Clinical research is focusing on SCD to identify patients at higher risk of dementia. Nevertheless, a consensus is lacking about how to manage patients with SCD.

From a sample of 445 SCD patients self-referred to our center, we considered: 119 patients followed-up for at least 10 years; 78 patients who underwent Alzheimer’s disease biomarker assessment (CSF or amyloid-PET), rated according to the AT(N) system.

During the follow-up, 55 patients (47.0%[38.0-56.1]) were diagnosed with MCI and 22 (18.8%[11.7-25.9]) with dementia. A patient developed Parkinson’s disease and a patient had a brain tumor. Mean progression time was 7.9(5.2) years to MCI and 10.39(4.7) to dementia. Thirty-eight (32.5%[24.0-41.0]) patients still were SCD at the end of the follow-up (15.2[5.4] years). In this group nine patients were diagnosed with depression, six had vascular leukoencephalopathy and two were diagnosed with obstructive sleep apnea syndrome (OSAS). Among 78 patients who underwent AD biomarker assessment 10 (12.8%[5.4-20.2]) were A+ (seven A+/T+/N- and five A+/T+/N+).

SCD should not be confused with mood disorder nor with normal cognition. We elaborated a management protocol to be applied both in clinical and in research settings: at the baseline evaluation, all the conditions possibly associated with SCD should be considered. If none of the baseline exams shows a possible explanation for the SCD, we classify patients as “SCD of unknown cause”. We suggest stratifying patients according to age at onset and APOE genotype. Regarding patients who undergo AD biomarker analysis, we suggest applying the ATN classification to classify patients as affected by “SCD not due to AD”, “Alzheimer’s pathologic changes with SCD” or “AD with SCD”. Patients in the two last groups should be followed-up yearly and receive psychological support.