Exploring Musculoskeletal Injuries Among Informal and Formal Carers of People With Dementia.

BACKGROUND: Carers of people with dementia manually handle the care recipients (eg, repetitive lifting, transferring, and pulling) as part of the care service, increasing the musculoskeletal injury risk to themselves. OBJECTIVE: We aimed to determine the prevalence of musculoskeletal injuries among informal and formal carers of people with dementia and the perceived associated risk factors. METHODS: Primary carers of people with dementia (26 males and 141 females) from Dementia Care Centers and Home Care programs completed a questionnaire providing information about (a) the carers' and their care recipients' characteristics, (b) musculoskeletal symptoms (via the Nordic Musculoskeletal Questionnaire) and related aspects, and (c) the caregiving activities exposing the carers to risk of musculoskeletal injury. RESULTS: Our results showed that 69.7% of informal and 86.7% of formal carers reported having more than 1 musculoskeletal injury, while 63.1% and 61.5%, respectively, reported having a musculoskeletal injury in the last year. Lower back had the highest injury prevalence (>10% for both groups). The 2 carer groups were not different in any of the variables. CONCLUSIONS: Our results reinforce calls for education and support of carers, regardless of their formal status, to enable injury-free and prolonged service provision.

Critical menarche age for late-life dementia and the role of education and socioeconomic status.

Estrogen exposure during menstrual years has been associated with late-life neuroprotection. We explored the presence of an age-sensitive menarche window for cognition in old age and the impact of socioeconomic status and education. We compared neuropsychological performance of 1082 older women [MeanAGE = 72.69 (5.48)] with menarche in childhood, early-, mid-, and late-adolescence and dementia prevalence, severity, and type, including the effects of education and socioeconomic status. Adjusting for covariates, menarche at 11-14 years of age was associated with better memory, executive and global cognitive functioning in old age, and stronger positive effects of education and socioeconomic status on cognition than those with menarche at 15-17 years. We found a critical age window for the neuroprotective effects of estrogens during early adolescence, putting women with later menarche at higher risk for cognitive decline. Effects of socioeconomic status and education in adulthood should be a focus of future research.

Cerebral Amyloidosis in Individuals with Subjective Cognitive Decline: From Genetic Predisposition to Actual Cerebrospinal Fluid Measurements.

The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer's Disease (AD), amyloid-beta 42 (Aß42) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) individuals were included in our analyses. Among the participants, 107 had available results regarding cerebrospinal fluid (CSF) Aß42 and Tau, while 742 had available genetic data to construct polygenic risk scores (PRSs) reflecting their genetic predisposition for CSF Aß42 and plasma total Tau levels. The associations between AD biomarkers and SCD were tested using logistic regression models adjusted for possible confounders such as age, sex, education, depression, and baseline cognitive test scores. Abnormal values of CSF Aß42 were related to 2.5-fold higher odds of SCD, while higher polygenic loading for Aß42 was associated with 1.6-fold higher odds of SCD. CSF Tau, as well as polygenic loading for total Tau, were not associated with SCD. Thus, only cerebral amyloidosis appears to be related to SCD status, either in the form of polygenic risk or actual CSF measurements. The temporal sequence of amyloidosis being followed by tauopathy may partially explain our findings.

Walking time and genetic predisposition for Alzheimer's disease: Results from the HELIAD study.

Objective: Our study aimed to explore whether physical condition might affect the association between genetic predisposition for Alzheimer's Disease (AD) and AD incidence. Methods: The sample of participants consisted of 561 community-dwelling adults over 64 years old, without baseline dementia (508 cognitively normal and 53 with mild cognitive impairment), deriving from the HELIAD, an ongoing longitudinal study with follow-up evaluations every 3 years. Physical condition was assessed at baseline through walking time (WT), while a Polygenic Risk Score for late onset AD (PRS-AD) was used to estimate genetic predisposition. The association between WT and PRS-AD with AD incidence was evaluated with Cox proportional hazard models adjusted for age, sex, education years, global cognition score and APOE ε-4 genotype. Then, the association between WT and AD incidence was investigated after stratifying participants by low and high PRS-AD. Finally, we examined the association between PRS-AD and AD incidence after stratifying participants by WT. Results: Both WT and PRS-AD were connected with increased AD incidence (p < 0.05), after adjustments. In stratified analyses, in the slow WT group participants with a greater genetic risk had a 2.5-fold higher risk of developing AD compared to participants with lower genetic risk (p = 0.047). No association was observed in the fast WT group or when participants were stratified based on PRS-AD. Conclusions: Genetic predisposition for AD is more closely related to AD incidence in the group of older adults with slow WT. Hence, physical condition might be a modifier in the relationship of genetic predisposition with AD incidence.

Longitudinal Cognitive Trajectories in Older Adults with Restless Legs Syndrome or Willis-Ekbom Disease.

Background: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) has occasionally but not consistently been associated with cognitive and most notably language and executive impairment. The present study was conducted to investigate the cognitive trajectories of older individuals with RLS/WED. Methods: Participants were drawn from the randomly selected, older (>64 years), population-based HELIAD cohort. Individuals without dementia and with available neuropsychological evaluations at baseline and follow-up were considered for potential eligibility. A comprehensive assessment examining five principal components of cognition (memory, visuo-spatial ability, attention, executive function, and language) was administered to the participants. Generalized estimating equation analyses were used to examine the unadjusted and adjusted (for critical factors and covariates) effects of RLS/WED on cognition over time. Results: A total of 1003 predominantly female (59.5%), older (72.9 ± 4.9 years) participants with follow-up evaluations after a mean of 3.09 ± 0.85 years and without dementia at baseline and follow-up were included in the present study. Among them, 81 were diagnosed with RLS/WED at baseline. Global cognition, memory, attention, and executive and visuo-perceptual skills did not differ between those with and without RLS/WED. However, the RLS/WED group performed worse on language at baseline by a standard deviation of 0.249, while demonstrating a mitigated language decline over time, by a standard deviation of 0.063. The unadjusted models yielded similar results. Conclusions: Our findings were indicative of a baseline language disadvantage among older individuals with RLS/WED, but the initial discrepancy tends to dissolve over time.

Genetic Predisposition for White Matter Hyperintensities and Risk of Mild Cognitive Impairment and Alzheimer's Disease: Results from the HELIAD Study.

The present study investigated the association of genetic predisposition for white matter hyperintensities (WMHs) with incident amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD), as well as whether such an association was influenced by age, sex, and cognitive reserve. Overall, 537 individuals without aMCI or dementia at baseline were included. Among them, 62 individuals developed aMCI/AD at follow up. Genetic propensity to WMH was estimated using a polygenic risk score for WMHs (PRS WMH). The association of PRS WMH with aMCI/AD incidence was examined using COX models. A higher PRS WMH was associated with a 47.2% higher aMCI/AD incidence (p = 0.015) in the fully adjusted model. Subgroup analyses showed significant results in the older age group, in which individuals with a higher genetic predisposition for WMHs had a 3.4-fold higher risk for developing aMCI/AD at follow up (p < 0.001), as well as in the lower cognitive reserve (CR, proxied by education years) group, in which individuals with a higher genetic predisposition for WMHs had an over 2-fold higher risk (p = 0.013). Genetic predisposition for WMHs was associated with aMCI/AD incidence, particularly in the group of participants with a low CR. Thus, CR might be a modifier in the relationship between genetic predisposition for WMHs and incident aMCI/AD.

Development of robust normative data for the neuropsychological assessment of Greek older adults.

OBJECTIVE: Normative data for older adults may be tainted by inadvertent inclusion of undiagnosed individuals at the very early stage of a neurodegenerative process. To avoid this pitfall, we developed norms for a cohort of older adults without MCI/dementia at 3-year follow-up. METHODS: A randomly selected sample of 1041 community-dwelling individuals (age ≥ 65) received a full neurological and neuropsychological examination on two occasions [mean interval = 3.1 (SD = 0.9) years]. RESULTS: Of these, 492 participants (Group 1; 65-87 years old) were without dementia on both evaluations (CDR=0 and MMSE ≥ 26); their baseline data were used for norms development. Group 2 (n = 202) met the aforementioned criteria only at baseline, but not at follow-up. Multiple linear regressions included demographic predictors for regression-based normative formulae and raw test scores as dependent variables for each test variable separately. Standardized scaled scores and stratified discrete norms were also calculated. Group 2 performed worse than Group 1 on most tests (p-values < .001-.021). Education was associated with all test scores, age with most, and sex effects were consistent with the literature. CONCLUSIONS: We provide a model for developing sound normative data for widely used neuropsychological tests among older adults, untainted by potential early, undiagnosed cognitive impairment, reporting regression-based, scaled, and discrete norms for use in clinical settings to identify cognitive decline in older adults. Additionally, our co-norming of a variety of tests may enable intra-individual comparisons for diagnostic purposes. The present work addresses the challenge of developing robust normative data for neuropsychological tests in older adults.

Genetic risk for Alzheimer's disease and adherence to the Mediterranean diet: results from the HELIAD study.

Obejctives: The aim of the current study was to investigate whether genetic risk factors may moderate the association between adherence to the Mediterranean diet and AD incidence.Mehtods: The sample was drawn from the HELIAD study, a longitudinal study with a follow-up interval of 3 years. In total 537 older adults without dementia or AD at baseline were included. Adherence to the Mediterranean diet was assessed at baseline and AD diagnosis was determined at both visits. A Polygenic Index for late onset AD (PGI-AD) was constructed. Cox proportional hazard models adjusted for age, sex, education, baseline Global cognition score and APOE e-4 genotype were employed to evaluate the association between PGI-AD and Mediterranean diet with AD incidence. Next, we examined the association between adherence to the Mediterranean diet and AD risk over time across participants stratified by low and high PGI-AD.Results: Twenty-eight participants developed AD at follow-up. In fully adjusted models both the PGI-AD and the adherence to the Mediterranean diet were associated with AD risk (p < 0.05 for both). In the low PGI-AD group, those with a low adherence had a 10-fold higher risk of developing AD per year of follow-up, than did the participants with a high adherence to the Mediterranean diet (p = 0.011), whereas no such association was found for participants in the high PGI-AD group.Discussion: The association of Mediterranean diet with AD risk is more prominent in the group of older adults with a low polygenic risk for developing AD. Our findings suggest that genetic risk factors should be taken into account when planning interventions aiming to improve cognitive health.

Depressive symptoms in the entire spectrum of cognitive ageing in Greece: evidence from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD).

OBJECTIVES: To study (i) the prevalence of mild and moderate-to-severe depressive symptoms in the entire spectrum of cognitive ageing in Greece and (ii) the relationship between these symptoms and demographic and clinical data. METHODS: The study was based on the randomly selected cohort of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Depressive symptoms were assessed with the 15-item version of the Geriatric Depression Scale. Participants also received a comprehensive neuropsychological assessment, while the clinical diagnoses of dementia and mild cognitive impairment were established according to international diagnostic criteria. Statistical analyses relied on comparison tests and a logistic (proportional odds) ordinal regression model. RESULTS: Depressive symptoms were detected in 19.5% of the 1936 study participants, while 11.3% of both people with MCI and dementia had moderate-to-severe depressive symptoms. The regression model revealed that older adults with more severe depressive symptoms were more likely female, cognitively impaired, less educated, were treated with psychotropic medication and lived in Attica versus Thessaly. CONCLUSIONS: Since depressive symptoms were detected in almost one in five older adults, healthcare professionals in Greece should safeguard the timely detection and effective treatment of such symptoms and the post-diagnostic care of older adults with depression.

Depressive symptoms are present in approximately 20% of older adults.More than 10% of older individuals with dementia or mild cognitive impairment report moderate-to-severe depressive symptoms.Female sex, lower education, lower cognitive performance, living in urban areas and treatment with psychotropic medication pertain to more severe depressive symptoms in ageing.Timely detection and effective treatment of depressive symptoms are crucial in the clinical practice of the care of older adults.Further research is needed in order to elucidate the complex relationship between depressive symptoms and cognitive impairment in ageing.

Trajectories of healthy aging and their association with prodromal parkinson disease: The HELIAD study.

Background: The aim of the present study was to investigate the association of prodromal PD (pPD) with trajectories of healthy aging, according to its latest definition by the WHO.Methods: In a sample of 1,226 older adults (704 women), PD diagnosis was reached through standard clinical research procedures. Probability of pPD was calculated according to the International Parkinson and Movement Disorder Society's research criteria for PD-free participants. A healthy aging metric was introduced using an item response theory approach (IRT) based on information from validated questionnaires assessing functionality. Four trajectories of healthy aging were created based on whether the healthy aging status of participants was above or below the median at baseline and follow up: High-High, High-Low, Low-High and Low-Low.Results: 34.3% belonged to the High-High group, 15.7% to the High-Low, 18.6% to the Low-High and 31.4% to the Low-Low group. Participants with possible/probable pPD were 78% less likely to belong in High-High trajectory of healthy aging as compared to those without pPD (OR = 0.22, 95%CI 0.06-0.79, p-value = 0,02).Conclusion: Our findings suggest an inverse association of pPD probability with healthy aging among older adults; Further research is needed to investigate the clinical implications of this association.

Exploring Verbal Fluency Strategies among Individuals with Normal Cognition, Amnestic and Non-Amnestic Mild Cognitive Impairment, and Alzheimer's Disease.

Background and Objectives: The present study explored the utilization of verbal fluency (VF) cognitive strategies, including clustering, switching, intrusions, and perseverations, within both semantic (SVF) and phonemic (PVF) conditions, across a continuum of neurocognitive decline, spanning from normal cognitive ageing (NC) to mild cognitive impairment (MCI) and its subtypes, amnestic (aMCI) and non-amnestic (naMCI), as well as AD. Materials and Methods: The study sample was derived from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. The sample included 1607 NC individuals, 146 with aMCI (46 single-domain and 100 multi-domain), 92 with naMCI (41 single-domain and 51 multi-domain), and 79 with AD. Statistical analyses, adjusting for sex, age, and education, employed multivariate general linear models to probe differences among these groups. Results: Results showed that AD patients exhibited poorer performance in switching in both VF tasks and SVF clustering compared to NC. Similarly, the aMCI group performed worse than the NC in switching and clustering in both tasks, with aMCI performing similarly to AD, except for SVF switching. In contrast, the naMCI subgroup performed similarly to those with NC across most strategies, surpassing AD patients. Notably, the aMCI subgroup's poor performance in SVF switching was mainly due to the subpar performance of the multi-domain aMCI subgroup. This subgroup was outperformed in switching in both VF tasks by the single-domain naMCI, who also performed better than the multi-domain naMCI in SVF switching. No significant differences emerged in terms of perseverations and intrusions. Conclusions: Overall, these findings suggest a continuum of declining switching ability in the SVF task, with NC surpassing both aMCI and AD, and aMCI outperforming those with AD. The challenges in SVF switching suggest executive function impairment associated with multi-domain MCI, particularly driven by the multi-domain aMCI.

Application of Machine Learning Techniques in the HELIAD Study Data for the Development of Diagnostic Models in MCI and Dementia.

The increase in the population's life expectancy leads to an increase in the incidence of dementia and, therefore, in diseases such as Alzheimer's. Towards this direction, the HELIAD1 study is the first large-scale epidemiological study aimed at assessing epidemiological data on dementia, mild mental decline, and other neuropsychiatric disorders associated with old age. This is a huge study with several computational challenges, most of which can be addressed by machine learning processes. The objectives of this study were to detect patterns in the HELIAD clinical data that classify with high accuracy various levels of cognitive impairment by training ML algorithms and hence apply derived model on future clinical data to predict with the same accuracy the class variable. We propose a machine learning method based on RUSBoost classifier to identify a critical subset of biomarkers that classify accurately between neurological patients with mild cognitive impairment (MCI) or dementia of the Alzheimer's type (DAT) and the cognitively healthy control (CHC) group. In this study we used a highly skewed (imbalanced) dataset with most observations (majority class) belonging to the CHC group. The method proposed predicts accurately the clinical diagnosis label and effectively classifies the neurological patients from the CHC class. In particular, the classification accuracy (actual vs predicted) for the three classes of the clinical diagnosis was 97%, 78%, and 91% for control, MCI, and dementia class, respectively.

Longitudinal Examination of Body Mass Index and Cognitive Function in Older Adults: The HELIAD Study.

Given the increase in the aging population and thus in the prevalence of dementia, the identification of protective factors against cognitive decline is necessary. In a cohort of 1076 non-demented adults ≥ 65 years old (59.7% women) from the HELIAD study, we assessed whether changes in body mass index (BMI) were associated with changes in cognition over a 3-year follow-up period separately for those ≤ 75 and >75 years old. We identified six BMI trajectory groups based on participants' BMI status at baseline and at the first follow-up visit; normal to normal BMI was the reference group. Major cognitive domains were evaluated, and a composite index reflecting global cognition was calculated. In participants aged ≤75 years, weight loss-moving from obesity to overweight or normal BMI-was associated with less decline in the memory composite score over time (ß = 0.141; p = 0.035), while 3-year maintenance of a BMI ≥ 25 kg/m2 was related to greater reduction in the visuospatial composite score over time (ß = -0.093; p = 0.020). Regarding participants aged >75 years, 3-year maintenance of a BMI ≥ 30 kg/m2 contributed to a slower rate of decline in the memory composite score over time (ß = 0.102; p = 0.042), whereas weight loss-from overweight to normal BMI-was associated with a decreased attention/processing speed composite score longitudinally (ß = -0.275; p = 0.043). Our findings indicated that the association between changes in BMI and cognitive functioning was modified by age. Weight management may have the potential to delay cognitive decline in older adults.

Genetic propensity for cerebral amyloidosis and risk of mild cognitive impairment and Alzheimer's disease within a cognitive reserve framework.

INTRODUCTION: We constructed a polygenic risk score (PRS) for ß-amyloid (PRSAß42) to proxy AD pathology and investigated its association with incident Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI) and the influence of cognitive reserve (CR), proxied by educational years, on the relationship between PRSAß42 and AD/aMCI risk. METHODS: A total of 618 cognitive-normal participants were followed-up for 2.92 years. The association of PRSAß42 and CR with AD/aMCI incidence was examined with COX models. Then we examined the additive interaction between PRSAß42 and CR and the CR effect across participants with different PRSAß42 levels. RESULTS: Higher PRSAß42 and CR were associated with a 33.9% higher risk and 8.3% less risk for AD/aMCI, respectively. An additive interaction between PRSAß42 and CR was observed. High CR was associated with 62.6% less risk of AD/aMCI incidence only in the high-PRSAß42 group. DISCUSSION: A super-additive effect of PRSAß42 and CR on AD/aMCI risk was observed. CR influence was evident in participants with high PRSAß42.

Genetically downregulated Interleukin-6 signalling is associated with a lower risk of frailty.

BACKGROUND: numerous studies point towards a critical role of Interleukin 6 (IL-6) pathway in frailty pathogenesis yet the causal relationship between the two remains elusive. METHODS: we selected genetic variants near the IL-6 receptor locus (IL-6R) associated with reduced C-reactive protein (CRP) levels, a downstream effector of IL-6 pathway, and we used them as genetic proxies of IL-6 signalling downregulation. We then performed a two-sample Mendelian randomisation (MR) to investigate the association with frailty status, as defined by the Frailty Index (FI) in 11,171 individuals from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD) study. MR analysis was repeated after excluding depression or cognition-related FI items as well as following age or sex stratification. Association with frailty was also examined using an alternative instrument, weighted on s-IL-6R levels. Replication was attempted in UK Biobank dataset. RESULTS: genetic predisposition to IL-6 signalling downregulation, weighted on CRP levels, was associated with lower risk of frailty, inserted either as categorical (odds ratio [95% confidence interval] = 0.15 [-3.39, -0.40], P = 0.013) or continuous variable (beta [se] = -0.09 [0.003], P = 0.0009). Sensitivity analyses revealed similar estimates across different MR methods with no evidence for horizontal pleiotropy or heterogeneity. Results remained robust after exclusion of depression or cognition-related FI items and following sex or age stratification. Genetically increased s-IL-6R levels were negatively correlated with frailty and this finding remained significant in a meta-analysis of UK Biobank and HELIAD cohorts. CONCLUSION: our results support a potential causal effect of IL-6 signalling on frailty and further suggest that downregulation of IL-6 levels may reduce frailty risk.

The Association of Adherence to the Mediterranean Diet with Depression in Older Adults Longitudinally Taking into Account Cognitive Status: Results from the HELIAD Study.

Although research has generally shown a negative association between depression and adherence to the Mediterranean diet (MeDi), the literature related to older adults is controversial, perhaps partially due to the fact that cognitive status has not been considered. The aim of the current work was to investigate the association between MeDi and incident depression in a representative cohort of people, taking into account their cognitive status in multiple ways. The sample was drawn from the HELIAD study, a longitudinal study including a follow-up of 3 years after the baseline assessment. In total, 879 participants without depression at baseline were included (55.4% women, mean age ± Standard Deviation: 73.3 ± 5.0 years). Depression was determined as a score in the Geriatric depression scale ≥6 and/or antidepressant medication and/or clinical diagnosis of depression. Cox proportional hazard models adjusted for age, sex and education were employed. In the basic model, adherence to the MeDi was negatively associated with depression. In the most conservative model, excluding participants with dementia and Mild Cognitive Impairment, and after controlling for the baseline Cognitive Status, each unit (range 0−55) increase in MeDi was associated with a 6.2% decrease in the risk for depression (p < 0.001). These findings indicate that MeDi is negatively associated with depression longitudinally in older adults, above and beyond cognitive status.

Mediterranean diet is associated with a lower probability of prodromal Parkinson's disease and risk for Parkinson's disease/dementia with Lewy bodies: A longitudinal study.

BACKGROUND AND PURPOSE: Lifestyle factors have been implicated in the long-lasting neurodegenerative process in prodromal Parkinson's disease (pPD). The aim was to investigate the associations between adherence to a Mediterranean diet (MeDi) and longitudinal changes of pPD probability and the development of Parkinson's disease (PD) or pPD in a Mediterranean older population. METHODS: Data from the Hellenic Longitudinal Investigation of Aging and Diet cohort (community-dwelling individuals, aged ≥ 65 years) were used. A detailed food frequency questionnaire was used to evaluate dietary intake and calculate MeDi adherence score, ranging from 0 to 55, with higher scores indicating higher adherence. The probability of pPD was calculated according to the updated Movement Disorder Society research criteria. RESULTS: In all, 1047 non-PD/dementia with Lewy bodies (DLB) participants were followed for 3 ± 1 years. MeDi adherence was associated with lower increase in pPD probability over time (b = -0.003, 95% confidence interval -0.006 to -0.001, p = 0.010). Forty-nine participants had incident possible/probable pPD (i.e., pPD probability ≥ 30%). Compared to the participants in the lowest quartile of MeDi adherence, those in the higher quartiles had an approximately 60%-70% lower risk for possible/probable pPD (p for trend 0.003). MeDi-pPD associations were driven by both motor and non-motor pPD markers and not from risk markers. Also, 21 participants were diagnosed with PD/DLB at follow-up. For each unit increase in the MeDi score, there was a 9%-10% lower risk for PD/DLB (hazard ratio 0.906 [95% confidence interval 0.823-0.997], p = 0.044). CONCLUSIONS: Mediterranean diet adherence is associated with lower increase in pPD probability over time and lower possible/probable pPD and PD/DLB incidence in older Mediterranean people. More studies are needed to confirm our results in other populations.

Predictive ability of the clock drawing test to detect mild cognitive impairment and dementia over time: Results from the HELIAD study.

Objective: We investigated the diagnostic accuracy of the Clock Drawing Test (CDT) in discriminating Mild Cognitive Impairment (MCI) and dementia from normal cognition. Additionally, its clinical utility in predicting the transition from normal cognition to MCI and dementia over the course of several years was explored. Method: In total, 1037 older adults (633 women) who completed the CDT in a baseline assessment were drawn from the population-based HELIAD cohort. Among these, 848 participants were identified as cognitively normal, 142 as having MCI and 47 with dementia during the baseline assessment. Of these individuals, 565 attended the follow-up assessment (mean interval: 3.21 years). ROC curve and binary logistic regression analyses were performed. Results: The CDT exhibited good diagnostic accuracy for the discrimination between dementia and normal cognition (AUC = .879, SN = .813, SP = .778, LR+ = 3.66, LR- = .240, < .001, d = 1.655) and acceptable diagnostic accuracy for the discrimination between dementia and MCI (AUC=.761, SN= .750, SP= .689, LR+ = 2.41, LR- = .362, p < .001, d = 1.003). We found limited diagnostic accuracy, however, for the discrimination between MCI and normal cognition (AUC = .686, SN = .764, SP = .502, LR+ = 1.53, LR- = .470, p < .001, d = .685). Moreover, the CDT significantly predicted the transition from normal cognition to dementia [Exp(B)= 1.257, p = .022], as well as the transition from MCI to normal cognition [Exp(B) = 1.334, p = .023] during the longitudinal investigation. Conclusions: The CDT is a neuropsychological test with acceptable diagnostic accuracy for the discrimination of dementia from MCI and normal cognition. Furthermore, it has an important predictive value for the transition from normal cognition to dementia and from MCI to normal cognition.

Longitudinal episodic memory trajectories in older adults with normal cognition.

OBJECTIVE: To determine the longitudinal trajectories and normative standards of episodic memory in older adults. METHODS: Participants were drawn from the cognitively normal(CN) subgroup of the population-based HELIAD cohort, a fairly representative cohort of the older Greek population. Verbal and non-verbal memory were assessed using the Greek Verbal Learning Test and Medical College of Georgia-Complex Figure Test. Baseline and longitudinal associations of memory performance with age, sex and formal education were explored with linear regression analysis and generalized estimated equations. RESULTS: A total of 1607 predominantly female (60%) individuals (73.82 ± 5.43 years), with a mean educational attainment of 8.17(±4.86) years were CN at baseline. Baseline analysis revealed a continuum of memory decline with aging and lower educational attainment. Women performed better in composite and verbal memory measures, while men performed better in non-verbal memory tasks. A subgroup of 761 participants with available assessments after 3.07(±0.82) years remained CN at follow-up. Composite memory scores yearly diminished by an additional 0.007 of a SD for each additional year of age at baseline. Regarding verbal learning, immediate free verbal recall, delayed free verbal recall and delayed cued verbal recall, an additional yearly decrease of 0.107, 0.043, 0.036 and 0.026 words were respectively recorded at follow-up, for each additional year of age at baseline. Women underwent steeper yearly decreases of 0.227 words in delayed cued verbal recall. No significant longitudinal associations emerged for immediate non-verbal memory, delayed non-verbal memory and immediate cued verbal recall. CONCLUSIONS: In the present study, aging (but not educational attainment) was consistently associated with steeper verbal memory decline.Supplemental data for this article is available online at https://doi.org/10.1080/13854046.2022.2059011 .

Language performance as a prognostic factor for developing Alzheimer's clinical syndrome and mild cognitive impairment: Results from the population-based HELIAD cohort.

OBJECTIVES: There is limited research on the prognostic value of language tasks regarding mild cognitive impairment (MCI) and Alzheimer's clinical syndrome (ACS) development in the cognitively normal (CN) elderly, as well as MCI to ACS conversion. METHODS: Participants were drawn from the population-based Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. Language performance was evaluated via verbal fluency [semantic (SVF) and phonemic (PVF)], confrontation naming [Boston Naming Test short form (BNTsf)], verbal comprehension, and repetition tasks. An additional language index was estimated using both verbal fluency tasks: SVF-PVF discrepancy. Cox proportional hazards analyses adjusted for important sociodemographic parameters (age, sex, education, main occupation, and socioeconomic status) and global cognitive status [Mini Mental State Examination score (MMSE)] were performed. RESULTS: A total of 959 CN and 118 MCI older (>64 years) individuals had follow-up investigations after a mean of ∼3 years. Regarding the CN group, each standard deviation increase in the composite language score reduced the risk of ACS and MCI by 49% (8-72%) and 32% (8-50%), respectively; better SVF and BNTsf performance were also independently associated with reduced risk of ACS and MCI. On the other hand, using the smaller MCI participant set, no language measurement was related to the risk of MCI to ACS conversion. CONCLUSIONS: Impaired language performance is associated with elevated risk of ACS and MCI development. Better SVF and BNTsf performance are associated with reduced risk of ACS and MCI in CN individuals, independent of age, sex, education, main occupation, socioeconomic status, and MMSE scores at baseline.