The study is carried out as part of the GR2021 Priority project "Healthy Brains for life (Age 20-99): Digitally-enhanced personalized medicine study ANANEOS" and code numbered GR-00546 and it will look at the decentralized and remote assessment of the symptoms of preclinical stages in Alzheimer's disease and movement disorders, e.g. Parkinson's. For this study we are looking for participants aged over 45 without cognitive complaints or with subjective perception of cognitive decline or with mild cognitive complaints. Specific aims for the proposed study: a) to develop novel sensitive measures that can provide an early identification of those SCD and MCI individuals harboring AD pathology that are at high risk of cognitive worsening over time; b) to track pre-motor stages in Parkinson's disease and trials that enable active digital functional biomarkers; c) to track disease progression during pre-dementia and pre-motor stages in clinical practice and trials with measures that enable to capture subtle changes.

Digital technologies, particularly those based on the use of smartphones, wearables and/or home-based monitoring devices, here defined as 'Remote Measurement Technologies' (RMTs), provide an opportunity to change radically the way in which functional assessment is undertaken in AD, RMTs have the potential to obtain better measurements of behavioural and biological parameters associated with individual Activities of Daily Living (ADL) when compared to the current subjective scales or questionnaires. Divergence from normative ADL profiles could objectively indicate the presence of specific incipient functional impairments even at the very early stages of AD.

Therefore, the main hypothesis of this project is that RMTs should allow the detection of impairments in functional components of ADLs that occur below the threshold of clinical scale detection or disability questionnaires.

ANANEOS is an independent Brain Registry (patient registry), created as an organized system to collect uniform data (clinical and other) to evaluate specified outcomes for the Neuropsychiatric Progression Index (NPI) and serves as a real-world view of clinical practice, patient outcomes, safety, and can serve a number of evidence development and decision making purposes.

Inclusion Criteria for Cohort participants:

• Male or female over 45 years of age.
• Subject is seen at a memory clinic or is part of an observational study.
• An informant (caregiver/family member) is available to collaborate.
• Diagnosis of individuals in the AD biological continuum with evidence of amyloid-beta accumulation based on the presence of Aβ load AD biomarkers (either in CSF or PET scan), MMSE, CDR score and cognitive tests as defined by the Guidance document of EMA (2016) or FDA (2018):
• preclinical AD: MMSE≥27 and CDR=0, either none or borderline cognitive deficits (compatible with FDA stages 1 and 2, with positive AD biomarkers). Patients reporting subjective cognitive decline who meet the criteria above are eligible for assignment to the preclinical AD group.
• prodromal AD/MCI due to AD: MMSE >23, CDR=0.5, impairment on cognitive testing with RBANS (compatible with stage 3 FDA, with positive AD biomarkers).
• Prodromal PD: Male or female age 60 years or older (except age 30 years or older for SNCA, or rate genetic mutations (such as Parkin or Pink1) participants).
• Individuals taking any of the following drugs: alpha methyldopa, methylphenidate, amphetamine derivatives or modafinil, must be willing and medically able to hold the medication for at least 5 half-lives before DaTscan imaging.
• Informed consent signed by the subject and informant.
• Informant should be able to read and communicate in the language of the recruitment centre and available to actively engage in tests and questionnaires.
• Subject and the informant own a smartphone.

Inclusion Criteria for Healthy volunteers:

• Male or female over 45 years of age.
• Individuals with no evidence of amyloid-beta accumulation based on the presence of Aβ load AD biomarkers (either in CSF or PET scan).
• Approximately age and gender matched to AD subjects on a group level.
• An informant is available to collaborate.
• MMSE >27, 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 centre.
• nformed consent signed by the subject and caregiver.
• Subject and informant own a smartphone.

Exclusion Criteria for Cohort participants:

• Presence of an additional neurological or psychiatric disease that may affect ADL, cognitive function or social interactions.
• Clinical diagnosis of PD, other parkinsonism, or dementia.
• Received any of the following drugs: dopamine receptor blockers (neuroleptics), metoclopramide and reserpine within 6 months of Screening visit.
• Current treatment with anticoagulants (e.g. coumadin, heparin) that might preclude safe completion of the lumbar puncture.
• 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.).
• TSH above normal range
• T3 or T4 outside normal range with clinically significant.

Exclusion Criteria for Healthy volunteers:

• Presence of an additional neurological or psychiatric 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.

The study is a decentralized, observational, digital assessment cohort study in healthy volunteers with negative AD biomarkers as control, subjects with MBI, preclinical AD and MCI due to AD dementia.