Probable Dementia Research Articles

PSYCHOMETRIC PROPERTIES OF THE NEUROPSYCHIATRIC INVENTORY QUESTIONNAIRE FOR THAI OLDER ADULTS WITH DEMENTIA

Abstract Psychiatric and behavioral symptoms are highly prevalent among persons living with dementia. Clinical evaluation of those symptoms is critical for assessment of dementia progression and development of effective treatment. The Neuropsychiatric Inventory Questionnaire (NPI-Q) is a brief informant-based instrument to assess the severity of 12 types of neuropsychiatric symptoms among persons with dementia and associated caregiver distress. Although Thailand is experiencing a rapid increase in the prevalence with dementia, there is no validated instrument to assess neuropsychiatric symptoms in Thailand. This study aims to examine the psychometric properties of the NPI-Q instrument among older adults with dementia in Thailand. Data were collected from 353 participants aged 60 and over with probable dementia, at least one neuropsychiatric symptom, and an adult family caregiver willing to participate in the study. We examined the internal consistency, factorial validity, and criterion validity of the NPI-Q instrument. NPI-Q has acceptable internal consistency (Cronbach’s α=0.77). Principal component analysis yielded a five-factor solution, which accounted for 63% of the variance. The five factors included (1) agitation, anxiety, and irritability, (2) delusions, hallucinations, apathy, and disinhibition, (3) euphoria, motor disturbance, and night disturbance, (4) depression, and (5) abnormal appetite. We found that higher NPI-Q severity score was significantly associated with higher geriatric depression, associated caregiver distress, caregiver burden, and caregiver depression and lower quality of life among older adults and their caregivers, which confirmed the criterion validity of the instrument. Findings provide support for use of the NPI-Q among older adults with dementia in Thailand.

Life satisfaction among persons living with dementia and those without dementia.

Despite possible major adverse cognitive, physical, social, and behavioral consequences, little is known about how persons living with dementia perceive satisfaction with life, a key component of well-being. We sought to examine (i) whether persons living with dementia perceive a lower level of satisfaction compared to their peers without dementia and (ii) whether the associations between individual characteristics and life satisfaction are different between persons living with and without dementia. Using a nationally representative sample of community-dwelling older adults aged ≥70 years in the U.S. from the Health and Retirement Study, we compared scores on the Satisfaction with Life Scale (SWLS), a self-reported 5-item scale ranging from 1 to 7 (more satisfaction), between persons with probable dementia (n= 341) and those without (n= 5530), adjusting for individual characteristics. We also tested whether the associations between the individual characteristics and SWLS differ by dementia status. Scores on SWLS did not differ between persons with probable dementia and those without when adjusting for individual characteristics including limitations in activities of daily living (ADL) (adjusted difference, -0.09; 95% CI, -0.33 to +0.15; p-value, 0.45). However, dementia status was associated with lower life satisfaction through the mediation of limitations in ADL (total effect, -0.29; bootstrapped 95% CI, -0.47 to -0.12). Most individual characteristics associated with lower life satisfaction were similar in the two groups, including younger age, more limitations in ADL, and depression. Less wealth was associated with lower satisfaction among persons without dementia but not among those with probable dementia. Dementia status was only modestly associated with lower life satisfaction through the mediation of limitations in ADL among participants who were able to provide response. Future research is warranted to determine whether life satisfaction can be used as a meaningful outcome when evaluating well-being among persons living with dementia.

Dementia neuropsychiatric prevalence, severity, and correlates in community‐dwelling Thai older adults

AbstractBackgroundThailand is experiencing a rapid increase in the number of older persons with dementia, yet little is known about the nature and consequences of dementia neuropsychiatric symptoms (NPS), particularly outside of clinical settings. We examined the prevalence, severity, and correlates of NPS, including correlation with family caregiver burden and distress, among community‐dwelling Thai older adults with probable dementia.MethodsThis study is based on analysis of baseline data from a hybrid type III cluster randomized design comparing two different implementation approaches of an evidence‐based exercise intervention for persons with dementia. A three‐step recruitment process was used for recruiting participants from the local healthcare system and included clinical case confirmation of probable degenerative dementia. To be eligible, participants needed to be age 60 and above, have probable dementia, have 1 or more NPS, be ambulatory, and have an adult (age 18+) family caregiver. 353 participants enrolled in the study and completed based assessments, including NPS assessment, caregiver stress associated with NPS, as well as other care recipient and caregiver characteristics. We examined NPS severity with caregiver distress and used ordinary least squares (OLS) regression to examine associations between PWD and caregiver characteristics and NPS severity.ResultsNPS prevalence varied from 18% for appetite/eating changes to 42% for delusions. NPS severity was significantly (P < .05) associated with caregiver stress for all individual NPS. Among PWD characteristics, higher ADL score (less functional impairment) was inversely associated with NPS total severity (b = ‐0.16, p < 0.05). More physical role limitation was significantly associated with higher NPS total severity (b = 0.77, p < 0.001). Among caregivers’ characteristics, higher burden was significantly associated with higher NPS total severity (b = 0.19, p < 0.001).ConclusionsOur study found that NPS are common among community dwelling PWD in Thailand and are associated with adverse impacts on both PWD and family caregivers. These findings highlight the clinical importance of NPS symptoms among Thai older adults. The high prevalence of psychotic symptoms in this community sample is noteworthy and deserves further attention. Results of the parent intervention study will be reported in 2023.

Older adults with underidentified dementia exhibit a fragile clinical and neuropsychiatric profile

AbstractBackgroundWorldwide prevalence of dementia in older adults ranges from 5‐7%, with higher rates observed in Latin America (8.5%). However, underdiagnosis remains frequent. Our aim is to identify the profile of individuals with probable dementia that were underidentified using an epidemiological cohort.MethodAn epidemiological study named ELSI‐Brazil was evaluated for potential underidentification of dementia. Individuals at or above 60 years of age with probable dementia were selected using semantic fluency test scores (adjusted for age and education) and loss of any basic activity of daily living (Katz scale<6). Groups were divided into reported and unreported diagnosis of dementia (UpD), according to previous history of Alzheimer’s disease. UpD group compounds individuals potentially living with probable dementia without a proper medical evaluation. Individuals were evaluated for self‐reported risk factors, previous medical history, frailty scores, cognitive tests and neuropsychiatric symptoms. A multivariate logistic regression was performed to demonstrate predictors of UpD.ResultAmong 5221 older adults of the ELSI‐Brazil sample, 474 individuals (mean age 73.30±8.65, 67% females) were classified as probable dementia (pD), and 4747 individuals (mean age 69.6±7.42, 59% females) as probable not dementia (pND). Among probable dementia, unreported dementia (UpD) comprehended 459 older adults (96.4%), with significantly more clinical comorbidities, such as hypertension, diabetes, ischemic events (stroke or myocardial infarction), hearing loss and malignancy (p < 0.001). They also presented higher neuropsychiatric symptoms, such as poor quality of sleep, frequent usage of sleep drugs, and depression (p<0.001). Strong predictors of UpD included frailty score (OR: 2.06 [1.58 ‐ 2.68]), poor sleep quality (OR: 1.46 [1.13 ‐ 1.90]), frequent usage of sleep drugs (OR: 1.54 [1.15 ‐ 2.05]), and recent hospitalization (OR: 1.67 [1.20 ‐ 2.30]).ConclusionA specific profile of vulnerability was demonstrated in older adults with unidentified probable dementia in this cohort. Frailty, poor sleep quality, frequent usage of sleep drugs, and recent hospitalization were important predictors of UpD. This study provides insights to guide public health policies and target individuals more vulnerable to underidentified dementia.

Racial disparities in predictors of dementia in a population‐based cohort

AbstractBackgroundIdentifying predictors of dementia may reduce its burden across the globe. Herein, we aimed at investigating predictors of probable dementia in different race groups of a middle‐income country.MethodThe ELSI‐Brazil cohort consists of 9412 individuals (63.55+‐10.14 years of age). This cohort comprises individuals at/ or above 50 years of age from across the country. Complex sampling warrants nationwide representativity for diseases with low prevalence. Probable dementia was defined as a brief cognitive screening (using category fluency test) score below normative data for age and education, associated with a Katz scale score below 6. Multivariate logistic regression models were performed to measure predictors of dementia in Black, Brown, White and Indigenous individuals. Asian ancestry individuals were excluded from this analysis due to the small sample size (n = 90).ResultThe frequency of individuals with probable dementia was statistically similar between groups, especifically 8.7% (n = 74/887) in black individuals, 7.8% (n = 17/220) in indigenous individuals, 7.5% (n = 301/4283) in Brown individuals, and 7.2% (n = 245/3590) in White individuals (p = 0.51). Indigenous individuals with probable dementia were significantly younger than other groups (59.1 years, p<0.001). Predictors of dementia differ significantly between groups, except for depression, which was the only predictor universally present. In Brown individuals, stroke and myocardial infarction were associated with predictors of dementia (OR: 2.34 [1.5 ‐ 3.5] and OR: 2.57 [1.69 ‐ 3.84] respectively), while the feeling of loneliness (OR: 1.69 [1.20 ‐ 2.42]) and being economically inactive (OR: 2.89 [1.68 ‐ 4.80]) were associated with dementia in White individuals. In Black individuals, recent hospitalization was a strong predictor (OR: 2.86 [1.47 ‐ 5.42]), while in Indigenous individuals, only depression was a predictor (OR: 19.22 [3.74 ‐ 352]), potentially associated with its small sample.ConclusionDistinct profile of predictors for probable dementia should be accounted for when evaluating distinct races groups. While depression was a predictor for all races, Brown individuals presented a clinical profile more vulnerable to cardiovascular events.

Functional fitness predicts global cognition scores

AbstractBackgroundAlzheimer’s disease (AD) is the 5th leading cause of death and the 6th most burdensome disease among US older adults. Given the concern with public health, understanding modifiable risk factors contributing to cognitive decline is imperative. With preliminary symptoms of cognitive decline occurring long before diagnosis, the ability to identify modifiable risk factors is key to primary prevention and maintenance of cognition. Often among individuals with AD, physical function is concurrently impaired. Thus, the primary aim of the present investigation is to determine the ability to predict global cognition scores from commonly used physical function assessments.MethodCommunity‐dwelling adults 60 years and older completed all assessments. Global cognition (percentile score) was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). All participants were free from mild cognitive impairment, dementia, and probable dementia. Physical function variables included maximal hand grip strength (average of right and left hands), lower‐body peak force development during a sit‐to‐stand task, and 10‐mfast walking time. Linear regression analysis was performed to determine the proportion of variance accounted for by the independent variables (sex, hand grip strength, peak force, 10‐meter walk time). Semi‐partial correlations were performed to determine the unique contribution from each independent variable.Result27% of the variance in global cognition was accounted for when including all independent variables. Semi‐partial correlations revealed the largest unique contribution was from the 10‐meter fast walking time, accounting for 19% of the variance (p < .001). Lower‐body peak force production accounted for 9% (p < .001). Sex accounted for 2.6% (p =.04) and hand grip strength accounted for 2% (p = .055).ConclusionThe current investigation provides support for the predictive capabilities of physical function assessments on cognitive ability—in particular, the time to complete a 10‐meter walk. This is paramount to future efficacious treatments with the inconsistent nature of current cognitive testing and implementation, primarily because of difficulties accessing qualified neuropsychological professionals. The physical function assessments presented here are cost effective and may serve as an early warning sign to cognitive decline.

Sex/Gender, Relationship Status, and Alzheimer’s and Related Dementia Diagnoses after Probable Dementia

AbstractBackgroundDifferences by relationship status have been found in both cognitive‐assessment scores and prevalence and incidence rates for Alzheimer’s disease and related dementias (ADRD), but little is known about delayed and missed ADRD diagnoses after cognitive impairment emerges. Existing research has reported underdiagnosis for people of color, men, and people with less education.MethodUsing data from the Health and Retirement Study (2000‐2018), we analyzed associations between relationship status and time to ADRD diagnosis following probable dementia (PD). We examined risk of ADRD diagnosis by sex/gender and relationship status (married/partnered or single at the time of the first PD‐scoring assessment), adjusting for race/ethnicity, age, and education. Cox proportional hazards modeling was used to account for right‐censoring, with the risk period beginning at the time of the incident PD. Failure occurred when ADRD diagnosis was self‐reported. We also examined time until diagnosis among all participants with a recorded case of incident PD (N = 3,216 subjects: 9,540 observations). Restricted mean times to diagnosis and multivariable‐adjusted hazard ratios (aHR) with 95% Confidence Intervals (95% C.I.) were reported.ResultTable 1 shows summary statistics; Table 2 provides hazard ratios; Table 3 shows mean times to diagnosis. Married/partnered women had the highest likelihood of receiving a diagnosis during the study period (HR: 1.197; 95% CI: 1.020‐1.360; p = <.001); single woman also had higher risk of diagnosis (HR: 1.178; 95% CI: 1.025–1.400; p = <.001). Mean time to diagnosis for men was 8.69 (±0.20); for women, 7.38 (±0.13). Singles received diagnoses sooner (7.32±0.135 years) than married/partnered people (8.39±0.169). Categorizing by sex/gender and relationship status, married/partnered women have the lowest mean times (7.00±0.148); single and married/partnered men’s mean times to diagnosis do not differ.ConclusionRelationship status is associated with women’s likelihood of reporting ADRD diagnosis and time to diagnosis, but not men’s. Further investigation is required to analyze potential sources of this disparity, including interactions with education, income, and insurance status, and additional gendered relationship, social, and familial factors.

Factors associated with risk of transition to high likelihood of dementia profile in population‐based surveys of aging: a longitudinal analysis

AbstractBackgroundDementia (Major Neurocognitive Disorder) is associated with acquired cognitive impairment and functional decline in daily life. Several population‐based surveys of aging similar to the American Health and Retirement Study exist worldwide. In these studies, cognitive performance and functional status are available, but not the diagnosis of dementia. We previously identified participants with high likelihood of dementia using cross‐sectional data from these studies and unsupervised machine‐learning (Cleret de Langavant et al., 2018; 2020). Here, we propose an application of this method by assessing simultaneously six waves, i.e., minimum 11‐year follow‐up for each participant, in order to study factors associated with risk of transition toward dementia.MethodWe used a modified version of a previously developed unsupervised machine‐learning algorithm in the Survey of Health, Ageing and Retirement in Europe (SHARE). We restrained the analysis to participants with available data at each wave (N = 5,536, 9 countries). Cognitive tests and autonomy variables were used to discriminate three groups: one healthy ageing group (Healthy), one characterised by mobility but no functional impairment (Mobility), and one with probable dementia (Dementia). We examined the role of several factors in transitioning from one group to another one using multi‐state models with age as time‐scale.ResultsHazard ratios (HR) examination confirmed that higher education lowers the risk of transition to mobility impairment and to dementia (HRhealthy→mobility = 0.46 [0.42 ‐ 0.50], HRmobility→dementia = 0.44 [0.32 ‐ 0.62], and HRhealthy→dementia = 0.58 [0.36 ‐ 0.92]). Similarly, obesity, stroke, hypertension, and poor hearing were significant risk factors. Isolation and depression were found to increase the risk of transition from Mobility to Dementia group (HRmobility→dementia = 2.97 [2.08 ‐ 4.24] & HRmobility→dementia = 2.23 [1.86 ‐ 2.67], respectively) and from Healthy to Dementia group (HRhealthy→dementia = 5.56 [2.39 ‐ 12.94]) & HRhealthy→dementia = 1.98 [1.33 ‐ 2.95], respectively). Results for smoking and alcohol were inconclusive.ConclusionWhile obesity, stroke, hypertension, poor hearing, depression and isolation were associated with an increased risk of transition to the Dementia group, high educational attainment was protective.

Plasma amyloid‐β profiles and the correlation with neuropsychological performance in patients with cognitive decline

AbstractBackgroundThis study aimed to investigate the relationship between the level of plasma amyloid‐β (Aβ) and neuropsychological performance in patients with cognitive decline, classified according to amyloid PET positivity using a highly sensitive nano‐biosensing platform.MethodA total of 44 patients with cognitive decline who underwent plasma Aβ analysis, amyloid PET scanning, and detailed neuropsychological tests were recruited in this study. The participants comprised 20 patients with subjective cognitive decline, 7 with amnestic mild cognitive impairment, and 17 with probable AD dementia. Patients were classified into a normal control (NC, N = 25) or Alzheimer’s disease (AD, N = 19) group based on amyloid PET positivity. Multiple linear regression was performed to determine whether plasma Aβ (Aβ40, Aβ42, and Aβ42/40) levels were associated with neuropsychological test results.ResultThe plasma levels of Aβ42/40 were significantly different between the NC and AD groups and were the best predictor of amyloid positivity by receiver operating characteristic curve analysis. There were significant differences in the neuropsychological performance of cognitive domains (language, visuospatial, verbal/visual memory, and frontal/executive functions) between the NC and AD groups. However, in multivariate regression analysis, upon inclusion of age, education, vascular risk factors, and apolipoprotein E ε4 status, higher levels of plasma Aβ42/40 showed significant negative correlations with verbal and visual memory performance, including immediate recall, delayed recall, and recognition tests.ConclusionWe suggest that our study might have clinical significance because plasma Aβ analysis using a highly sensitive nano‐biosensing platform could not only be a useful non‐invasive method for diagnosing AD, but also showed a significant association with memory performance in patients with cognitive decline. Further investigations with a larger sample size are necessary to clarify the possible relevance of plasma Aβ as a blood‐based biomarker for precise AD diagnosis.

Tau protein spreads through functionally connected neurons in Alzheimer’s disease

AbstractBackgroundRecent studies in Alzheimer’s disease (AD) suggest that tau proteins spread through the brain following neuronal connections. Several mechanisms could be involved in this process: spreading between brain regions that interact strongly (functionally connected); through the pattern of anatomical connections (structural connectivity); or simple diffusion to spatially adjacent regions (Euclidean distance (EC)). We investigated this by modelling the tau‐spreading process on these different networks, and compared the modelled tau‐depositions with tau‐depositions at several stages of the AD continuum as measured with in‐vivo 18F‐flortaucipir PET.MethodsWe collected 10‐minutes eyes‐closed, whole‐head magnetoencephalography (MEG) recordings from 82 subjects (Table‐1) with and without Aβ‐pathology (CSF‐Aβ42 and/or amyloid‐PET) from the Amsterdam Dementia Cohort. Subjects were classed as controls (subjective cognitive decline (SCD) Aβ‐,n=25), preclinical AD (SCD Aβ+,n=16), mild cognitive impairment (MCI) due to AD (n=16) and probable AD dementia (n=25). Tau propagation was modelled as an epidemic process (susceptible‐infected (SI) model) on structural networks (Exponential Distance Rule (EDR) or EC), or functional networks (corrected‐amplitude envelope correlation (AEC‐c) in alpha (8‐13Hz) and beta (13‐30Hz) bands) derived from source‐reconstructed MEG data. The group‐level control network was used as backbone for the SI‐model to predict tau spread in the next stages of the AD continuum; parameters were tuned to produce an optimum correlation to the group‐specific tau propagation patterns as measured with dynamic 130‐minutes 18F‐flortaucipir PET, according to 50 regions‐of‐interest (ROIs) in an adjusted version of the probabilistic Hammers atlas. Tau propagation was modelled to start from one seed region (ROI14), which was selected based on its reliability to accurately measure tau deposition.ResultThe functional network predicted tau‐spread with highest accuracy in the preclinical AD stage (AEC‐c alpha r=0.59; AEC‐c beta r=0.58), followed by the structural network (r=0.45) and simple diffusion (r=0.44), Figure‐1, Figure‐2, Figure‐3. Prediction accuracy declined for the MCI and AD dementia stages (AEC‐c alpha r=0.50 and r=0.33; AEC‐c beta r=0.40 and r=0.37; structural r=0.29 and r=0.25; diffusion r=0.29 and r=0.25, respectively).ConclusionUsing a relatively simple SI‐model we predicted tau propagation in preclinical AD with an accuracy of approximately 60%. Our results suggest that tau spreads through functional connections, rather than structural connections or simple diffusion.

Comparison of Algorithms for Dementia Classification in the Survey of Health, Ageing and Retirement in Europe

AbstractBackgroundLow dementia rates, reflecting underdiagnosis in representative cohort studies, limit statistical power of etiological and preventative research. Although several algorithms for automated classification of presence or absence of dementia have been validated in the Health and Retirement Study (HRS), no such algorithm has yet been applied to the Survey of Health, Ageing and Retirement in Europe (SHARE).MethodThe Langa‐Weir classification (LW) was adapted to readily available indicators in SHARE, including immediate and delayed recall. Adapted algorithms additionally included instrumental activities of daily living (IADL) and used cut‐offs defined by either sample‐ or population‐level distributions. Performance was compared to logistic and bayesian‐logistic regression models and a gradient boosting machine (XGBoost) with the same indicators, adjusting for age groups, gender and educational level. The bayesian‐logistic regression used priors for sociodemographic indicators and global dementia incidence. Accuracy, specificity and sensitivity were compared with a train‐test split approach in SHARE wave 7 (2017).ResultIn total, N = 72,329 participants (57% female) above age 50 had no missing data on self‐reported dementia diagnosis, immediate or delayed recall and IADLs. LW based on immediate and delayed recall with a score cutoff based on dementia population‐incidence performed best overall (Accuracy = .92, Balanced Accuracy = .75, Sensitivity = .58, Specificity = .92), and showed greatest similarities to participants with self‐reported dementia diagnosis regarding risk factors and comorbidities (i.e., gripstrength, numerical performance, verbal fluency). Results from XGBoost suggested comparable performance however with risk of overfitting.ConclusionLW adaptations outperformed regression models regarding sensitivity. Comparisons of risk factor and comorbidity distributions suggest meaningful differences in comorbidities and risk factors in participants classified with and without dementia. With a lack of proxy assessments in SHARE, a suspected healthy volunteer bias and the absence of standardized cognitive assessments, probable dementia detection in SHARE necessarily comes with less confidence compared to algorithms tested in HRS. Nonetheless, performance of LW adaptations in SHARE is in line with previous validation studies in HRS. Future research should validate the algorithms through more extensive cognitive assessments once available.

The Frontal Assessment Battery (FAB) effectively discriminates between MCI and dementia within the clinical spectrum of neurochemically confirmed Alzheimer's disease.

This study aimed at testing the ability of the frontal assessment battery (FAB) to differentiate between patients with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD), as well as comparing its discriminative power to that of the Mini-Mental State Examination (MMSE). The present retrospective cohort included N = 107 Aβ-positive patients diagnosed with either MCI due to AD (N = 40) or probable AD dementia (ADD; N = 67). A two-step multiple logistic regression (MLR) was run to predict an MCI vs. ADD diagnosis based on FAB scores. Within the baseline step, demographics, disease duration, MMSE scores, and information on cognitive phenotypes were entered, with the FAB being added within the second step. Receiver-operating characteristics analyses were also run to derive intrinsic and post-test diagnostics. Within the baseline MLR step, only lower MMSE scores predicted the occurrence of ADD; by adding the FAB, which likewise was able to discriminate between MCI and ADD (p = 0.016), a significant increase in model fit was detected (p = 0.007). The diagnostic efficiency of the FAB (AUC = 0.85) was comparable (p = 0.583) to that of the MMSE (AUC = 0.82), also yielding good intrinsic and post-test diagnostics, which were comparable to those of the MMSE. The FAB is a diagnostically sound screener to discriminate between MCI and ADD, independently of patients' overall cognitive profile. In doing so, the FAB is comparable to the MMSE, and the complementation of the latter with the former is advisable in order to increase the accuracy in differentiating between MCI and ADD within screening sessions.

Cross-sectional Associations of β-Amyloid, Tau, and Cerebrovascular Biomarkers With Neurodegeneration in Probable Dementia With Lewy Bodies.

Although alpha-synuclein-related pathology is the hallmark of dementia with Lewy bodies (DLB), cerebrovascular and Alzheimer disease pathologies are common in patients with DLB. Little is known about the contribution of these pathologies to neurodegeneration in DLB. We investigated associations of cerebrovascular, β-amyloid, and tau biomarkers with gray matter (GM) volume in patients with probable DLB. We assessed patients with probable DLB and cognitively unimpaired (CU) controls with 11C-Pittsburgh compound B (PiB) and 18F-flortaucipir PET as markers of β-amyloid and tau, respectively. MRI was used to assess white matter hyperintensity (WMH) volume (a marker of cerebrovascular lesion load) and regional GM volume (a marker of neurodegeneration). We used correlations and analysis of covariance (ANCOVA) in the entire cohort and structural equation models (SEMs) in patients with DLB to investigate associations of WMH volume and regional β-amyloid and tau PET standardized uptake value ratios (SUVrs) with regional GM volume. We included 30 patients with DLB (69.3 ± 10.2 years, 87% men) and 100 CU controls balanced on age and sex. Compared with CU controls, patients with DLB showed a lower GM volume across all cortical and subcortical regions except for the cuneus, putamen, and pallidum. A larger WMH volume was associated with a lower volume in the medial and orbital frontal cortices, insula, fusiform cortex, and thalamus in patients with DLB. A higher PiB SUVr was associated with a lower volume in the inferior temporal cortex, while flortaucipir SUVr did not correlate with GM volume. SEMs showed that a higher age and absence of the APOE ε4 allele were significant predictors of higher WMH volume, and WMH volume in turn was a significant predictor of GM volume in medial and orbital frontal cortices, insula, and inferior temporal cortex. By contrast, we observed 2 distinct paths for the fusiform cortex, with age having an effect through PiB and flortaucipir SUVr on one path and through WMH volume on the other path. Patients with probable DLB have widespread cortical atrophy, most of which is likely influenced by alpha-synuclein-related pathology. Although cerebrovascular, β-amyloid, and tau pathologies often coexist in probable DLB, their contributions to neurodegeneration seem to be region specific.

Impact of diagnosed (vs undiagnosed) dementia on family caregiving experiences.

Most older adults with Alzheimer's disease and related dementias (ADRD) do not receive a timely formal diagnosis, although formal diagnosis is linked to improved outcomes. Little is known about how a recognized formal diagnosis impacts family caregivers, who provide crucial support for older adults experiencing ADRD. We analyzed 2017 National Health and Aging Trends Study and linked National Study of Caregiving data for a nationally representative sample of 724 (weighted n=5,431,551) caregivers who assisted an older adult with probable dementia. Probable dementia was determined via previously validated composite measure. We modeled caregiver experiences as a function of recognized formal ADRD diagnosis using weighted, logistic regression and adjusting for the relevant older adult and caregiver characteristics. Among caregivers who assisted an older adult with probable dementia, those assisting an individual with recognized formal ADRD diagnosis were significantly more likely to report emotional difficulty (aOR: 1.77; p=0.03) and family disagreement over the older adult's care (aOR: 5.53; p=0.03). They were also more likely to assist with communication during doctors' visits (aOR: 9.71; p < 0.001) and to receive caregiving-related training (aOR: 2.59; p=0.01). While a timely ADRD diagnosis may help ensure access to needed supports for older adult and caregiver alike, diagnosis must be linked to support as they navigate resultant complex emotions. Formal diagnosis is linked to caregiver integration with, and support from, the older adult's team of health care providers; therefore, reducing existing disparities in timely diagnosis is necessary to ensure all caregivers have equal access to support.

Estimating Likelihood of Dementia in the Absence of Diagnostic Data: A Latent Dementia Index in 10 Genetically Informed Studies.

Epidemiological research on dementia is hampered by differences across studies in how dementia is classified, especially where clinical diagnoses of dementia may not be available. We apply structural equation modeling to estimate dementia likelihood across heterogeneous samples within a multi-study consortium and use the twin design of the sample to validate the results. Using 10 twin studies, we implement a latent variable approach that aligns different tests available in each study to assess cognitive, memory, and functional ability. The model separates general cognitive ability from components indicative of dementia. We examine the validity of this continuous latent dementia index (LDI). We then identify cut-off points along the LDI distributions in each study and align them across studies to distinguish individuals with and without probable dementia. Finally, we validate the LDI by determining its heritability and estimating genetic and environmental correlations between the LDI and clinically diagnosed dementia where available. Results indicate that coordinated estimation of LDI across 10 studies has validity against clinically diagnosed dementia. The LDI can be fit to heterogeneous sets of memory, other cognitive, and functional ability variables to extract a score reflective of likelihood of dementia that can be interpreted similarly across studies despite diverse study designs and sampling characteristics. Finally, the same genetic sources of variance strongly contribute to both the LDI and clinical diagnosis. This latent dementia indicator approach may serve as a model for other research consortia confronted with similar data integration challenges.

Conceptualizing and Operationalizing Collaboration Among Multiple Caregivers of Older Adults.

In many families, multiple caregivers support older adults living with dementia. Studying collaboration among caregivers requires consideration of conceptual and methodological issues that have not been fully explored. This study presents a framework for conceptualizing caregiver collaboration and an index that captures variation in collaboration among multiple caregivers within care networks. We used data from the 2015 waves of the National Health and Aging Trends Study and National Study of Caregiving (NSOC) to operationalize collaboration among multiple caregivers (N = 1,298) of 552 care recipients (Mage = 83.69, SD = 7.73; 71.6% women; 47.9% possible/probable dementia; 38.9% people of color). The care collaboration index considered individual and overlapping contributions while controlling for the size of the care network (caregivers in network responding to NSOC survey) and total network size (number of caregivers in network) in the statistical model. Larger care networks enabled more collaboration, both in general and across most types of tasks (βs > 0.38). Collaboration was greater among those caring for a Black or Hispanic care recipient, both in general and for household and medical/health tasks specifically (βs > 0.11). Collaboration was also greater among those caring for recipients with probable dementia, both in general and for most tasks (βs > 0.11) but not transportation-related tasks (p = .219). Results are examined in the context of care network dynamics and proposed mechanisms linking care collaboration to outcomes for caregivers and recipients. Strengths and limitations of our conceptualization and operationalization of collaboration are discussed.

Caregiving for Foreign-Born Older Adults With Dementia.

This study examines how nativity, dementia classification, and age of migration (AOM) of older foreign-born (FB) adults are associated with caregiver psychological well-being and care burden. We used linked data from Round 1 and Round 5 of the National Health and Aging Trends Study and Round 5 of the National Study of Caregiving for a sample of nondementia caregivers (n = 941), dementia caregivers (n = 533), and matched care recipients. Ordinary least squares regression models were estimated, adjusting for caregiver characteristics. Relative to nondementia caregivers, dementia caregivers were more likely to provide care for an older FB adult (8.69% vs. 26.70%), reported more assistance with caregiving activities, worse quality of relationship with care recipients, and higher care burden than nondementia caregivers. In adjusted models, interactions of nativity status × dementia and AOM × dementia revealed that overall, caregivers of older FB adults with dementia who migrated in late life (50+) reported lower psychological well-being than those caring for older FB older adults who migrated at (20-49 years) and (0-19 years). Moderating effects of AOM on the link between dementia caregiving and care burden were not observed. Age of migration of older FB adults with probable dementia may have unique effects on the caregiver's psychological well-being. Our results underscore the importance of considering sociocultural factors of FB adults beyond nativity and the need for research to develop culturally appropriate interventions to enhance psychological well-being and reduce the care burden among dementia caregivers.

Abstract 10180: Systolic Blood Pressure Time in Target Range and Cognitive Outcomes: Insights From the SPRINT Trial

Introduction: Systolic blood pressure (SBP) time in target range (TTR) was proven to be a new parameter to predict cardiovascular outcomes. However, the prognostic value for cognitive function is unclear. Hypothesis: Higher TTR was associated with lower incidence of cognitive outcomes. Methods: We performed a post hoc analysis from the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized controlled trial comparing intensive (&lt;120 mm Hg) and standard (&lt;140 mm Hg) SBP interventions in 9361 individuals with hypertension. SBP target range was defined as 110 to 130 mm Hg for the intensive group and 120 to 140 mm Hg for the standard group. Participants who had less than 3 SBP measurements during this period or no cognitive assessment in the follow-up were excluded. TTR was calculated by linear interpolation using SBP from baseline to the first 3 months of follow-up. Cognitive outcomes were probable dementia, mild cognitive impairment (MCI), and a composite of probable dementia or MCI. Cox regression models were used to evaluate the relationship between TTR and cognitive outcomes. Results: A total of 8415 patients were included in this study. In univariate Cox regression analysis, higher time in target range was associated with lower risk of probable dementia. After adjustment for age, sex and race, a 1-SD increase in TTR was independently associated with a 16% lower risk of probable dementia (hazard ratio [HR] =0.84, 95% CI 0.75-0.93, P =0.002) (Figure). When we further added demographics, medical history and mean SBP to the multivariate Cox regression model, TTR remained significantly associated with a decreased risk of probable dementia (HR =0.84, 95% CI 0.74-0.96, P =0.012). No significant relationship was found between TTR and MCI or a composite of probable dementia or MCI. Conclusions: In this post hoc analysis of the SPRINT trial, SBP time in target range was an independent predictor of probable dementia beyond mean SBP levels.

Abstract 9705: Diastolic Blood Pressure and Intensive Blood Pressure Control on Cognitive Outcomes: Insights From the SPRINT Trial

Introduction: The potential benefits or harms of intensive systolic blood pressure (SBP) lowering on cognitive function in individuals with low diastolic blood pressure (DBP) remain unclear. Hypothesis: The effects of intensive SBP lowering on cognitive outcomes were consistent across baseline DBP levels. Methods: In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 8563 participants with at least one follow-up cognitive assessment were included. Cognitive outcomes were the occurrence of probable dementia, mild cognitive impairment (MCI), and a composite of probable dementia or MCI. Cox regression models and likelihood ratio tests were used to assess the interaction between DBP quartiles and intensive SBP control on cognitive outcomes. Results: The incidence rates of cognitive outcomes among participants in the lowest DBP quartile were higher than those in the other three DBP quartiles (Figure 1). However, participants in the intensive group had a lower incidence rate of probable dementia or MCI than those in the standard group, regardless of DBP quartiles. There were no significant interactions between SBP intervention and DBP quartiles for probable dementia ( P for interaction =0.06), MCI ( P for interaction =0.80), or a composite of probable dementia or MCI ( P for interaction =0.24) (Figure 2). Conclusions: In this post hoc analysis of the SPRINT study, patients with lower DBP had a higher incidence of cognitive impairment. However, the effects of intensive SBP lowering on cognitive outcomes were consistent across different DBP groups.

Diverse limbic comorbidities cause limbic and temporal atrophy in lewy body disease

BackgroundIn contrast to Alzheimer's disease (AD)-related pathology, the influence of comorbid limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) or argyrophilic grains (AG) on structural imaging in Lewy body disease (LBD) has seldom been evaluated. ObjectiveThis study aimed to investigate whether non-AD limbic comorbidities, including LATE-NC and AG, cause cortical atrophy in LBD. MethodsSeventeen patients with pathologically confirmed LBD with lower Braak neurofibrillary tangle stage (<IV) and 10 healthy controls (HC) were included. Based on the presence of comorbid LATE-NC or AG, LBD patients were subdivided into nine patients with these proteinopathies (mixed LBD [mLBD]) and eight without (pure LBD [pLBD]). In addition to clinical feature evaluation, gray matter atrophy on voxel-based morphometry was compared between the two LBD and HC groups. ResultsThe mean age at antemortem magnetic resonance imaging of the mLBD patients was higher than that of the pLBD patients (84.3 ± 3.9 vs. 76.5 ± 10.5; p = .046). Irrespective of the presence or absence of comorbid LATE-NC or AG, all patients were clinically diagnosed with probable dementia with Lewy bodies or Parkinson's disease with dementia, respectively. Compared to the pLBD group, the mLBD group showed more conspicuous cortical atrophy of the bilateral hippocampus, amygdala, and temporal pole. ConclusionsNon-AD limbic comorbidities, including LATE-NC and AG, are associated with limbic and temporal atrophy in older patients with LBD. Therefore, the possibility of non-AD limbic comorbidities should be considered in the diagnosis of elderly patients with dementia with clinical symptoms of LBD and medial temporal atrophy.