This study will investigate the efficacy of novel biomarkers, namely blood-based biomarkers, pupillometry and actigraphy to track and predict progression of Alzheimer's disease (AD). Furthermore, the study will investigate the diagnostic value of pupillometry and actigraphy for AD.

This study consist of three sub-studies.

In study 1, participants diagnosed with mild cognitive impairment due to AD or mild to moderate AD will be followed for up to 24 months with repeated blood samples, pupillometry, actigraphy, cognitive tests and a control brain scan.

In study 2, patients under investigation of a neurodegenerative disease who have a planned lumbar puncture in the Memory clinic will be invited to this study. Participants will undergo pupillometry and blood samples two times approximately one and four weeks after the lumbar puncture.

In study 3, participants with a dementia diagnosis will undergo pupillometry and actigraphy at a single visit.

1. Longitudinal study:

   Inclusion criteria:

   • MCI due to AD, or mild or moderate AD dementia according to the National Institute on Aging and Alzheimer's Association (NIA-AA) diagnostic criteria
   • Caregiver willing to participate as an informant
   • MMSE >19 at inclusion
   • Brain FDG-PET/MRI or FDG/PET-CT
   • Able to cooperate to the investigations and give informed consent

   Exclusion criteria:

   • Other neurological or psychiatric illness that may affect neurofilament light (NfL) levels (severe neuropathy, multiple sclerosis (MS), stroke within the last 3 months, Wernicke encephalopathy)
   • Diagnosis of previous or current major psychiatric disorder (schizophrenia, bipolar disorder, psychosis) within last 2 years
   • Excessive alcohol intake or substance abuse within the last 2 years
   • Ophthalmological disorders that may affect pupillometry
   • Participating in drug trials or other intervention trials

2. Short-term study:

   Inclusion criteria:

   • Patients under investigation of a neurodegenerative disease
   • MMSE >19
   • Scheduled lumbar puncture/lumbar puncture performed within the last week prior to inclusion
   • Written consent form to the Danish Dementia Biobank
   • Able to cooperate to the investigations

   Exclusion criteria:

   • Other neurological or psychiatric illness that may affect NfL levels (severe neuropathy, MS, stroke within the last 3 months, Wernicke encephalopathy)
   • Excessive alcohol intake or substance abuse within the last 2 years
   • Ophthalmological disorders that may affect pupillometry
   • Participating in drug trials or other intervention trials

3. Cross-sectional study:

Inclusion criteria - Patients:

• A diagnosis of a dementia disorder
• Caregiver willing to participate as an informant
• MMSE >15 at inclusion
• Able to cooperate to the investigations
• Able to give informed consent

Exclusion criteria - Patients:

• Diagnosis of previous or current major psychiatric disorder (schizophrenia, bipolar disorder, psychosis) within last 2 years
• Excessive alcohol intake or substance abuse within the last 2 years
• Other known brain disorder
• Ophthalmological disorders that may affect pupillometry
• Participating in drug trials or other intervention trials

Inclusion criteria - Healthy Controls:

• Able to cooperate to the investigations
• Normal cognition
• Age 50-90 year

Exclusion criteria - Healthy Controls:

• Diagnosis of previous or current major psychiatric disorder (schizophrenia, bipolar disorder, psychosis) within last 2 years
• Excessive alcohol intake or substance abuse within the last 2 years
• Other known brain disorder
• Ophthalmological disorders that may affect pupillometry

In the longitudinal study (1) the investigators will include 100 patients diagnosed with mild cognitive impairment due to Alzheimer's disease or diagnosed with mild to moderate Alzheimer's disease. In the short-term study (2) the investigators will include 40 patients who are under investigation of a neurodegenerative disease. In the cross-sectional study (3) the investigatorswill include 50 patients with Alzheimer's disease, 50 healthy controls without brain disease, and 100 patients with other forms of dementia (dementia with Lewy body, vascular dementia, normal pressure hydrocephalus, frontotemporal dementia).