The use of multi level statistical models towards the identification of Alzheimer's disease and related cognitive disorders

With the gradual increase in the population longevity, chronic conditions have become more prevalent particularly in the elderly. Cognitive disorders like Alzheimer’s disease and mild cognitive impairment (MCI) being amongst the most common comorbidities in that age group. Cognitive disorders have a significant impact in the quality of life of patients, their families and their caregivers. In the absence of a disease-modifying drug treatment, early detection and management of key risk-factors remains a key strategy for health services. Primary Health Care (PHC) is the first point of entry of patients with the health care services plays a significant role in the early detection as well as in the management of comorbidities parallel to cognitive disorders. The aim of this doctoral thesis is to apply multilevel statistical models as well as machine learning methods towards the detection of cognitive disorders, modifiable risk-factors and comorbidities. MethodsThe current doctoral thesis made use of the data from the research project named “Thalis University of Crete: A multi-disciplinary network for the study of Alzheimer’s disease and related disorders”. The study took place in the district of Heraklion, Crete, Greece between March 2013 and December 2014 and took place in two phases. During the 1st phase of the study 3,140 participant were recruited from 14 selected PHC units located within the district. All participants completed a structured and pre-tested questionnaire which elicited information regarding basic socio-demographic characteristics, health-related habits, chronic illnesses and prescribed medication and finally the Mini Mental State Examination (MMSE) cognitive test. Participants who scored below 24 units in the MMSE as well as a selected matched sample of those with MMSE score > 24 were invited to participate in the 2nd phase of the study where a complete neuropsychologic and neuropsychiatric evaluation by a team of experts took place. For the diagnosis of dementia (all types) and mild cognitive impairment the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) was used. A two-level multiple logistic regression model was used in order to investigate the impact of selected modifiable risk-factors in the presence of probable cognitive impairment (according to MMSE score). The impact of selected comorbidities on MMSE scores was investigated with the use of multiple regression analyses. Generalized Linear Model Lasso Regularization was used for feature selection in the MMSE items. Finally, two-layered artificial neural networks were used in order to classify patients as cognitively impaired (dementia or MCI) versus non-impaired. ResultsA total of 3140 participants were recruited in the first phase of the study (43.2% were males; with a mean age of 73.7±7.8 years). The average MMSE score for the total population was 26.0±3.8; 26.7±3.5 in male and 25.4±3.9 in female participants (p<0.0001). Low MMSE scores were detected in 20.2% of participants; 25.9% for females vs 12.8% for males; p<0.0001. Female gender (Odds ratio -OR- 2.72; 95% CI 2.31 to 3.47), age (OR=1.11; 95% CI 1.10 to 1.13), having received only primary or no formal education (OR=2.87; 95% CI 2.26 to 3.65), alcohol intake (OR=1.19; 95% CI 1.03 to 1.37), reporting one or more sleep complaints (OR 1.63; 95% CI 1.14 to 2.32), dyslipidemia (OR=0.80; 95% CI 0.65 to 0.98) and history of depression (OR=1.90; 95% CI 1.43 to 2.52) were associated with the presence of low MMSE scores. Among participants with low MMSE scores 344 (54.1%) underwent comprehensive neuropsychiatric evaluation and 185 (53.8%) were diagnosed with MCI 118 (34.3%) with dementia. Mental and behavioral disorders (F00-F99) and diseases of the nervous system (G00-G99) increased the odds of low MMSE scores in both genders. Generalized linear model lasso regularization indicated that 7/30 MMSE questions contributed the most to the classification of patients as impaired (dementia/MCI) vs. non-impaired with a combined accuracy of 82.0%. These MMSE items were questions 5, 13, 19, 20, 22, 23, and 26 of the Greek version of MMSE assessing orientation in time, repetition, calculation, registration, and visuo-constructive ability.ConclusionsResults of the present doctoral thesis indicated a relatively high prevalence of low MMSE scores amongst elderly PHC visitors and validated the associations with selected modifiable risk factors. Findings of this thesis have also identified the associations of certain chronic illness complexes (according to ICD-10) with low MMSE scores. Finally, machine learning algorithms have provided evidence that seven of the MMSE items could provide sufficient power to classify participants as cognitively impaired (dementia or MCI).Με την αύξηση του προσδόκιμου ζωής τις τελευταίες δεκαετίες, αρκετά χρόνια νοσήματα και καταστάσεις παρατηρούνται ολοένα και πιο συχνά στους ηλικιωμένους. Οι νεύρο-γνωστικές διαταραχές όπως η νόσος Alzheimer και η ήπια νοητική διαταραχή βρίσκονται ανάμεσα στις πιο συχνά παρατηρούμενες συννοσηροτήτες σε αυτή την ηλικιακή ομάδα. Οι γνωστικές διαταραχές έχουν σημαντικό αντίκτυπο στη ποιότητα ζωής τόσο των νοσούντων, όσο και των οικογενειών αλλά και των φροντιστών τους. Απουσία κάποιας φαρμακευτικής αγωγής η οποία να βοηθά στην ύφεση της νόσου, το βάρος των υπηρεσιών υγείας πέφτει στην αναγνώριση και τη διαχείριση των τροποποιήσιμων παραγόντων κινδύνου. Η Πρωτοβάθμια Φροντίδα Υγείας (ΠΦΥ) που αποτελεί το πρώτο σημείο επαφής του πληθυσμού με τις υπηρεσίες υγείας, καλείται να παίξει ένα σημαντικό ρόλο τόσο στην πρώιμη αναγνώριση της νόσου όσο και στη διαχείριση των συνοσηροτήτων. Στόχος της παρούσας διδακτορικής διατριβής είναι η εφαρμογή των πολυεπίπεδων μοντέλων στατιστικής ανάλυσης αλλά και μηχανικής μάθησης στην αναγνώριση των γνωστικών διαταραχών, των τροποποιήσιμων παραγόντων κινδύνου αλλά και των συνοδών χρόνιων νοσημάτων.ΜεθοδολογίαΗ παρούσα διδακτορική διατριβή χρησιμοποίησε δεδομένα από το ερευνητικό πρόγραμμα «ΘΑΛΗΣ Πανεπιστήμιο Κρήτης: Διεπιστημονικό δίκτυο μελέτης της νόσου Alzheimer και συναφών διαταραχών». Η συγκεκριμένη μελέτη έλαβε χώρα μεταξύ Μαρτίου 2013 και Δεκεμβρίου 2014 στο νομό Ηρακλείου Κρήτης, είχε συγχρονικό χαρακτήρα και εκτελέστηκε σε δύο φάσεις. Στην 1η φάση στρατολογήθηκαν 3,140 επισκέπτες από 14 επιλεγμένες δομές ΠΦΥ εντός της διοικητικής περιφέρειας του νομού. Οι συμμετέχοντες συμπλήρωσαν ένα δοκιμασμένο και δομημένο ερωτηματολόγιο το οποίο συνέλεξε βασικά δημογραφικά χαρακτηριστικά, συνήθειες υγείας, χρόνια νοσήματα και φαρμακευτική αγωγή και περιλάμβανε τον διαγνωστικό έλεγχο Mini Mental State Examination (MMSE). Όσοι συμμετέχοντες βρέθηκαν με βαθμολογία στο διαγνωστικό έλεγχο MMSE < 24 καθώς και ένα επιλεγμένο δείγμα με βαθμολογία MMSE ≥ 24 κλήθηκαν να συμμετάσχουν στη 2η φάση της μελέτης που ήταν μια πλήρης νευροψυχολογική και νευροψυχιατρική αξιολόγηση από μια ομάδα ειδικών. Για τη διάγνωση των καταστάσεων άνοιας και ήπιας νοητικής διαταραχής χρησιμοποιήθηκαν τα κριτήρια Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). H διερεύνηση των συσχετίσεων επιλεγμένων τροποποιήσιμων παραγόντων κινδύνου και της ύπαρξης πιθανής γνωστικής διαταραχής (σύμφωνα με τη βαθμολογία του ελέγχου MMSE) πραγματοποιήθηκε με τη χρήση πολυεπίπεδου μοντέλου πολλαπλής λογιστικής παλινδρόμησης. Οι συσχετίσεις μεταξύ κατηγοριών χρόνιων νοσημάτων και πιθανής γνωστικής διαταραχής διερευνήθηκαν με τη χρήση μοντέλων πολλαπλής λογιστικής παλινδρόμησης. Εν συνεχεία με τη χρήση των γενικευμένων γραμμικών μοντέλων LASSO Regularization πραγματοποιήθηκε επιλογή των στατιστικά κυριότερων ερωτήσεων της κλίμακας MMSE οι οποίες ταξινομούν τους ασθενείς σε πάσχοντες από νεύρο-γνωστική διαταραχή (άνοια ή ήπια νοητική διαταραχή) και σε μη-πάσχοντες. Τέλος, έγινε χρήση μοντέλων τεχνητών νευρωνικών δικτύων σε δύο επίπεδα προκειμένου να υπολογιστεί η διαγνωστική ακρίβεια των ερωτήσεων της Κλίμακας MMSE όπως αυτές προέκυψαν από τη διαδικασία LASSO Regularization στην ορθή ταξινόμηση των συμμετεχόντων και υπολογίστηκε η θετική και αρνητική διαγνωστική αξία. ΑποτελέσματαΤρεις χιλιάδες εκατόν σαράντα άτομα συμμετείχαν στην 1η φάση της μελέτης (43.2% ήταν άντρες με μέση ηλικία 73.7±7.8 έτη). Η μέση βαθμολογία της Κλίμακας MMSE ήταν 26.0±3.8 στο σύνολο του πληθυσμού; 26.7±3.5 στους άντρες συμμετέχοντες και 25.4±3.9 στις γυναίκες (p<0.0001). Χαμηλές βαθμολογίες στη δοκιμασία MMSE ανιχνεύθηκαν στο 20.2% του συνόλου των συμμετεχόντων: 25.9% στις συμμετέχουσες γυναίκες και 12.8% στους συμμετέχοντες άντρες (p<0.0001). Ανάμεσα στους παράγοντες κινδύνου για χαμηλή βαθμολογία στη κλίμακα MMSE ήταν το γυναικείο φύλο (Odds Ratio – OR- 2.72; 95% Confidence Interval – CI- 2.31 έως 3.47), η ηλικία (OR 2.72; 95% CI 2.31 έως 3.47), η λήψη πρωτοβάθμιας ή καθόλου επίσημης εκπαίδευσης (OR=2.87; 95% CI 2.26 έως 3.65), η κατανάλωση αλκοόλ (OR=1.19; 95% CI 1.03 έως 1.37), η ύπαρξη ενός ή περισσοτέρων προβλημάτων ύπνου (OR 1.63; 95% CI 1.14 έως 2.32), η ύπαρξη υπερλιπιδαιμίας (OR=0.80; 95% CI 0.65 έως 0.98) και η ύπαρξη κατάθλιψης (OR=0.80; 95% CI 0.65 έως 0.98). Οι συμμετέχοντες που βρέθηκαν με χαμηλή βαθμολογία στο διαγνωστικό έλεγχο MMSE κλήθηκαν να συμμετάσχουν στη 2η φάση της μελέτης και 344 (54.1%) συμμετείχαν. Εκατόν ογδόντα πέντε (53.8%) διαγνώσθηκαν με ήπια νοητική διαταραχή και 118 (34.3%) με άνοια (οποιαδήποτε τύπου). Η ύπαρξη ψυχολογικών και συμπεριφορικών διαταραχής (ICD 10: F00-F99) και νοσημάτων του νευρικού συστήματος (G00-G99) υπολογίστηκε ότι σχετίζονται με αυξημένο κίνδυνο για χαμηλή βαθμολογία στη δοκιμασία MMSE. Έπειτα από χρήση των γενικευμένων γραμμικών μοντέλων LASSO Regularization προέκυψε ότι επτά από τις 30 ερωτήσεις της δοκιμασίας MMSE συνεισφέρουν περισσότερο στην ταξινόμηση των ασθενών ως πάσχοντες από νεύρο-γνωστική διαταραχή. Οι ερωτήσεις αυτές ήταν οι ερωτήσεις 5, 13, 19, 20, 22, 23 και 26 στην Ελληνική εκδοχή της κλίμακας MMSE οι οποίες εξετάζουν τον προσανατολισμό στον χρόνο, την επανάληψη, τον υπολογισμό, την καταγραφή και την οπτικό-κατασκευαστική δυνατότητα. Οι παραπάνω ερωτήσεις με τη χρήση τεχνητών νευρωνικών δικτύων δύο επιπέδων υπολογίστηκε ότι έχουν 82.0% συνδυασμένη διαγνωστική ακρίβεια στην ανίχνευση νεύρο-γνωστικών διαταραχών.ΣυμπεράσματαΤα αποτελέσματα της παρούσας διδακτορικής διατριβής υπέδειξαν μια σχετικά υψηλή συχνότητα γνωστικών διαταραχών στους επισκέπτες 60 ετών και άνω των επιλεγμένων δομών ΠΦΥ και επιβεβαίωσαν τις συσχετίσεις με επιλεγμένους τροποποιήσιμους παράγοντες κινδύνου. Επιπλέον αναγνωρίστηκαν συγκεκριμένα συμπλέγματα χρόνιων νοσημάτων (κατά την ταξινόμηση ICD-10) τα οποία συσχετίστηκαν με την ύπαρξη χαμηλής βαθμολογίας στην δοκιμασία MMSE. Τέλος, τα αποτελέσματα της παρούσας διατριβής υπέδειξαν ότι επτά από της ερωτήσεις της βαθμολογίας MMSE παρείχαν ισχυρές ενδείξεις για την ύπαρξη άνοιας ή ήπιας νοητικής διαταραχής

Post-market outcome of an extract of traditional Cretan herbs on upper respiratory tract infections: a pragmatic, prospective observational study

Abstract Background The beneficial effects of traditional herbs of Crete, Greece for the treatment of upper respiratory tract infections have been reported in observational and laboratory studies. Following a published, double blind, randomized, placebo controlled trial, this study aimed to assess the effectiveness of an extract of three Cretan herbs on the treatment of upper respiratory tract infections, upon its market release. Methods An observational study was conducted in Heraklion, Crete, Greece. Participants were patients presenting at selected pharmacies with symptoms of upper respiratory tract infection, choosing to receive the extract for their treatment. Patients’ symptoms (local, general, total) where recorded at three time points within 1 week, using a questionnaire developed based on the Wisconsin Upper Respiratory System Survey. For each patient, symptoms were scored on a 0–7 Likert scale and three indexes were calculated: the score of local symptoms, the score of general symptoms and the total score of symptoms. Effectiveness was assessed by examining the reduction in these indexes over the 1-week observation period. Results Mean score of general symptoms was 19.1 (SE: 0.9) in day 1, dropping to 8.6 (SE: 0.6) and 3.1 (SE: 0.4) in days 4 and 7 respectively. Mean score of local symptoms declined from 7.9 (SE: 0.5) in day 1 to 2.3 (SE: 0.3) in day 4 and to 0.5 (SE: 0.1) in day 7. Total score of symptoms reached 27.0 (SE: 1.2) in day 1, decreasing to 10.9 (SE: 0.8) in day 4 and to 3.5 (SE: 0.5) in day 7. The percentage of participants reporting fever was 82.1% at baseline, 8.0% in day 4 and 2.0% in day 7 (p < 0.0001 for paired differences). Multiple regression models indicated that supplementary medication intake did not seem to affect symptoms’ severity or the day patients reported that their symptoms ceased completely. Conclusions This pragmatic study added evidence about the potential therapeutic effects of an extract of Cretan herbs on the amelioration of upper respiratory tract infection symptoms

Internet use, eHealth literacy and attitudes toward computer/internet among people with schizophrenia spectrum disorders: a cross-sectional study in two distant European regions

Abstract Background Individuals with schizophrenia spectrum disorders use the Internet for general and health-related purposes. Their ability to find, understand, and apply the health information they acquire online in order to make appropriate health decisions – known as eHealth literacy – has never been investigated. The European agenda strives to limit health inequalities and enhance mental health literacy. Nevertheless, each European member state varies in levels of Internet use and online health information-seeking. This study aimed to examine computer/Internet use for general and health-related purposes, eHealth literacy, and attitudes toward computer/Internet among adults with schizophrenia spectrum disorders from two distant European regions. Methods Data were collected from mental health services of psychiatric clinics in Finland (FI) and Greece (GR). A total of 229 patients (FI = 128, GR = 101) participated in the questionnaire survey. The data analysis included evaluation of frequencies and group comparisons with multiple linear and logistic regression models. Results The majority of Finnish participants were current Internet users (FI = 111, 87%, vs. GR = 33, 33%, P < .0001), while the majority of Greek participants had never used computers/Internet, mostly due to their perception that they do not need it. In both countries, more than half of Internet users used the Internet for health-related purposes (FI = 61, 55%, vs. GR = 20, 61%). The eHealth literacy of Internet users (previous and current Internet users) was found significantly higher in the Finnish group (FI: Mean = 27.05, SD 5.36; GR: Mean = 23.15, SD = 7.23, P < .0001) upon comparison with their Greek counterparts. For current Internet users, Internet use patterns were significantly different between country groups. When adjusting for gender, age, education and disease duration, country was a significant predictor of frequency of Internet use, eHealth literacy and Interest. The Finnish group of Internet users scored higher in eHealth literacy, while the Greek group of never Internet users had a higher Interest in computer/Internet. Conclusions eHealth literacy is either moderate (Finnish group) or low (Greek group). Thus, exposure to ICT and eHealth skills training are needed for this population. Recommendations to improve the eHealth literacy and access to health information among these individuals are provided

Internet use, eHealth literacy and attitudes toward computer/internet among people with schizophrenia spectrum disorders: a cross-sectional study in two distant European regions

Abstract Background Individuals with schizophrenia spectrum disorders use the Internet for general and health-related purposes. Their ability to find, understand, and apply the health information they acquire online in order to make appropriate health decisions – known as eHealth literacy – has never been investigated. The European agenda strives to limit health inequalities and enhance mental health literacy. Nevertheless, each European member state varies in levels of Internet use and online health information-seeking. This study aimed to examine computer/Internet use for general and health-related purposes, eHealth literacy, and attitudes toward computer/Internet among adults with schizophrenia spectrum disorders from two distant European regions. Methods Data were collected from mental health services of psychiatric clinics in Finland (FI) and Greece (GR). A total of 229 patients (FI = 128, GR = 101) participated in the questionnaire survey. The data analysis included evaluation of frequencies and group comparisons with multiple linear and logistic regression models. Results The majority of Finnish participants were current Internet users (FI = 111, 87%, vs. GR = 33, 33%, P < .0001), while the majority of Greek participants had never used computers/Internet, mostly due to their perception that they do not need it. In both countries, more than half of Internet users used the Internet for health-related purposes (FI = 61, 55%, vs. GR = 20, 61%). The eHealth literacy of Internet users (previous and current Internet users) was found significantly higher in the Finnish group (FI: Mean = 27.05, SD 5.36; GR: Mean = 23.15, SD = 7.23, P < .0001) upon comparison with their Greek counterparts. For current Internet users, Internet use patterns were significantly different between country groups. When adjusting for gender, age, education and disease duration, country was a significant predictor of frequency of Internet use, eHealth literacy and Interest. The Finnish group of Internet users scored higher in eHealth literacy, while the Greek group of never Internet users had a higher Interest in computer/Internet. Conclusions eHealth literacy is either moderate (Finnish group) or low (Greek group). Thus, exposure to ICT and eHealth skills training are needed for this population. Recommendations to improve the eHealth literacy and access to health information among these individuals are provided

Epidemiology and burden of systemic lupus erythematosus in a Southern European population: data from the community-based lupus registry of Crete, Greece

Objectives Several population-based studies on systemic lupus erythematosus (SLE) have been reported, yet community-based, individual-case validated, comprehensive reports are missing. We studied the SLE epidemiology and burden on the island of Crete during 1999-2013. Methods Multisource case-finding included patients &gt;= 15 years old. Cases were ascertained by the ACR 1997, SLICC 2012 criteria and rheumatologist diagnosis, and validated through synthesis of medical charts, administrative and patient-generated data. Results Overall age-adjusted/sex-adjusted incidence was 7.4 (95% CI 6.8 to 7.9) per 100 000 persons/year, with stabilising trends in women but increasing in men, and average (+/- SD) age of diagnosis at 43 (+/- 15) years. Adjusted and crude prevalence (December 2013) was 123.4 (113.9 to 132.9) and 143 (133 to 154)/10(5) (165/10(5) in urban vs 123/10(5) in rural regions, p&lt;0.001), respectively. Age-adjusted/sex-adjusted nephritis incidence was 0.6 (0.4 to 0.8) with stable trends, whereas that of neuropsychiatric SLE was 0.5 (0.4 to 0.7) per 100 000 persons/year and increasing. Although half of prevalent cases had mild manifestations, 30.5% developed organ damage after 7.2 (+/- 6.6) years of disease duration, with the neuropsychiatric domain most frequently afflicted, and 4.4% of patients with nephritis developed end-stage renal disease. The ACR 1997 and SLICC 2012 classification criteria showed high concordance (87%), yet physician-based diagnosis occurred earlier than criteria-based in about 20% of cases. Conclusions By the use of a comprehensive methodology, we describe the full spectrum of SLE from the community to tertiary care, with almost half of the cases having mild disease, yet with significant damage accrual. SLE is not rare, affects predominantly middle-aged women and is increasingly recognised in men. Neuropsychiatric disease is an emerging frontier in lupus prevention and care

Altered hippocampal connectivity dynamics predicts memory performance in neuropsychiatric lupus: a resting-state fMRI study using cross-recurrence quantification analysis

Objective Τo determine whole-brain and regional functional connectivity (FC) characteristics of patients with neuropsychiatric SLE (NPSLE) or without neuropsychiatric manifestations (non-NPSLE) and examine their association with cognitive performance.Methods Cross-recurrence quantification analysis (CRQA) of resting-state functional MRI (rs-fMRI) data was performed in 44 patients with NPSLE, 20 patients without NPSLE and 35 healthy controls (HCs). Volumetric analysis of total brain and specific cortical and subcortical regions, where significant connectivity changes were identified, was performed. Cognitive status of patients with NPSLE was assessed by neuropsychological tests. Group comparisons on nodal FC, global network metrics and regional volumetrics were conducted, and associations with cognitive performance were estimated (at p&lt;0.05 false discovery rate corrected).Results FC in patients with NPSLE was characterised by increased modularity (mean (SD)=0.31 (0.06)) as compared with HCs (mean (SD)=0.27 (0.06); p=0.05), hypoconnectivity of the left (mean (SD)=0.06 (0.018)) and right hippocampi (mean (SD)=0.051 (0.0.16)), and of the right amygdala (mean (SD)=0.091 (0.039)), as compared with HCs (mean (SD)=0.075 (0.022), p=0.02; 0.065 (0.019), p=0.01; 0.14 (0.096), p=0.05, respectively). Hyperconnectivity of the left angular gyrus (NPSLE/HCs: mean (SD)=0.29 (0.26) and 0.10 (0.09); p=0.01), left (NPSLE/HCs: mean (SD)=0.16 (0.09) and 0.09 (0.05); p=0.01) and right superior parietal lobule (SPL) (NPSLE/HCs: mean (SD)=0.25 (0.19) and 0.13 (0.13), p=0.01) was noted in NPSLE versus HC groups. Among patients with NPSLE, verbal episodic memory scores were positively associated with connectivity (local efficiency) of the left hippocampus (r2=0.22, p=0.005) and negatively with local efficiency of the left angular gyrus (r2=0.24, p=0.003). Patients without NPSLE displayed hypoconnectivity of the right hippocampus (mean (SD)=0.056 (0.014)) and hyperconnectivity of the left angular gyrus (mean (SD)=0.25 (0.13)) and SPL (mean (SD)=0.17 (0.12)).Conclusion By using dynamic CRQA of the rs-fMRI data, distorted FC was found globally, as well as in medial temporal and parietal brain regions in patients with SLE, that correlated significantly and adversely with memory capacity in NPSLE. These results highlight the value of dynamic approaches to assessing impaired brain network function in patients with lupus with and without neuropsychiatric symptoms

Additional file 2: of Internet use, eHealth literacy and attitudes toward computer/internet among people with schizophrenia spectrum disorders: a cross-sectional study in two distant European regions

Tables with the full regression models. (DOCX 20 kb

Cognitive screening tools for primary care settings: examining the ‘Test Your Memory’ and ‘General Practitioner assessment of Cognition’ tools in a rural aging population in Greece

Background: Under conditions of high demand for primary care services in a setting of low financial resources, there is need for brief, easily administered cognitive screening tools for use in the primary care setting, especially in rural areas. However, interpretation of these cognitive tests’ results requires knowledge on their susceptibility to cultural, educational and demographic patient characteristics. Objectives: To assess the clinical validity of the ‘Test Your Memory’ (TYM) and ‘General Practitioner assessment of Cognition’ (GPCog) which was specifically designed for primary care practice, in a rural primary care setting in Greece, utilizing the ‘Mini Mental State Examination’ (MMSE) as a reference standard. Methods: The MMSE, TYM, and GPCog were administered to a random sample of 319 community dwelling Greek adults aged 60 to 89 years in 11 rural Primary Healthcare Centres of the Prefecture of Heraklion on the island of Crete, Greece. Analyses examined (a) The association of each instrument with demographic factors and MMSE and (b) optimal cut-off scores, sensitivity and specificity against MMSE-based cognitive impairment risk using ROC analyses with the MMSE 23/24 point cut-off as a reference standard. Results: We found a sensitivity of 80% and a specificity of 77% for TYM (35/36 or 38/39 cut-off, depending on education). Corresponding values were 89% and 61% for GPCog (7/8 cut-off), respectively. Conclusion: The TYM and GPCog instruments appear to be suitable for routine use in the primary care setting as tools for cognitive impairment risk detection in elderly rural populations