Neurocognitive Impairment in Long COVID: A Systematic Review.

OBJECTIVE: Although Coronavirus disease 2019 (COVID-19) is primarily a respiratory infectious disease, it has also been associated with a wide range of other clinical manifestations. It is widely accepted in the scientific community that many patients after recovery continue to experience COVID-19-related symptoms, including cognitive impairment. The aim of this systematic review was to investigate the cognitive profile of patients with long-COVID syndrome. METHODS: A systematic search of empirical studies was conducted through the PubMed/Medline and Scopus electronic databases. Cross-sectional and longitudinal studies published between 2020 and 2023 were included. RESULTS: Of the 516 studies assessed for eligibility, 36 studies met the inclusion criteria. All included studies support the presence of persistent cognitive changes after COVID-19 disease. Executive function, memory, attention, and processing speed appear to be the cognitive domains that are predominantly associated with long-COVID syndrome, whereas language is an area that has not been sufficiently investigated. CONCLUSIONS: In this review, the high frequency of cognitive impairment after COVID-19 is evident. If we consider that cognitive functioning affects our ability to live independently and is a key determinant of our quality of life, it is imperative to precisely define those factors that may induce cognitive impairment in COVID-19 survivors, with the ultimate goal of early diagnosis of cognitive changes and, consequently, the development of targeted rehabilitation interventions to address them.

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.

Associations between fruit and vegetable intakes and incident depression in middle-aged and older adults from 10 diverse international longitudinal cohorts.

BACKGROUND: Emerging observational evidence supports a role for higher fruit and vegetable intake in protecting against the development of depression. However, there is a scarcity of research in older adults or in low- to middle-income countries (LMICs). METHODS: Participants were 7801 community-based adults (mean age 68.6 ± 8.0 years, 55.8 % female) without depression, from 10 diverse cohorts, including four cohorts from LMICs. Fruit and vegetable intake was self-reported via comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated measures, and depression defined applying validated cut-offs. The associations between baseline fruit and vegetable intakes and incident depression over a follow-up period of three to nine years were examined using Cox regression. Analyses were performed by cohort with results meta-analysed. RESULTS: There were 1630 cases of incident depression (21 % of participants) over 40,258 person-years of follow-up. Higher intake of fruit was associated with a lower risk of incident depression (HR 0.87, 95%CI [0.77, 0.99], I2 = 4 %). No association was found between vegetable intake and incident depression (HR 0.93, 95%CI [0.84, 1.04], I2 = 0 %). LIMITATIONS: Diverse measures used across the different cohorts and the modest sample size of our study compared with prior studies may have prevented an association being detected for vegetable intake. CONCLUSIONS: Our study supports a role for fruit, but not vegetable intake in protecting against depression. Research investigating different types of fruits and vegetables using standardised measures in larger cohorts of older adults from low- and middle-income countries is warranted.

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.

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 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.

Exploring How Sociocultural Factors Affect the Experience of Completing Neuropsychological Assessments Within Older Greek-Australians.

OBJECTIVE: The field of cultural neuropsychology has grown exponentially over the last three decades. With a limited culturally informed evidence base to guide neuropsychological practice, the acceptability of existing paradigms has been called into question when applied to culturally diverse and educationally disadvantaged groups. This qualitative study aimed to explore the experiences of Greek Australian older adults who underwent a cognitive assessment to better understand potential barriers and facilitators to engagement and to improve neuropsychological assessment outcomes. METHOD: Semi-structured interviews were developed to explore cultural attitudes and contextual factors relating to neuropsychological assessment. Interviews were conducted by Greek-speaking neuropsychologists using a sample of 10 healthy elderly Greek Australians following the completion of a comprehensive neuropsychological assessment. Data were analyzed using a phenomenological design within a critical realist framework. RESULTS: Analysis revealed the emergence of three broad themes: sociocultural factors, experiences within the broader medical system, and the assessment experience. Engagement with cognitive assessment was influenced by several factors, including rapport building, understanding of the assessment, and use of inappropriate tests. Furthermore, level and quality of education, sex differences, language barriers, acculturation, previous experiences of prejudice, anxiety, and a preference for Greek-speaking clinicians were additional factors reported to affect the client experience and validity of assessment outcomes. CONCLUSION: Neuropsychological assessment is, in part, affected by culturally reinforced attitudes. Failing to adjust the relationship between the clinician and client, test environment, style of communication, and the use of culturally inappropriate tests is likely to affect the validity of assessment outcomes.

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.

Protecting the Brain While Healing Hearts: The Protective Role of Cognitive Reserve in Cardiac Surgery.

OBJECTIVE: One of the most significant complications following coronary artery bypass grafting (CABG) is postoperative cognitive decline (POCD). CABG patients frequently experience considerable postoperative cognitive dysfunction (POCD), including decline in attention, orientation, memory, judgment, and social functioning. DESIGN: These negative effects may potentially be resolved by a protective factor, cognitive reserve (CR) that has been considered to function as a buffer against the consequences of neuropathology. SETTING: We explored the frequency of POCD and CR in coronary artery disease patients undergoing CABG. We hypothesized that high levels of CR would protect against POCD after cardiac surgery. PARTICIPANTS: We assessed 101 patients before surgery, and 4 months after cardiopulmonary bypass surgery with the use of extracorporeal circulation. MEASUREMENTS: Measures of cognitive functions, CR, anxiety, and depression were included in the assessment. RESULTS: Each patient was placed in the high (n = 50) or low CR (n = 51) group, based on median split. Chi-square tests effect showed that patients with low CR were more likely to a great extend to demonstrate postsurgical cognitive decline in attention, memory, visuospatial perception and executive functions than patients with high CR upon postsurgery neuropsychological assessment. CONCLUSIONS: Our results suggest that CR can forecast neuropsychological outcomes of cardiac surgery, recognizing the patients with low CR and help them to participate to interventions programs that could slow cognitive aging or reduce the risk of dementia and enhance their overall postsurgical functional outcome.

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.

Do normative data specific to Greek Australian older adults improve validity of neuropsychological assessment results?

OBJECTIVE: This study aimed to compare Greek Australian and English language normative data with regard to impairment rates yielded within a healthy Greek Australian older adult sample. We also examined whether optimal cut scores could be identified and capable of sensitively and specifically distinguishing between healthy Greek Australians from those with a diagnosis of Alzheimer's disease (AD). METHOD: Ninety healthy Greek Australian older adults and 20 demographically matched individuals with a diagnosis of AD completed a range of neuropsychological measures, including the Wechsler Adult Intelligence Scale-Fourth Edition, Greek Adaptation (WAIS-IV GR), verbal and visual memory, language and naming, and executive functions. Impairment rates derived from the use of either Greek Australian or English language normative data were calculated and compared, using a 1.5 standard deviation criterion to denote impairment. Receiver operating characteristics curve analysis was used to investigate the sensitivity and specificity of alternate cut scores. RESULTS: Impairment rates derived from the Greek Australian normative data showed that rates of impairment generally fell within the expected 7% range. In contrast, impairment rates for all tests derived using English language normative data were significantly higher and ranged from 11%-66%. Comparisons between healthy and AD participants with moderate dementia showed significant differences across all measures. Area under the curve results ranged from .721 to .999 across all measures, with most tests displaying excellent sensitivity and specificity. CONCLUSIONS: English language normative data were found to be inappropriate for use with Greek Australian elders, potentially leading to erroneous diagnostic outcomes. The use of minority group specific normative data and associated cut points appear to partially ameliorate this issue. Clinical implications are discussed alongside future research directions.

Syntactic and affective prosody recognition: Schizophrenia vs. Autism spectrum disorders.

Patients with a recent diagnosis of schizophrenia and individuals receiving a diagnosis of autism spectrum disorder without accompanying intellectual impairment (ASD w/o intellectual impairment) during their adulthood share several clinical characteristics. Exploring under-investigated aspects of these two clinical conditions may shed light on their possible connection and facilitate differential diagnosis at very early stages. To this end, we explored the ability of 15 adults with a recent diagnosis of schizophrenia, 15 individuals diagnosed with ASD w/o intellectual impairment as adults, and 15 healthy adults to resolve sentence ambiguities with the use of syntactic prosody, and to decode happiness, anger, sadness, surprise, fear, and neutrality based on affective prosody. Results revealed intact perception of syntactic prosody in adults with schizophrenia, but impaired affective prosody recognition, which could be attributed, however, to emotion processing difficulties overall. On the other hand, individuals with ASD w/o intellectual impairment were impaired on prosody comprehension per se, as evidenced in the most challenging conditions, namely the subject-reading condition and the emotion of surprise. The differences in prosody comprehension ability between the two clinical conditions may serve as an indicator, among other signs, during the diagnostic evaluation.

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.

Cognitive Impairment in MRI-Negative Epilepsy: Relationship between Neurophysiological and Neuropsychological Measures.

BACKGROUND: Epileptic patients frequently encounter cognitive impairment. Functions that are mostly affected involve memory, attention, and executive function; however, this is mainly dependent on the location of the epileptic activity. The aim of the present study is to assess cognitive functions in MRI-negative epilepsy patients by means of neurophysiological and neuropsychological measures, as well as study the concept of transient cognitive impairment in patients with epileptiform discharges during EEG acquisition. METHODS: The patients were enrolled from an outpatient Epilepsy/Clinical Neurophysiology clinic over a time period of 6 months. The study sample comprised 20 MRI-negative epilepsy patients (mean age ± standard deviation (SD), 30.3 ± 12.56 years; age range, 16-60 years; average disease duration, 13.95 years) and 10 age-matched controls (mean age ± SD, 24.22 ± 15.39 years), who were also education-matched (p > 0.05). Patients with epileptogenic lesions were excluded from the study. Informed consent was obtained from all subjects involved in the study. Auditory ERPs and the cognitive screening tool EpiTrack were administered to all subjects. RESULTS: Latencies of P300 and slow waves were prolonged in patients compared to controls (p < 0.05). The ASM load and patients' performance in the EpiTrack maze subtest were the most significant predictors of P300 latency. A decline in the memory, attention, and speed of information processing was observed in patients with cryptogenic epilepsy compared to age-matched controls, as reflected by P300 latency and EpiTrack scores.

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.

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

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.