Selection of normal (not super-normal) subjects

• Bias-free recruitment modalities (eg, to guarantee representativeness for the whole country population, recruitment should avoid clustered data within just one site, and data should be gathered pairwise—for age, sex, education—within each recruitment site)  • Avoid convenience samples unless compliant with the inclusion/exclusion criteria  • Avoid voluntary exclusion of otherwise healthy individuals positive to biomarkers for brain amyloidosis, tau, or other neurodegeneration that define risk or preclinical stage for neurocognitive disorders  • Avoid voluntary exclusion of subjects with subjective cognitive decline (SCD) from samples explicitly recruited as normal controls  • Do not seek demonstration of stable cognitive health with longitudinal neuropsychological and neurological assessment (“robust norms”)

Inclusion Criteria

• Age: if feasible, 40 years or older  • Self-identified as “cognitively normal”  • Denies a worrying cognitive decline  • Judged to be cognitively normal by a family member (or other knowledgeable informant); cut-off of 3.3 on the short form of the Informant Questionnaire on Cognitive Decline (IQCoDe)(1) or equivalent  • MoCA score greater than or equal to 23(2,3) (MMSE greater than or equal to 27 if MoCA cannot be used). Please note: values to be corrected by age and education

Exclusion Criteria

Clinical findings  • Sensory or motor deficits interfering with test administration  • Continuous moderate-to-intense pain  • Current psychiatric diagnosis (including major depression). Geriatric Depression Scale (15-items) score of 6 or greater (4) Medical history  • Head injury with loss of consciousness for more than 5 minutes  • General anesthesia within the last 3 months  • Prior recurrent psychiatric disorder requiring hospitalization  • Use of psychoactive drugs, alcohol abuse  • Significant cerebrovascular disease (eg, TIA, stroke, general atherosclerosis)  • Severe active medical condition (cancer, organ failure, unstable heart condition) that may interfere with test administration

Convenience samples

• May be used if compliant with the above features  • May be used ad interim when proper samples are unavailable  • Specific research samples (only SCD, or composed of subjects all having specific risk factors) are not appropriate

References.

1. Quinn TJ, Fearon P, Noel-Storr AH, Young C, McShane R, Stott DJ. Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations. Cochrane Database Syst Rev. 10 aprile 2014;(4):Cd010079.

2. Roalf DR, Moberg PJ, Xie SX, Wolk DA, Moelter ST, Arnold SE. Comparative accuracies of two common screening instruments for classification of Alzheimer’s disease, mild cognitive impairment, and healthy aging. Alzheimers Dement. settembre 2013;9(5):529–37.

3. van Steenoven I, Aarsland D, Hurtig H, Chen-Plotkin A, Duda JE, Rick J, et al. Conversion between mini-mental state examination, montreal cognitive assessment, and dementia rating scale-2 scores in Parkinson’s disease. Mov Disord. dicembre 2014;29(14):1809–15.

4. Friedman B, Heisel MJ, Delavan RL. Psychometric properties of the 15-item geriatric depression scale in functionally impaired, cognitively intact, community-dwelling elderly primary care patients. J Am Geriatr Soc. settembre 2005;53(9):1570–6.