Personalized screening and risk profiles for Mild Cognitive Impairment via a Machine Learning Framework: Implications for general practice.

OBJECTIVES: Diagnosis of Mild Cognitive Impairment (MCI) requires lengthy diagnostic procedures, typically available at tertiary Health Care Centers (HCC). This prospective study evaluated a flexible Machine Learning (ML) framework toward identifying persons with MCI or dementia based on information that can be readily available in a primary HC setting. METHODS: Demographic and clinical data, informant ratings of recent behavioral changes, self-reported anxiety and depression symptoms, subjective cognitive complaints, and Mini Mental State Examination (MMSE) scores were pooled from two aging cohorts from the island of Crete, Greece (N = 763 aged 60-93 years) comprising persons diagnosed with MCI (n = 277) or dementia (n = 153), and cognitively non-impaired persons (CNI, n = 333). A Balanced Random Forest Classifier was used for classification and variable importance-based feature selection in nested cross-validation schemes (CNI vs MCI, CNI vs Dementia, MCI vs Dementia). Global-level model-agnostic analyses identified predictors displaying nonlinear behavior. Local level agnostic analyses pinpointed key predictor variables for a given classification result after statistically controlling for all other predictors in the model. RESULTS: Classification of MCI vs CNI was achieved with improved sensitivity (74 %) and comparable specificity (73 %) compared to MMSE alone (37.2 % and 94.3 %, respectively). Additional high-ranking features included age, education, behavioral changes, multicomorbidity and polypharmacy. Higher classification accuracy was achieved for MCI vs Dementia (sensitivity/specificity = 87 %) and CNI vs Dementia (sensitivity/specificity = 94 %) using the same set of variables. Model agnostic analyses revealed notable individual variability in the contribution of specific variables toward a given classification result. CONCLUSIONS: Improved capacity to identify elderly with MCI can be achieved by combining demographic and medical information readily available at the PHC setting with MMSE scores, and informant ratings of behavioral changes. Explainability at the patient level may help clinicians identify specific predictor variables and patient scores to a given prediction outcome toward personalized risk assessment.

Study of Alzheimer's disease- and frontotemporal dementia-associated genes in the Cretan Aging Cohort.

Using exome sequencing, we analyzed 196 participants of the Cretan Aging Cohort (CAC; 95 with Alzheimer's disease [AD], 20 with mild cognitive impairment [MCI], and 81 cognitively normal controls). The APOE ε4 allele was more common in AD patients (23.2%) than in controls (7.4%; p < 0.01) and the PSEN2 p.Arg29His and p.Cys391Arg variants were found in 3 AD and 1 MCI patient, respectively. Also, we found the frontotemporal dementia (FTD)-associated TARDBP gene p.Ile383Val variant in 2 elderly patients diagnosed with AD and in 2 patients, non CAC members, with the amyotrophic lateral sclerosis/FTD phenotype. Furthermore, the p.Ser498Ala variant in the positively selected GLUD2 gene was less frequent in AD patients (2.11%) than in controls (16%; p < 0.01), suggesting a possible protective effect. While the same trend was found in another local replication cohort (n = 406) and in section of the ADNI cohort (n = 808), this finding did not reach statistical significance and therefore it should be considered preliminary. Our results attest to the value of genetic testing to study aged adults with AD phenotype.

The Impact of Socioeconomic Factors and Geriatric Syndromes on Frailty among Elderly People Receiving Home-Based Healthcare: A Cross-Sectional Study.

Purpose: To evaluate frailty and its relationship with geriatric syndromes in the context of socioeconomic variables. Patients and Methods: In this cross-sectional study, elderly people aged 65 years old and over who received homecare in the reference region of Crete, Greece, were enrolled. Geriatric syndromes such as frailty, dementia, and depression were evaluated using the SHARE-Frailty Index (SHARE-Fi), the Montreal Cognitive Assessment (MoCA), and the Geriatric Depression Scale (GDS), respectively. Level of education, annual individual income, disability in Activities of Daily Living (ADL) and homebound status were also assessed as 'socioeconomic factors.' Results: The mean age of 301 participants was 78.45 (±7.87) years old. A proportion of 38.5% was identified as frail. A multiple logistic regression model revealed that elderly people with cognitive dysfunction were more likely to be frail (OR = 1.65; 95% CI: 0.55−4.98, p = 0.469) compared to those with normal cognition, but this association was not significant. Although elderly people with mild depression were significantly more likely to be frail (OR = 2.62; CI: 1.33−5.17, p = 0.005) compared to those with normal depression, the association for elderly people with severe depression (OR = 2.05, CI: 0.80−5.24, p = 0.134) was not significant. Additionally, comorbidity (OR = 1.06, CI: 0.49−2.27, p = 0.876) was not associated with frailty, suggesting that comorbidity is not a risk factor for frailty. In addition, patients with mild depression were significantly more likely to report frailty (OR = 2.62, CI:1.33−5.17, p = 0.005) compared to those with normal depression, whereas elders with an annual individual income (>EUR 4500) were less likely to be frail (OR = 0.45, CI: 0.25−0.83, p = 0.011) compared to those with

Evidence of Age-Related Hemodynamic and Functional Connectivity Impairment: A Resting State fMRI Study.

Purpose: To assess age-related changes in intrinsic functional brain connectivity and hemodynamics during adulthood in the context of the retrogenesis hypothesis, which states that the rate of age-related changes is higher in late-myelinating (prefrontal, lateral-posterior temporal) cerebrocortical areas as compared to early myelinating (parietal, occipital) regions. In addition, to examine the dependence of age-related changes upon concurrent subclinical depression symptoms which are common even in healthy aging. Methods: Sixty-four healthy adults (28 men) aged 23-79 years (mean 45.0, SD = 18.8 years) were examined. Resting-state functional MRI (rs-fMRI) time series were used to compute voxel-wise intrinsic connectivity contrast (ICC) maps reflecting the strength of functional connectivity between each voxel and the rest of the brain. We further used Time Shift Analysis (TSA) to estimate voxel-wise hemodynamic lead or lag for each of 22 ROIs from the automated anatomical atlas (AAL). Results: Adjusted for depression symptoms, gender and education level, reduced ICC with age was found primarily in frontal, temporal regions, and putamen, whereas the opposite trend was noted in inferior occipital cortices (p < 0.002). With the same covariates, increased hemodynamic lead with advancing age was found in superior frontal cortex and thalamus, with the opposite trend in inferior occipital cortex (p < 0.002). There was also evidence of reduced coupling between voxel-wise intrinsic connectivity and hemodynamics in the inferior parietal cortex. Conclusion: Age-related intrinsic connectivity reductions and hemodynamic changes were demonstrated in several regions-most of them part of DMN and salience networks-while impaired neurovascular coupling was, also, found in parietal regions. Age-related reductions in intrinsic connectivity were greater in anterior as compared to posterior cortices, in line with implications derived from the retrogenesis hypothesis. These effects were affected by self-reported depression symptoms, which also increased with age.

Cognitive impairment in a primary healthcare population: a cross-sectional study on the island of Crete, Greece.

OBJECTIVES: Cognitive impairment is known to have a significant impact on the quality of life of individuals and their caregivers, yet it is often underdiagnosed. The objective of this study is to assess the extent of cognitive impairment among elders visiting primary healthcare (PHC) practice settings, to explore associated risk factors and discuss current care challenges for PHC providers. DESIGN: A cross-sectional study was conducted between March 2013 and May 2014. SETTING: Fourteen PHC units located in rural and urban areas of the Heraklion district in Crete, Greece. PARTICIPANTS: Consecutive visitors aged at least 60 years attending selected PHC practices. PRIMARY AND SECONDARY OUTCOME MEASURES: The Mini-Mental State Examination (MMSE) was used to indicate cognitive status. Associations of low MMSE scores (≤23/24, adjusted for education level) with 12 socio-demographic factors, comorbidities and lifestyle factors were assessed. RESULTS: A total of 3140 PHC patients met inclusion criteria (43.2% male; mean age 73.7±7.8 years). The average MMSE score 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 (adjusted OR (AOR)=2.72; 95% CI 2.31 to 3.47), age (AOR=1.11; 95% CI 1.10 to 1.13), having received only primary or no formal education (AOR=2.87; 95% CI 2.26 to 3.65), alcohol intake (AOR=1.19; 95% CI 1.03 to 1.37), reporting one or more sleep complaints (AOR 1.63; 95% CI 1.14 to 2.32), dyslipidaemia (AOR=0.80; 95% CI 0.65 to 0.98) and history of depression (AOR=1.90; 95% CI 1.43 to 2.52) were associated with low MMSE scores. CONCLUSIONS: This study identified a relatively high prevalence of low MMSE scores among persons attending PHC practices in a southern European community setting and associations with several known risk factors.

Erythroderma as a paraneoplastic manifestation of small cell lung cancer.

Erythroderma is a rare clinical entity characterized by generalized erythema affecting the whole or most of the body's skin surface. It is associated with a variety of underlying conditions, including preexisting dermatoses, infections, connective tissue disorders, drugs, malignancies, or it may be idiopathic. A case of a 73-year-old man, with a 5-month history of erythroderma, eventually diagnosed with small cell lung cancer is presented. This is the first reported case indicating an association between erythroderma and small cell lung cancer, extending, thus, current knowledge regarding small cell lung cancer-related paraneoplastic manifestations as well as erythroderma's causative factors.

The impact of mild cognitive impairment on the self-regulation process: A comparison study of persons with mild cognitive impairment and cognitively healthy older adults.

This study examined whether mild cognitive impairment affects the associations between personal expectations (i.e. optimism and self-efficacy), illness-related coping, and quality of life. In total, two groups of older adults participated: 127 persons diagnosed with mild cognitive impairment and 225 cognitively healthy older persons (cognitively non-impaired group). Several significant relationships observed in the cognitively non-impaired group did not reach significance among mild cognitive impairment patients, with the opposite trend noted for others (e.g. between palliative coping and physical health). These findings indicate that mild cognitive impairment may lead to problems in the self-regulation process and highlight the significance of the interplay between neurocognitive and psychosocial aspects of self-regulation.

Frailty Status Affects the Decision for Long-Term Anticoagulation Therapy in Elderly Patients with Atrial Fibrillation.

BACKGROUND: Elderly patients are underrepresented in the studies concerning anticoagulation therapy (AT) in atrial fibrillation (AF), while patients' frailty status is lacking in most of the studies. OBJECTIVE: Our objective was to evaluate AT in AF elderly patients and study the effect of patients' frailty status on their long-term AT. METHODS: We conducted an observational prospective study that enrolled consecutive AF patients (≥ 75 years) who were hospitalized in the Department of Internal Medicine of the University Hospital of Heraklion, Crete, Greece from 1 June 2015 to 1 June 2016. We recorded the AT on admission and at discharge, all-cause mortality, and hospital readmission in a follow-up period of 1 year after hospital discharge. Frailty status was assessed by pre-established scores. RESULTS: One hundred and four consecutive patients (49% male; median age 87 years) were enrolled, 78 (78.8%) of whom received AT at discharge. Patients who did not receive AT at discharge had a higher HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older age, Reduced platelet count or function, Re-bleeding, Hypertension, Anemia, Genetic factors, Excessive fall risk and Stroke) score (5.5 ± 1.15 vs. 4.79 ± 1.68; p = 0.032), a lower Katz score (2.48 ± 2.23 vs. 4.08 ± 2.25; p = 0.006), and a higher Clinical Frailty Scale score (7 ± 1.95 vs. 5.57 ± 2.05; p = 0.006). Sixty-five patients (62.5%) were readmitted to a hospital during the follow-up period. In-hospital death occurred in five patients (4.8%) and 57 patients (57.6%) died within the follow-up period. CONCLUSION: A high percentage of the elderly AF patients did not receive AT, even at discharge. Patients who did not receive AT at discharge had higher bleeding and frailty scores. In the 1-year follow-up period after hospital discharge, high all-cause mortality and a high number of hospital readmissions were recorded.

Myelin content changes in probable Alzheimer's disease and mild cognitive impairment: Associations with age and severity of neuropsychiatric impairment.

BACKGROUND: Existing indices of white matter integrity such as fractional anisotropy and magnetization transfer ratio may not provide optimal specificity to myelin content. In contrast, myelin water fraction (MWF) derived from the multiecho T2 relaxation time technique may serve as a more direct measure of myelin content. PURPOSE/HYPOTHESIS: The goal of the present study was to identify markers of regional demyelination in patients with probable Alzheimer's disease (AD) and mild cognitive impairment (MCI) in relation to age and severity of neuropsychiatric impairment. POPULATION: The sample included patients diagnosed with probable AD (n = 25) or MCI (n = 43), and cognitively intact elderly controls (n = 33). FIELD STRENGTH/SEQUENCE ASSESSMENT: Long T2 , short T2 , and MWF values were measured with a 1.5T scanner in periventricular and deep normal-appearing white matter (NAWM), serving as indices of intra/extracellular water content and myelin content. A comprehensive neuropsychological and neuropsychiatric assessment was administered to all participants. STATISTICAL TESTS, RESULTS: AD patients displayed higher age-adjusted long and short T2 values and reduced MWF values in left temporal/parietal and bilateral periventricular NAWM than controls and MCI patients (P < 0.004; one-way analysis of covariance [ANCOVA] tests). Short T2 /MWF values in temporal, frontal, and periventricular NAWM of controls and/or MCI patients were significantly associated with episodic and semantic memory performance and depressive symptomatology (P < 0.004; partial correlation indices). The impact of age on memory performance was significantly (P < 0.01; mediated linear regression analyses) mediated by age-related changes in short T2 and MWF values in these regions. DATA CONCLUSION: Age-related demyelination is associated with memory impairment (especially in prodromal dementia states) and symptoms of depression in an anatomically specific manner. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1359-1372.

Cope's sign and complete heart block in a 78-year-old patient with biliary colic.

INTRODUCTION: Acute cholecystitis and biliary colic may have signs and symptoms similar to those of Acute Coronary Syndrome(ACS) along with ischemic ECG changes. Cholecystitis and/or biliary colic have been both reported as trigger factors for bradyarrhythmia in the literature. CASE REPORT: A 78-year-old male patient was admitted to our Emergency Department (ED) due to acute abdominal pain. The ECG on admission showed sinus bradycardia with a rate of 40 beats per minute (bpm) without signs of acute ischemia and a brief period (7 s) of complete atrioventricular (AV) block. He was initially treated with analgesics. After the remission of the pain, a subsequent ECG was performed which showed sinus bradycardia of 55 bpm. The AV block terminated one hour after the patient's admission. The patient remained hemodynamically stable during the episode. He underwent an ultrasound of the abdomen in the ED which revealed sludge and one stone in the gallbladder without signs of inflammation. Laboratory test results for D-dimer and troponin were negative, while the coronary angiography showed coronary vessels without significant lesions. CONCLUSION: Biliary colic can cause severe reversible reflex bradycardia (Cope's Sign), even complete heart block. Pain relief is very important in the management of such cases.

Cultural adaptation, standardization and clinical validity of the test your memory dementia screening instrument in Greek.

BACKGROUND/AIMS: To adapt and standardize the Test Your Memory (TYM) dementia screening instrument in Greek. METHODS: Normative data on the Greek version of the TYM were obtained from a community sample of 239 adults aged 21-92 years. Clinical validity was assessed in a cohort of 134 Neurology Clinic patients. Concurrent validity was examined through comparisons with the Mini-Mental State Examination (MMSE) and the Greek Everyday Function Scale. RESULTS: Correlations between the TYM and the MMSE were 0.73 and 0.82 in the community and patient samples, respectively. Scores on both tests were moderately associated with everyday functional capacity. Using age- and education-corrected cutoff scores ranging from 26/50 to 45/50 points, the sensitivity of the TYM for Alzheimer's disease detection was found to be higher than that of the MMSE (0.82 vs. 0.70), although its specificity was lower (0.71 vs. 0.90). CONCLUSION: Findings are consistent with previous reports in a variety of cultural settings supporting the potential utility of the TYM as a dementia screening tool.

Pharmacotherapy of lupus nephritis: time for a consensus?

BACKGROUND: The optimal therapy for lupus nephritis has been the subject of considerable debate. OBJECTIVE: To provide evidence- and expert-based recommendations. METHODS: To review the literature and the European League Against Rheumatism recommendations. RESULTS: Risk stratification based on histological, demographical, clinical and laboratory characteristics allows the identification of patients at high risk for loss of renal function, and thus more likely to benefit from more aggressive therapy. Achieving remission within the first months of treatment, irrespective of the agent used, correlates with good long-term renal outcomes; maintenance of remission can be achieved with less toxic therapies. Aggressive management of atherosclerosis risk factors and renoprotective therapy for those patients with chronic renal disease improve long-term survival and prognosis.

Concurrent CMV and EBV DNAemia is significantly correlated with a delay in the response to HAART in treatment-naive HIV type 1-positive patients.

The purpose of this study was to assess the qualitative single and multiple herpes virus DNAemia in the peripheral blood leukocytes (PBLs) of HIV-1-positive patients and its impact on the response to highly active antiretroviral therapy (HAART) and immune reconstitution. All (163) HIV-1-positive patients attending "Syngros AIDS Referral Center" from November 2000 to February 2001 were recruited. CMV, HSV-1, HSV-2, EBV, and HHV-8 DNA were detected in PBLs by polymerase chain reaction (PCR). Patients' follow-up comprised regular measurements of CD4(+) T cell count and HIV-1 viral load (VL) for an average period of 21 months. Immune reconstitution was defined as an increase in the CD4 T cell count by above 200 cells/micro l, while response to HAART was defined as a decrease in HIV-1 VL to undetectable levels. Single and multiple herpetic DNAemia in PBLs was found to be significantly higher in HIV-1-positive patients compared to healthy controls (p < 0.02) for all the viruses detected apart from HSV-2, which was not detected in the PBLs of either population. Concurrent CMV and EBV DNAemia significantly correlates with a delay in the response to HAART (p = 0.033) in treatment-naive patients. Untreated patients with a CD4(+) T cell count <200 cells/micro l, and with either CMV or EBV DNAemia, presented a delayed increase in the CD4 count after initiation of HAART (p = 0.035 and p = 0.037 respectively), while multiple herpetic DNAemia in the above patients was borderline associated with immune reconstitution (p = 0.068). Conclusively, CMV and EBV DNAemia may be poor prognostic factors for the response to HAART in treatment-naive HIV-1 patients.