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Introduction: Neuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or "irritative" network. Methods: Neuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups. Results: There were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment. Discussion: The findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.
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BACKGROUND: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long-term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA-H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA-H. METHODS: The current study investigated the performance of the MoCA-H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA-H. RESULTS: In a multiple regression model accounting for age, sex, and education, cultural-linguistic group accounted for 6.89% of variance in the total MoCA-H score. Differences between languages in mean score of up to 2.6 points were observed. CONCLUSIONS: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA-H such that optimal performance cut points for identification of cognitive impairment derived in English-speaking populations are likely inappropriate for use in non-English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA-H.
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BACKGROUND: Existing traditional cognitive screening tools for dementia have various limitations, including overreliance on tests assessing verbal memory and, to a lesser extent, on some aspects of executive functioning. Comprehensive neuropsychological assessment is sensitive to impairment but time-intensive and expensive. Virtual reality may provide a dynamic and unique understanding of cognitive performance and increase the ecological validity of cognitive assessment. The use of virtual reality in screening for cognitive function in older persons is promising, but evidence for its use remains sparse. OBJECTIVE: Our primary aim was to examine the feasibility and acceptability of a newly developed, virtual reality assessment module, 'Leaf Café', a computer-based program that assesses cognition in an engaging, efficient, and ecologically relevant way. The secondary aim was to assess the ability of the module to discriminate between performances of younger and older adults. METHODS: A cross-sectional study was carried out in Sydney, Australia, targeting adults aged 18 years and above. Participants completed a traditional cognitive screening tool (Telephone Interview for Cognitive Status-Modified, TICS-M) and Leaf Café, a low-immersive virtual reality module designed to evaluate learning and memory, perceptual-motor function, and executive functioning. The total performance score for each participant, ranging from 0 to 180, was correlated with their cognitive performance assessed by TICS-M, using Pearson's correlation coefficient. Following module completion, participants were presented with an open and closed-question survey to capture their perceptions, attitudes, and feedback on the module, encompassing practicality, acceptability, and enjoyment. Both descriptive and content analyses were employed to interpret the obtained data. RESULTS: A sample of 131 participants (mean age 54.9 years, SD = 20.8, range 20-85) took part. The majority were female (71.8%) and born in an English-speaking country (75.8%). The mean amount of time spent in the module was 32.8 min (SD = 13.3) with a mean module score of 107.6 (SD = 38.7). Most participants completed the highest level (5; 80.5%). There was a significant correlation between Leaf Café total scores with TICS-M cognitive scores overall, and for both younger (aged 18-64 years) and older adult (aged 65 + years) groups. No significant difference was found on performance between age groups on TICS-M performance, however, younger adults had significantly better performance on the Leaf Café module than older adults (M = 124.1 vs 95.9; p < .001). Participants had similar response proportions regarding user experience with most agreeing that the module was easy to use (84%) and to navigate (85%). Compared with younger adults, older adults had lower rates of agreement on the module's design (36.8% vs 64.3%; p = .020) and support experienced (20.5% vs 53.6%; p = .007). Participants highlighted the significance of practicality and the cognitive challenges presented by the module, in terms of memory strain and user interface concerns. Feedback encompassed different opinions on the usefulness of music, with suggestions for improvements centred around clearer instructions, varied game dynamics, and considerations for diverse user needs. CONCLUSIONS: Leaf Café is a feasible and acceptable tool to be used for screening for cognitive impairment in older adults and has real-world assessment value. Further verification on the game's utility in detecting cognitive impairment is required.
Subject(s)
Cognitive Dysfunction , Humans , Male , Female , Aged , Aged, 80 and over , Middle Aged , Cross-Sectional Studies , Feasibility Studies , Cognitive Dysfunction/diagnosis , Cognition/physiology , Neuropsychological TestsABSTRACT
OBJECTIVES: Hearing-related third-party disability is the transferrable impact of presbycusis on an affected individual's surrounding social network. Previous research suggests that interventions to overcome hearing-related communication challenges benefit both the individual with presbycusis and their communication partner. However, there have been no comparisons of the effects of different interventions on third-party disability. We conducted meta-analyses of hearing aid or communication-based longitudinal interventions to determine if: both kinds of interventions significantly benefit communication partners across three categories of third-party disability (communication, emotional health and lifestyle outcomes), hearing aid and communication interventions differ in the size of treatment effects, and demographic variables moderate intervention efficacy. DESIGN: Four databases were systematically searched for studies published after 1990 that included preintervention and postintervention data for communication partners of individuals receiving a hearing aid or communication-based intervention. Studies were included if participants had presbycusis, were aged 45 or over, with no known physical or mental disorders, and had a willing study partner over 18 years old. Databases were last comprehensively and hand-searched in January 2023. One researcher applied the inclusion and exclusion criteria to select studies and complete data extraction. Depending on study design, risk of bias was assessed using the "Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group" or the "Risk of Bias 2." Random effects models were run for effect sizes for both intervention types (together and separately) for each third-party disability category. Meta-regressions were run to inspect the effect of demographic variables on intervention efficacy. RESULTS: Six studies satisfied inclusion criteria and showed that for both hearing and communication interventions, communication partners experienced significant improvements in all three outcomes. Communication interventions showed greater benefits for lifestyle outcomes, but hearing aid and communication interventions did not differ for communication and emotional health outcomes. Meta-regressions revealed previously undetected relationships between demographic variables and intervention efficacy. CONCLUSIONS: The results of this meta-analysis and meta-regressions may have clinical and real-world implications in terms of highlighting the widespread benefits of these interventions, and the need to build in greater consideration of an individual's wider network when designing and implementing interventions. Noted limitations included certain combinations of intervention type and third-party disability category that were underrepresented (in absolute and/or relative terms), a lack of combined intervention (hearing aids and communication training) studies, and variation in the types of questionnaires used between studies. The current study discusses possible ways to unite the current literature for more consistent research practices.
Subject(s)
Presbycusis , Humans , Adolescent , Hearing Tests , Communication , Quality of Life , HearingABSTRACT
BACKGROUND: Frontal variant Alzheimer's disease (fvAD) is considered a rare form of Alzheimer's disease (AD) which may be misdiagnosed as behavioural variant frontotemporal dementia (bvFTD). The literature has tended to conflate behavioural and executive dysfunction in fvAD cohorts and uses both AD diagnostic criteria and bvFTD diagnostic criteria to classify fvAD cohorts. The primary aim of this narrative synthesis was to summarise neuropsychological findings in fvAD cohorts in the context of established AD pathology. METHODS: EMBASE, PsycINFO, PROQUEST and MEDLINE databases were searched for studies eligible for inclusion. Studies with both neuropsychological and biomarker evidence were included in the final narrative synthesis. RESULTS: Ten studies were reviewed, including samples totalling 342 fvAD participants, 178 typical AD participants and 250 bvFTD participants. The review revealed areas worthy of further investigation that may aid differential diagnosis, including the degree of executive dysfunction in fvAD cohorts relative to bvFTD cohorts, the onset of behavioural and cognitive symptomatology, and similarities between fvAD and typical AD cognitive profiles. CONCLUSION: There was insufficient neuropsychological evidence to clearly differentiate fvAD and bvFTD cognitive phenotypes, however, the review has highlighted distinctive features of the two disorders that may guide differential diagnosis in future research. Moreover, the review has highlighted issues involving disparate diagnostic criteria used to classify fvAD cohorts, contributing to variation in findings.
Subject(s)
Alzheimer Disease , Frontotemporal Dementia , Humans , Frontotemporal Dementia/diagnosis , Frontotemporal Dementia/psychologyABSTRACT
Episodic memory deficits are a common consequence of aging and are associated with a number of neurodegenerative disorders (e.g., Alzheimer's disease). Given the importance of episodic memory, a great deal of research has investigated how we can improve memory performance. Transcranial electrical stimulation (TES) represents a promising tool for memory enhancement but the optimal stimulation parameters that reliably boost memory are yet to be determined. In our double-blind, randomised, sham-controlled study, 42 healthy adults (36 females; 23.3 ± 7.7 years of age) received anodal transcranial direct current stimulation (tDCS), theta transcranial alternating current stimulation (tACS) and sham stimulation during a list-learning task, over three separate sessions. Stimulation was applied over the left temporal lobe, as encoding and recall of information is typically associated with mesial temporal lobe structures (e.g., the hippocampus and entorhinal cortex). We measured word recall within each stimulation session, as well as the average number of intrusion and repetition errors. In terms of word recall, participants recalled fewer words during tDCS and tACS, compared to sham stimulation, and significantly fewer words recalled during tACS compared with tDCS. Significantly more memory errors were also made during tACS compared with sham stimulation. Overall, our findings suggest that TES has a deleterious effect on memory processes when applied to the left temporal lobe.
Subject(s)
Memory, Episodic , Transcranial Direct Current Stimulation , Adult , Female , Humans , Prefrontal Cortex/physiology , Learning/physiology , Mental Recall/physiologyABSTRACT
INTRODUCTION: Behaviour change interventions represent key means for supporting healthy ageing and reducing dementia risk yet brief, scalable behaviour change interventions targeting dementia risk reduction in older adults is currently lacking. Here we describe the aims and design of the three-month Brain Bootcamp initiative that seeks to target multiple dementia risk and protective factors (healthy eating, physical, social and cognitive inactivity), through the use of multiple behaviour change techniques, including goal-setting for behaviour, information about health consequences and physical prompts to change behaviours that reduce dementia risk among older adults. Our secondary aim is to understand participants' views of dementia prevention and explore the acceptability and integration of this campaign into daily life. METHODS: Brain Bootcamp is a pre-post feasibility trial conducted in Sydney, Australia beginning in January 2021 until late August. Participants aged ≥65 years living independently in the community (n = 252), recruited through social media and flyers, will provide information about their demographics, medical history, alcohol consumption, smoking habits, mental health, physical activity, cognitive activity, and diet to generate a dementia risk profile at baseline and assess change therein at three-month follow-up. During the intervention, participants will receive a resource pack containing their individual risk profile, educational booklet on dementia risk factors and four physical items designed to prompt physical, social and mental activity, and better nutrition. Outcome measures include change in dementia risk scores, dementia awareness and motivation. A qualitative process evaluation will interview a sample of participants on the acceptability and feasibility of the intervention. DISCUSSION: This will be the first short-term multi-domain intervention targeting dementia risk reduction in older adults. Findings will generate a new evidence base on how to best support efforts targeting lifestyle changes and to identify ways to optimise acceptability and effectiveness towards brain health for older adults. TRIAL REGISTRATION NUMBER: ACTRN 381046 (registered 17/02/2021); Pre-results.
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Dementia , Healthy Aging , Aged , Humans , Brain , Dementia/prevention & control , Feasibility Studies , HabitsABSTRACT
People live and age together in social groups. Across a range of outcomes, research has identified interdependence in the cognitive and health trajectories of ageing couples. Various types of memory decline with age and people report using a range of internal and external, social, and material strategies to compensate for these declines. While memory compensation strategies have been widely studied, research so far has focused only on single individuals. We examined interdependence in the memory compensation strategies reported by spouses within 58 older couples. Couples completed the Memory Compensation Questionnaire, as well as an open-ended interview about their memory compensation practices. We found that internal, intra-individual memory compensation strategies were not associated within couples, but external, extra-individual strategies showed interdependence. Individuals' scores on material/technological compensation strategies were positively correlated with their partners'. Reported reliance on a spouse was higher for men and increased with age. Our open-ended interviews yielded rich insights into the complex and diverse resources that couples use to support memory in day-to-day life. Particularly evident was the extent of interaction and coordination between social and material compensation, such that couples jointly used external compensation resources. Our results suggest that individuals' reports of their compensation strategies do not tell the whole story. Rather, we propose that older couples show interdependence in their memory compensation strategies, and adopt complex systems of integrated material and social memory compensation in their day-to-day lives.
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Introduction: High blood pressure in midlife is an established risk factor for cognitive decline and dementia but less is known about the impact of raised blood pressure on cognition in childhood and early adulthood. Method: We systematically reviewed and quantified the existing evidence base relating to blood pressure in early life and subsequent cognitive performance. Medline, Embase, PsycINFOo, Scopus, and Web of Science were searched from inception to July 2020. We included longitudinal cohort and case-control studies involving participants aged 0-40 years with a baseline and at least one follow-up blood pressure assessment alongside at least one measure of cognition, occurring at the same time as, or subsequent to blood pressure measures. Risk of bias was assessed independently by two reviewers. PROSPERO registration CRD42020214655. Results: Of a total of 5638 records identified, three cohort and two case-control studies were included with ages ranging from 3 to early 30s. Repeated blood pressure measurements averaged over 25 years or cumulative blood pressure in the 25-30 years prior to assessment of cognitive function were associated with poorer cognitive performance in the two largest cohort studies. The smallest cohort study reported no evidence of an association and the results from the two case-control studies were contradictory. All studies were at risk of bias. Conclusion: Overall, the evidence in this area is lacking and study quality is mixed. Our review highlights an urgent need for studies evaluating the potential for a relationship between raised blood pressure and poorer cognition in early life given the potential for possible risk reduction if such a relationship exists.
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Addressing midlife hearing loss could prevent up to 9% of new cases of dementia, the highest of any potentially modifiable risk factor identified in the 2017 commissioned report in The Lancet. In Australia, hearing loss is the second-most common chronic health condition in older people, affecting 74% of people aged over 70. Estimates indicate that people with severe hearing loss are up to 5-times more likely to develop dementia, but these estimates vary between studies due to methodological limitations. Using data from the Sydney Memory and Aging Study, in which 1,037 Australian men and women aged between 70 and 90 years were enrolled and completed biennial assessments from 2005-2017, investigations between hearing loss and baseline cognitive performance as well as longitudinal risk of neurocognitive disorder were undertaken. Individuals who reported moderate-to-severe hearing difficulties had poorer cognitive performances in the domains of Attention/Processing Speed and Visuospatial Ability, and on an overall index of Global Cognition, and had a 1.5-times greater risk for the neurocognitive disorder during 6-years' follow-up. Hearing loss independently predicted risk for MCI but not dementia. The presence of hearing loss is an important consideration for neuropsychological case formulation in older adults with cognitive impairment. Hearing loss may increase cognitive load, resulting in observable cognitive impairment on neuropsychological testing. Individuals with hearing loss who demonstrate impairment in non-amnestic domains may experience benefits from the provision of hearing devices; This study provides support for a randomized control trial of hearing devices for improvement of cognitive function in this group.
Subject(s)
Cognitive Dysfunction , Dementia , Hearing Loss , Aged , Aged, 80 and over , Australia , Cognition , Cohort Studies , Female , Hearing Loss/epidemiology , Hearing Loss/psychology , Humans , Longitudinal Studies , Male , Neuropsychological TestsABSTRACT
Nonverbal memory tests have great potential value for detecting the impact of lateralized pathology and predicting the risk of memory loss following right temporal lobe resection (TLR) for temporal lobe epilepsy (TLE) patients, but this potential has not been realized. Previous reviews suggest that stimulus type moderates the capacity of nonverbal memory tests to detect right-lateralized pathology (i.e., faces > designs), but the roles of other task-related factors have not been systematically explored. We address these limitations using mixed model meta-regression (k = 158) of right-lateralization effects (right worse than left TLE) testing the moderating effects of: 1) stimulus type (designs, faces, spatial), 2) learning format (single trial, repeated trials), 3) testing delay (immediate or long delay), and 4) testing format (recall, recognition) for three patient scenarios: 1) presurgical, 2) postsurgical, and 3) postsurgical change. For presurgical patients the size of the right-lateralization effect was significantly moderated by stimulus type (faces > designs), testing format (recall > recognition) and its interaction with the learning format (repeated trials more affected by format effect than single trials) of the nonverbal memory tests. For postsurgical patients and presurgical-postsurgical change, test format moderated the size of the right-lateralization effect (recognition > recall) and this explained and overshadowed effects of stimulus type (i.e., faces > designs). This comprehensive review reveals the value of recognition testing in gauging the risk of nonverbal memory decline.
Subject(s)
Epilepsy, Temporal Lobe , Epilepsy , Epilepsy, Temporal Lobe/diagnosis , Epilepsy, Temporal Lobe/pathology , Epilepsy, Temporal Lobe/surgery , Functional Laterality , Humans , Magnetic Resonance Imaging , Memory Disorders , Neuropsychological Tests , Temporal Lobe/pathologyABSTRACT
To improve understanding of Alzheimer's disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such datasets makes this a non-trivial task. Here, a machine learning approach was applied to impute longitudinal neuropsychological test scores across two observational studies, namely the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) providing an overall harmonised dataset. MissForest, a machine learning algorithm, capitalises on the underlying structure and relationships of data to impute test scores not measured in one study aligning it to the other study. Results demonstrated that simulated missing values from one dataset could be accurately imputed, and that imputation of actual missing data in one dataset showed comparable discrimination (p < 0.001) for clinical classification to measured data in the other dataset. Further, the increased power of the overall harmonised dataset was demonstrated by observing a significant association between CVLT-II test scores (imputed for ADNI) with PET Amyloid-ß in MCI APOE-ε4 homozygotes in the imputed data (N = 65) but not for the original AIBL dataset (N = 11). These results suggest that MissForest can provide a practical solution for data harmonization using imputation across studies to improve power for more nuanced analyses.
Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Cognition , Neuroimaging , Aged , Aged, 80 and over , Algorithms , Alzheimer Disease/complications , Alzheimer Disease/etiology , Amyloid beta-Peptides/metabolism , Australia , Biomarkers , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Computational Biology/methods , Data Analysis , Female , Humans , Longitudinal Studies , Male , Neuroimaging/methods , Positron-Emission Tomography , Reproducibility of ResultsABSTRACT
BACKGROUND: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer's disease dementia (AD)) as an 'Inception cohort' who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an 'Enrichment cohort' (as of 10 April 2019). OBJECTIVE: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. METHODS: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. RESULTS: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aß-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. CONCLUSION: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.
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BACKGROUND: Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable. OBJECTIVE: Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years. METHODS: Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed by a discovery phase analyses of additional regions. SCPs were aged 70â+âat baseline, scoring at/above normative memory (CVLT-II) levels for demographically similar individuals aged 30-44 years old, and in the unimpaired range for all other cognitive domains over the course of the study. RESULTS: In linear mixed models, following adjustment for multiple comparisons, there were no significant differences between rates of thinning or volume atrophy between SCPs and TOAs in previously identified ROIs, or the discovery phase analyses. With only amyloid-ß negative individuals in the analyses, again there were no significant differences between SCPs and TOAs. CONCLUSION: The increased methodological rigor in classifying groups, together with the influence of cognitive reserve, are discussed as potential factors accounting for our findings as compared to the extant literature on those with superior cognitive performance for their age.
Subject(s)
Aging/pathology , Atrophy/pathology , Brain Cortical Thickness , Cerebral Cortex/pathology , Cognition/physiology , Aged , Aged, 80 and over , Aging/psychology , Atrophy/diagnostic imaging , Atrophy/psychology , Cerebral Cortex/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Organ Size/physiologyABSTRACT
. BACKGROUND: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. OBJECTIVE: The aim of this study was to assess whether the association was present in cognitively normal older adults. METHODS: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. RESULTS: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) É4 and rs11023139 in individuals with high amyloid-ß burden. APOE É4/rs11023139-A carriers declined significantly faster than APOE É4/rs11023139-G_G carriers in measures of global cognition (pâ=â0.011) and verbal episodic memory (pâ=â0.020). CONCLUSION: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE É4 cognitively normal older adults with a high neocortical amyloid-ß burden.
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Age-related decrease in testosterone levels is a potential risk factor for cognitive decline in older men. However, observational studies and clinical trials have reported inconsistent results on the effects of testosterone on individual cognitive domains. Null findings may be attributed to factors that studies have yet to consider. In particular, individual variations in polyglutamine (CAG) length in the androgen receptor (AR) gene could alter androgenic activity in brain regions associated with cognitive processes including memory and executive functions. However, the role of AR CAG repeat length as a moderator of the relationship between testosterone levels and cognition has not been investigated. Therefore, we aimed to examine the relationship between baseline calculated free testosterone (cFT) levels, change in cFT levels over 18 months and CAG repeat length on cognitive performance in memory, executive function, language, attention and processing speed domains. These relationships were examined in 304 cognitively normal older male participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. In the attention and processing speed domain, a short CAG repeat length appears to exacerbate the effects of low baseline cFT levels that are also lower than expected at follow-up. These results highlight that individual variations in AR CAG repeat length should be considered in future studies and clinical trials that examine the complex relationship between testosterone and cognition.
Subject(s)
Receptors, Androgen , Trinucleotide Repeats , Aged , Australia , Cognition , Humans , Male , Receptors, Androgen/genetics , Testosterone , Trinucleotide Repeats/geneticsABSTRACT
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.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Aged , Alzheimer Disease/complications , Australia , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Disease Progression , Humans , Neuropsychological TestsABSTRACT
We examined whether mesial temporal (Me) tau relates to cognitive performance in 47 amyloid-ß (Aß)-negative, cognitively normal older adults (>60 years old). Me-tau was measured using [18F]flortaucipir-positron emission tomography standardized uptake value ratio. The effect of continuous and categorical (stratified at standardized uptake value ratio = 1.2 [21% Me-positive]) Me-tau on cognition (mini-mental state examination, pre-Alzheimer's cognitive composite, a memory composite, and a nonmemory composite score) was examined using general linear models, and associations between Me-tau and [18F]flortaucipir signal in the neocortex were assessed using voxelwise regressions (continuous) and voxelwise contrasts (categorical). In addition, we assessed the effect of age and Aß burden on Me-tau. Both continuous and categorical Me-tau was associated with worse cognitive performance across all tests and with higher lateral temporal and parietal [18F]flortaucipir signal. Furthermore, we observed a marginal association between Me-tau and age, whereas there was no association with Aß burden. Our findings indicate that Me-tau in Aß-negative cognitively normal individuals, which is likely age-related (i.e., primary age-related tauopathy), might not be as benign as commonly thought.
Subject(s)
Aging/metabolism , Aging/psychology , Cognition/physiology , Neocortex/metabolism , tau Proteins/metabolism , Aged , Amyloid beta-Peptides/metabolism , Carbolines , Female , Humans , Male , Mental Status and Dementia Tests , Positron-Emission Tomography , RadiopharmaceuticalsABSTRACT
OBJECTIVES: This cross-sectional study aimed to investigate the acceptability and usability of the Cogstate Brief Battery (CBB) in a community-based sample of Australian Indigenous people from the Torres Strait region, based on a user experience framework of human-computer interaction. METHODS: Two-hundred community participants completed the four subtests of the CBB on an iPad platform, during a free adult health check on two islands in the region, between October and December 2016. Acceptability was defined as completing the learning trial of a task and usability as continuing a task through to completion, determined by examiner acumen and internal Cogstate completion and integrity criteria. These were combined into a single dichotomous completion measure for logistic regression analyses. Performance-measured as reaction times and accuracy of responses-was analyzed using linear regression analyses. RESULTS: CBB completion ranged from 82.0% to 91.5% across the four tasks and the odds of completing decreased with age. After adjusting for age, iPad/tablet familiarity increased the odds of completion for all tasks while level of education and employment increased the odds for some tasks only. These variables accounted for 18.0%-23.8% of the variance in reaction times on speeded tasks. Age and education had the most effect, although semipartial correlations were modest. CONCLUSIONS: When administered in a health-screening context, the acceptability and usability of the CBB were greatest in young- to middle-aged participants with some education and iPad/tablet experience. Older and more vulnerable participants may have benefited from additional time and practice on the CBB prior to administration.