Rate Of Memory Decline Research Articles

Effect of a cash transfer intervention on memory decline and dementia probability in older adults in rural South Africa

Evidence on cash transfers as a population-level intervention to support healthy cognitive aging in low-income settings is sparse. We assessed the effect of a cash transfer intervention on cognitive aging outcomes in older South African adults. We leveraged the overlap in the sampling frames of a Phase 3 randomized cash transfer trial [HIV Prevention Trial Network (HPTN) 068, 2011-2015] and an aging cohort [Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community (HAALSI), 2014-2022] in rural Mpumalanga Province, South Africa. In 2011/12, young women and their primary caregivers were randomly assigned 1:1 to receive a monthly cash transfer or control. In 2014/2015, 862 adults aged 40+ y living in trial households were enrolled in the HAALSI cohort, with cognitive data collected in three waves over 7 y. We estimated the impact of the intervention on rate of memory decline and dementia probability scores. Memory decline in the cash transfer arm was 0.03 SD units (95% CI: 0.002, 0.05) slower per year than in the control arm. Dementia probability scores were three percentage points lower in the cash transfer arm than the control arm (β = -0.03; 95% CI: -0.05, -0.001). Effects were consistent across subgroups. A modestly sized household cash transfer delivered over a short period in mid- to later-life led to a meaningful slowing of memory decline and reduction in dementia probability 7 y later. Cash transfer programs could help stem the tide of new dementia cases in economically vulnerable populations in the coming decades.

Could differential under-reporting of loneliness between men and women bias the gender-specific association between loneliness duration and rate of memory decline? A probabilistic bias analysis of effect modification.

Gender is an observed effect modifier of the association between loneliness and memory aging. However, this effect modification may be a result of information bias due to differential loneliness under-reporting by gender. We applied probabilistic bias analyses to examine whether effect modification of the loneliness-memory decline relationship by gender is retained under three simulation scenarios with various magnitudes of differential loneliness under-reporting between men and women. Data were from biennial interviews with adults aged 50+ in the US Health and Retirement Study from 1996-2016 (5,646 women and 3,386 men). Loneliness status (yes vs. no) was measured from 1996-2004 using the CES-D loneliness item and memory was measured from 2004-2016. Simulated sensitivity and specificity of the loneliness measure were informed by a validation study using the UCLA Loneliness Scale as a gold standard. The likelihood of observing effect modification by gender was higher than 90% in all simulations, although the likelihood reduced with an increasing difference in magnitude of the loneliness under-reporting between men and women. The gender difference in loneliness under-reporting did not meaningfully affect the observed effect modification by gender in our simulations. Our simulation approach may be promising to quantify potential information bias in effect modification analyses.

Mid-Life Household Food Insecurity and Subsequent Memory Function and Rate of Decline in Rural South Africa, 2004-2022.

We aimed to investigate mid-life food insecurity over time in relation to subsequent memory function and rate of decline in Agincourt, rural South Africa. Data from the longitudinal Agincourt Health and Socio-Demographic Surveillance System (Agincourt HDSS) were linked to the population-representative Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI). Food insecurity (yes vs. no) and food insecurity intensity (never/rarely/sometimes vs. often/very often) in the past month were assessed every 3 years from 2004 to 2013 in Agincourt HDSS. Cumulative exposure to each food insecurity measure was operationalized as 0, 1, and ≥2 time points. Episodic memory was assessed from 2014/15 to 2021/22 in HAALSI. Mixed-effects linear regression models were fitted to investigate the associations of each food insecurity measure with memory function and rate of decline over time. A total of 3,186 participants (mean age [SD] in 2004: 53 [12.87]; range: 30-96) were included and 1,173 (36%) participants experienced food insecurity in 2004, while this figure decreased to 490 (15%) in 2007, 489 (15%) in 2010, and 150 (5%) in 2013. Experiencing food insecurity at one time point (vs. never) from 2004 to 2013 was associated with lower baseline memory function (β = -0.095; 95% CI: -0.159 to -0.032) in 2014/15 but not rate of memory decline. Higher intensity of food insecurity at ≥2 time points (vs. never) was associated with lower baseline memory function (β = -0.154, 95% CI: -0.338 to 0.028), although the estimate was imprecise. Other frequencies of food insecurity and food insecurity intensity were not associated with memory function or decline in the fully adjusted models. In this setting, mid-life food insecurity may be a risk factor for lower later-life memory function, but not decline.

The effect of basal forebrain atrophy on the rate of cognitive decline in older adults without dementia

AbstractBackgroundIn early Alzheimer’s disease, degeneration of the cholinergic basal forebrain (BF) system correlates with amyloid‐β (Aβ) burden and contributes to cognitive decline, particularly in the domains of memory and attention processing. However, the nature of these interrelationships remains unclear. This study investigated the effects of Aβ and BF atrophy on cognitive decline of memory and attention in older individuals without dementia.MethodThe BF volumes were quantified from MRIs of 577 participants (73.3 ± 6.3 years old, 55.1% female) from the Australian Imaging, Biomarker and Lifestyle (AIBL) study, including 495 cognitive unimpaired (CU) individuals and 82 with mild cognitive impairment. Aβ‐PET assessment was completed at baseline, and Aβ+ was determined using Centiloid > 20. The cognitive decline in memory and attention was assessed using the relevant AIBL composite scores, over 6.0 ± 3.1 years (up to 13 years). BF z‐scores were calculated using the mean and standard deviation of BF volumes in the CU Aβ‐ group, and z‐scores < ‐1 was classified as BF atrophy (BF+). Participants were then grouped according to the Aβ status and presence of BF atrophy (Table 1). Linear mixed‐effects models assessed differences in rates of cognitive decline in memory and attention across different classification groups. Magnitudes of differences in slopes of decline were expressed using Cohen’s d. ResultIn Aβ‐ individuals, BF atrophy was associated with faster rates of cognitive decline in both memory and attention, with medium effect sizes (Table 2 and Figure 1). In re‐analyses restricted to Aβ+ subjects, BF atrophy remained related to memory decline (p = 0.035, d = 0.33) but not to decline in attention. Compared to Aβ‐ subjects without BF atrophy, both Aβ+ groups had faster decline in both domains, with large effect sizes (all d > 0.8).ConclusionThese findings indicate that the effects of Aβ and BF atrophy are additive in terms of their influence on the rate of decline in memory. However, BF atrophy influences the rate of decline in attention only in the absence of abnormal Aβ burden.

Urban but not rural patterns of ambient air pollution exposure is associated with an accelerated rate of late life memory decline in the Wisconsin Longitudinal Study

AbstractBackgroundExposure to ambient air pollution is an emerging risk factor for dementia, yet air pollution levels are found to vary by neighborhood affluence and across rural/urban settings. In this study, we leverage data from the Wisconsin Longitudinal Study (WLS) to evaluate the effects of ambient air pollution exposure on the rate of memory decline in late life, while accounting for both local (neighborhood) and regional (urbanization) residency characteristics.MethodAnnualized rate of change for both immediate and delayed recall trials of a 10‐item word list were calculated between 2010‐1 (baseline) and 2021‐2 (follow‐up) data collection waves. Yearly averages of geocoded regional air pollution data were obtained for 5 pollutants at baseline: particulate matter > 2.5um (PM2.5), ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO). Principal component analysis was performed to reduce multicollinearity among the 5 pollutants in subsequent analyses. Annualized rate of change in memory measures were regressed on resultant pollutant factor scores, additionally controlling for baseline age, adolescent IQ, education, health conditions (heart disease, stroke, hypertension, diabetes), neighborhood‐level deprivation, ApolipoproteinE‐4 (ApoE‐4) status, and sex.Result3,601 WLS participants were included in analyses, with a mean age of 70.4±3.4 years at baseline and 80.1±3.4 years at follow‐up. PCA yielded a 2‐factor solution classifying air pollutants into distinct urban (PM2.5, NO2, and CO2) versus rural (SO2 and O3) composites. Linear regression analysis revealed that greater annualized decline in delayed recall was predicted by higher exposure to urban air pollutants (but not rural), adolescent IQ, older age at baseline, and a history of heart disease. Air pollution exposure did not predict annualized change in immediate recall.ConclusionUsing longitudinal data from the WLS cohort, we find that higher levels of urban ambient air pollutant exposure predicted a more precipitous decline in delayed memory across late life. This finding remained significant after controlling for relevant confounders including neighborhood disadvantage, adolescent IQ, and ApoE‐4 status. Although the effect size of pollution exposure on the rate of memory decline was small, it remains a modifiable risk factor and stands to inform public policies to optimize late life cognition.

The cortical glucose metabolism signatures of cognitive resilience in amyloid positive cognitively unimpaired elderly adults

AbstractBackgroundβ‐amyloid (Aβ) positive (A+) cognitively unimpaired (CU) individuals who maintain normal cognitive function at follow‐up may have good cognitive resilience (CR). A+/CU Individuals with high CR may have hypermetabolism. In this study, we explored the cortical glucose metabolism features of CR in A+/CU elderly adults.MethodWe analyzed 855 ADNI participants with Aβ PET (18F‐florbetapir (FBP) or 18F‐florbetaben (FBB)), CSF p‐Tau181, 18F‐fluorodeoxyglucose (FDG) PET and longitudinal residual hippocampal volume (rHCV) and cognitive assessments. A+/T+/N+ were defined as AD summary cortical standardized uptake value ratio (SUVR) for FBP ≥1.11 or FBB ≥1.08, CSF p‐Tau≥23pg/ml, and rHCV≤‐0.67 respectively. We compared intensity‐ and spatial‐normalized FDG SUVR images between 96 A‐/T‐/N‐/CU individuals (Reference group) and 68 A+/CU individuals who maintained CU at follow‐up regardless of T+ or N+ (CR group). Cortical regions with higher FDG SUVR in the CR group were identified as the CR_metaROI. Baseline CR_metaROI FDG‐SUVRs were compared between different stages of AD. Finally, we determined whether CR_metaROI FDG‐SUVR can modulate the association of Aβ PET and CSF p‐Tau with longitudinal changes of cognition, controlling for age, sex, and education.ResultCR_metaROI was primarily located in the precentral and postcentral regions (Fig. 1). AD dementia patients had lower CR_metaROI FDG SUVRs than the CU (standardized β (βstd) = ‐0.326[95% confidence interval (ci): ‐0.534, ‐0.119], p = 0.002) and MCI (βstd = ‐0.303[95%ci: ‐0.496, ‐0.111], p = 0.002) groups (Fig. 2A), and A+/CU group had higher (βstd = 0.605[95%ci: 0.352, 0.859], p<0.001) CR_metaROI FDG SUVRs than the A‐/CU group (Fig. 2B). A‐/T+ and A+/T‐ individuals had lower (βstd = ‐0.248[95%ci: ‐0.4474, ‐0.022], p = 0.031) and higher (βstd = 0.305[95%ci: 0.093, 0.516], p = 0.005) CR_metaROI FDG SUVRs than the A‐/T‐ group respectively (Fig. 2C). The A+/T‐/N+ group had higher (βstd = 0.466[95%ci: 0.153, 0.779], p = 0.004) CR_metaROI FDG SUVRs than the A‐/T‐/N‐group (Fig. 2D). Moreover, higher baseline metaROI FDG‐SUVRs were associated with slower rates of decline in memory, executive function and preclinical Alzheimer cognitive composite scores upon the same levels of Aβ PET (Fig. 3A‐C) and CSF p‐Tau (Fig. 3D‐F).ConclusionWe identified a metabolism signature of CR in A+/CU elderly adults. These findings may provide novel insights into understanding the hypermetabolism patterns of CR in aging people.

Concurrent hearing and vision impairment and 8-year memory decline in community-dwelling older adults.

Hearing and vision impairments are risk factors for cognitive decline; less is known about dual sensory impairment. This study quantifies the association between dual sensory impairment and 8-year change in memory among older adults. Data (N=5552) were from the National Health and Aging Trends Study. Memory (immediate/delayed word recall, subjective memory) was measured annually (2011 to 2019). Hearing and vision impairments were measured by self-report. Association between dual sensory impairment and 8-year change in memory was assessed using multivariate linear mixed effect models and generalized logistic mixed models. Rate of memory decline was most accelerated among participants with dual sensory impairment. For example, 8-year decline in delayed word recall was -1.03 (95% confidene interval: -1.29, -0.77) for dual sensory impairment versus -0.79 (-0.92, -0.67) for single and -0.56 (-0.63, -0.48) for no impairment. Older adults with dual sensory impairment may be at particularly higher risk for cognitive decline.

Rate of memory decline is associated with neuronal nuclear protein (NeuN) positive cells count in middle temporal gyrus in the Adult Changes in Thought (ACT) autopsy cohort

AbstractBackgroundThe trace of memory has not been well studied in middle temporal gyrus (MTG). Although neuronal loss is minimal in most cortical regions of the aging brain, changes in synaptic physiology of ageing neurons may contribute to altered connectivity. In the Adult Changes in Thought (ACT) autopsy cohort, we explored if memory decline is associated with NeuN (neuronal nuclear protein), a biomarker for mature neurons, in MTG.MethodACT study participants were 5,763 older adults randomly sampled from an integrated healthcare delivery system in King County, Washington. We standardized composite memory scores to N(0,1) at baseline. We calculated slopes of memory decline over time using mixed‐effects models, where time was parameterized as years before death.Among 69 individuals who underwent brain autopsy, we measured NeuN positive cell count from whole slide image analysis using HALO in five tissue layers (molecular, external granular, external pyramidal, internal granular, internal pyramidal + multiform) from brain tissue in MTG. In each layer, we normalized NeuN positive cell count over the tissue area. We derived an average NeuN positive cell count (ANPCC) by averaging the values across the layers (Figure 1).We regressed ANPCC on memory slope, adjusting for age at death and sex. In secondary models, we added disease severity (Braak staging) and presence of APOE ε4 alleles separately. We also analyzed layer‐specific ANPCC.Result64 individuals were included for analysis (Table 1).Memory decline in this sample was 0.10 units per year, similar to the entire cohort. Slower decline in memory (β = 0.10; p‐value = 0.002) was significantly associated with increased average ANPCC (Table 2). Adjusting for Braak staging and APOE ε4 gave similar results. Findings were statistically significant across all but the molecular layer.ConclusionANPCC is associated with slower memory decline in multiple neocortical layers in MTG, irrespective of disease staging or APOE genotype. Since Alzheimer’s disease afflicts adult neuronal populations, survival mechanisms in mature neurons are likely to be either reversed or circumvented during neurodegeneration. Further analyses are needed to understand the functional range of NeuN and processes that lead to loss of NeuN immunoreactivity in cells.

Plasma Serotonin 2A Receptor Autoantibodies Predict Rapid, Substantial Decline in Neurocognitive Performance in Older Adult Veterans with TBI.

Traumatic brain injury (TBI) was associated with increased plasma serotonin 2A receptor (5-HT2AR) autoantibodies in adults who experienced neurodegenerative complications. We tested whether the baseline presence of plasma serotonin 2A receptor (5-HT2AR) autoantibodies was a significant predictor of the two-year rate of cognitive decline in middle-aged and older adult TBI. Plasma from thirty-five middle-aged and older adult veterans (mean 65 years old) who had suffered traumatic brain injury was subjected to protein-A affinity chromatography. One-fortieth dilution of the resulting immunoglobulin (Ig) G fraction was tested for binding (in ELISA) to a linear synthetic peptide corresponding to the second extracellular loop region of the human 5-HT2A receptor. All available patients completed baseline and two-year follow-up neurocognitive tests of memory (St Louis University Mental Status), processing speed (Digit Symbol Substitution Test) and executive function (Trails-making Test, Part B). Change in cognitive performance was computed as (two-year - baseline) raw test score. Eighteen patients completed both baseline and two-year follow up neurocognitive tests. TBI patients harboring plasma 5-HT2AR autoantibodies at the baseline examination (n=13) did not differ significantly in their baseline clinical characteristics (age, education level) compared to TBI patients lacking baseline plasma autoantibodies (n=5). Plasma serotonin 2AR antibody-positive patients experienced a significantly greater post-baseline decline in performance on the St Louis University Mental Status test (P=0.0118) and in the Digit Symbol Substitution Test (P=0.011), but not in Trails-making Part B (P=0.129) compared to serotonin 2AR antibody-negative patients. In multivariable linear regression analyses that adjusted for age, baseline presence of plasma 5-HT2AR autoantibody was a significant predictor of the two-year rate of decline in memory, and processing speed. Binding of plasma autoantibody to the serotonin 2A receptor peptide in the enzyme linked immunosorbent assay was also significantly higher (at 1/160th titer of the protein-A eluate= 1 μg/mL IgG) in TBI patients harboring vs. those not harboring baseline plasma 5-HT2AR autoantibodies. These data suggest that plasma 5-hydroxytryptamine 2A receptor autoantibodies which were increased in approximately two-thirds of middle-aged and older adults following traumatic brain injury predicts rapid and substantial declines in cognitive function (memory and processing speed), independent of age.

Social support, social strain and declines in verbal memory: sex-specific associations based on 16-year follow-up of the English Longitudinal Study of Ageing cohort

Objectives Previous investigations of cognitive aging have mainly focused on structural aspects of social relations (e.g. network size and composition), thereby neglecting the role of qualitative aspects of social relations. The current longitudinal study examined sex-specific differences in verbal memory decline by measures of perceived relationship quality (social support/strain) by relationship type. Method In the English Longitudinal Study of Ageing (ELSA), 10,109 participants aged 50–89 years were assessed at wave 1 (baseline: 2002–03) and followed to wave 9 (2017–18). Verbal memory was assessed by immediate and delayed word-recall tasks. Social support/strain was measured by relationship type (spouse; children; family; friends). Random effects within-between (REWB) modelling was used to separate between- and within-person effects. We estimated associations between social support/strain and (1) baseline levels of memory (main effects), and (2) rate of decline in memory (interaction with time-since-baseline). Results Longitudinal associations were most prominent for men, specific to relationship type, and showed between- rather than within-person effects. Among men, higher spousal strain was associated with faster memory decline (βbetween-effect×time = −0.043; 95% CI [−0.084, −0.002]; p = .039), whilst greater support from children was associated with slower decline (βbetween-effect×time = 0.020; 95% CI [0.002, 0.039]; p = .033). Men with higher strain from friends showed lower baseline memory (βbetween-effect = −0.382; 95% CI [−0.627, −0.137]; p=.002) and faster decline (βbetween-effect×time = −0.047; 95% CI [−0.095, 0.000]; p = .051). Conclusion Between-person differences in social support/strain were modestly associated with memory decline, especially among men.

Association of Perceived Job Insecurity With Subsequent Memory Function and Decline Among Adults 55 Years or Older in England and the US, 2006 to 2016

Intensified global economic competition and recent financial crises, including those associated with the COVID-19 pandemic, have contributed to uncertainty about job security. However, little is known about the association of perceived job insecurity with memory function and decline among older adults. To investigate the association between perceived job insecurity and subsequent memory function and rate of memory decline among older adults in the US and England. This 10-year prospective population-based cohort study used data from the US Health and Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA) collected from 2006 to 2016. Participants included 9538 adults 55 years or older. Data were analyzed from August 1 to 31, 2021. Perceived job insecurity (yes vs no) at baseline. Episodic memory z scores at baseline and rate of decline during the follow-up. Among the 9538 study participants, the mean (SD) age at baseline was 60.97 (6.06) years, and 4981 (52.22%) were women. A total of 2320 participants (24.32%) reported job insecurity at baseline (1088 of 3949 [27.55%] in England and 1232 of 5589 [22.04%] in the US). Perceived job insecurity after 55 years of age was associated with lower baseline memory z scores in the fully adjusted model (β = -0.04 [95% CI, -0.08 to -0.01]) but not with rate of memory decline (β = 0.01 [95% CI, -0.01 to 0.01]). The association appeared to be stronger in the US than in England (job insecurity × US, β = -0.05 [95% CI, -0.11 to 0.02]), but the estimate was imprecise, potentially owing to low statistical power. The findings of this cohort study suggest that exposure to job insecurity in middle to late life was associated with worse memory function among older adults in the US and England. This association may vary across socioeconomic and social welfare contexts, although future studies with large samples from diverse socioeconomic settings are warranted.

Cerebrospinal fluid neurofilament light predicts the rate of executive function decline in younger-onset dementia

IntroductionDetermining disease severity and predicting prognosis in younger onset-dementia (YOD) remains challenging. Whether CSF biomarkers neurofilament light (NfL), tau and amyloidβ 42 (Aβ42) can help provide such information has been underexplored. MethodsPatients with YOD and CSF analysis were identified. We compared baseline NfL, tau and Aβ42 concentrations with contemporaneous Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG) scores to assess their association with severity of cognitive impairment. Cognitive decline, as measured by longitudinal NUCOG assessment, was correlated against baseline biomarker levels to assess their utility in predicting the rate of cognitive decline. Results78 patients with YOD (mean age = 56 years, SD = 8) and CSF analysis were identified. Dementia types included Alzheimer's disease, behavioural variant frontotemporal dementia, dementia not-otherwise-specified and other. Tau was associated with contemporaneous memory dysfunction (r = −0.556, 95% CI:[−0.702,-0.393], p < .001). 21 patients had longitudinal cognitive assessment up to 82 months from CSF sampling. NfL was associated with the rate of executive function decline (r = 0.755, 95% CI:[0.259,0.937], p < .001). Aβ42 was associated with the rate of memory decline (r = −0.582, 95% CI:[−0.855,-0.274], p = .007) and rate of total NUCOG decline (r = −0.515, 95% CI: [−0.809, −0.227], p = .017). ConclusionCSF tau is related to contemporaneous memory impairment in YOD. NfL and Aβ42 levels are associated with the rate of executive function and memory decline, respectively, and may have a role in prognostication in YOD.

Sex-specific genetic predictors of memory performance.

There are notable sex differences in the clinical manifestation of Alzheimer's disease (AD), including differences in baseline and longitudinal changes in memory performance. However, sex-stratified models have not been routinely incorporated into genetic studies of cognitive performance or decline. We sought to identify sex-specific genetic predictors of memory performance in aging adults. We obtained harmonized memory scores from 11,601 females and 8,885 males from 7 cohorts of cognitive aging. We calculated scores using latent variable modeling techniques anchored on overlapping neuropsychological test items across datasets to perform both sex-stratified and sex-interaction genome-wide association studies in each cohort using mixed-effects regression models to assess genetic associations with baseline memory score and rate of memory decline. Covariates included age at baseline and population principal components. We then combined results in a fixed-effect meta-analysis. As expected, we observed robust associations at the APOE locus in males and females in both baseline and longitudinal models. Additionally, we identified a sex-specific locus for longitudinal memory performance (interaction-p=2.54e-6) on chromosome 7 within LINC-PINT that was genome-wide significant in males (index SNP= rs66754621; p=1.62e-8; MAF=0.20), but not females (p=0.65). This variant is in an enhancer region within several brain regions, as well as within a promoter-anchored chromatin interaction loop and a methylation eQTL in the prefrontal cortex. No female-specific loci were identified. Interestingly, we did observe nominal associations in baseline memory at some known AD loci, including male-specific effects at MS4A6A, FERMT2, and KAT8 (interaction ps=0.0026, 0.027, and 0.0058, respectively) and opposing effects between males and females at INPP5D (interaction p=0.0021). These results highlight a novel male-specific locus of memory performance on chromosome 7 near the LINC-PINT gene. LINC-PINT is upregulated in the substantia nigra in Parkinson's disease and is downregulated in multiple brain regions over the course of normal aging, making it a fascinating male-specific candidate gene. Replicate and functional analyses of the region are ongoing to verify our finding and elucidate the biological mechanism. Our results add to the growing body of literature suggesting that there are sex-specific genetic contributors to cognitive decline.

Area‐level deprivation is associated with rate of memory decline in late life within a community‐based cohort

AbstractBackgroundResiding in a disadvantaged neighborhood is associated with adverse health outcomes, as well as increased risk for dementia. However, it remains unclear whether area‐level deprivation impacts the rate of age‐related memory decline, especially in community‐based populations.MethodWe quantified late life neighborhood level disadvantage using the 2013 Area Deprivation Index (ADI) for 2,554 participants with complete data of interest within the Wisconsin Longitudinal Study – a same‐aged, community‐based cohort of randomly selected 1957 Wisconsin high school graduates. Delayed recall for a 10‐item word list was assessed at two timepoints in mid to late life (Time 1 (∼2004): age 64.39 + 0.74 years; and Time 2 (∼2011): age 71.28 + 0.97 years). We used multivariate linear regression models to evaluate whether ADI was associated with memory performance at each time point, and with the annualized rate of change in memory performance over time.ResultIncreasing ADI was significantly correlated with lower adolescent IQ, less educational attainment, lower net worth, higher vascular risk scores, elevated depression metrics, and increasing age (all p&lt;0.001). Mean ADI did not differ by sex, but was significantly higher in ApoE‐4 positive carriers (t(2552) =2.257, p=0.024). Results of multivariate regression indicated that greater area‐level deprivation (higher ADI) was not associated with delayed recall performance at Time 1 (b = 0.001; 95% CI: ‐0.003 to 0.005, P=0.790), but was associated with poorer delayed recall performance at Time 2 (B = ‐0.004; 95% CI: ‐0.007 to ‐0.001, P=0.019). Higher ADI also predicted greater annualized rate of decline in delayed recall between timepoints (B = ‐0.001; 95% CI: ‐0.001 to ‐9.9^10‐5, P=0.025). These findings held after controlling for individual‐level demographic and socioeconomic variables (age, sex, adolescent IQ, years of education, net worth), genetic risk (ApoE‐4 carrier status), depression, hearing loss, and a modified CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) risk score calculated at Time 1.ConclusionEven after accounting for established individual‐level demographic, socioeconomic, health, and genetic risk factors for cognitive decline, greater neighborhood disadvantage is associated with an accelerated rate of annualized decline in delayed recall performance across mid to late life in a community sample.

Working life job strain status and cognitive aging in Europe: A 12-year follow-up study

BackgroundTo examine the association of job strain with cognitive ability and the influence of life-course job strain on later life cognitive decline. MethodsData were derived from six waves of the Survey of Health, Aging, and Retirement in Europe. The study sample consists of 13349 participants aged 50 to 98 years at wave 2 and has been followed up for 12-years. Job strain status across working life was assessed using a short demand-control job strain model containing two core dimensions: job demands and job control collected in wave 3. Cognitive abilities concerning episodic memory was assessed by immediate recall and delayed recall tests, executive function was evaluated by verbal fluency test collected in all waves (waves 2–7) except wave 3. Mixed-effects model was used to estimate working life job strain and its cumulative effect on cognitive decline. ResultsBoth passive and high strain jobs were associated with lower levels of cognitive ability (episodic memory and verbal fluency) in comparison with active job. Long exposure to active- or low strain-job was associated with higher cognitive ability whereas long exposure to passive job or moderate duration of high strain job was associated with lower cognitive ability. The rate of memory decline was positively related to moderate duration of passive job and negatively related to long-term exposure to low strain job. LimitationsInformation on working conditions was based on self-reported recollections. ConclusionsWorking life variation in job strain status and their duration may explain individual differences in cognitive ability in later life.

Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer’s Disease in the FIT-AD Trial

Background:Utilities of blood-based biomarkers in Alzheimer’s disease (AD) clinical trials remain unknown.Objective:To evaluate the ability of plasma neurofilament light chain (NfL) to predict future declines in cognition and activities of daily living (ADL) outcomes in 26 older adults with mild-to-moderate AD dementia from the FIT-AD Trial.Methods:Plasma NfL was measured at baseline and 3 and 6 months. Cognition and ADL were assessed using the AD Assessment Scale-Cognition (ADAS-Cog) and AD Uniform Dataset Instruments and Disability Assessment for Dementia (DAD), respectively, at baseline, 3, 6, 9, and 12 months. Linear mixed effects models were used to examine the associations between baseline or change in plasma NfL and changes in outcomes.Results:Higher baseline plasma NfL was associated with greater rate of decline in ADAS-Cog from baseline to 6 months (standardized estimate of 0.00462, p = 0.02853) and in ADL from baseline to 12 months (standardized estimate of –0.00284, p = 0.03338). Greater increase in plasma NfL in short term from baseline to 3 months was associated with greater rate of decline in memory and ADL from 3 to 6 months (standardized estimate of –0.04638 [0.003], p = 0.01635; standardized estimate of –0.03818, p = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of –0.01492, p = 0.01082).Conclusion:This study demonstrated that plasma NfL might have the potential to predict cognitive and function decline up to 12 months. However, future studies with bigger sample sizes need to confirm the findings.

Musical instrument engagement across the life course and episodic memory in late life: An analysis of 60 years of longitudinal data from the Wisconsin Longitudinal Study.

BackgroundAs the global burden of dementia increases, the absence of treatment underscores the need for identification of factors that may improve cognitive reserve–the ability to stave off cognitive decline in old age. The beneficial association between musical instrument engagement and episodic memory has been identified in children, young adults, and older adults. Yet, previous studies in musical instrument engagement have rarely examined the potential for adolescence and adulthood exposures to independently improve cognition, nor have they been linked with the rate of memory decline over time in older adults. We investigated whether adolescent musical instrument engagement and continued musical instrument engagement over the adult life course were separately associated with higher episodic memory, as well as rate of decline in a large longitudinal cohort.MethodsData were from a prospective cohort of high school graduates from 1957. High school music engagement (HSME) was ascertained through graduate yearbooks and assessed as membership in musical performance groups. A questionnaire was used to assess musical engagement through adulthood (MEA) at ages 35, 55, and 65. The episodic memory score was composed of immediate and delayed recall task scores, and was assessed when participants were aged approximately 65 and 72 years old among 5,718 individuals. Linear mixed models were used to assess the association between music, and memory performance and decline over time.ResultsOf high school graduates who participated in the study, 38.1% played music in high school, and 21.1% played music in adulthood. While musical engagement was more common in those who played in childhood, 40% of those who played continuously as an adult did not play in high school. High HSME (B = 0.348, p = 0.049) and continuous MEA (B = 0.424, p = 0.012) were associated with higher memory scores at age 65 after covariate adjustment. When examining memory decline, the benefits of high HSME decreased over time (B = -0.435, p = 0.048), while the rate of decline did not differ between MEA groups. Exploratory models revealed differential benefits for HSME and immediate recall, and MEA and delayed recall.ConclusionThis study provides further evidence that musical engagement in childhood or adulthood is associated with non-musical cognitive reserve. These two exposures may act differentially in different domains of episodic memory. Further work is needed to determine the relationship between musicianship and the rate of cognitive decline.

Entorhinal Perfusion Predicts Future Memory Decline, Neurodegeneration, and White Matter Hyperintensity Progression in Older Adults.

Altered cerebral blood flow (CBF) has been linked to increased risk for Alzheimer's disease (AD). However, whether altered CBF contributes to AD risk by accelerating cognitive decline remains unclear. It also remains unclear whether reductions in CBF accelerate neurodegeneration and development of small vessel cerebrovascular disease. To examine associations between CBF and trajectories of memory performance, regional brain atrophy, and global white matter hyperintensity (WMH) volume. 147 Alzheimer's Disease Neuroimaging Initiative participants free of dementia underwent arterial spin labeling (ASL) magnetic resonance imaging (MRI) to measure CBF and serial neuropsychological and structural MRI examinations. Linear mixed effects models examined 5-year rate of change in memory and 4-year rate of change in regional brain atrophy and global WMH volumes as a function of baseline regional CBF. Entorhinal and hippocampal CBF were examined in separate models. Adjusting for demographic characteristics, pulse pressure, apolipoprotein E ɛ4 positivity, cerebrospinal fluid p-tau/Aβ ratio, and neuronal metabolism (i.e., fluorodeoxyglucose standardized uptake value ratio), lower baseline entorhinal CBF predicted faster rates of decline in memory as well as faster entorhinal thinning and WMH progression. Hippocampal CBF did not predict cognitive or brain structure trajectories. Findings highlight the importance of early cerebrovascular dysfunction in AD risk and suggest that entorhinal CBF as measured by noninvasive ASL MRI is a useful biomarker predictive of future cognitive decline and of risk of both.

Elevated plasma neurofilament light predicts a faster rate of cognitive decline over 5 years in participants with objectively-defined subtle cognitive decline and MCI.

Neurofilament light (NFL) reflects neuroaxonal damage and is implicated in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Little is known about NFL in pre-MCI stages, such as in individuals with objectively-defined subtle cognitive decline (Obj-SCD). Two hundred ninety-four participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent baseline blood draw and serial neuropsychological testing over 5 years of follow-up. Individuals with Obj-SCD and MCI showed elevated baseline plasma NFL relative to the cognitively normal (CN) group. Across the sample, elevated NFL predicted faster rate of cognitive and functional decline. Within the Obj-SCD and MCI groups, higher NFL levels predicted faster rate of decline in memory and preclinical AD composite score compared to the CN group. Findings demonstrate the utility of plasma NFL as a biomarker of early AD-related changes, and provide support for the use of Obj-SCD criteria in clinical research to better capture subtle cognitive changes.

Adverse Childhood Experiences and Rate of Memory Decline From Mid to Later Life: Evidence From the English Longitudinal Study of Ageing.

Evidence on the role of early-life adversity in later-life memory decline is conflicting. We investigated the relationships between adverse childhood experiences (ACEs) and memory performance and rate of decline over a 10-year follow-up among middle-aged and older adults in England. Data were from biennial interviews with 5,223 participants aged 54 years or older in the population-representative English Longitudinal Study of Ageing from 2006/2007 to 2016/2017. We examined self-reports of 9 ACEs prior to age 16 years that related to abuse, household dysfunction, and separation from family. Memory was assessed at each time point as immediate and delayed recall of 10 words. Using linear mixed-effects models with person-specific random intercepts and slopes and adjusted for baseline age, participants' baseline age squared, sex, ethnicity, and childhood socioeconomic factors, we observed that most individual and cumulative ACE exposures had null to weakly negative associations with memory function and rate of decline over the 10-year follow-up. Having lived in residential or foster care was associated with lower baseline memory (adjusted β=-0.124 standard deviation units; 95% confidence interval: -0.273, -0.025) but not memory decline. Our findings suggest potential long-term impacts of residential or foster care on memory and highlight the need for accurate and detailed exposure measures when studying ACEs in relation to later-life cognitive outcomes.