Verbal Memory Decline Research Articles

Exploring the effects of COVID-19 on verbal memory function in schizophrenia: Multiple case study and brief literature review

Individuals recovering from COVID-19 may experience persistent impairment in verbal memory performance, potentially due to illness-related hippocampal injury. Although verbal memory dysfunction is central to schizophrenia, the interactions between this vulnerability and COVID-19 remain unclear, with no imaging studies addressing the issue to-date. To explore this gap and generate hypotheses for future research, we adopted a multiple case study approach. Two pairs of individuals with an ICD-10 diagnosis of schizophrenia were selected, each consisting of one case with a positive COVID-19 anamnesis and one without. We calculated the Reliable Change Index to estimate the clinical significance of verbal memory performance changes, with annualized change rates in hippocampal volumes assessed against normative data. Compared to their matches, COVID-19 positive cases did not show mutually consistent changes in verbal memory performance: one case experienced a significant decline in verbal memory and learning, while the other showed a general normalization of test scores. Left hippocampal volumes showed a comparatively slowed increase, while the right hippocampi decreased in volume, although these atrophy rates did not exceed those expected in general population samples. Based on these findings, we hypothesize that COVID-19 alone does not lead to verbal memory decline in schizophrenia. Instead, the relationship between the diseases may depend on additional factors. Our case pairs differed in body mass index, systolic blood pressure, sex, phase of illness, and whole grey matter volume trajectories, leading us to hypothesize that these variables represent additional predictors or moderators of this relationship.

Preventing Verbal Memory Decline: Anatomic Clues to Predict Risk of Laser Ablation Versus Resection?

Preventing Verbal Memory Decline: Anatomic Clues to Predict Risk of Laser Ablation Versus Resection?

Territory-Related Functional Connectivity Changes Associated with Verbal Memory Decline in Patients with Unilateral Asymptomatic Internal Carotid Stenosis.

Verbal memory decline is a common complaint of patients with severe asymptomatic stenosis of the internal carotid artery (aICS). Previous publications explored the associations between verbal memory decline and altered functional connectivity (FC) after aICS. Patients with severe aICS may show reduced perfusion in the ipsilateral territory and redistribution of cerebral blood flow to compensate for the deficient regions, including expansion of the posterior and contralateral ICA territories via the circle of Willis. However, aICS-related FC changes in anterior and posterior territories and the impact of the sides of stenosis were less explored. This study aims to investigate the altered FC in anterior and posterior circulation territories of patients with left or right unilateral aICS and its association with verbal memory decline. We enrolled 15 healthy controls (HCs), 22 patients with left aICS (aICSL), and 33 patients with right aICS (aICSR) to receive fMRI, Mini-Mental State Examination (MMSE), the Digit Span Test (DST), and the 12-item Chinese version of Verbal Learning Tests. We selected brain regions associated with verbal memory within anterior and posterior circulation territories. Territory-related FC alterations and verbal memory decline were identified by comparing the aICSL and aICSR groups with HC groups (P < .05, corrected for multiple comparisons), respectively. Furthermore, the association between altered FC and verbal memory decline was tested with the Pearson correlation analysis. Compared with HCs, patients with aICSL or aICSR had significant impairment in delayed recall of verbal memory. Decline in delayed recall of verbal memory was significantly associated with altered FC between the right cerebellum and right middle temporal pole in the posterior circulation territory (r = 0.40, P = .03) in the aICSR group and was significantly associated with altered FC between the right superior medial frontal gyrus and left lingual gyrus in the anterior circulation territory (r = 0.56, P = .01) in the aICSL group. Patients with aICSL and aICSR showed different patterns of FC alterations in both anterior and posterior circulation territories, which suggests that the side of aICS influences the compensatory mechanism for decline in delayed recall of verbal memory.

Midlife Residential Greenness and Late-Life Cognitive Decline among Nurses' Health Study Participants.

Midlife residential exposure to greenspace may slow cognitive decline by increasing opportunities for physical activity and social connection, restoring attention, or reducing stress or adverse environmental exposures. However, prospective studies on the association between greenness and cognitive decline are sparse. We investigated the prospective association between greenness at midlife and cognitive decline later in life. We explored effect measure modification by apolipoprotein E (APOE)-ɛ4 carrier status, neighborhood socioeconomic status (NSES), and rural/urban regions. The Nurses' Health Study () started in 1976 with married female nurses, 30-55 years of age, located across 11 US states. We examined 16,962 nurses who were enrolled in a substudy starting in 1995-2001 (mean ) through 2008. We assessed average summer residential greenness in a buffer using Landsat Normalized Difference Vegetation Index data from 1986-1994. Starting in 1995-2001, participants underwent up to four repeated measures of five cognitive tests. A global composite score was calculated as the average of all -scores for each task to evaluate overall cognition. We used linear mixed models to evaluate the association of average greenness exposure at midlife with cognitive decline in later life, adjusted for age, education, NSES, and depression. In adjusted models, higher midlife greenness exposure [per interquartile range (IQR): 0.18] was associated with a 0.004-unit (95% CI: 0.001, 0.006) slower annual rate of cognitive decline. For comparison, we found that 1 year of age is related to a mean annual difference for global cognition in the full sample; thus, higher midlife greenness appeared equivalent to slowing cognitive decline by months. In analysis exploring gene-environment interactions, we found that among APOE-ɛ4 carriers, an IQR increase in greenness was associated with a rate of decline that was slower by 0.01 units of global composite score (95% CI: 0.0004, 0.02). This association was attenuated among APOE-ɛ4 noncarriers. We did not observe associations between greenness and baseline or annual rate of cognitive decline of verbal memory. Higher midlife greenness exposure is associated with slower cognitive decline later in life. Future research is necessary to confirm these findings. https://doi.org/10.1289/EHP13588.

Sleep disturbances, cognitive decline, and AD biomarkers alterations in early Parkinson's disease.

We aimed to investigate whether each type of sleep disturbances (i.e., pRBD, EDS, and insomnia) is specifically associated with faster decline in global cognition and different cognitive domains among de novo PD patients. We also assessed the influence of sleep disturbances on core AD CSF biomarkers alterations and conversion to dementia. Prospectively longitudinal data were obtained from the PPMI cohort. Sleep disturbances and cognition ability were assessed by questionnaires at baseline and follow-up visits. Generalized linear mixed models were utilized to assess the effect of sleep disturbances on cognitive decline and core AD CSF biomarkers change. The associations between sleep disturbances and conversion to dementia were analyzed using Cox regression analysis. Baseline pRBD was associated with faster decline in global cognition and all cognitive domains, including verbal episodic memory, visuospatial ability, executive function, language, and processing speed. EDS was associated with faster decline in three cognitive domains, including verbal episodic memory, executive function/working memory, and processing speed. Insomnia was associated with faster decline in global cognition and verbal episodic memory. Meanwhile, pRBD and EDS were associated with longitudinal decrease of CSF Aβ42. Baseline pRBD increased the risk of conversion to dementia. The risk of dementia in PD patients with multiple sleep disturbances also increased compared with those without sleep disturbance. Sleep disturbances (i.e., pRBD, EDS, and insomnia) were associated with cognitive decline in early PD. EDS and pRBD were associated with decrease of CSF Aβ42. Moreover, pRBD was associated with conversion to dementia.

Verbal memory network mapping in individual patients predicts postoperative functional impairments.

Verbal memory decline is a significant concern following temporal lobe surgeries in patients with epilepsy, emphasizing the need for precision presurgical verbal memory mapping to optimize functional outcomes. However, the inter-individual variability in functional networks and brain function-structural dissociations pose challenges when relying solely on group-level atlases or anatomical landmarks for surgical guidance. Here, we aimed to develop and validate a personalized functional mapping technique for verbal memory using precision resting-state functional MRI (rs-fMRI) and neurosurgery. A total of 38 patients with refractory epilepsy scheduled for surgical interventions were enrolled and 28 patients were analyzed in the study. Baseline 30-min rs-fMRI scanning, verbal memory and language assessments were collected for each patient before surgery. Personalized verbal memory networks (PVMN) were delineated based on preoperative rs-fMRI data for each patient. The accuracy of PVMN was assessed by comparing post-operative functional impairments and the overlapping extent between PVMN and surgical lesions. A total of 14 out of 28 patients experienced clinically meaningful declines in verbal memory after surgery. The personalized network and the group-level atlas exhibited 100% and 75.0% accuracy in predicting postoperative verbal memory declines, respectively. Moreover, six patients with extra-temporal lesions that overlapped with PVMN showed selective impairments in verbal memory. Furthermore, the lesioned ratio of the personalized network rather than the group-level atlas was significantly correlated with postoperative declines in verbal memory (personalized networks: r = -0.39, p = .038; group-level atlas: r = -0.19, p = .332). In conclusion, our personalized functional mapping technique, using precision rs-fMRI, offers valuable insights into individual variability in the verbal memory network and holds promise in precision verbal memory network mapping in individuals.

Alzheimer’s and neurodegenerative disease biomarkers in blood predict brain atrophy and cognitive decline

BackgroundAlthough blood-based biomarkers have been identified as cost-effective and scalable alternatives to PET and CSF markers of neurodegenerative disease, little is known about how these biomarkers predict future brain atrophy and cognitive decline in cognitively unimpaired individuals. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether plasma biomarkers of Alzheimer’s disease (AD) pathology (amyloid-β [Aβ42/40], phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal brain volume loss and cognitive decline. Additionally, we determined whether sex, APOEε4 status, and plasma amyloid-β status modified these associations.MethodsPlasma biomarkers were measured using Quanterix SIMOA assays. Regional brain volumes were measured by 3T MRI, and a battery of neuropsychological tests assessed five cognitive domains. Linear mixed effects models adjusted for demographic factors, kidney function, and intracranial volume (MRI analyses) were completed to relate baseline plasma biomarkers to baseline and longitudinal brain volume and cognitive performance.ResultsBrain volume analyses included 622 participants (mean age ± SD: 70.9 ± 10.2) with an average of 3.3 MRI scans over 4.7 years. Cognitive performance analyses included 674 participants (mean age ± SD: 71.2 ± 10.0) with an average of 3.9 cognitive assessments over 5.7 years. Higher baseline pTau-181 was associated with steeper declines in total gray matter volume and steeper regional declines in several medial temporal regions, whereas higher baseline GFAP was associated with greater longitudinal increases in ventricular volume. Baseline Aβ42/40 and NfL levels were not associated with changes in brain volume. Lower baseline Aβ42/40 (higher Aβ burden) was associated with a faster decline in verbal memory and visuospatial performance, whereas higher baseline GFAP was associated with a faster decline in verbal fluency. Results were generally consistent across sex and APOEε4 status. However, the associations of higher pTau-181 with increasing ventricular volume and memory declines were significantly stronger among individuals with higher Aβ burden, as was the association of higher GFAP with memory decline.ConclusionsAmong cognitively unimpaired older adults, plasma biomarkers of AD pathology (pTau-181) and astrogliosis (GFAP), but not neuronal injury (NfL), serve as markers of future brain atrophy and cognitive decline.

Cognitive change in prevalent and incident hearing loss: The Maastricht Aging Study.

Hearing loss (HL) has been associated with cognitive decline and dementia. We examined the temporal association between prevalent and incident HL and cognitive change. A total of 1823 participants (24-82 years) from the Maastricht Aging Study (MAAS) were assessed at baseline, 6 and 12 years, including pure-tone audiometry. Linear-mixed models were used to test the association between HL and cognition, adjusted for demographics and other dementia risk factors. Participants with prevalent and incident HL showed a faster decline in verbal memory, information processing speed, and executive function than participants without HL. Decline was steady from baseline to 6 and 12 years for prevalent HL, but time-delayed from 6 to 12 years for incident HL. Having a hearing aid did not change associations. Findings support the notion that HL is a risk factor for cognitive decline independent of other dementia risk factors. Onset of HL preceded onset of cognitive decline. We examined cognitive change in prevalent and incident hearing loss. Prevalent and incident hearing loss were associated with faster cognitive decline. For prevalent hearing loss, decline was steady from baseline to 6 and 12 years. Onset of hearing loss preceded the onset of cognitive decline. Having a hearing aid did not change the observed associations.

Effects of Virtual Reality Physical and Cognitive Training Intervention On Cognitive Abilities of Elders with Mild Cognitive Impairment.

Virtual reality (VR) technology has become increasingly used for assessment and intervention in the neuroscience field. We aimed to investigate the effects of a VR Training System, named VRADA (VR Exercise App for Dementia and Alzheimer's Patients), on the cognitive functioning of older people with mild cognitive impairment (MCI). In this intervention study, 122 older adults with MCI were randomly assigned to five groups (the VRADA group (n = 28), a bike group (n = 11), a physical exercise group (n = 24), a mixed group (physical and cognitive exercise) (n = 31), and a non-contact control group (n = 28). The VRADA group underwent 32 physical and cognitive training sessions, performed 2 or 3 times weekly for 12 weeks in the VR environment. All participants had detailed neuropsychological assessments before and after intervention. A series of linear regression models revealed that the VRADA group showed improvement or no deterioration in cognitive decline in global cognitive function (MMSE), verbal memory (Rey Auditory Verbal Learning Test and WAIS forward test), and executive functions, mental flexibility (Trail Making Test B). This interventionstudy indicates that the VRADA system improves the cognitive function of elders with MCI.

Pet Ownership, Living Alone, and Cognitive Decline Among Adults 50 Years and Older

It remains unclear whether pet ownership is associated with cognitive decline and to what extent pet ownership mitigates the association between living alone and cognitive decline. To explore the association of pet ownership with cognitive decline, the interaction between pet ownership and living alone, and the extent to which pet ownership mitigates the association between living alone and cognitive decline in older adults. This cohort study used data from waves 5 (June 2010 to July 2011) to 9 (from June 2018 to July 2019) in the English Longitudinal Study of Ageing. Participants included adults 50 years and older. Data were analyzed from April 1 to June 30, 2023. Pet ownership and living alone in wave 5. In waves 5 to 9, verbal memory and verbal fluency were assessed, and composite verbal cognition was further calculated. Of the 7945 participants included, the mean (SD) age was 66.3 (8.8) years, and 4446 (56.0%) were women. Pet ownership was associated with slower rates of decline in composite verbal cognition (β = 0.008 [95% CI, 0.002-0.014] SD/y), verbal memory (β = 0.006 [95% CI, 0.001-0.012] SD/y), and verbal fluency (β = 0.007 [95% CI, 0.001-0.013] SD/y). Three-way interaction tests showed that living alone was a significant modifier in all 3 associations. Stratified analyses showed that pet ownership was associated with slower rates of decline in composite verbal cognition (β = 0.023 [95% CI, 0.011-0.035] SD/y), verbal memory (β = 0.021 [95% CI, 0.008-0.034] SD/y), and verbal fluency (β = 0.018 [95% CI, 0.005-0.030] SD/y) among individuals living alone, but not among those living with others. Joint association analyses showed no significant difference in rates of decline in composite verbal cognition, verbal memory, or verbal fluency between pet owners living alone and pet owners living with others. In this cohort study, pet ownership was associated with slower rates of decline in verbal memory and verbal fluency among older adults living alone, but not among those living with others, and pet ownership offset the associations between living alone and declining rates in verbal memory and verbal fluency. Further studies are needed to assess whether pet ownership slows the rate of cognitive decline in older adults living alone.

Effects of healthy aging and mnemonic strategies on verbal memory performance across the adult lifespan: Mediating role of posterior hippocampus.

In this study, we aimed to understand the contributions of hippocampal anteroposterior subregions (head, body, tail) and subfields (cornu ammonis 1-3 [CA1-3], dentate gyrus [DG], and subiculum [Sub]) and encoding strategies to the age-related verbal memory decline. Healthy participants were administered the California Verbal Learning Test-II to evaluate verbal memory performance and encoding strategies and underwent 4.7 T magnetic resonance imaging brain scan with subsequent hippocampal subregions and subfields manual segmentation. While total hippocampal volume was not associated with verbal memory performance, we found the volumes of the posterior hippocampus (body) and Sub showed significant effects on verbal memory performance. Additionally, the age-related volume decline in hippocampal body volume contributed to lower use of semantic clustering, resulting in lower verbal memory performance. The effect of Sub on verbal memory was statistically independent of encoding strategies. While total CA1-3 and DG volumes did not show direct or indirect effects on verbal memory, exploratory analyses with DG and CA1-3 volumes within the hippocampal body subregion suggested an indirect effect of age-related volumetric reduction on verbal memory performance through semantic clustering. As semantic clustering is sensitive to age-related hippocampal volumetric decline but not to the direct effect of age, further investigation of mechanisms supporting semantic clustering can have implications for early detection of cognitive impairments and decline.

Socioeconomic position, modifiable dementia risk and cognitive decline: results of 12‐year Maastricht Aging Study

AbstractBackgroundEvidence of modifiable risk factors for cognitive decline and dementia is accumulating, showing the potential of dementia risk reduction via lifestyle modification and cardiovascular risk management. People with low socioeconomic status (SES) have increased dementia risk and on average worse health. This study investigated whether the association between a modifiable dementia risk score and rate of cognitive decline differs across SES strata.MethodData were used from Maastricht Aging Study (MAAS), a prospective cohort study with a 12‐year follow‐up. Participants aged ≥40 years with complete dementia risk profiles were included (n = 1223). The validated ’LIfestyle for BRAin health’ (LIBRA) index was used to assess the modifiable dementia risk fraction. Cognitive performance was serially assessed at baseline, 6 and 12 years and measured in the domains of information processing speed, executive functioning and verbal memory function. A SES compound score was calculated from equivalent income and educational level and divided into tertiles (low, middle, high). Linear mixed models were used to study the association between LIBRA, SES and their interaction on the rate of cognitive decline.ResultParticipants in the lowest SES tertile displayed more decline in information processing speed (vs. middle SES: X2 = 7.08, p = 0.029; vs. high SES: X2 = 9.49, p = 0.009) and verbal memory (vs. middle SES: X2 = 9.28, p&lt;0.001; vs. high SES: X2 = 16.68, p&lt;0.001) compared to their middle‐ and high‐SES counterparts. Higher (unhealthier) LIBRA scores were also associated with more decline in information processing speed (X2 = 12.66, p = 0.002) and verbal memory (X2 = 4.63, p = 0.032). No consistent effect modification by SES on the association between LIBRA and cognition was found.ConclusionThis study shows that lower SES and higher modifiable dementia risk predict faster decline in information processing speed and verbal memory function over 12 years. Results suggest that lifestyle is an important determinant of cognitive decline across SES groups. Yet, people with low SES had a more unfavourable modifiable risk score suggesting more potential for lifestyle‐based interventions. LIBRA could be useful as a participant selection tool or as a surrogate outcome measure in lifestyle intervention trials, and can inform people about individual risk behaviours as part of public health initiatives.

Association of plasma Alzheimer’s and neurodegenerative disease biomarkers with brain volume loss and cognitive decline

AbstractBackgroundAlthough plasma Alzheimer’s disease (AD) and neurodegenerative disease biomarkers have been associated with reduced cognition and lower brain volume, few studies have examined whether plasma biomarkers measured in predominately cognitively unimpaired adults are associated with longitudinal brain volume loss and cognitive decline. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether plasma biomarkers of AD pathology (Aß42/40, phosphorylated tau [pTau‐181]), reactive astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal brain volume loss and cognitive decline.MethodPlasma biomarkers (Aß42/40, pTau‐181, GFAP, NfL) were measured using Quanterix SIMOA assays. Baseline visits were considered the earliest visits that had concurrent 3T MRI scans and plasma biomarker measurements, and the earliest visits that had concurrent cognitive assessments and plasma biomarker measurements. Composite Z scores were computed to reflect 5 cognitive domains (Figure 1). Linear mixed effects models adjusted for baseline age, sex, race, education, estimated glomerular filtration rate, and total intracranial volume (brain volume analyses), were used to examine the association of plasma biomarkers with baseline and longitudinal brain volume and cognition. False Discovery Rate correction was used to adjust for multiple comparisons.ResultBrain volume analyses included 628 participants (mean age±SD: 71.0±10.2; Table 1) with an average of 3.3 MRI scans over 4.7 years. Cognition analyses included 686 participants (mean age±SD: 71.4±10.1) with an average of 3.9 cognitive assessments over 5.7 years. Although Aß42/40 was unrelated to brain volume changes, higher pTau‐181 was associated with longitudinal declines in total gray matter volume and regional declines in medial temporal regions. Higher GFAP was associated with longitudinal increases in ventricular volume, whereas NfL was not associated with brain volume change (Table 2). Both lower Aß42/40 and higher pTau‐181 were associated with a decline in verbal memory. Additionally, lower Aß42/40 was associated with a decline in visuospatial performance. Further, higher GFAP was associated with a decline in verbal fluency (Figure 1).ConclusionPlasma biomarkers of AD pathology and astrogliosis may serve as markers of future brain atrophy and cognitive decline.

Preoperative white matter network organization and memory decline after epilepsy surgery.

Risk for memory decline is a common concern for individuals with temporal lobe epilepsy (TLE) undergoing surgery. Global and local network abnormalities are well documented in TLE. However, it is less known whether network abnormalities predict postsurgical memory decline. The authors examined the role of preoperative global and local white matter network organization and risk of postoperative memory decline in TLE. One hundred one individuals with TLE (n = 51 with left TLE and 50 with right TLE) underwent preoperative T1-weighted MRI, diffusion MRI, and neuropsychological memory testing in a prospective longitudinal study. Fifty-six age- and sex-matched controls completed the same protocol. Forty-four patients (22 with left TLE and 22 with right TLE) subsequently underwent temporal lobe surgery and postoperative memory testing. Preoperative structural connectomes were generated via diffusion tractography and analyzed using measures of global and local (i.e., medial temporal lobe [MTL]) network organization. Global metrics measured network integration and specialization. The local metric was calculated as an asymmetry of the mean local efficiency between the ipsilateral and contralateral MTLs (i.e., MTL network asymmetry). Higher preoperative global network integration and specialization were associated with higher preoperative verbal memory function in patients with left TLE. Higher preoperative global network integration and specialization, as well as greater leftward MTL network asymmetry, predicted greater postoperative verbal memory decline for patients with left TLE. No significant effects were observed in right TLE. Accounting for preoperative memory score and hippocampal volume asymmetry, MTL network asymmetry uniquely explained 25%-33% of the variance in verbal memory decline for left TLE and outperformed hippocampal volume asymmetry and global network metrics. MTL network asymmetry alone produced good diagnostic classification of memory decline in left TLE (i.e., an area under the receiver operating characteristic curve of 0.80-0.84 and correct classification of 65%-76% of cases with cross-validation). These preliminary data suggest that global white matter network disruption contributes to verbal memory impairment preoperatively and predicts postsurgical verbal memory outcomes in left TLE. However, a leftward asymmetry of MTL white matter network organization may confer the highest risk for verbal memory decline. Although this requires replication in a larger sample, the authors demonstrate the importance of characterizing preoperative local white matter network properties within the to-be-operated hemisphere and the reserve capacity of the contralateral MTL network, which may eventually be useful in presurgical planning.

Differences in the association between midlife hypertension status and late‐life cognition and cognitive change: results from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study

AbstractBackgroundThis study evaluates the association of midlife hypertension status and domain‐specific late‐life cognitive change allowing for possible differences by sex.MethodThe Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort is a multi‐ethnic study of 1,712 Kaiser Permanente Northern California members age 65+ at enrollment in 2017. For 1,696 participants, we categorized the last examined clinical blood pressure measures from 1964‐1985 (mean age = 37.5) as hypotensive, normotensive, prehypertensive, or hypertensive. Verbal episodic memory and executive function were assessed using Spanish and English Neuropsychological Assessment Scales across three interview waves over 4 years and scores were z‐standardized to the baseline. Sex‐stratified linear mixed models with random intercepts estimated the associations of midlife hypertension status with domain‐specific baseline cognition and cognitive change using years since baseline as timescale. Models adjusted for age at blood pressure measurement, KHANDLE baseline age, race, ethnicity, education, practice effects, and interview mode (phone vs in‐person).ResultA greater proportion of men than women had midlife pre‐hypertension (44% vs 31%) or hypertension (21% vs 11%) (Table 1). Among men and women, midlife hypertension status was not associated with baseline executive function or verbal episodic memory (Table 2). Compared to men with normal midlife blood pressure, those with midlife hypotension (b = ‐0.10, 95% CI: ‐0.17, ‐0.04) or midlife hypertension experienced steeper declines in executive functioning (b = ‐0.05, 95% CI: ‐0.10, ‐0.004). Among women, only midlife hypertension was associated with decline in executive function (b = ‐0.04 95% CI: ‐0.09, 0.003), though not significantly different from normotensive women. Compared to normotensive men, those with midlife hypotension (b = ‐0.17, 95%CI: ‐0.27, ‐0.07) and those with pre‐hypertension (b = ‐0.06, 95% CI: ‐0.12, ‐0.004) experienced steeper decline in verbal episodic memory. Among women, only midlife hypertension was associated with steeper declines executive function (b = ‐0.04, 95% CI: ‐0.09, 0.003), though not significantly different from normotensive women. Though effect estimates of midlife hypertension status on cognitive outcomes differed by sex, these differences were not statistically significant.ConclusionBoth hypotension and hypertension 30‐50 years prior to cognitive assessments predicted accelerated cognitive decline in older men. Patterns were less consistent for women but not statistically distinguishable from associations among men.

Associations between normal cognitive aging and neurodegeneration

AbstractBackgroundMultiple cognitive domains, including learning, memory and psychomotor speed, show significant reductions with age. These changes are thought to reflect normal cognitive aging. However, since cerebrospinal fluid (CSF) neurodegenerative biomarkers, such as total‐tau (t‐tau) and Neurofilament light chain (NfL), also show age‐related increases in normal aging, we aimed to investigate whether age‐associated cognitive decline may be mediated by age‐associated neurodegenerative changes.MethodWe included 114 cognitively healthy participants aged 40‐80 years from The Norwegian Dementia Disease Initiation Study. All had normal concentrations of CSF Aβ42/40 ratio. Cognitively healthy was defined as demographically adjusted T‐scores ≥35 on standardized cognitive tests. We fitted mediation models using structural equation modelling (SEM), with either CSF NfL or t‐tau as a mediator between age and CERAD learning, CERAD recall, TMT‐A and TMT‐B. All variables were standardized prior to analyses; in addition, both t‐tau and NfL were log transformed due to skewness.ResultsSee table 1 for demographic and clinical characteristics. Whilst neither NfL nor t‐tau showed statistically significant mediation of age‐related cognitive decline, our results nevertheless suggest a partial mediation of NfL on age‐related cognitive decline. Here, relationships between age and CERAD learning, CERAD Recall, and TMT‐A performance were weakened whereas higher NfL was associated with worse performance, in particular for delayed memory recall. This was not observed for t‐tau in any models. See figure 1‐2.ConclusionAge‐related decline in verbal learning, memory and psychomotor speed may be partially attributable to NfL‐associated neurodegenerative changes in cognitively healthy adults. As NfL reflects axonal degeneration, these results may reflect white matter neurodegeneration in aging.

Tau pathway‐based gene analysis in the Alzheimer’s disease continuum identifies CLU and FYN associated with tau deposition on PET in a Korean Cohort

AbstractBackgroundAbnormal tau protein aggregation and spreading in the brain is closely linked to cognitive impairment and neurodegeneration in Alzheimer’s disease (AD). The role of genetic variation in brain tau aggregation has not been fully elucidated. Here, we performed pathway‐based candidate gene association analysis to identify novel genes associated with brain tau deposition on PET in a well‐characterized Korean AD continuum Cohort.MethodWe analyzed data for 145 older adults (69 cognitively normal (CN), 38 mild cognitive impairment (MCI), and 38 AD) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of AD (KBASE). We selected 15 candidate genes related to both tau pathways and AD, curated from existing pathway databases, literature mining, and genome‐wide association study findings. We performed gene‐based association analysis of tau deposition measured by 18F‐AV‐1451 PET scans using PLINK. In addition, we performed whole brain voxel‐wise association analysis of identified single nucleotide polymorphisms (SNPs) to investigate their topographic distributions of differences in tau deposition across the whole brain using SPM12. We examined the interaction of the identified SNPs with APOE ε4 carrier status.ResultGene‐based analysis identified CLU and FYN as significantly associated with tau deposition after adjusting for multiple testing. The most significant signals originated from rs149413552 in CLU and rs57650567 in FYN. A voxel‐wise analysis for the two SNPs showed that individuals carrying at least one minor allele demonstrated greater tau throughout the temporal, parietal, and frontal lobes than individuals having no minor alleles (Fig. 1). The two SNPs were associated with greater cortical atrophy of AD‐signature regions and worse global cognition. rs149413552 in CLU was also associated with longitudinal decline in global cognition and immediate verbal memory over two years. APOE ε4 and the two SNPs appeared to exert additive effects on tau levels (Fig. 2). An interaction between rs57650567 in FYN and APOE ε4 carrier status was observed (Fig. 2)Conclusion CLU and FYN may play a specific role in tau pathophysiology. These risk genes may prove useful for biomarker and therapeutic development. Larger and multiethnic studies are needed to confirm these findings and to determine generalizability across populations.

Persistent financial adversity across adulthood and cognitive ageing: A lifecourse investigation.

AbstractBackgroundCognitive decline in older age has significant health, economic and social consequences and there is evidence that financial adversity might play a role. Financial adversity, for many, is not an acute but a chronic stressor. However, little is known about the effect of persistence exposure to financial adversity across the lifecourse on cognitive ageing.MethodUsing data from the 1946 British birth cohort (N = 2,759) with an embedded neuroimaging study (Insight46; N = 356‐468), we examined the prospective association between financial adversity (low household income, financial hardships; 26‐53 years) and cognitive performance (69 years) and decline (53‐69 years), as well as volumetric measures of brain health (69‐71 years) in older adulthood. Cognitive decline was modelled using latent growth curves, with derived intercepts and slopes used in subsequent regression analyses, adjusted for sex, childhood socioeconomic circumstances (SEC), baseline cognition and internalising symptoms, and educational attainment. Sex, childhood SEC and APOE‐ɛ4 genetic risk were further tested as moderators in regression models using interaction terms. This study has been pre‐registered (https://doi.org/10.17605/OSF.IO/6Y9NV).ResultIncreased exposure to financial adversity showed dose‐response associations with slower verbal memory decline and lower processing speed and verbal memory at 69 years (Table 1). Each increased period of exposure to low household income or financial hardships was associated with a 0.11 and 0.08 standard deviation (SD) decrease in processing speed, and a 0.32 and 0.22 SD decrease in verbal memory at 69 years, respectively. Males persistently exposed to financial hardships showed slower processing speed decline but increased brain atrophy compared to females. Those whose fathers were in unskilled profession or unemployed in childhood, and who also persistently experienced low income themselves showed greater brain atrophy (Fig. 1). APOE‐ɛ4 carriers who persistently experienced financial adversity were also at greater risk for brain atrophy (Fig. 2).ConclusionPersistent financial adversity is directly associated with cognitive performance and may be differentially associated with brain atrophy depending on demographic and genetic factors. Reducing the frequency of financial adversity over the lifecourse may improve cognitive performance and protect against genetic susceptibility to brain atrophy and subsequent dementia risk in the ageing population.

Sleep Quality and Cognitive Decline Across the Adult Age Range: Findings from the Maastricht Aging Study (MAAS).

Sleep disturbances have been linked with cognitive decline and a higher risk of dementia. However, there is a lack of studies with sufficient follow-up duration, a detailed neuropsychological assessment and adequate control of main confounders. To investigate the relation between self-reported sleep quality and cognitive decline over 12 years in cognitively healthy individuals from the general population. We used data from the Maastricht Aging Study (MAAS), a Dutch population-based prospective cohort study of 1,823 community-dwelling adults aged 24 to 82 years at baseline. Cognitive performance was measured at baseline, 6 and 12 years on verbal memory, executive functions, and information processing speed. Sleep quality was assessed at baseline using the sleep subscale score of the 90-item Symptom Checklist (SCL-90). Additional modifiable dementia risk factors were summarized in the LIfestyle for BRAin health (LIBRA) risk score. Weighted linear mixed models tested the association between continuous scores and tertiles of subjective sleep quality and change in cognitive performances over time. Models were adjusted for age, gender, educational level, LIBRA, and use of hypnotic (sleep) medication. Worse sleep quality was associated with faster decline in processing speed. At older age (≥65 years), it was also associated with faster decline in verbal memory. Association were independent of other modifiable dementia risk factors and use of hypnotic medication. Directionally similar but non-significant associations were found between worse sleep quality and executive functions. In this population-based study across the adult age range, poor self-reported sleep was associated with accelerated cognitive decline.

98 Cognitive Outcomes Following Bilateral Focused Ultrasound Thalamotomy for Tremor

Objective:Essential tremor (ET) is the most common movement disorder, characterized by bilateral action tremors of the upper extremities. Surgical interventions can be considered for severe cases that are refractory to medication. Magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus of the thalamus (Vim) is a recently approved, minimally invasive treatment for unilateral tremor. While patients are generally pleased with unilateral treatment, many patients are bothered by tremor on the untreated side. Historically, bilateral thalamotomy has been associated with a higher rate of adverse events, including cognitive impairment. MRgFUS Vim thalamotomy for bilateral tremor is currently being investigated. The goal of the present study was to evaluate the effect of bilateral MRgFUS Vim thalamotomy on cognition.Participants and Methods:Twelve patients with medication-refractory essential tremor (mean age = 68.77 +/- 11.78 years, mean education = 14.34 +/- 2.71 years, 8 male) were included in the present study. Three of the 12 patients met criteria for mild cognitive impairment (MCI). All patients successfully underwent unilateral MRgFUS thalamotomy at least 48 weeks before the second thalamotomy. A battery of neuropsychological tests was administered to patients before (considered baseline in the present study) and three months following the second thalamotomy. Baseline evaluations occurred on average 144.64 +/- 91.53 weeks (range: 55.00 - 346.58) after the first thalamotomy. The neuropsychological battery assessed domains of processing speed (Oral Symbol Digit Modalities Test, D-KEFS Color-Word Naming and Reading), attention (WAIS-IV Digit Span Forward), executive function (D-KEFS Color-Word Inhibition and Inhibition/Switching), working memory (WAIS-IV Digit Span Backward and Sequencing), verbal fluency (D-KEFS Letter Fluency and Animal Fluency), confrontation naming (Boston Naming Test), verbal memory (Hopkins Verbal Learning Test-Revised), and visuospatial perception (Judgment of Line Orientation). Alternate versions of tests were used when possible. Cognitive changes were analyzed at the group and individual level. Group level changes were assessed with paired sample t-tests (corrected for multiple comparisons). At the individual level, postoperative declines &gt; 1.5 SD from baseline were considered clinically significant.Results:Participants’ baseline intellectual functioning ranged from low average to superior (as measured by the WTAR). The mean baseline score on the Montreal Cognitive Assessment was 24.58 (range: 17 - 30). At the group level, there were no significant changes in cognitive scores from baseline to follow-up (all p values &gt; 0.635). At the individual level, one patient with MCI declined &gt; 1.5 SD on the verbal memory composite. No other patients showed declines &gt; 1.5 SD.Conclusions:Our preliminary findings suggest that bilateral MRgFUS Vim thalamotomy is relatively safe from a cognitive perspective. However, a single patient with MCI exhibited clinically significant postoperative decline in verbal memory. Future studies with larger sample sizes are needed to investigate the factors that increase the risk of postoperative cognitive decline, including pre-existing cognitive impairment, older age, and lesion size.