Functionally annotated electrophysiological neuromarkers of healthy ageing and memory function.

The unprecedented increase in life expectancy presents a unique opportunity and the necessity to explore both healthy and pathological aspects of ageing. Electroencephalography (EEG) has been widely used to identify neuromarkers of cognitive ageing due to its affordability and richness in information. However, despite the growing volume of data and methodological advancements, the abundance of contradictory and non-reproducible findings has hindered clinical translation. To address these challenges, our study introduces a comprehensive workflow expanding on previous EEG studies and investigates various static and dynamic power and connectivity estimates as potential neuromarkers of cognitive ageing in a large dataset. We also assess the robustness of our findings by testing their susceptibility to band specification. Finally, we characterise our findings using functionally annotated brain networks to improve their interpretability and multi-modal integration. Our analysis demonstrates the effect of methodological choices on findings and that dynamic rather than static neuromarkers are not only more sensitive but also more robust. Consequently, they emerge as strong candidates for cognitive ageing neuromarkers. Moreover, we were able to replicate the most established EEG findings in cognitive ageing, such as alpha oscillation slowing, increased beta power, reduced reactivity across multiple bands, and decreased delta connectivity. Additionally, when considering individual variations in the alpha band, we clarified that alpha power is characteristic of memory performance rather than ageing, highlighting its potential as a neuromarker for cognitive ageing. Finally, our approach using functionally annotated source reconstruction allowed us to provide insights into domain-specific electrophysiological mechanisms underlying memory performance and ageing. HIGHLIGHTS: We provide an open and reproducible pipeline with a comprehensive workflow to investigate static and dynamic EEG neuromarkers. Neuromarkers related to neural dynamics are sensitive and robust. Individualised alpha power characterises cognitive performance rather than ageing. Functional annotation allows cross-modal interpretation of EEG findings.

Influence of intergenerational social mobility on brain structure and global cognition: findings from the Whitehall II study across 20 years.

BACKGROUND: Whether changes in socioeconomic position (SEP) across generations, i.e. intergenerational social mobility, influence brain degeneration and cognition in later life is unclear. OBJECTIVE: To examine the association of social mobility, brain grey matter structure and global cognition. METHODS: We analysed T1 brain MRI data of 771 old adults (69.8 ± 5.2 years) from the Whitehall II MRI substudy, with MRI data collected between 2012 and 2016. Social mobility was defined by SEP changes from their fathers' generation to mid-life status. Brain structural outcomes include grey matter (GM) volume and cortical thickness (CT) covering whole brain. Global cognition was measured by the Mini Mental State Examination. We firstly conducted analysis of covariance to identify regional difference of GM volume and cortical thickness across stable high/low and upward/downward mobility groups, followed with diagonal reference models studying the relationship between mobility and brain cognitive outcomes, apart from SEP origin and destination. We additionally conducted linear mixed models to check mobility interaction over time, where global cognition was derived from three phases across 2002 to 2017. RESULTS: Social mobility related to 48 out of the 136 GM volume regions and 4 out of the 68 CT regions. Declined volume was particularly seen in response to downward mobility, whereas no independent association of mobility with global cognition was observed. CONCLUSION: Despite no strong evidence supporting direct influence of mobility on global cognition in later life, imaging findings warranted a severe level of neurodegeneration due to downward mobility from their father's generation.

Estimating Gender Differences in the Association between Cognitive Resilience and Mild Cognitive Impairment Incidence.

INTRODUCTION: Recent evidence suggests that the influence of verbal intelligence and education on the onset of subjective cognitive decline may be modulated by gender, where education contributes less to cognitive resilience (CR) in women than in men. This study aimed to examine gender differences in the association between CR and mild cognitive impairment (MCI) incidence in an Australian population-based cohort. METHODS: We included 1,806 participants who had completed at least the first two waves and up to four waves of assessments in the Personality and Total Health (PATH) Through Life study (baseline: 49% female, male = 62.5, SD = 1.5, age range = 60-66 years). CR proxies included measures of educational attainment, occupation skill, verbal intelligence, and leisure activity. Discrete-time survival analyses were conducted to examine gender differences in the association between CR proxies and MCI risk, adjusting for age and apolipoprotein E4 status. RESULTS: Gender differences were only found in the association between occupation and MCI risk, where lower occupation skill was more strongly associated with higher risk in men than in women (odds ratio [OR] = 1.30, 95% confidence interval [CI] [1.07, 1.57]). In both genders, after adjusting for education and occupation, one SD increase in leisure activity was associated with lower MCI risk by 32% (OR = 0.76, 95% CI [0.65, 0.89]). Higher scores in verbal intelligence assessment were associated with reduced risk of MCI by 28% (OR = 0.78, 95% CI [0.69, 0.89]). CONCLUSION: Occupational experience may contribute to CR differently between genders. Life course cognitive engagement and verbal intelligence may be more protective against MCI than education and occupation for both men and women.

Outcomes of home design to support healthy cognitive ageing: modified e-Delphi exercise with older people and housing-related professionals.

BACKGROUND: There is emerging agreement that living in a home designed to support healthy cognitive ageing can enable people to live better with dementia and cognitive change. However, existing literature has used a variety of outcome measures that have infrequently been informed by the perspectives of older people or of professional in design and supply of housing. The DesHCA (Designing Homes for Healthy Cognitive Ageing) study aimed to identify outcomes that were meaningful for these groups and to understand their content and meanings. METHODS: A presurvey of older people and housing professionals (n = 62) identified potential outcomes. These were then used in three rounds of a modified e-Delphi exercise with a panel of older people and housing professionals (n = 74) to test meanings and identify areas of agreement and disagreement. Descriptive statistics were used to present findings from previous rounds. RESULTS: The survey confirmed a wide range of possible outcomes considered important. Through the e-Delphi rounds, panellists prioritised outcomes relating to living at home that could be influenced by design, and clarified their understanding of the meanings of outcomes. In subsequent rounds, they commented on earlier results. The exercise enabled five key outcome areas to be identified - staying independent, feeling safe, living in an adaptable home, enabling physical activity and enabling enjoyed activities- which were then tested for their content and applicability in panellists' views. CONCLUSION: The five key outcome areas appeared meaningful to panellists, whilst also demonstrating nuanced meanings. They indicate useful outcomes for future research, though will require careful definition in each case to become measures. Importantly, they are informed by the views of those most immediately affected by better or poorer home design.

Salivary Antimicrobial Peptide in Patients With Dementia Before and After Clinical Oral Rehabilitation Programme: A Randomised Controlled Trial.

BACKGROUND: Emerging evidence suggests a link between salivary metabolite changes and neurodegenerative dementia, with antimicrobial peptides (AMPs) implicated in its pathogenesis. OBJECTIVE: We investigated the effects of a clinical oral rehabilitation programme tailored for dementia patients on salivary flow rate, AMP levels and oral health-related quality of life (OHRQoL). METHODS: Eligible patients were randomly assigned to either the experimental group (EG; n = 28) or the control group (CG; n = 27). Both groups received a leaflet on oral health. In addition, the EG received an oral care intervention that included individual lessons on oral muscle exercises and oral self-care practices. Saliva samples and OHRQoL data were collected at baseline and follow-up visits. Generalised estimating equation models were used to analyse the changes over time. RESULTS: At the 3-month follow-up, EG showed significantly lower histatin 5 (HTN-5) levels (ß = -0.08; effect size [ES] = 0.72) than CG. At 6 months, EG exhibited improved salivary flow rate (ß = 0.89; ES = 0.89) and OHRQoL (ß = 6.99; ES = 1.31) compared to CG. Changes in salivary flow rate (ß = 4.03), HTN-5 level (ß = -0.78) and beta-defensin 2 level (BD-2) (ß = -0.91) at 3 months predicted improved OHRQoL at 6 months (all p < 0.05). CONCLUSIONS: Our clinical oral rehabilitation programme reduced the level of salivary HTN-5, increased salivary flow rate and enhanced OHRQoL in dementia patients. Furthermore, changes in salivary flow rate, HTN-5 level and BD-2 level were associated with improvements in patients' OHRQoL.

Neighbourhood deprivation across eight decades and late-life cognitive function in the Lothian Birth Cohort 1936: a life-course study.

INTRODUCTION: although neighbourhood may predict late-life cognitive function, studies mostly rely on measurements at a single time point, with few investigations applying a life-course approach. Furthermore, it is unclear whether the associations between neighbourhood and cognitive test scores relate to specific cognitive domains or general ability. This study explored how neighbourhood deprivation across eight decades contributed to late-life cognitive function. METHODS: data were drawn from the Lothian Birth Cohort 1936 (n = 1,091) with cognitive function measured through 10 tests at ages 70, 73, 76, 79 and 82. Participants' residential history was gathered with 'lifegrid' questionnaires and linked to neighbourhood deprivation in childhood, young adulthood and mid-to-late adulthood. Associations were tested with latent growth curve models for levels and slopes of general (g) and domain-specific abilities (visuospatial ability, memory and processing speed), and life-course associations were explored with path analysis. RESULTS: higher mid-to-late adulthood neighbourhood deprivation was associated with lower age 70 levels (ß = -0.113, 95% confidence intervals [CI]: -0.205, -0.021) and faster decline of g over 12 years (ß = -0.160, 95%CI: -0.290, -0.031). Initially apparent findings with domain-specific cognitive functions (e.g. processing speed) were due to their shared variance with g. Path analyses suggested that childhood neighbourhood disadvantage is indirectly linked to late-life cognitive function through lower education and selective residential mobility. CONCLUSIONS: to our knowledge, we provide the most comprehensive assessment of the life-course neighbourhood deprivation and cognitive ageing relationship. Living in advantaged areas in mid-to-late adulthood may directly contribute to better cognitive function and slower decline, whereas an advantaged childhood neighbourhood likely affects functioning through cognitive reserves.

Hearing aid use and gender differences in the auditory-cognitive cascade in the oldest old.

OBJECTIVES: This study analyzed cognitive differences between hearing-aid (HA) and non-HA users. We hypothesized that HA-use attenuates the auditory-cognitive cascade, thereby, the latter is more conspicuous in non-HA users. Since hearing impairment (HI) shows male predominance, we hypothesized gender differences within the auditory-cognitive relationship. METHODS: Non-frail community-dwellers ≥ 80 years were assessed for HI (pure tone audiogram-PTA; speech reception threshold-SRT) and global and domain-specific cognitive impairments (Mini-Mental State Examination-MMSE; Montreal Cognitive Assessment-MOCA; Reaction Time Test-RT1-4). Pearson and partial correlations (correcting for age and PTA) assessed auditory-cognitive associations within gender and HA subgroups. Fisher's z test compared correlations between HA and non-HA users. RESULTS: 126 participants (age range 80-91 years) were included. HA-use prevalence was 21%. HA-users were older with worse HI (mean PTA 49.5dBHL). HA-users exhibited no significant auditory (PTA, SRT) and cognitive (MMSE, MOCA, RT1- RT4) correlations. Male non-HA users, displayed a significant association between HI and global cognition, processing speed, selective and alternating attention. Significant differences were noted between MMSE and PTA and SRT (z-score 2.28, 3.33, p = 0.02, <0.01, respectively) between HA and non-HA users. CONCLUSION: Male non-HA users displayed an association between HI and global and domain-specific (processing speed; selective and alternating attention) cognitive decline. Associations between global cognition and HI were significantly different between HA and non-HA users. This may be partially attributable to underlying subgroups sample sizes and statistical power disparity. If larger scale longitudinal or interventional studies confirm these findings, timely HI assessment and management may be the cornerstone for delaying cognitive decline.

Swedish Normative Data for Mindmore: A Comprehensive Cognitive Screening Battery, Both Digital and Self-Administrated.

OBJECTIVE: Cognitive impairment is a key element in most mental disorders. Its objective assessment at initial patient contact in primary care can lead to better adjusted and timely care with personalised treatment and recovery. To enable this, we designed the Mindmore self-administrative cognitive screening battery. What is presented here is normative data for the Mindmore battery for the Swedish population. METHOD: A total of 720 healthy adults (17 to 93 years) completed the Mindmore screening battery, which consists of 14 individual tests across five cognitive domains: attention and processing speed, memory, language, visuospatial functions and executive functions. Regression-based normative data were established for 42 test result measures, investigating linear, non-linear and interaction effects between age, education and sex. RESULTS: The test results were most affected by age and to a lesser extent by education and sex. All but one test displayed either linear or accelerated age-related decline, or a U-shaped association with age. All but two tests showed beneficial effects of education, either linear or subsiding after 12 years of educational attainment. Sex affected tests in the memory and executive domains. In three tests, an interaction between age and education revealed an increased benefit of education later in life. CONCLUSION: This study provides normative models for 14 traditional cognitive tests adapted for self-administration through a digital platform. The models will enable more accurate interpretation of test results, hopefully leading to improved clinical decision making and better care for patients with cognitive impairment.

To what degree is late life cognitive decline driven by age-related neuropathologies?

The ageing brain is vulnerable to a wide array of neuropathologies. Prior work estimated that the three most studied of these, Alzheimer's disease, infarcts, and Lewy bodies, account for ∼40% of the variation in late life cognitive decline. However, that estimate did not incorporate many other diseases that are now recognized as potent drivers of cognitive decline [e.g. limbic predominant age-related TDP-43 encephalopathy (LATE-NC), hippocampal sclerosis, other cerebrovascular conditions]. We examined the degree to which person-specific cognitive decline in old age is driven by a wide array of neuropathologies. Deceased participants (n = 1164) from two longitudinal clinical-pathological studies, the Rush Memory and Aging Project and Religious Orders Study, completed up to 24 annual evaluations including 17 cognitive performance tests and underwent brain autopsy. Neuropathological examinations provided 11 pathological indices, including markers of Alzheimer's disease, non- Alzheimer's disease neurodegenerative diseases (i.e. LATE-NC, hippocampal sclerosis, Lewy bodies), and cerebrovascular conditions (i.e. macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis, and arteriolosclerosis). Mixed effects models examined the linear relation of pathological indices with global cognitive decline, and random change point models examined the relation of the pathological indices with the onset of terminal decline and rates of preterminal and terminal decline. Cognition declined an average of about 0.10 unit per year (estimate = -0.101, SE = 0.003, P < 0.001) with considerable heterogeneity in rates of decline (variance estimate for the person-specific slope of decline was 0.0094, P < 0.001). When considered separately, 10 of 11 pathological indices were associated with faster decline and accounted for between 2% and 34% of the variation in decline, respectively. When considered simultaneously, the 11 pathological indices together accounted for 43% of the variation in decline; Alzheimer's disease-related indices accounted for 30-36% of the variation, non-Alzheimer's disease neurodegenerative indices 4-10%, and cerebrovascular indices 3-8%. Finally, the 11 pathological indices combined accounted for less than a third of the variation in the onset of terminal decline (28%) and rates of preterminal (32%) and terminal decline (19%). Although age-related neuropathologies account for a large proportion of the variation in late life cognitive decline, considerable variation remains unexplained even after considering a wide array of neuropathologies. These findings highlight the complexity of cognitive ageing and have important implications for the ongoing effort to develop effective therapeutics and identify novel treatment targets.

Does predictive cueing of presentation time modulate alpha power and facilitate visual working memory performance in younger and older adults?

Selective attention and working memory (WM) are vulnerable to age-related decline. Older adults perform worse on, and are less able to modulate alpha power (8-12 Hz) than younger adults in tasks involving cues about 'where' or 'when' a memory set will appear. However, no study has investigated whether alpha power is modulated by cues predicting the presentation time of a memory set. Here, we recorded electroencephalography while 24 younger (18-33 years) and 23 older (60-77 years) adults completed a modified delay match-to-sample task where participants were cued to the duration of a memory set (0.1 s or 0.5 s). We found: (1) predictive cues increased WM storage; (2) no differences in preparatory alpha power between predictive and neutral cue types, but preparatory alpha suppression was weaker in older adults; (3) retention period oscillatory power differed between presentation times, but these differences were no longer present when comparing trial types from the onset of the memory set; and (4) oscillatory power in the preparatory and retention periods were unrelated to performance. Our results suggest that preparatory alpha power is not modulated by predictive cues towards presentation time, however, reductions in alpha/beta power during visual WM retention may be linked to encoding, rather than retention.

The longitudinal association between cognitive impairment and incident visual impairment in a multiethnic Asian population: a prospective cohort study.

BACKGROUND: The relationship between baseline cognitive impairment (CI) and incident visual impairment (VI) in Asians is unclear. OBJECTIVE: To determine the associations between baseline CI with incident VI and visual acuity (VA) at 6-year follow-up in multiethnic Asians. DESIGN: Cohort. SETTING: Population-based. SUBJECTS: Two thousand three hundred and twenty-four adults aged ≥60 years from the Singapore Epidemiology of Eye Diseases Study (response rate 64%). METHODS: CI was defined using the validated Abbreviated Mental Test (AMT). VA was objectively measured using a LogMAR chart. Any incident VI was defined as having no VI (Snellen's VA better than or equal to 20/40) at baseline but present (VA worse than 20/40) at 6-year follow-up. VI severity was defined according to the International Classification of Diseases, 11th Revision. Associations were assessed using logistic and linear regression models. RESULTS: Of the 2,324 participants, 248 had CI at baseline. Presence of baseline CI was associated with more than twice the odds of any incident VI, incident mild and moderate-severe VI (OR [95% confidence interval]: 2.48 [1.55-3.90], 2.07 [1.17-3.55], and 2.61 [1.36-4.93], respectively) and worse VA (ß [95% confidence interval]: 0.026 [0.006-0.046]) at 6-year follow-up. The leading causes of incident VI were cataract and under-corrected refractive error. CONCLUSIONS: Older adults with CI had more than double the odds of VI development and poorer VA than their cognitively intact counterparts, and most causes of incident VI were correctable. Strategies such as targeted vision screening and early intervention for early detection and management of vision loss in patients with cognitive decline are warranted.

Association between childhood friendship and cognitive ageing trajectory in later life: evidence from the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: Childhood experience has been suggested to affect cognitive function in later life. However, the association between childhood friendship status and cognitive ageing trajectory in middle-aged and older adults has not been fully assessed. This study examined the association between childhood friendship status and cognitive ageing trajectory and identified factors modifying this association. METHODS: We used four waves of data from the China Health and Retirement Longitudinal Study (CHARLS), a national representative longitudinal study of adults aged 45 years or older, 2011-2018. The CHARLS included surveys on childhood friendship and cognitive assessments. Childhood friendship status was categorised as poor, fair, and good. To examine the association between childhood friendship and cognitive ageing trajectory in later life, we applied multilevel linear regression models, and explored potential influences of sociodemographic factors, health status and behaviours, and childhood conditions on this association. RESULTS: Of the 4,350 participants, 1,919 (44.1%) were women. The mean age was 56.29 ± 7.80 years. We found childhood friendship was significantly associated with cognitive ageing trajectory in later life, with a dose-response relationship. After adjusting for covariates, comparing to participants with poor childhood friendships, those with better childhood friendships had lower rates of cognitive decline (ß = 0.12, 95% confidence interval [CI]: 0.03 to 0.22 [interaction term of fair friendship and time]; ß = 0.19, 95% CI: 0.10 to 0.28 [interaction term of good friendship and time]) and higher level of cognitive functions (ß = 0.40, 95% CI: 0.22 to 0.58 [fair friendships]; ß = 0.61, 95% CI: 0.43 to 0.79 [good friendships]). These associations were stronger for those who were female, less educated, and had experienced more adverse childhood experiences. CONCLUSIONS: Childhood friendship is associated with cognitive ageing in later life. Enhancing childhood friendships can play an important role to promote healthy ageing in the future.

Increased habitual flavonoid intake predicts attenuation of cognitive ageing in twins.

BACKGROUND: Although the pathophysiology of cognitive decline is multifactorial, and modifiable by lifestyle, the evidence for the role of diet on cognitive function is still accumulating, particularly the potentially preventive role of constituents of plant-based foods. METHODS: We aimed to determine whether higher habitual intake of dietary flavonoids, key components of plant-based diets, were associated with improved cognition and medial temporal lobe volumes using three complementary approaches (longitudinal, cross-sectional and co-twin analyses). In 1126 female twins (n=224 with a 10-year follow-up of diet and cognition data) aged 18-89 years, habitual intakes of total flavonoids and seven subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymeric flavonoids (and proanthocyanidins separately)) were calculated using validated food frequency questionnaires. Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery test. Hippocampal volumes were measured in a subset using magnetic resonance imaging (16 monozygotic-twin pairs). Statistical models were adjusted for a range of diet and lifestyle factors. RESULTS: Higher intakes of flavanones (tertile (T)3-T1=0.45, 95%CI 0.13,0.77; p=0.01) and anthocyanins (T3-T1=0.45, 95%CI 0.08,0.81; p=0.02) were associated with improvements in age-related cognition score over 10 years. In cross-sectional analysis higher intake of flavanones (T3-T1= 0.12, 95% CI 0.02, 0.21; p=0.02) and proanthocyanidins (T3-T1= 0.13, 95% CI 0.02, 0.24; p=0.02) were associated with improved paired-associates learning. Higher intake of anthocyanins was significantly associated with improved executive function (T3-T1= -0.52, 95% CI 0.19, 0.84; p=0.001) and with faster simple reaction times (T3-T1= -18.1, 95% CI -35.4, -0.7; p=0.04). In co-twin analysis, those with higher anthocyanin (2.0%, p=0.01) and proanthocyanidin (2.0%, p=0.02) intakes at baseline had the largest left hippocampal volumes after 12 years. CONCLUSION: Small increases in habitual intake of flavonoid-rich foods (containing anthocyanins, flavanones and proanthocyanidins; equivalent to approximately two servings of oranges and blueberries per day) over long time periods have the potential to attenuate cognitive ageing.

Cognitive ageing is premature among a community sample of optimally treated people living with HIV.

OBJECTIVES: Evidence of premature cognitive ageing amongst people living with HIV (PLHIV) remains controversial due to previous research limitations including underpowered studies, samples with suboptimal antiretroviral access, varying rate of virological control, high rate of AIDS, over-representation of non-community samples, and inclusion of inappropriate controls. The current study addresses these limitations, while also considering mental health and non-HIV comorbidity burden to determine whether PLHIV showed premature cognitive ageing compared with closely comparable HIV-negative controls. METHODS: This study enrolled 254 PLHIV [92% on antiretroviral therapy; 84% with HIV RNA < 50 copies/mL; 15% with AIDS) and 72 HIV-negative gay and bisexual men [mean (SD) age = 49 (10.2) years] from a single primary care clinic in Sydney, Australia. Neurocognitive function was evaluated with the Cogstate Computerized Battery (CCB) at baseline and 6 months after. Linear mixed-effects (LME) models examined main and interaction effects of HIV status and chronological age on the CCB demographically uncorrected global neurocognitive z-score (GZS), adjusting for repeated testing, and then adjusting sequentially for HIV disease markers, mental health and comorbidities. RESULTS: HIV status and age interacted with a lower GZS (ß = -0.43, P < 0.05). Higher level of anxiety symptoms (ß = -0.11, P < 0.01), historical AIDS (ß = -0.12, P < 0.05) and historical HIV brain involvement (ß = -0.12, P < 0.05) were associated with lower GZS. CONCLUSIONS: We found a robust medium-sized premature ageing effect on cognition in a community sample with optimal HIV care. Our study supports routine screening of cognitive and mental health among PLHIV aged ≥ 50 years.

Role of cardiometabolic risk in the association between accumulation of affective symptoms across adulthood and mid-life cognitive function: national cohort study.

BACKGROUND: Affective symptoms are associated with cognition in mid-life and later life. However, the role of cardiometabolic risk in this association has not been previously examined. AIMS: To investigate how cardiometabolic risk contributes to associations between affective symptoms and mid-life cognition. METHOD: Data were used from the National Child Development Study (NCDS), a sample of people born in Britain during one week in 1958. Measures of immediate and delayed memory, verbal fluency and information processing speed and accuracy were available at age 50. Affective symptoms were assessed at ages 23, 33 and 42 years and a measure of accumulation was derived. A cardiometabolic risk score was calculated from nine cardiometabolic biomarkers at age 44. Path models were run to test these associations, adjusting for sex, education, socioeconomic position and affective symptoms at age 50. RESULTS: After accounting for missing data using multiple imputation, path models indicated significant indirect associations between affective symptoms and mid-life immediate memory (ß = -0.002, s.e. = 0.001, P = 0.009), delayed memory (ß = -0.002, s.e. = 0.001, P = 0.02) and verbal fluency (ß = -0.002, s.e. = 0.001, P = 0.045) through cardiometabolic risk. CONCLUSIONS: These findings suggest that cardiometabolic risk may play an important role in the association between affective symptoms and cognitive function (memory and verbal fluency). Results contribute to understanding of biological mechanisms underlying associations between affective symptoms and cognitive ageing, which can have implications for early detection of, and intervention for, those at risk of poorer cognitive outcomes.

Aggregation of Abnormal Memory Scores and Risk of Incident Alzheimer's Disease Dementia: A Measure of Objective Memory Impairment in Amnestic Mild Cognitive Impairment.

OBJECTIVES: The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer's disease (AD) dementia. METHODS: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ -1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years. RESULTS: Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81-.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40-2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status. CONCLUSIONS: Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.

Age-Related Decline in the Topological Efficiency of the Brain Structural Connectome and Cognitive Aging.

Brain disconnection model has been proposed as a possible neural mechanism for cognitive aging. However, the relationship between structural connectivity degeneration and cognitive decline with normal aging remains unclear. In the present study, using diffusion MRI and tractography techniques, we report graph theory-based analyses of the brain structural connectome in a cross-sectional, community-based cohort of 633 cognitively healthy elderly individuals. Comprehensive neuropsychological assessment of the elderly subjects was performed. The association between age, brain structural connectome, and cognition across elderly individuals was examined. We found that the topological efficiency, modularity, and hub integration of the brain structural connectome exhibited a significant decline with normal aging, especially in the frontal, parietal, and superior temporal regions. Importantly, network efficiency was positively correlated with attention and executive function in elderly subjects and had a significant mediation effect on the age-related decline in these cognitive functions. Moreover, nodal efficiency of the brain structural connectome showed good performance for the prediction of attention and executive function in elderly individuals. Together, our findings revealed topological alterations of the brain structural connectome with normal aging, which provides possible structural substrates underlying cognitive aging and sensitive imaging markers for the individual prediction of cognitive functions in elderly subjects.

The effect of opioids on the cognitive function of older adults: results from the Personality and Total Health through life study.

BACKGROUND: chronic pain, a common complaint among older adults, affects physical and mental well-being. While opioid use for pain management has increased over the years, pain management in older adults remains challenging, due to potential severe adverse effects of opioids in this population. OBJECTIVE: we examined the association between opioid use, and changes in cognitive function of older adults. DESIGN: prospective study. SETTING: community dwelling older adults. SUBJECTS: study population consisted of 2,222 individuals aged 65-69 years at baseline from the Personality and Total Health Through Life Study in Australia. METHODS: medication data were obtained from the Pharmaceutical Benefits Scheme. Cognitive measures were obtained from neuropsychological battery assessment. Opioid exposure was quantified as Total Morphine Equivalent Dose (MED). The association between change in cognitive function between Wave 2 and Wave 3, and cumulative opioid use was assessed through generalized linear models. RESULTS: cumulative opioid exposure exceeding total MED of 2,940 was significantly associated with poorer performance in the Mini Mental State Examination (MMSE). Compared with those not on opioids, individuals exposed to opioids resulting in cumulative total MED of greater than 2,940 had significantly lower scores in the MMSE (Model 1: ß = -0.34, Model 2: ß = -0.35 and Model 3: ß = -0.39, P < 0.01). Performance in other cognitive assessments was not associated with opioid use. CONCLUSION: prolonged opioid use in older adults can affect cognitive function, further encouraging the need for alternative pain management strategies in this population. Pain management options should not adversely affect healthy ageing trajectories and cognitive health.

Frailty-a risk factor of global and domain-specific cognitive decline among a nationally representative sample of community-dwelling older adult U.S. Medicare beneficiaries.

OBJECTIVES: frail older adults may be more vulnerable to stressors, resulting in steeper declines in cognitive function. Whether the frailty-cognition link differs by cognitive domain remains unclear; however, it could lend insight into underlying mechanisms. METHODS: we tested whether domain-specific cognitive trajectories (clock-drawing test, (CDT), immediate and delayed recall, orientation to date, time, president and vice-president naming) measured annually (2011-2016) differ by baseline frailty (physical frailty phenotype) in the National Health and Aging Trends Study (n = 7,439), a nationally representative sample of older adult U.S. Medicare beneficiaries, using mixed effects models to describe repeated measures of each cognitive outcome. To determine if the association between frailty and subsequent cognitive change differed by education, we tested for interaction using the Wald test. RESULTS: we observed steeper declines for frail compared to non-frail participants in each domain-specific outcome, except for immediate recall. Largest differences in slope were observed for CDT (difference = -0.12 (standard deviations) SD/year, 95%CI: -0.15, -0.08). By 2016, mean CDT scores for frail participants were 1.8 SD below the mean (95%CI: -1.99, -1.67); for non-frail participants, scores were 0.8 SD below the mean (95%CI: -0.89, -0.69). Associations differed by education for global cognitive function (Pinteraction < 0.001) and for each domain-specific outcome: CDT (Pinteraction < 0.001), orientation (Pinteraction < 0.001), immediate (Pinteraction < 0.001) and delayed (Pinteraction < 0.001) word recalls. CONCLUSION: frailty is associated with lower levels and steeper declines in cognitive function, with strongest associations for executive function. These findings suggest that aetiologies are multifactorial, though primarily vascular related; further research into its association with dementia sub-types and related pathologies is critical.

Contribution of IQ in young adulthood to the associations of education and occupation with cognitive ability in older age.

BACKGROUND: Studies suggest that a higher education and occupation are each associated with a higher late-life cognitive ability, but their inter-relationships in their association with cognitive ability and the contribution of peak IQ in young adulthood ('pre-morbid IQ') often remain unclear. METHODS: Cross-sectional analysis of 623 participants aged ≥65 years of the BioCog study. Education was coded according to the International Standard Classification of Education (ISCED; range 1 to 6). Occupation was coded as 'semi/unskilled', 'skilled manual', 'skilled non-manual', 'managerial', 'professional'. A summary score of global ability ('g') was constructed from six cognitive tests. Pre-morbid IQ was estimated from vocabulary. The Geriatric Depression Scale assessed symptoms of depression. Age- and sex-adjusted analyses of covariance were performed. RESULTS: Education (partial eta2 0.076; p < 0.001) and occupation (partial eta2 = 0.037; p < 0.001) were each significantly associated with g. For education, the association was attenuated but remained statistically significant when pre-morbid IQ was controlled for (partial eta2 0.036; p < 0.001) and was unchanged with additional adjustment for depression (partial eta2 0.037; p < 0.001). For occupation, the association with g was no longer significant when pre-morbid IQ (partial eta2 = 0.015; p = 0.06) and depression (partial eta2 = 0.011; p = 0.18) were entered as covariates in separate steps. When education and occupation were entered concurrently into the fully adjusted model, only education was independently associated with g (partial eta2 0.030; p < 0.001; occupation, p = 0.93). CONCLUSION: While a higher education and a higher occupation were each associated with a higher late-life cognitive ability, only for education some unique contribution to cognitive ability remained over and above its relationship with pre-morbid IQ, depression, and occupation. Further research is needed to address whether a longer time spent in education may promote late-life cognitive ability.