_bl, Ventricles_bl and MidTemp_bl;
  5. Biomarkers: baseline Cerebrospinal fluid (CSF) Amyloid-beta(ABETA_bl), total tau, and phosphorylated tau (Sachdev, 2013; Thomas, 2017; Park, 2015);
  6. Genetic data: APOE4 genotype (Sachdev, 2013; Thomas, 2017; Park, 2015).

Clinical Dementia Rating (CDR)

The Washington University Clinical Dementia Rating Scale (CDR) is a global assessment instrument that yields global and Sum of Boxes (SOB) scores, with the global score regularly used in clinical and research settings to stage dementia severity.The utilization of CDR-SOB scores for staging dementia severity offers several advantages over the global score because the optimal characteristics of both scores can be combined into a single score.

  1. CDR-SOB scores are much simpler to calculate than the global score and they do not require an algorithm for computation, which will ultimately result in fewer calculation errors for those not using the online system.
  2. CDR-SOB scores can be treated as interval data in statistical analyses, whereas global CDR scores are ordinal by the nature of the algorithm approach to condensing the data.
  3. The advantage to using CDR-SOB scores for staging of dementia severity is the increased precision afforded for tracking changes across time.

Measurement of CDR: The CDR is obtained through semistructured interviews of patients and informants, and cognitive functioning is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18. The CDR demonstrates good reliability11,12 and has been validated against neuropathologic finding13–15.

Mini Mental State Examination (MMSE)

The Mini Mental State Examination (MMSE) is an 11-question measure that can be used to systematically and thoroughly assess mental status. Specific tasks contain five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The maximum score is 30 and A score of 23 or lower is indicative of cognitive impairment. The MMSE is effective as a screening assessment to separate patients with cognitive impairment from cognitive normal. However, the tool is not able to diagnose the case for changes in cognitive function. Therefore, it may be difficult for MMSE to distinguish LMCI,EMCI and AD. There should be overlaps among the three assessments MMSE, ADAS-13 and CDRSB. The correlation between MMSE and CDRSB is -0.71 and the correlation between MMSE and ADAS-13 is -0.69. The negative sign of the correlation may come from the way of questions.

Alzheimer’s Disease (AD) Assessment Scale-Cognitive Subscale (ADAS-Cog)

The Alzheimer’s Disease (AD) Assessment Scale-Cognitive Subscale (ADAS-Cog) is developed in 1980s and it is considered the gold standard for assessing the efficacy of antidementia treatments. The ADAS-Cog is often employed in these pre-dementia studies; however, the ADAS-Cog was developed for use in studies of dementia where cognitive impairments are more severe. In previous study, people have already raised concerns about whether the ADAS-Cog is able to detect important changes at earlier stages of disease progression. In our study, we have more than half of the patients who are CN and MCI, who are not exactly targeted for this assessment.

Measurement of ADAS-Cog: The cognitive subscale (ADAS-Cog) (ADAS-11 in ADNI) includes 11 tasks that include both subject-completed tests and observer-based assessments. Specific tasks include Word Recall, Naming Objects and Fingers, Commands, Constructional Praxis, Ideational Praxis, Orientation, Word Recognition, and Language. ADAS-Cog-13 includes all ADAS-Cog-11 items as well as a test of delayed word recall and a number cancellation or maze task. ADAS-Cog-13 scores range from 0 to 85.

There should be an overlap between ASAS-13 and CDRSB and the correlation of this two assesment is 0.71, which is relative high comparing to other variables.