TABLE 1.
Eligibility criteria
| Inclusion criteria |
|---|
| 1. Provision of informed consent. |
| 2. Age ≥ 65 years. |
| 3. Sufficient cognitive performance to provide informed consent, as determined by clinical evaluation. |
| 4. Diagnosis of late‐onset AD or mild cognitive impairment of the AD type, supported by typical clinical presentation and/or progression and at least one objective finding (e.g., significantly decreased perfusion or metabolism in both brain hemispheres in the temporal lobes or hippocampal atrophy, as determined by CT, MRI, PET/CT, or SPECT; pathological concentrations of AD biomarkers in cerebrospinal fluid [low Aβ42 concentration, low Aβ42/40 ratio, and/or high p‐tau concentration, as determined by laboratory analysis]; or absence of other significant pathology). Diagnostic support from at least one cerebral imaging modality (CT, MRI, PET/CT, or SPECT). Patients with normal white‐matter changes for their age were not excluded. |
| 5. Serum or plasma anti‐herpes simplex virus IgG positivity. |
| 6. Hetero‐ or homozygous APOE ε4 genotype carriership. |
| 7. At least 1 month stability of medication regimens for other conditions. |
| Exclusion criteria |
|---|
| 1. Known allergy to valacyclovir or acyclovir. |
| 2. Inability to adhere to a treatment regimen. Assistance from non‐study personnel involved in the daily administration of medication was encouraged and was not a reason for exclusion. |
| 3. Kidney failure or decreased kidney function (estimated glomerular filtration rate < 30 ml/min/1.73 m2). a |
| 4. Ongoing anticoagulant treatment, excluding the use of antiplatelet drugs in normal doses. |
| 5. Unstable or life‐threatening disease with expected survival time < 1 year. |
| 6. Severe somatic condition projected to obstruct study participation. |
| 7. Diagnosis of major neurocognitive disorder other than AD. |
| 8. Known severe neurological or neurocognitive disease. |
| 9. Psychiatric condition requiring treatment that is likely to obstruct study participation (e.g., depression or psychosis). |
| 10. Current or recent (in the last 5 years) history of substance addiction. |
| 11. Condition rendering examination in the supine position impossible. b |
| 12. Claustrophobia or other contraindication to PET/CT examination. b |
a
Calculated using the Chronic Kidney Disease Epidemiology Collaboration equation from the serum creatinine level, sex, and age.
b
Only for participation at the University Hospital of Umeå study site.
Abbreviations: Aβ, amyloid beta; AD, Alzheimer's disease; APOE, apolipoprotein E; CT, computed tomography; IgG: immunoglobulin G; MRI, magnetic resonance imaging; PET, positron emission tomography; p‐tau, phosphorylated tau; SPECT, single‐photon emission computed tomography.