scholarly journals CSF tau and β-amyloid predict cerebral synucleinopathy in autopsied Lewy body disorders

Neurology ◽  
2018 ◽  
Vol 90 (12) ◽  
pp. e1038-e1046 ◽  
Author(s):  
David J. Irwin ◽  
Sharon X. Xie ◽  
David Coughlin ◽  
Naomi Nevler ◽  
Rizwan S. Akhtar ◽  
...  
Keyword(s):  
Lewy Body ◽  
Mean Difference ◽  
Csf Biomarkers ◽  
Cerebral Pathology ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Regression Diagnostic ◽  
Cortical Regions ◽  
And Control ◽  
T Tau

ObjectiveTo test the association of antemortem CSF biomarkers with postmortem pathology in Lewy body disorders (LBD).MethodsPatients with autopsy-confirmed LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and cognitively normal (n = 36) controls were studied. In LBD, neuropathologic criteria defined Lewy body α-synuclein (SYN) stages with medium/high AD copathology (SYN + AD = 10) and low/no AD copathology (SYN − AD = 14). Ordinal pathology scores for tau, β-amyloid (Aβ), and SYN pathology were averaged across 7 cortical regions to obtain a global cerebral score for each pathology. CSF total tau (t-tau), phosphorylated tau at threonine181, and Aβ1-42 levels were compared between LBD and control groups and correlated with global cerebral pathology scores in LBD with linear regression. Diagnostic accuracy for postmortem categorization of LBD into SYN + AD vs SYN − AD or neocortical vs brainstem/limbic SYN stage was tested with receiver operating curves.ResultsSYN + AD had higher CSF t-tau (mean difference 27.0 ± 8.6 pg/mL) and lower Aβ1-42 (mean difference −84.0 ± 22.9 g/mL) compared to SYN − AD (p < 0.01, both). Increasing global cerebral tau and plaque scores were associated with higher CSF t-tau (R2 = 0.15–0.16, p < 0.05, both) and lower Aβ1-42 (R2 = 0.43–0.49, p < 0.001, both), while increasing cerebral SYN scores were associated with lower CSF Aβ1-42 (R2 = 0.31, p < 0.001) and higher CSF t-tau/Aβ1-42 ratio (R2 = 0.27, p = 0.01). CSF t-tau/Aβ1-42 ratio had 100% specificity and 90% sensitivity for SYN + AD, and CSF Aβ1-42 had 77% specificity and 82% sensitivity for neocortical SYN stage.ConclusionsHigher antemortem CSF t-tau/Aβ1-42 and lower Aβ1-42 levels are predictive of increasing cerebral AD and SYN pathology. These biomarkers may identify patients with LBD vulnerable to cortical SYN pathology who may benefit from both SYN and AD-targeted disease-modifying therapies.

Association Between CSF Beta-Amyloid and Apathy in Early-Stage Alzheimer Disease

2019 ◽  
Vol 32 (3) ◽  
pp. 164-169 ◽  
Author(s):  
A. Vergallo ◽  
L. Giampietri ◽  
C. Pagni ◽  
F. S. Giorgi ◽  
V. Nicoletti ◽  
...  
Keyword(s):  
Early Stage ◽  
Clinical Feature ◽  
Csf Biomarkers ◽  
Potential Association ◽  
Modifying Effect ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Item Scores ◽  
T Tau ◽  
Late Stages

Aim: The apathetic syndrome is a common clinical feature in patients with Alzheimer diseases (AD), from preclinical phases to late stages of dementia, and it is strongly related to major disease outcomes. Unfortunately, no specific pharmacological treatments for apathy have been accomplished so far. Translational evidences have previously shown that a link between apathy and hallmarks of AD-related pathophysiology, that is, β-amyloid (Aβ) plaques and neurofibrillary tangles, exists. However, only few studies investigated the association between core biomarkers of AD and apathy scores, finding conflicting results. Methods: Thirty-seven patients were identified as having AD dementia according to National Institute on Aging–Alzheimer Association 2011 criteria. All participants underwent an extensive diagnostic workup including cerebrospinal fluid (CSF) assessment to measure the concentrations of Aβ42, t-tau, and pTau181. To follow, they were stratified as: apathy absence, apathy mild, and apathy severe according to the Neuro Psychiatric Inventory-apathy item scores. We investigated for potential associations between apathy scores and CSF biomarkers concentrations as well as for differences in terms of clinical and CSF biomarkers data across the 3 apathy groups. Results: The CSF Aβ42 concentrations were negatively correlated with apathy scores. In addition, patients with severe apathy had significantly lower Aβ42 levels compared to nonapathetic ones. Conclusion: Based on our results, we encourage further studies to untangle the potential association between the complex pathophysiological dynamics of AD and apathy which may represent an innovative reliable clinical outcome measure to use in clinical trials, investigating treatments with either a symptomatic or a disease-modifying effect.

scholarly journals Cardiorespiratory fitness alters the influence of a polygenic risk score on biomarkers of AD

Neurology ◽  
2017 ◽  
Vol 88 (17) ◽  
pp. 1650-1658 ◽  
Author(s):  
Stephanie A. Schultz ◽  
Elizabeth A. Boots ◽  
Burcu F. Darst ◽  
Henrik Zetterberg ◽  
Kaj Blennow ◽  
...  
Keyword(s):  
Cardiorespiratory Fitness ◽  
Risk Score ◽  
Csf Biomarkers ◽  
Polygenic Risk Score ◽  
Regression Analyses ◽  
Cross Sectional ◽  
Polygenic Risk ◽  
Β Amyloid ◽  
Adverse Influence ◽  
T Tau

Objective:To examine whether a polygenic risk score (PRS) derived from APOE4, CLU, and ABCA7 is associated with CSF biomarkers of Alzheimer disease (AD) pathology and whether higher cardiorespiratory fitness (CRF) modifies the association between the PRS and CSF biomarkers.Methods:Ninety-five individuals from the Wisconsin Registry for Alzheimer's Prevention were included in these cross-sectional analyses. They were genotyped for APOE4, CLU, and ABCA7, from which a PRS was calculated for each participant. The participants underwent lumbar puncture for CSF collection. β-Amyloid 42 (Aβ42), Aβ40, total tau (t-tau), and phosphorylated tau (p-tau) were quantified by immunoassays, and Aβ42/Aβ40 and tau/Aβ42 ratios were computed. CRF was estimated from a validated equation incorporating sex, age, body mass index, resting heart rate, and self-reported physical activity. Covariate-adjusted regression analyses were used to test for associations between the PRS and CSF biomarkers. In addition, by including a PRS×CRF term in the models, we examined whether these associations were modified by CRF.Results:A higher PRS was associated with lower Aβ42/Aβ40 (p < 0.001), higher t-tau/Aβ42 (p = 0.012), and higher p-tau/Aβ42 (p = 0.040). Furthermore, we observed PRS × CRF interactions for Aβ42/Aβ40 (p = 0.003), t-tau/Aβ42 (p = 0.003), and p-tau/Aβ42 (p = 0.001). Specifically, the association between the PRS and these CSF biomarkers was diminished in those with higher CRF.Conclusions:In a late-middle-aged cohort, CRF attenuates the adverse influence of genetic vulnerability on CSF biomarkers. These findings support the notion that increased cardiorespiratory fitness may be beneficial to those at increased genetic risk for AD.

scholarly journals Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression

2019 ◽  
Vol 30 (4) ◽  
pp. 2144-2156 ◽  
Author(s):  
Anders M Fjell ◽  
Donatas Sederevicius ◽  
Markus H Sneve ◽  
Ann-Marie Glasø de Lange ◽  
Anne CecilieSjøli Bråthen ◽  
...  
Keyword(s):  
Sleep Quality ◽  
Sleep Problems ◽  
Older Individuals ◽  
Accumulation Pattern ◽  
Anatomical Distribution ◽  
Healthy Older Adults ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Cortical Regions ◽  
The Relationship

Abstract Sleep problems are related to the elevated levels of the Alzheimer’s disease (AD) biomarker β-amyloid (Aβ). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aβ accumulation. Here, we tested whether the relationship between cortical Aβ accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aβ correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aβ relationship followed closely the Aβ accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aβ accumulation may involve Homer1 activity in the cortical regions, where harbor Aβ deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.

scholarly journals Association of amyloid-β CSF/PET discordance and tau load 5 years later

Neurology ◽  
2020 ◽  
Vol 95 (19) ◽  
pp. e2648-e2657 ◽  
Author(s):  
Juhan Reimand ◽  
Lyduine Collij ◽  
Philip Scheltens ◽  
Femke Bouwman ◽  
Rik Ossenkoppele ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Tau Pathology ◽  
Cognitively Normal ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Tau Pet

ObjectiveTo investigate the association between discordant β-amyloid (Aβ) PET and CSF biomarkers at baseline and the emergence of tau pathology 5 years later.MethodsWe included 730 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [18F]florbetapir PET and CSF Aβ42 available. Aβ CSF/PET status was determined at baseline using established cutoffs. Longitudinal data were available for [18F]florbetapir (Aβ) PET (baseline to 4.3 ± 1.9 years), CSF (p)tau (baseline to 2.0 ± 0.1 years), cognition (baseline to 4.3 ± 2.0 years), and [18F]flortaucipir (tau) PET (measured 5.2 ± 1.2 years after baseline to 1.6 ± 0.7 years later). We used linear mixed modeling to study the association between Aβ CSF/PET status and tau pathology measured in CSF or using PET. We calculated the proportion of CSF+/PET− participants who during follow-up (1) progressed to Aβ CSF+/PET+ or (2) became tau-positive based on [18F]flortaucipir PET.ResultsAβ CSF+/PET+ (n = 318) participants had elevated CSF (p)tau levels and worse cognitive performance at baseline, while CSF+/PET− (n = 80) participants were overall similar to the CSF−/PET− (N = 306) group. Five years after baseline, [18F]flortaucipir PET uptake in the CSF+/PET− group (1.20 ± 0.13) did not differ from CSF−/PET− (1.18 ± 0.08, p = 0.69), but was substantially lower than CSF+/PET+ (1.48 ± 0.44, p < 0.001). Of the CSF+/PET− participants, 21/64 (33%) progressed to Aβ CSF+/PET+, whereas only one (3%, difference p < 0.05) became tau-positive based on [18F]flortaucipir PET.ConclusionsAβ load detectable by both CSF and PET seems to precede substantial tau deposition. Compared to participants with abnormal Aβ levels on both PET and CSF, the CSF+/PET− group has a distinctly better prognosis.

scholarly journals CSF neurofilament light concentration is increased in presymptomatic CHMP2B mutation carriers

Neurology ◽  
2017 ◽  
Vol 90 (2) ◽  
pp. e157-e163 ◽  
Author(s):  
Nina Rostgaard ◽  
Peter Roos ◽  
Erik Portelius ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Continuous Process ◽  
Csf Biomarkers ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Preclinical Phase ◽  
Mutation Carriers ◽  
Amyloid Aβ ◽  
Multiplexed Immunoassay ◽  
T Tau

ObjectiveA rare cause of familial frontotemporal dementia (FTD) is a mutation in the CHMP2B gene on chromosome 3 (FTD-3), described in a Danish family. Here we examine whether CSF biomarkers change in the preclinical phase of the disease.MethodsIn this cross-sectional explorative study, we analyzed CSF samples from 16 mutation carriers and 14 noncarriers from the Danish FTD-3 family. CSF biomarkers included total tau (t-tau) and neurofilament light chain (NfL) as a marker for neurodegeneration, phosphorylated tau (p-tau) as a marker for tau pathology, β-amyloid (Aβ) 38, 40, and 42 (Aβ38, Aβ40, and Aβ42) to monitor Aβ metabolism, and YKL-40 as a marker of neuroinflammation. Aβ isoform concentrations were measured using a multiplexed immunoassay; t-tau, p-tau, NfL, and YKL-40 concentrations were measured using sandwich ELISAs.ResultsCSF NfL concentration was significantly increased in mutation carriers vs noncarriers. Further, CSF NfL concentration was significantly higher in symptomatic mutation carriers compared to presymptomatic carriers, and also significantly higher in presymptomatic carriers compared to noncarriers. No differences in t-tau and p-tau and YKL-40 concentrations between controls and mutation carriers were observed. CSF concentrations of the Aβ peptides Aβ38 and Aβ40 but not Aβ42 were significantly lower in mutation carriers compared to noncarriers.ConclusionsIncreased NfL levels in presymptomatic individuals and in symptomatic patients with FTD-3 indicate a continuous process of neurodegeneration from the presymptomatic to symptomatic state. Although not specific for FTD-3 pathology, our data suggest that CSF NfL could serve as a valuable biomarker to detect onset of neurodegeneration in FTD-3 mutation carriers.

scholarly journals Core cerebrospinal fluid biomarker profile in cerebral amyloid angiopathy

Neurology ◽  
2018 ◽  
Vol 90 (9) ◽  
pp. e754-e762 ◽  
Author(s):  
Andreas Charidimou ◽  
Jan O. Friedrich ◽  
Steven M. Greenberg ◽  
Anand Viswanathan
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Meta Analysis ◽  
Csf Biomarkers ◽  
Amyloid Angiopathy ◽  
Healthy Controls ◽  
Comparison Groups ◽  
Amyloid Aβ ◽  
Cerebral Amyloid ◽  
T Tau ◽  
Fluid Biomarker

ObjectiveTo perform a meta-analysis of 4 core CSF biomarkers (β-amyloid [Aβ]42, Aβ40, total tau [t-tau], and phosphorylated tau [p-tau]) to assess which of these are most altered in sporadic cerebral amyloid angiopathy (CAA).MethodsWe systematically searched PubMed for eligible studies reporting data on CSF biomarkers reflecting amyloid precursor protein metabolism (Aβ42, Aβ40), neurodegeneration (t-tau), and tangle pathology (p-tau) in symptomatic sporadic CAA cohorts vs controls and patients with Alzheimer disease (AD). Biomarker performance was assessed in random-effects meta-analysis based on ratio of mean (RoM) biomarker concentrations: (1) in patients with CAA vs healthy controls and (2) in patients with CAA vs patients with AD. RoM >1 indicates higher biomarker concentration in patients with CAA vs comparison population and RoM <1 indicates higher concentration in comparison groups.ResultsThree studies met inclusion criteria. These comprised 5 CAA patient cohorts (n = 59 patients) vs healthy controls (n = 94 cases) and AD cohorts (n = 158). Three core biomarkers differentiated CAA from controls: CSF Aβ42 (RoM 0.49, 95% confidence interval [CI] 0.38–0.64, p < 0.003), Aβ40 (RoM 0.70, 95% CI 0.63–0.78, p < 0.0001), and t-tau (RoM 1.54, 95% CI 1.15–2.07, p = 0.004); p-tau was marginal (RoM 1.24, 95% CI 0.99–1.54, p = 0.062). Differentiation between CAA and AD was strong for CSF Aβ40 (RoM 0.76, 95% CI 0.69–0.83, p < 0.0001), but not Aβ42 (RoM 1.00; 95% CI 0.81–1.23, p = 0.970). For t-tau and p-tau, average CSF ratios in patients with CAA vs patients with AD were 0.63 (95% CI 0.54–0.74, p < 0.0001) and 0.60 (95% CI 0.50–0.71, p < 0.0001), respectively.ConclusionSpecific CSF patterns of Aβ42, Aβ40, t-tau, and p-tau might serve as molecular biomarkers of CAA, but analyses in larger CAA cohorts are needed.

Sex differences in CSF biomarkers vary by Alzheimer disease stage and APOE ε4 genotype

Neurology ◽  
2020 ◽  
Vol 95 (17) ◽  
pp. e2378-e2388 ◽  
Author(s):  
Rosha Babapour Mofrad ◽  
Betty M. Tijms ◽  
Philip Scheltens ◽  
Frederik Barkhof ◽  
Wiesje M. van der Flier ◽  
...  
Keyword(s):  
Sex Differences ◽  
Alzheimer Disease ◽  
Clinical Disease ◽  
Disease Stage ◽  
Subjective Cognitive Decline ◽  
Csf Biomarkers ◽  
Β Amyloid ◽  
Disease Stages ◽  
T Tau

ObjectiveTo evaluate sex differences in CSF biomarkers, taking the potential modifying role of clinical disease stage and APOE ε4 genotype into account.MethodWe included participants (n = 1,801) with probable Alzheimer disease (AD) dementia (n = 937), mild cognitive impairment (MCI; n = 437), and subjective cognitive decline (SCD; n = 427). Main outcomes were CSF β-amyloid1–42 (Aβ42), total tau (t-Tau), and tau phosphorylated at threonine 181 (p-Tau) levels. Age-corrected 3-way interactions between sex, disease stage (i.e., syndrome diagnosis at baseline), and APOE ε4 were tested with linear regression analyses for each outcome measure. In case of significant interactions (p < 0.05), sex differences were further evaluated by stratifying analyses for clinical disease stage and APOE ε4 genotype, including age as a covariate.ResultsThree-way interactions were significant for t-Tau (p < 0.001) and p-Tau (p < 0.01) but not Aβ42. In APOE ε4 carriers, women showed higher p-Tau concentrations than men in SCD (Cohen d [95% confidence interval]: t-Tau = 0.52 [0.19–0.84], p < 0.001; p-Tau = 0.44 [0.11–0.77] p = 0.004) and MCI (Cohen d [95% CI]: t-Tau = 0.54 [0.28–0.80], p < 0.001; p-Tau = 0.52 [0.26–0.77], p < 0.001) but not in AD dementia. In APOE ε4 noncarriers, women showed higher p-Tau concentrations in MCI (Cohen d [95% CI]: t-Tau = 0.49 [0.17–0.80], p = 0.002; p-Tau = 0.47 [0.16–0.78], p = 0.003) and AD dementia (Cohen d [95% CI]: t-Tau = 0.42 [0.19–0.65], p < 0.001; p-Tau = 0.38 [0.15–0.61] p = 0.002) but not in SCD.ConclusionsWithin APOE ε4 carriers, sex differences in CSF p-Tau are more evident in early disease stages, whereas for APOE ε4 noncarriers, sex differences are more evident in advanced disease stages. These findings suggest that the effect of APOE ε4 on sex differences in CSF biomarkers depends on disease stage in AD.

scholarly journals Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer’s disease

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria João Leitão ◽  
Anuschka Silva-Spínola ◽  
Isabel Santana ◽  
Veronica Olmedo ◽  
Alicia Nadal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Analytical Performance ◽  
Csf Biomarkers ◽  
Parameter Method ◽  
Routine Practice ◽  
Amyloid Pet ◽  
Β Amyloid ◽  
T Tau

Abstract Background Ongoing efforts within the Alzheimer’s disease (AD) field have focused on improving the intra- and inter-laboratory variability for cerebrospinal fluid (CSF) biomarkers. Fully automated assays offer the possibility to eliminate sample manipulation steps and are expected to contribute to this improvement. Recently, fully automated chemiluminescence enzyme immunoassays for the quantification of all four AD biomarkers in CSF became available. The aims of this study were to (i) evaluate the analytical performance of the Lumipulse G β-Amyloid 1-42 (restandardized to Certified Reference Materials), β-Amyloid 1-40, total Tau, and pTau 181 assays on the fully automated LUMIPULSE G600II; (ii) compare CSF biomarker results of the Lumipulse G assays with the established manual ELISA assays (INNOTEST®) from the same company (Fujirebio); and (iii) establish cut-off values and the clinical performance of the Lumipulse G assays for AD diagnosis. Methods Intra- and inter-assay variation was assessed in CSF samples with low, medium, and high concentrations of each parameter. Method comparison and clinical evaluation were performed on 40 neurological controls (NC) and 80 patients with a diagnosis of probable AD supported by a follow-up ≥ 3 years and/or positive amyloid PET imaging. A small validation cohort of 10 NC and 20 AD patients was also included to validate the cut-off values obtained on the training cohort. Results The maximal observed intra-assay and inter-assay coefficients of variation (CVs) were 3.25% and 5.50%, respectively. Method comparisons revealed correlation coefficients ranging from 0.89 (for Aβ40) to 0.98 (for t-Tau), with those for Aβ42 (0.93) and p-Tau (0.94) in-between. ROC curve analysis showed area under the curve values consistently above 0.85 for individual biomarkers other than Aβ40, and with the Aβ42/40, Aβ42/t-Tau, and Aβ42/p-Tau ratios outperforming Aβ42. Validation of the cut-off values in the independent cohort showed a sensitivity ranging from 75 to 95% and a specificity of 100%. The overall percentage of agreement between Lumipulse and INNOTEST was very high (> 87.5%). Conclusions The Lumipulse G assays show a very good analytical performance that makes them well-suited for CSF clinical routine measurements. The good clinical concordance between the Lumipulse G and INNOTEST assays facilitates the implementation of the new method in routine practice.

CSF β-amyloid as a putative biomarker of disease progression in multiple sclerosis

2016 ◽  
Vol 23 (8) ◽  
pp. 1085-1091 ◽  
Author(s):  
Anna M Pietroboni ◽  
Francesca Schiano di Cola ◽  
Marta Scarioni ◽  
Chiara Fenoglio ◽  
Barbara Spanò ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Enzyme Linked Immunosorbent Assay ◽  
Csf Biomarkers ◽  
Newly Diagnosed ◽  
Potential Biomarker ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Brain Tissue Damage

Background: Neurodegeneration plays a major role in determining disability in multiple sclerosis (MS) patients. Hence, there is increasing need to identify reliable biomarkers, which could serve as prognostic measure of disease progression. Objectives: To assess whether cerebrospinal fluid (CSF) tau and β-amyloid (Aβ) levels were altered in newly diagnosed MS patients and correlated with disability. Moreover, we investigated whether these CSF biomarkers associate with macroscopic brain tissue damage measures. Methods: CSF Aβ and tau levels were determined by enzyme-linked immunosorbent assay in CSF samples from 48 newly diagnosed MS patients, followed-up clinically for 3 years by recording their Expanded Disability Status Scale score at 6-month intervals, and 45 controls. All patients underwent magnetic resonance imaging at baseline and at the end of follow-up to quantify their lesion load (LL). Results: CSF Aβ levels were significantly reduced in patients compared to controls ( p < 0.001). Lower CSF Aβ levels at baseline were a disability predictor at 3-year follow-up ( p = 0.009). CSF tau levels correlated with T2- and T1-LL ( p < 0.001). Conclusion: CSF Aβ reduction is a promising biomarker of neurodegeneration and may predict patients’ clinical outcome. Therefore, CSF Aβ should be considered as a potential biomarker of prognostic value.

scholarly journals Cognitive Profile and Markers of Alzheimer Disease–Type Pathology in Patients With Lewy Body Dementias

Neurology ◽  
2021 ◽  
Vol 96 (14) ◽  
pp. e1855-e1864
Author(s):  
Erica Howard ◽  
David J. Irwin ◽  
Katya Rascovsky ◽  
Naomi Nevler ◽  
Sanjana Shellikeri ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Lewy Body ◽  
Digit Span ◽  
Onset Time ◽  
Analysis Of Covariance ◽  
Csf Biomarkers ◽  
Available N ◽  
Confrontation Naming ◽  
T Tau ◽  
Dementia Onset

ObjectiveTo determine whether patients with Lewy body dementia (LBD) with likely Alzheimer disease (AD)–type copathology are more impaired on confrontation naming than those without likely AD-type copathology.MethodsWe selected 57 patients with LBD (dementia with Lewy bodies [DLB], n = 38; Parkinson disease dementia [PDD], n = 19) with available AD CSF biomarkers and neuropsychological data. CSF β-amyloid1-42 (Aβ42), phosphorylated-tau (p-tau), and total-tau (t-tau) concentrations were measured. We used an autopsy-validated CSF cut point (t-tau:Aβ42 ratio > 0.3, n = 43), or autopsy data when available (n = 14), to categorize patients as having LBD with (LBD + AD, n = 26) and without (LBD − AD, n = 31) likely AD-type copathology. Analysis of covariance tested between-group comparisons across biologically defined groups (LBD + AD, LBD − AD) and clinical phenotypes (DLB, PDD) on confrontation naming (30-item Boston Naming Test [BNT]), executive abilities (letter fluency [LF], reverse digit span [RDS]), and global cognition (Mini-Mental State Examination [MMSE]), with adjustment for age at dementia onset, time from dementia onset to test date, and time from CSF to test date. Spearman correlation related cognitive performance to CSF analytes.ResultsPatients with LBD + AD performed worse on BNT than patients with LBD − AD (F = 4.80, p = 0.03); both groups performed similarly on LF, RDS, and MMSE (all p > 0.1). Clinically defined PDD and DLB groups did not differ in performance on any of these measures (all p > 0.05). A correlation across all patients showed that BNT score was negatively associated with CSF t-tau (ρ = −0.28, p < 0.05) and p-tau (ρ = −0.26, p = 0.05) but not Aβ42 (p > 0.1).ConclusionMarkers of AD-type copathology are implicated in impaired language performance in LBD. Biologically based classification of LBD may be advantageous over clinically defined syndromes to elucidate clinical heterogeneity.

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