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Introduction Subjective cognitive decline (SCD) manifesting before clinical impairment could serve as a target population for early intervention trials in Alzheimer's disease (AD). A working group, the Subjective Cognitive Decline Initiative (SCD-I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed. Methods Members of the SCD-I met to identify and agree on topics relevant to SCD criteria operationalization in research settings. Initial ideas and recommendations were discussed with other SCD-I working group members and modified accordingly. Results Topics included SCD inclusion and exclusion criteria, together with the informant's role in defining SCD presence and the impact of demographic factors. Discussion Recommendations for the operationalization of SCD in differing research settings, with the aim of harmonization of SCD measurement across studies are proposed, to enhance comparability and generalizability across studies. [ABSTRACT FROM AUTHOR]

Background: We examined relationships between cerebral amyloid-beta (Aβ) and cognitive-gait dual-task performance in 27 cognitively normal, mobility unimpaired elders. Methods: We assessed Aβ on Pittsburgh Compound B (PiB)-PET. We measured gait speed separately and while performing working-memory, response-inhibition, motor-sequencing, and phone-dialing tasks. We compared dual-task costs on gait and cognitive performance in high-Aβ (PiB(+)) and low-Aβ (PiB(-)) groups and examined the association between Aβ and dual-task performance decrements. Results: PiB(+) (n = 16) were comparable with the PiB(-) (n = 11) individuals on demographics, general cognitive and physical performance, and key brain MRI characteristics. PiB(+) group demonstrated greater dual-task costs on gait speed on all cognitive tasks (p < .05) except on response inhibition. Dual-task costs on cognition were similar between groups. Overall, Aβ was associated with dual-task decrement on gait speed but not on dual-task decrement on cognitive performance. Conclusions: Preliminary evidence indicates that cerebral Aβ is associated with gait slowing on dual-tasking in healthy older adults. [ABSTRACT FROM AUTHOR]

Background: In many developed countries, cognitive functioning (as measured by neuropsychological tests) appears to be improving over time in the population at large, in parallel with the declining age-specific incidence of dementia. Here, we investigated cohort effects in the age-associated trajectories of verbal memory function in older adults. We sought to determine whether they varied by decade of birth and, if so, whether the change would be explained by increasing educational attainment.Methods: Pooling data from two prospective US population-based studies between 1987 and 2015, we identified four birth cohorts born 1902-1911, 1912-1921, 1922-1931, and 1932-1943. Among these cohorts, we compared age-associated trajectories both of performance and of practice effects on immediate and delayed recall of a 10-item Word List. We used mixed effects models, first including birth cohorts and cohort X age interaction terms, and then controlling for education and education X age interaction.Results: We observed significant cohort effects in performance (baseline and age-associated trajectories) in both immediate recall and delayed recall, with function improving between the earliest- and latest-born cohorts. For both tests, we also observed cohort effects on practice effects with the highest levels in the latest-born cohorts. Including education in the models did not attenuate these effects.Conclusions: In this longitudinal population study, across four decade-long birth cohorts, there were significant improvements in test performance and practice effects in verbal memory tests, not explained by education. Whether this reflects declining disease incidence or other secular trends awaits further investigation. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationships over time between dual trajectories of depressive symptoms and several cognitive domains.Methods: In a 5-year longitudinal study, 1,978 randomly selected individuals aged 65+ years at recruitment were assessed annually. Repeated measures were of depressive symptoms on the modified Center for Epidemiologic Studies Depression Scale and composite scores in the cognitive domains of attention, executive function, memory, language, and visuospatial function. Latent class trajectories were identified for depression and for each cognitive domain and their associations investigated using dual trajectory modeling. Cognitive trajectories with z scores below -1 were designated as persistently low.Results: Five depressive symptom trajectories were observed: rarely depressed (60.5%); low-grade, decreasing symptoms (18.5%); low-grade, increasing symptoms (9.6%); moderate-grade symptoms (7.4%); and consistent higher-grade symptoms (4.0%). For each cognitive domain six trajectories were observed. The rarely depressed and low-grade decreasing symptom groups were the least likely to have persistently low cognition. The symptom trajectory most strongly associated with persistently low functioning in each domain was not the higher-grade group but rather the low-grade increasing group in the case of attention and the moderate-grade trajectory in the other four domains.Conclusion: Consistently higher-grade depressive symptoms are less strongly associated with poor cognitive functioning than with either moderate- or low-grade increasing depressive symptom trajectories, over time and across different domains. Examining both depression and cognition longitudinally allows heterogeneity of both to be addressed, revealing latent groups with potential diagnostic and prognostic implications. [ABSTRACT FROM AUTHOR]

Social cognition is the cognitive domain that processes social information, the means by which we make sense of ourselves in relation to others and our environments. Impaired social cognition is associated with functional dependence on others and can have dire social consequences leading to social isolation, increasing the risk for morbidity and mortality. Social cognition is be impaired in neurodegenerative disorders including Alzheimer's disease (AD). The most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) include social cognition as one of six core domains of neurocognitive function, alongside memory, executive control, complex attention, language, and visuospatial/perceptuomotor function, that can be impaired in the neurocognitive disorders. We have previously reported population-based norms from older adults on two social cognition measures, the Social Norms Questionnaire [SNQ-22], assessing social perception, and the 10-question version of the Reading the Mind in the Eyes Test [RMET-10], measuring Theory of Mind (ToM). Here, we report on the utility of a social cognition composite measure comprising the SNQ-22 and the RMET-10. Participants are 902 adults from a population-based cohort in Pennsylvania. The mean age is 76.6 years (SD 8.06). We created a social cognition composite comprising standardized z-scores on the Social Norms Questionnaire and the 10-item Reading the Mind in the Eyes Test. We described its distribution in the population-based sample of older adults, its association with demographic factors, other cognitive and behavioral measures, the Clinical Dementia Rating (CDR®). We compared sensitivity, specificity, and the area under the curve of social cognition to those of other cognitive domains for mild cognitive impairment (MCI). We calculated the impact of including social cognition as a sixth cognitive domain on the estimated prevalence of (cohort proportion classified as) neuropsychologically defined MCI. Better social cognition was associated with younger age, female sex, higher education, better general cognition (MMSE), fewer depressive symptoms, and lower Clinical Dementia Rating (CDR). Adjusting for demographics, associations with higher MMSE and fewer depressive symptoms, anxiety symptoms, and subjective cognitive complaints remained significant. The sensitivity and specificity of social cognition for CDR = 0.5 were comparable to those of the traditional five cognitive domains. Including social cognition as the sixth domain of cognition resulted in a 5% increase in the estimated prevalence of MCI. Better social cognition was associated with younger age, female sex, higher education, better general cognition (MMSE), fewer depressive symptoms, and lower Clinical Dementia Rating (CDR). Adjusting for demographics, associations with higher MMSE and fewer depressive symptoms, anxiety symptoms, and subjective cognitive complaints remained significant. We found that social cognition had sensitivity, specificity for CDR that was comparable to those of the five conventional cognitive domains of attention, executive functions, language, memory, and visuospatial function. The AUC values in the 0.6 – 0.7 range, which were comparable to the reported values in the literature. Considering neuropsychologically defined MCI, the inclusion of social cognition as the sixth domain of cognition resulted in about 5% of the sample becoming newly classified as MCI. These individuals differed from those already classified as MCI only in having higher MMSE scores; but they differed from those still classified as normal in having more anxiety symptoms, lower reading levels, and impairment in the CDR domain of home and hobbies. It appears a worthwhile consideration for standard cognitive assessments in older adults to routinely include brief objective assessments of the social cognition domain. The word reported here was supported in part by research grant # R37AG023657 from the National Institute on Aging, National Institutes of Health, US Department of Health and Human Services. [ABSTRACT FROM AUTHOR]

The article discusses a study on the relationship between subjective cognitive complaints (SCC) and amyloid-beta deposition relative to the personality traits of older individuals with normal cognition. Topics covered include the use of the Memory Functioning Questionnaire General Frequency of Forgetting factor as a predictor for Alzheimer's Disease, the link between neuroticism and conscientiousness in SCC and risk for dementia, and education as not associated in any variable.

Background: Incident dementia increases with age and is associated with amyloid deposition. There is little knowledge about the progression of amyloid deposition in non‐demented individuals age 80+. The purpose of this study was to determine the relationship between changes in amyloid deposition over time and incident dementia in non‐demented individuals followed for a period of 11 years. Methods: We examined a group of elderly participants (baseline age: 85.86 + 2.84) who had clinical evaluations from 2009 to 2020 and up to 5 measurements of Pittsburgh compound‐B (PiB)‐PET. 94 participants had two PiB‐PET scans, 76 three, 18 four, and 10 five. Mean age was 95 at 2020, at which time 49% of the participants with two or more scans developed dementia and 61% were deceased. Results: There was a gradual increase in amyloid deposition in all participants whether they were considered amyloid positive or negative at baseline. Time to dementia in baseline amyloid negative participants was 7.09 + 2.90 years (range 2.92 – 11.22), and in amyloid positive participants 5.6 + 2.10 (range 2.27 – 9.67). Baseline amyloid deposition was a significant predictor of increase deposition over time. In a Cox model controlled for age, sex, education level, APOE‐4 allele, mortality, and baseline MMSE, change in amyloid deposition from 2009 to 2010‐11 was not significantly associated with incident dementia (HR 2.19 (0.41‐11.73). Baseline continuous measures of amyloid deposition, cortical thickness and white matter lesions (WMLs) were strong predictors of dementia. Approximately 70% of the participants who converted to dementia had either significant amyloid deposition (SUVR ≥1.67), cortical thickness, or WMLs positivity at baseline. Conclusions: There was a substantial and steady amyloid deposition in this age group. There were very few (10%) participants who developed dementia without being amyloid positive. Individuals classified as amyloid negative at baseline became incident amyloid positive (SUVR > 1.67) prior to the dementia diagnosis, and most individuals who were amyloid positive at baseline developed dementia, especially when neurodegeneration was present. [ABSTRACT FROM AUTHOR]

Background: The APOE 2/3/4 polymorphism is the greatest risk factor for Alzheimer's disease (AD). This polymorphism is also associated with variation in plasma ApoE levels and explains about 20‐25% of its genetic variance; while APOE*4 lowers, APOE*2 increases ApoE levels. Lower plasma ApoE levels have also been reported to be a risk factor of future AD and all dementia, independent of the APOE 2/3/4 polymorphism (Ann Neurol 2015;77:301). To our knowledge, no genome‐wide association study (GWAS) has been reported on plasma ApoE levels. This study was aimed to identify novel genetic factors affecting plasma ApoE levels as well as to confirm if baseline plasma ApoE levels predict future AD dementia in an older and longitudinally followed cohort of the Ginkgo Evaluation of Memory (GEM) study. Method: Baseline plasma ApoE levels were measured using an immunoturbidimetric assay in 3,031 older subjects (aged 72 to 96 years; 94.1% White). Genome‐wide genotype was performed on the available 2,737 DNA samples (96% White). Due to the small number in other ethnicities, we only included the 2,852 White subjects (2,412 cognitively normal, 440 with incident AD dementia) for plasma ApoE analysis. GWAS analysis on plasma ApoE levels was performed on 2,580 White subjects where both genotype and ApoE level data were available. Result: As expected, the risk for AD increased from E2/2 through to E4/4 genotypes (p for trend =1.7E‐10). There was no significant difference in plasma ApoE levels between cognitively normal and AD dementia subjects (p=0.55). GWAS analysis revealed the expected associations of APOE*2 (β= 1.12; p= 3.57E‐79) and APOE*4 (β= ‐0.35; p= 2.21E‐11) with plasma ApoE levels. In addition, we observed 5 novel genome‐wide significant associations on chromosomes 1 (β= 0.921; p= 5.36E‐10), 4 (β= 0.796; p= 4.31E‐08;), 7 (β= 0.722; p= 9.64E‐09), 11 (β= 0.268; p= 2.58E‐08), and 20 (β= 1.379; p=8.25E‐09). Conclusion: We have identified multiple novel associations affecting plasma ApoE levels in addition to the established APOE association. However, we could not replicate the reported association of plasma ApoE levels with future AD, probably because of the older nature of our cohort. [ABSTRACT FROM AUTHOR]

Background. Risk factors for cognitive decline in ageing are multifactorial, including medical co-morbidities and familial genetic risk. [ABSTRACT FROM PUBLISHER]

Objectives: To identify, characterize and compare the frequency of mild cognitive impairment (MCI) subtypes at baseline in a large, late-life cohort (n = 3063) recruited into a dementia prevention trial. Method: A retrospective, data-algorithmic approach was used to classify participants as cognitively normal or MCI with corresponding subtype (e.g. amnestic vs. non-amnestic, single domain vs. multiple domain) based on a comprehensive battery of neuropsychological test scores, with and without Clinical Dementia Rating (CDR) global score included in the algorithm. Results: Overall, 15.7% of cases (n = 480) were classified as MCI. Amnestic MCI was characterized as unilateral memory impairment (i.e. only verbal or only visual memory impaired) or bilateral memory impairment (i.e. both verbal and visual memory impaired). All forms of amnestic MCI were almost twice as frequent as non-amnestic MCI (10.0% vs. 5.7%). Removing the CDR = 0.5 ('questionable dementia') criterion resulted in a near doubling of the overall MCI frequency to 28.1%. Conclusion: Combining CDR and cognitive test data to classify participants as MCI resulted in overall MCI and amnestic MCI frequencies consistent with other large community-based studies, most of which relied on the 'gold standard' of individual case review and diagnostic consensus. The present data-driven approach may prove to be an effective alternative for use in future large-scale dementia prevention trials. [ABSTRACT FROM AUTHOR]