bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does inflammation explain the link between multiple sensory impairment and dementia?
Authors: Brenowitz Willa D , Eastman Jennifer Ann , Leng Yue , Yaffe Kristine 
Published: December 2021

AbstractBackgroundMultiple sensory impairments are associated with increased risk of dementia, but the underlying mechanisms are unclear. One potential explanation is that the association is due to shared risk factors such as inflammation. Our objective was to evaluate whether multisensory impairment was associated with markers of inflammation (interleukin‐6, and C‐Reactive Protein (CRP) independent of other health conditions and test whether inflammation might explain the association between multisensory impairments and dementia risk.MethodWe studied 1,794 black and white older adults from the Health, Aging, and Body Composition Study, a prospective cohort study of older adults who were aged 70‐79 and dementia‐free at enrollment. Sensory abilities were assessed at study years 3‐5, vision was measured by log contrast sensitivity, hearing by pure tone average at 500, 1,000, 2,000, and 4,000 Hz; smell by the 12‐item Cross Cultural Smell Identification Test; and touch by vibration detection threshold of the big toe. A multisensory score (0‐12) was calculated based on sample quartiles and summed across each sensory domain. Interleukin‐6, and CRP were assayed based on blood sample near baseline and log transformed. Incident dementia over follow‐up was determined based on a combination of hospitalization records, dementia medications, or clinically significant cognitive decline. Using regression models, we investigated the associations between inflammation biomarkers, multisensory impairment, and dementia with adjustment for demographics, health conditions, and health behaviors.ResultBoth measures of inflammation were associated with higher multisensory impairment scores. 1‐log interleukin‐6 was associated with 0.25 points worse multisensory score (95%CI: 0.10, 0.40; p>0.001), 1‐log CRP levels was associated with 0.11 points worse multisensory score (95%CI: 0.01, 0.20; p=0.02). Higher level of interleukin‐6 (HR = 1.18; 95% CI: 1.02, 1.37; p=0.03) but not CRP (p=0.84) was associated increased dementia risk. In adjusted models, a 1‐point increase in the multisensory score was associated with a 14% higher risk of dementia (95% CI: 1.08; 1.20), estimates were similar even after including interleukin‐6 as an explanatory variable.ConclusionInflammation was independently associated with worse multisensory impairment scores. Although inflammation is also associated with dementia, it did not explain the association between multisensory impairment and dementia.
Brief smell identification test performance in RBD, DLB and AD
Authors: Forsberg Leah K. , Syrjanen Jeremy A , Ferman Tanis J , Boeve Bradley F. , Miyagawa Toji , Graff‐Radford Neill R. , Knopman David S. , Graff‐Radford Jonathan , Savica Rodolfo , Savica Rodolfo , Jones David T. , Fields Julie A. , Lucas John A. , Allen Laura A , St. Louis Erik K , Silber Michael H , Petersen Ronald C. 
Published: December 2021

AbstractBackgroundImpaired olfaction has been associated with neurodegenerative diseases and may be a useful tool to aid in diagnosis or track disease progression. We sought to compare olfaction in participants with the clinical diagnoses of idiopathic REM sleep behavior disorder (RBD), dementia with Lewy bodies (DLB), or Alzheimer’s disease dementia (AD).MethodParticipants from the Mayo Clinic Alzheimer’s Disease Research Center database who had a diagnosis of RBD (n=27, 56% male), DLB (n=51, 84% male), or AD (n=83, 47% male), and were given the Brief Smell Identification Test (B‐SIT) were included in this analysis. The B‐SIT score was calculated as the sum of correct responses (12 possible). Scores were categorized as reflecting anosmia (<6), hyposmia (6‐10), and normal olfactory function (>10). All participants underwent clinical and neuropsychological evaluations.ResultGlobal cognition was lower in AD and DLB than RBD (MMSE 21.5 ±4.9 in AD, 23.3 ±4.3 in DLB, 28.8 ± 1.2 in RBD; p <0.001). The mean B‐SIT total score was significantly lower for DLB (4.5 ± 3.1) compared to RBD (7.5 ± 3.0) or AD (7.0 ± 2.7) (p<0.001) using an ANOVA F‐test. Anosmia was present in 76% of DLB, which compared to 32% in RBD, and 32% in AD (p=0.9). Hyposmia was present in 18% of DLB, 47% of RBD, and 52% of AD (p=ns). Of 22 patients with normal olfaction, X% were DLB, X% RBD, and X% AD (p=X). An item analysis illustrated that participants with DLB were less likely to identify Menthol, Clove, Strawberry, Smoke, and Soap than those with RBD and AD. On serial examination, 12 RBD (60%) patients’ B‐SIT score decreased by at least one point at their most recent visit compared to their baseline visit.ConclusionThese findings suggest that impaired olfactory function is frequent in RBD, DLB and AD, with olfaction being worst in DLB in this cohort. Olfaction was declining in most of those with RBD who underwent serial evaluations. Further analyses are needed to determine if any scents are more sensitive to phenotype, progression, and degree of cognitive impairment. Supported by: NIH grants AG016574, NS100620, AG056639, AG015866
Evaluation of blood pressure and cognitive function using individual participant data meta‐analysis: The Life‐Course Blood Pressure Cognition (LCBP‐COG) study
Authors: Xu Ying , McFall G. Peggy , Rydén Lina , Skoog Johan , Tully Phillip J , Anderson Craig S , Anstey Kaarin J , Cherbuin Nicolas , Dixon Roger A , Skoog Ingmar , Peters Ruth 
Published: December 2021

AbstractBackgroundThe prognostic significance of various blood pressure (BP) indices (i.e. systolic BP [SBP], diastolic BP [DBP], pulse pressure [PP] and mean arterial pressure [MAP]) on cardio‐ and cerebrovascular health vary across age groups. We examined the association between baseline BP indices in mid‐ and late‐life and cognitive function over a 9‐15 year period.MethodWe performed pooled analyses of data from 3 longitudinal cohort studies. The Personality and Total Health (PATH) Through Life study of adults initially aged 40‐44 and 60‐64 years in Australia, and Victoria Longitudinal Study (VLS) of adults initially aged 55‐85 years in Canada, included four waves of data collection every 4‐5 years. The Gothenburg H70 Birth cohort study of adults initially aged 70 years included three waves of data collection every 4‐5 years. The association between baseline BP and cognitive decline on the Mini‐Mental State Examination (MMSE) was categorized using the reliable change index (Duff K. 2012) and analyzed using logistic regression adjusted for age, sex, and study. Additional analyses examined relationships between baseline BP and repeated cognitive measures of memory, attention and processing speed, and executive function, using linear mixed models (PATH and H70). Only participants with complete BP and cognitive measures were included.ResultData from 2912 participants (mean baseline age 54.3 years, range 40 to 83 years, 1395 (47.9%) male) were included. Examining baseline BP and age, we observed SBP increasing with age until a small decrease at around 80 years. DBP and MAP also showed an increase with age until early late‐life (around 60 years) and were lower at older ages, PP consistently increased (Figure 1). There were no relationships between baseline BP measures and MMSE. For PATH only, higher SBP (P=0.002), DBP (P=0.0007) and MAP (P=0.0006) at age 40 years, and higher DBP (P=0.004) at 60 years, were associated with greater annual deterioration in attention and processing speed (symbol‐digit‐modalities test) over the subsequent decade (Figure 2).ConclusionHigher BP in midlife and DBP in early late‐life, were associated with a greater decline in measures of attention and processing speed. We observed no associations between BP and MMSE decline.
Longitudinal motor decline in dementia with Lewy bodies and Parkinson’s disease dementia in a community autopsy cohort
Authors: Choudhury Parichita , Zhang Nan , Shprecher David , Belden Christi , Goldfarb Danielle , Shill Holly , Mehta Shyamal , Driver‐Dunckley Erika , Serrano Geidy E , Beach Thomas G , Adler Charles , Atri Alireza 
Published: December 2021

AbstractBackgroundAlthough parkinsonism is a core feature of Parkinson’s Disease Dementia (PDD) and Dementia with Lewy bodies (DLB), its evolution is less delineated. We aimed to assess differences in severity and progression of parkinsonian motor symptoms and signs in a community autopsy cohort with clinicopathologic diagnosis of DLB, PDD or Alzheimer’s Disease (AD).MethodData included were from 194 participants in the Arizona study of Aging and Neurodegenerative Disorders with clinicopathologic diagnosis of DLB (n=48), PDD (n=98) (±AD co‐pathology) or pure AD (n=48), and at least two movement exams performed by movement disorders subspecialists who classified PD and parkinsonism according to MDS‐UPDRS criteria. DLB was subgrouped by presence or absence of parkinsonism at final exam (DLB+Park and DLB–Park). Between group trajectory of UPDRS‐II and UPDRS‐III scores were explored using piecewise‐linear and non‐linear MMRM multivariate analysis.ResultOver 1435 participant‐years of longitudinal data were included in the analyses (Figure 1). Mean±SD age at baseline movement exam and death were 76.0±7.5 and 83.4±6.8 years, respectively. At baseline, most participants did not have dementia or substantial motor abnormalities (except motor abnormalities in PDD). DLB (73.9%) and PDD (69.2%) groups had more males than AD (33.3%). Parkinsonism was present in 65.6% of DLB at last exam. Piecewise‐linear MMRM analysis showed baseline UPDRS‐II and UPDRS‐III scores were highest (p<0.001) for PDD (mean±SE: 14.3±0.78 and 27.4±1.64), followed by DLB+Park (5.0±1.05 and 17.4±3.10), DLB‐Park (3.7±2.54 and 3.8±1.35) and AD (3.2±0.88 and 8.0±1.94). Annual rate of increase in UPDRS‐II was greatest for DLB+Park (1.44±0.20) and PDD (1.04±0.08), followed by DLB‐Park (0.89±0.18) and AD (0.30±0.11). Annual rate of increase in UPDRS‐III was highest for PDD and DLB+Park (2.12±0.20 vs 2.64±0.42), followed by DLB‐Park and AD (1.31 ± 0.38 and 0.64 ± 0.22). Preliminary non‐linear MMRM models (Figure 2) further supported substantial between group/subgroup differences in motor trajectories, and progression in DLB‐Park.ConclusionThese preliminary results in a large, well‐characterized clinicopathological community‐based autopsy cohort support that DLB+Park experience comparable, or greater, parkinsonian motor progression to PDD. Future modeling/sensitivity analyses will better delineate expected trajectories of motor progression to add prognostication value in clinic and design of DLB clinical trials.
Microstructural alterations in medial temporal and frontal white matter tracts are associated with subjective cognitive decline
Authors: Archer Derek B , Moore Elizabeth E. , Pamidimukkala Ujwala , Shashikumar Niranjana , Pechman Kimberly R. , Blennow Kaj , Zetterberg Henrik , Landman Bennett A. , Hohman Timothy J. , Jefferson Angela L. , Gifford Katherine A. 
Published: December 2021

AbstractBackgroundSubjective cognitive decline (SCD) is a perceived cognitive change prior to objective cognitive deficits, and although it is associated with Alzheimer’s disease (AD) pathology, it likely results from multiple underlying pathologies. We investigated the association of white matter microstructure to SCD as a sensitive and early marker of cognitive decline and quantified the contribution of white matter microstructure separate from amyloidosis.MethodVanderbilt Memory & Aging Project participants with diffusion MRI data and a 45‐item measure of SCD were included (n=237, 73±7 years, 37% female). A subset of participants (n=104) underwent a fasting lumbar puncture for quantification of amyloid‐β (CSF Aβ42). Diffusion MRI data was post‐processed using the free‐water (FW) elimination technique, which allowed quantification of extracellular (FW) and intracellular compartment (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) microstructure. Microstructural values were quantified within 11 cognitive‐related white matter tracts, including medial temporal lobe, frontal transcallosal, and fronto‐parietal tracts. General linear modeling related each tract to SCD adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile scores, APOE‐ε4 carrier status, diagnosis, Geriatric Depression Scale scores, and total white matter volume. Competitive model analyses were conducted to determine if white matter microstructural values have a unique role in SCD separate from CSF Aβ42.ResultFW‐corrected radial diffusivity (RDT) was related to SCD in 6 tracts: cingulum bundle (β=3.52x106; p=0.001), inferior longitudinal fasciculus (β=2.77x106; p=0.005), as well as inferior frontal gyrus (IFG) pars opercularis (β=1.98x106; p=0.008), IFG pars triangularis (β=2.69x106; p=0.008), medial frontal gyrus (β=2.46x106; p=0.007), and middle frontal gyrus (β=2.47x106; p=0.014) transcallosal tracts. While CSF Aβ42 was related to SCD in our cohort (β=‐0.021; p=0.020), competitive model analyses revealed that fornix and IFG pars triangularis transcallosal tract RDT contributed unique variance to SCD beyond CSF Aβ42.ConclusionMedial temporal lobe and frontal transcallosal tract microstructure is an important driver of SCD independent of early AD pathology. Given RDT appears to be the most significant predictor of SCD, demyelination may be an early contributor to cognitive decline. These results highlight the value of incorporating multiple biomarkers to help disentangle the mechanistic heterogeneity of SCD as an early stage of cognitive decline.
Implementation of remote neuropsychological assessments in the Insight 46 study: Lessons learned from the transition to videoconferencing and telephone assessments
Authors: Street Rebecca E , Lu Kirsty , Freiberger Tamar , Murray‐Smith Heidi , Keuss Sarah E , Baker John , Wong Andrew , Richards Marcus , Fox Nick C , Crutch Sebastian J , Schott Jonathan M 
Published: December 2021

AbstractBackgroundInsight 46 is a longitudinal neuroscience sub‐study of the MRC National Survey of Health and Development (the British 1946 Birth Cohort). In March 2020, the COVID‐19 pandemic, and the introduction of lockdown measures across the UK, demanded a transition from traditional face‐to‐face data collection methods to teleconference‐based testing, to ensure the safety of our vulnerable cohort and the ongoing collection of longitudinal data. We present our approach to adapting and expanding our existing telephone assessment procedures to include as many tests as possible from our standard neuropsychology battery.MethodsParticipants with a computer or tablet with a webcam, microphone, and screen dimensions greater than 9 inches were offered a Microsoft Teams videoconference assessment; those without were offered a telephone visit to ensure maximum data collection. Videoconference and telephone batteries were created under copyright agreements. Item‐by‐item responses were collected digitally, and audio‐recording software was used to capture verbal responses where appropriate. Pre‐visit packs containing assessment materials in sealed envelopes (to prevent advance sight of materials) were sent ahead of each assessment. Due to specific equipment or software requirements, computerised assessments could not be performed (see Table 1).Result65% of the remaining eligible participants completed a remote assessment (see table 2). Despite offering one‐to‐one videoconferencing training, a major reason for drop‐out was concerns about technology, in addition to hearing difficulties and other health considerations. During administration, challenges included ensuring a standardised research environment and overcoming technological issues. Detailed scripts and protocols were implemented to guarantee uniform administrations, as well as detailed recording of unexpected events such as distractions and technology failures.ConclusionOur methods allowed for the continuation of longitudinal data collection, demonstrating the feasibility of teleneuropsychology in elderly populations. Positive feedback demonstrated participants’ acceptance of telehealth approaches and their appreciation of the value of continuing research. Future implementation of these methods could increase retention in populations previously prevented by physical barriers. However, careful consideration must be given to the validity and reliability of remote administration, and the differences between telephone and videoconferencing methods.
Incidence and prevalence of coexistent retinal diseases and cognitive impairment or dementia: A systematic review
Authors: Xu Ying , Phu Jack , Aung Htein Linn , Hesam‐Shariati Negin , Auty Jack , Keay Lisa , Tully Phillip J , Booth Andrew , Anderson Craig S , Anstey Kaarin J , Peters Ruth 
Published: December 2021

AbstractBackgroundAs chronic and progressive age‐related diseases, there are commonalities between age‐related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), and cognitive impairment (CI) and dementia. We undertook a systematic review to quantify such associations.MethodMEDLINE, EMBASE, PsycINFO and CINAHL were searched (from inception to June 2020) for observational studies reporting incidence or prevalence of AMD, glaucoma or DR in people with CI or dementia, and CI or dementia among people with AMD, glaucoma or DR. A 9‐item quality assessment tool was used to categorize studies as having low, moderate or high risk of bias. Rates of comorbid disease were extracted and presented in forest plots. Prospero registration [CRD42020189484].ResultOf 6,803 abstracts reviewed, 76 were considered for full‐text analysis, of which 47 were included for syntheses. There were 27 and 20 assessed as having low and moderate risk of bias, respectively.Incidence of dementia in people with age‐related retinal diseases ranged from 9.5 to 20 (AMD), from 1.1 to 11.6 (glaucoma) and was 32.9 (DR) per 1000 person‐years, respectively (Figure 1). There were no reports on the incidence of CI in AMD, glaucoma or DR, nor of retinal diseases in CI or dementia.There were two studies reporting prevalence of AMD or glaucoma in people with CI (Figure 2). Prevalence of DR in those with CI ranged from 11.4% to 70.1%. Prevalence of AMD, glaucoma and DR among people with dementia ranged from 1.4% to 52.6%, from 0.2% to 25.9% and from 11 to 20%, respectively.Prevalence of CI in people with AMD, glaucoma and DR ranged from 8.4% to 52.4%, from 2.8% to 90.2% and from 3.9% to 45.2%, respectively (Figure 3). Prevalence of dementia in people with AMD, glaucoma and DR ranged from 9.9% to 62.6%, 2.5% to 3% and 0.8% to 12.5%, respectively.ConclusionThere are wide ranging estimates of incidence and prevalence of retinal diseases in relation to CI/dementia. Further research is required to better understand the reasons for such variations.
Levels of circulating memory CD8 T cells that induce AD‐like pathology in mice correlate with cognition and decreased CSF Aβ1‐42 in AD and control patients
Authors: Wheeler Christopher J. , Van Dam Debby , Vermeiren Yannick , De Reu Hans , De Deyn Peter Paul , Yamamoto Vicky , Trujillo Kristina 
Published: December 2021

AbstractBackgroundWe previously engineered mice to accumulate age‐related, antigen‐specific memory CD8 T cells as in humans. These mice spontaneously develop all major hallmarks of AD with aging. Analogous T cells reactive to an epitope on Amyloid Precursor Protein (APP) were found in aging humans, accumulated in AD brain, and decreased in AD blood where their levels accurately tracked the disease in initial analysis. Here, we examine whether levels of these blood T cells are associated with established AD biomarkers.MethodAntigen‐specific CD8 T cells in blood were quantified by flow cytometric analysis after staining with anti‐CD8, anti‐KLRG1 and APP peptide‐HLA‐A2 multimers in normal aging, MCI with or without AD biomarkers, and confirmed late‐onset AD patient cohorts (n = 50). Aβ1‐42, total Tau, and pTau181 were quantified in CSF, and cognitive performance assessed by MMSE.ResultPercentage of APP‐specific memory CD8 T cells was significantly decreased with dementia (0.68 + 0.29% for MMSE <25; 1.63 + 0.32% for MMSE >24), reaching minimal levels in AD. Although the paucity of APP‐specific CD8 T cells in AD blood precluded meaningful correlations, decreases in the larger parental (KLRG1+) memory CD8 T cell population correlated with decreased CSF Aβ1‐42 in AD (r = 0.511; P = 0.003; n = 31). Decreasing APP‐specific CD8 T cells in blood also correlated with lower CSF Ab1‐42 in normal aging patients (r = 0.518; P = 0.028; n = 18). No significant correlations between T cell levels and total Tau or pTau181 were observed.ConclusionOur results reveal that age‐related memory CD8 T cells in blood decrease with dementia, and in proportion to decreased CSF Aβ1‐42 in both AD and normal aging. Given that decreased CSF Aβ1‐42 is among the earliest biomarkers for AD, this validates our previous findings that loss of APP‐specific memory CD8 T cells from blood accurately tracks the AD continuum in humans. Our findings also support the notion that antigen‐specific memory CD8 T cells are associated with the earliest detectable pathologic changes in AD, and as such may represent novel cause‐associated biomarker candidates to predict and track the disease.
How to define ‘N’ in the ATN classification in subjective cognitive decline: The SCIENCe project
Authors: Ebenau Jarith L. , Verberk Inge M.W. , Verfaillie Sander C.J. , van den Bosch Karlijn A. , Scheltens Philip , Prins Niels D. , Barkhof Frederik , Van Berckel Bary N.M. , Teunissen Charlotte E. , van der Flier Wiesje M. 
Published: December 2021

AbstractBackgroundDifferent biomarkers have been suggested to measure neurodegeneration (N) in the ATN classification. We aimed to compare N biomarkers measured with different modalities and assess their association with clinical progression.MethodWe included 401 individuals with subjective cognitive decline (SCD, 61±9y, 42%F, MMSE28±2, follow‐up 3±3y). We used the following biomarkers for N: CSF t‐tau, medial temporal atrophy (MTA) visual rating on MRI, hippocampal volume (HV), serum neurofilament light (NfL) and serum glial fibrillary acidic protein (GFAP). We first compared biomarkers (Pearson correlation) and assessed the association between N biomarkers and progression to mild cognitive impairment or dementia (Cox proportional hazards analysis). We additionally investigated whether the addition of N biomarkers improved a Cox model with CSF abeta and p‐tau as predictors (likelihood ratio test). Last, we compared associations between N biomarkers and MMSE score over time (linear mixed models). Models were corrected for age and sex, and additionally for intracranial volume when HV was used as predictor. P‐tau, t‐tau, NfL and GFAP were log‐transformed, abeta and HV were inverted, and all biomarkers were z‐transformed.ResultN biomarkers were weakly to moderately correlated (range r ‐0.20 – 0.58, Figure 1). Of these, NfL and GFAP, both serum markers, correlated most strongly (r 0.58). T‐tau was strongly correlated with p‐tau, although these biomarkers supposedly represent separate biomarker groups (r 0.89). T‐tau, HV, NfL and GFAP individually predicted clinical progression (range hazard ratios 1.4 – 2.1). Models including abeta and p‐tau improved when HV, NfL or GFAP were added as predictors (t‐tau not entered due to collinearity with p‐tau, Table 1). Last, t‐tau, HV and GFAP were individually associated with MMSE slope (range betas −0.17 – −0.15).ConclusionIn a sample of cognitively normal individuals, correlations between different N biomarkers were low, indicating they do not reflect the same underlying pathology. T‐tau was strongly associated with p‐tau, thereby disqualifying as measure for N. HV, NfL and GFAP predicted clinical progression. Our results do not allow to choose one most suitable biomarker for N, but illustrate room for improved prediction beyond abeta and p‐tau.