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

peer reviewedOBJECTIVES: 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

Assessing the impact of frailty on cognitive function in older adults receiving home care

It is commonly accepted that frailty and dementia-related cognitive decline are strongly associated. However, degree of this association is often debated, especially in homebound elders with disabilities. Therefore, this study aimed to investigate the association of frailty on cognitive function in older adults receiving homecare. A screening for frailty and cognitive function was conducted at 12 primary healthcare settings of the nationally funded program “Help at Home” in Heraklion Crete, Greece. Cognitive function and frailty were assessed using the Montreal Cognitive Assessment questionnaire and the SHARE-f index, respectively. Barthel-Activities of Daily Living and the Charlson Comorbidity Index were also used for the identification of disability and comorbidity, respectively. The mean age of the 192 participants (66% female) was 78.04 ± 8.01 years old. In depth-analysis using multiple linear regression, revealed that frailty was not significantly associated with cognitive decline (frail vs. non-frail (B’=-2.39, p=0.246) even after adjusting for depression and multi-comorbidity. Importantly, as protective factors for cognitive decline progression and thus dementia development, was scientifically correlated with annual individual income >4500 (B'=2.31, p=0.005) - poverty threshold- compared to those with <4500 and, higher education level as compared to Uneducated (B’=2.94, p=0.019). However, depression was associated with cognitive decline regardless of socioeconomic variables. In conclusion, our results suggest that health professionals caring for frail people with cognitive impairment, must focus on early recognition and management of depression

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

peer reviewedPurpose: 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

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 <EUR 4500 per year. Conclusions: Our data analysis shows that higher annual individual income and mild depression were independently associated with frailty, suggesting that a lower poverty threshold and mild depression are risk factors for frailty

Evidence of age-related hemodynamic and functional connectivity impairment: a resting state fMRI study

Summarization: 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.Presented on: Frontiers in Neurolog

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 (&lt;= 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&lt;0.0001). Low MMSE scores were detected in 20.2% of participants; 25.9% for females vs 12.8% for males; p&lt;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

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally