2.1. Study population

This study is a part of a larger study on progression of cognitive impairment in MCI. All participants signed an informed consent which followed the Tenets of the Declaration of Helsinki (www.wma.net/policy). The study is a case-control study.

Patients were diagnosed at the Memory Clinic of the Geriatric Department, Landspitali University Hospital, Reykjavik, Iceland. The diagnosis of MCI for inclusion in the study was made according to the Petersen criteria [18], [19] based on information on cognitive impairment compared to earlier abilities from the patients and their relatives but without any change in abilities of daily life. The Informant Questionnaire on Cognitive Decline in the Elderly [20] was used in evaluating the changes seen by the relatives during the preceding years. An Mini Mental State Examination score [21] of 24 or above and an Informant Questionnaire on Cognitive Decline in the Elderly score of 4.0 or less were used for inclusion. All patients went through a standardized procedure with neuropsychological testing and brain magnetic resonance imaging for evaluation of MTA. In some cases, analysis of β amyloid and tau proteins from cerebrospinal fluid was also performed.

All participants underwent comprehensive eye examination and were excluded if they had retinal or optic nerve disease such as glaucoma and age-related macular degeneration or trauma, diabetes mellitus, or other systemic diseases that can affect the eye. The healthy cohort included individuals with no history of cognitive impairment. All participants were of Caucasian origin. Sixty patients were originally recruited for oximetry. Thirteen patients were excluded because of retinal or optic disc disease or because of nonattendance on measurement day. In all, 47 patients went through oximetry. From the group of 47 patients, we were able to pair 44 with a healthy cohort, according to age (where no more than 7 years were between paired individuals). Of those 44, two were excluded because of bad image quality. Therefore, the final number of included participants was 42 in each group; the MCI group and the group of healthy control subjects.

Each participant answered a questionnaire on medical history, medications, and smoking. Blood pressure and heart rate were measured (Omron M6 Comfort [HEM-7000-E]; Omron Healthcare Europe, Hoofddorp, the Netherlands) as well as finger pulse oximetry (healthy cohort: Ohmeda Biox 3700; Ohmeda, Boulder, CO, USA; patient group: Masimo Rad 57, Masimo Corp., CA, USA) and intraocular pressure (iCare Tonometer TAO1; Tiolat Oy, Helsinki, Finland). Pupils were dilated with 1% tropicamide (Mydriacyl; S.A. Alcon-Couvreur N.V., Puurs, Belgium), which was supplemented with 10% phenylephrine hydrochloride (AK-Dilate; Akorn Inc., Lake Forest, IL, USA).

Magnetic resonance imaging of the brain was obtained from every participant with visual evaluation of atrophy of the medial temporal lobes scoring atrophy from 0 (no atrophy) to 4 (maximal atrophy, [22]). For the purpose of this study, the same experienced radiologist scored all the images consecutively.

Optical coherence tomography (OCT) imaging was performed on most MCI patients. Peripapillary scans were obtained with Topcon 3D OCT 2000 (Topcon Inc. Tokyo, Japan).

All the cases were diagnosed in a consensus meeting of at least three geriatricians. Based on all available information, the participants were grouped into one of two groups:

Clinical signs and biomarkers consistent with AD (n = 16)

Clinical signs of MCI but without clear biomarkers for AD (n = 25).

One patient had clinical signs and biomarkers that were consistent with early Lewy body dementia.

The consensus diagnosis was made according to ICD-10 (the 10th revision of the International Statistical Classification of Diseases and Related Health Problems by the World health organization). Patients that did not fulfill the diagnosis of MCI by neuropsychological testing but still experienced loss of memory were considered to be in very early stage of MCI and were included in the study. Details on participants can be found in Table 1.

Demographics of the study groups

Abbreviations: MAP, mean arterial pressure; MCI, mild cognitive impairment; min, minutes; SD, standard deviation.

NOTE. Heart rate, finger oximetry, and blood pressure measurements were missing for four individuals (three healthy and one MCI).