• Inclusion criteria
Subjects enrolled in this study are diagnosed based on the established criteria as described below by physicians/medical doctors with expertise in Alzheimer's disease and other neurodegenerative disorders. To be eligible to participate in this study, a subject must meet the following criteria:
1a. For subjects in the Alzheimer's continuum and those with non-AD pathologic changes, (n=3,110):
* Male or female over 50 years of age.
* Approximately age and gender matched among groups as classified below.
* A study partner (caregiver/family member) is available to collaborate to visit the site together with the subject and give necessary information on the subject.
* Physician's clinical judgement of individuals by classifying into three syndromal stages of cognitive continuum: cognitively unimpaired, mild cognitive impairment, and dementia as described in 2018 NIA-AA research framework \[39\], \[40\] while taking into account of clinical assessment performance such as MMSE and CDR scores. This syndromic staging is applicable to all members of a research cohort independent from biomarker profiles.
* Numeric clinical staging in 2018 NIA-AA research framework may also be applied to cognitive staging in the Alzheimer's continuum \[40\] .
* cognitively unimpaired
* mild cognitive impairment
* mild dementia
* moderate dementia
* severe dementia
* AT(N) biomarker profile as evidenced by CSF test results is combined with the clinical staging for the classification of each subject.
* Aβ biomarker positive subjects without cognitive impairment, those with MCI, and those with dementia are considered as preclinical AD, MCI due to AD, and dementia due to AD, respectively. In case otherwise stated, these nomenclatures are used throughout this study.
* Informed consent signed by the subject and/or study partner.
* Study partners should be able to read and communicate in the language of the Hospital site and available to actively engage in tests and questionnaires.
* Subject or the study partner owns a smart phone.
* Their house should allow appropriate Wi-Fi and/or phone line connectivity.
* For those participating in the sub-study from each intended respective subject grouping described in Sub-study section, signature on an additional Informed Consent
1b. Healthy volunteer subjects (n=400):
* Male or female over 50 years of age.
* Individuals with all AT(N) biomarkers at normal levels (i.e., A-,T-, (N)-) as confirmed by negative status of respective AD biomarker test utilized in this study.
* Approximately age and gender matched to subjects in the Alzheimer's continuum and those with non-AD pathologic changes on a group level.
* A study partner is available to collaborate.
* Cognitively unimpaired as defined by syndrome staging of cognitive continuum in 2018 NIA-AA research framework \[40\], \[41\] supported by each of the following test scores: MMSE ≥27, and CDR 0.
* In otherwise good health conditions, or with diagnosis mild chronic disorders (of metabolic, respiratory, immunological, cardiologic, and metabolic origin) or any other affections that are controlled by the therapy and do not importantly limit ADLs or social interactions.
* Able to read and to communicate in the language of the recruitment center.
* Informed consent signed by the subject and study partner.
* Subject or study partner owns a smart phone.
* Their house should allow appropriate Wi-Fi and/or phone line connectivity.
* For those participating in the sub-study from each intended respective subject grouping described in Sub-study section, signature on an additional Informed Consent
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study. Those criteria would be applied at the subject screening:
2a. For subjects in the Alzheimer's continuum and those with non-AD pathologic changes:
* Presence of an additional neurological, psychiatric, or chronic disease that may affect ADL, cognitive function or social interactions.
* Abnormal VB12 value.
* Any other kind of disorders that relevantly affect mobility and/or ADL, cognitive function or social interactions (e.g., immune-mediated inflammatory disorders, recovery from recent trauma, stroke, etc.). MRI assessment should be utilized for verifying those disorders.
* TSH above normal range
* T3 or T4 outside normal range with clinically significant.
* Positive test for SARS-CoV-2 on a nasopharyngeal swab
* Failure to show negative PCR results for Covid19 or proof of vaccination
2b. Healthy volunteer subjects:
* Presence of an additional neurological, psychiatric, or chronic disease that may affect ADL, cognitive function or social interactions.
* Diagnosis of any disorders or post traumatic conditions that are not fully controlled by the therapy and produce relevant limitations of ADL, cognitive function or social interactions.
* Positive test for SARS-CoV-2 on a nasopharyngeal swab
* Failure to show negative PCR results for Covid19 or proof of vaccination
