Medial Temporal Atrophy Scores Research Articles

Cholinergic hyperintensity pathways are associated with cognitive performance in patients with asymptomatic carotid artery stenosis

ObjectivesWe aimed to determine whether asymptomatic carotid artery stenosis (ACS) induced cognitive impairments were related to the cholinergic hyperintensity pathway. MethodsThis cross-sectional study included patients with moderate-to-severe ACS, who were categorized into mild cognitive impairment (MCI) and normal cognition groups on the basis of Montreal Cognitive Assessment (MoCA) scores. The cholinergic pathway hyperintensity scale (CHIPS), Fazekas, and medial temporal atrophy (MTA) scores were assessed. SPSS software was used for statistical analyses. ResultsA total of 117 ACS patients (70.89 ± 8.81 years) and 105 controls (67.87 ± 9.49 years) were evaluated (t = 2.46, p = 0.015). The ACS group showed a worse median Mini-Mental Status Examination (MMSE) score (z = −2.41, p = 0.016) and MoCA score (z = −3.51, p < 0.001), and a significantly higher median total CHIPS score (z = 4.88, p < 0.001) and mean Fazekas score (t = 2.39, p = 0.018). In the correlation analysis, the MoCA score showed a significant negative correlation with the CHIPS score (ρ = −0.41, p < 0.001) and Fazekas score (ρ = −0.31, p < 0.001) in ACS group. Logistic regression analyses suggested that CHIPS scores were risk factors for MCI in patients with ACS (odds ratio [OR] = 1.07, 95% Confidence Interval [CI]1.01–1.13 and controls (OR = 1.09, 95%CI 1.01–1.17), while the MTA and Fazekas scores showed no predictive power. The receiver operating characteristic curve showed that the area under the curve of the CHIPS score for predicting MCI was 0.71 in ACS group, but was only 0.57 in controls. ConclusionsPatients with ACS showed poorer cognitive performance and higher CHIPS and Fazekas scores. CHIPS, but not Fazekas, scores were risk factors for cognitive impairment and were a valuable factor to predict MCI in patients with ACS.

The impact of medial temporal and parietal atrophy on cognitive function in dementia

Although medial temporal atrophy (MTA) and parietal atrophy (Koedam score) have been used to diagnose Alzheimer’s disease (AD), early detection of other dementia types remains elusive. The study aims to investigate the association between these brain imaging markers and cognitive function in dementia. This cross-sectional study collected data from the Memory Clinic of Dr. Sardjito General Hospital Yogyakarta, Indonesia from January 2020 until December 2022. The cut-off value of MTA and Koedam score was set with Receiver Operating Curve. Multivariate analysis was performed to investigate the association between MTA and Koedam score with cognitive function. Of 61 patients, 22.95% had probable AD, 59.01% vascular dementia, and 18.03% mixed dementia. Correlation test showed that MTA and Koedam score were negatively associated with Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) score. MTA score ≥ 3 (AUC 0.69) and Koedam score ≥ 2 (AUC 0.67) were independently associated with higher risk of poor cognitive function (OR 13.54, 95% CI 1.77–103.43, p = 0.01 and OR 5.52, 95% CI 1.08–28.19, p = 0.04). Higher MTA and Koedam score indicate worse cognitive function in dementia. Future study is needed to delineate these findings as prognostic markers of dementia severity.

A Practical Screening Combination for the Discrimination of Alzheimer’s Type Memory Impairment Continuum: The 5-word Test and Magnetic Resonance Imaging-visual Rating Scale

Introduction: Alzheimer’s disease (AD) is a continuum with four clinical stages: asymptomatic, subjective cognitive impairment (SCI), mild cognitive impairment (MCI), and AD dementia (ADD). Identification of the predementia stages had become particularly essential after the recent approval of three anti-amyloid-β monoclonal antibodies. This study aimed to evaluate their contribution to the diagnosis of AD by using two practical instruments: The 5-word test (5WT) and medial temporal atrophy (MTA) scoring together. Materials and Methods: Twenty six ADD, 29 MCI, and 25 SCI patients matched for age, sex, and education were included. The Addenbrooke’s Cognitive Examination-Revised version, which includes the Mini-Mental Status Examination, and 5WT were applied. MTA is scored on coronal T1 magnetic resonance images, between 0 and 4 (0: Severe atrophy, 4: No atrophy). A receiver operating characteristic curve analysis was performed to test the success of the MTA score, screening tests, and scores formed from various combinations of these two in classifying the groups. Results: MTA + 5WT had the highest area under curve (AUC) differentiating SCI versus MCI with a sensitivity of 0.80 and a specificity of 0.83, and differentiating SCI versus ADD with a sensitivity and specificity of 1.0. For differentiating MCI versus ADD, MTA + 5WT had a very good performance with an AUC of 0.93, a specificity of 0.96, and a moderate sensitivity of 0.76. Conclusion: Combining 5WT for memory test with MTA for atrophy rating becomes a perfect method in a clinical setting for evaluating patients with memory complaints and thus carefully selecting the candidates for advanced biological diagnosis.

The Memory Alteration Test Is Correlated with Clinical, Cerebrospinal Fluid, and Brain Imaging Markers of Alzheimer Disease in Lima, Peru

Introduction: As disease-modifying therapies become available for Alzheimer’s disease (AD), detection of AD in early stages of illness (mild cognitive impairment [MCI], early dementia) becomes increasingly important. Biomarkers for AD in low- and middle-income countries (LMICs) are costly and not widely available; hence, it is important to identify cognitive tests that correlate well with AD biomarker status. In this study, we evaluated the memory alteration test (M@T) to detect biomarker-proven AD and quantify its correlation with neurodegeneration and cerebrospinal fluid (CSF) AD biomarkers in a cohort of participants from Lima, Peru. Methods: This is a secondary analysis of a cohort of 185 participants: 63 controls, 53 with amnestic MCI (aMCI), and 69 with dementia due to AD. Participants underwent testing with M@T and a gold standard neuropsychological battery. We measured total tau (t-tau), phosphorylated tau (p-tau), and beta-amyloid (β-amyloid) in CSF, and evaluated neurodegeneration via medial temporal atrophy score in MRI. We used receiver-operator curves to determine the discriminative capacity of the total M@T score and its subdomains. We used the Pearson coefficient to correlate M@T score and CSF biomarkers. Results: The M@T had an area under the curve (AUC) of 0.994 to discriminate between controls and cognitively impaired (aMCI or AD) patients, and an AUC of 0.98 to differentiate between aMCI and AD patients. Free-recall and cued recall had the highest AUCs of all subdomains. Total score was strongly correlated with t-tau (−0.77) and p-tau (−0.72), and moderately correlated with β-amyloid (0.66). The AUC for discrimination of neurodegeneration was 0.87. Conclusion: The M@T had excellent discrimination of aMCI and dementia due to AD. It was strongly correlated with CSF biomarkers and had good discrimination of neurodegeneration. In LMICs, the M@T may be a cost-effective screening tool for aMCI and dementia caused by AD.

Glycemic variability correlates with medial temporal lobe atrophy and decreased cognitive performance in patients with memory deficits.

In the past, researchers have observed a significant link between glycemia and dementia. Medial temporal atrophy (MTA) is regarded as a common marker of dementia. The correlation between glycemic variability and MTA is unclear, and it has not been determined whether glycemic variability can be utilized as a biomarker of MTA and cognitive performance. The patients in a memory clinic who underwent brain MRI scans and cognitive assessments within the first week of their hospital visit, were enrolled. All participants underwent three fasting blood glucose and one HBA1c assessments on three self-selected days within 1 week of their first visit. The variability independent of the mean (VIM) was employed. Validated visual scales were used to rate the MTA results. The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales were employed to assess the cognitive functions of the participants. Spearman's correlation and regression models were used to examine the relationship between the MMSE and MoCA scales, and also determine the link between the MRI characteristics and cognitive status, where vascular risk factors, educational status, age, gender, and mean glucose parameters served as covariates. Four hundred sixty-one subjects completed the MMSE scale, while 447 participants completed the MoCA scale. Data analysis revealed that 47.72% of the participants were men (220/461), and the median age of the patients was 69.87 ± 5.37 years. The findings of Spearman's correlation analysis exhibited a strong negative relationship between the VIM and MMSE score (r = -0.729, P < 0.01), and the MoCA score (r = -0.710, P < 0.01). The VIM was regarded as an independent risk factor for determining cognitive impairment in both the MMSE and MoCA assessments. The results were unaffected by sensitivity analysis. In addition, a non-linear relationship was observed between the VIM and MTA scores. The variability in the blood glucose levels, which was presented as VIM, was related to the reduced cognitive function, which was reflected by MMSE and MoCA scales. The relationship between the VIM and the MTA score was non-linear. The VIM was positively related to the MTA score when the VIM was less than 2.42.

The Relative Frequency of Small Vessel Cerebrovascular Disease and Brain Atrophy in MRI of Patients with Psoriasis.

Psoriasis is a systemic autoimmune disease that is associated with numerous comorbidities. This study aimed to compare the prevalence of small vessel cerebrovascular disease (SVCD) and atrophic brain changes in MRI of patients with psoriasis and normal subjects. This case-control study was performed on 27 patients with psoriasis and 27 normal individuals who were referred to Shohada-e-Tajrish Hospital, Tehran, Iran during 2019 and 2020. Basic demographic and clinical information of participants were recorded. Brain MRI was performed for all individuals to examine the medial temporal atrophy (MTA) score, global cortical atrophy (GCA) score, and Fazekas scale. Finally, the relative frequencies of each parameter between the two groups were compared. There was no significant difference in the frequency of the Fazekas scale, GCA, and MTA scores between the two groups. However, a mild trend was found for a higher frequency of Fazekas scale, GCA, and MTA scores in controls in comparison with the case group. While there was no significant relationship between the Fazekas scale and disease duration (p=0.16), a significant and positive correlation was found between disease duration and GCA and MTA scores [p<0.001). There was no significant relationship between Fazekas, GCA and MTA status and other parameters. The increase in disease duration was significantly associated with an increase in the incidence of cerebral atrophy, which may suggest the need for screening in terms of CNS involvement in psoriasis patients.

Visualization of atrophy of medial temporal lobes and the septal nuclei in patients with transient ischaemic attack and controls

IntroductionTransient ischaemic attack (TIA) is associated with increased risk of cognitive decline and dementia as early as one-year post-event. Regional brain atrophy measurements may predict future cognitive decline. Aims: 1) To determine whether Medial Temporal Atrophy (MTA) scores and interseptal distance (ISD) measurements are greater in patients with TIA compared to controls; and 2) To determine whether MTA and ISD predicts cognitive change one year after TIA. MethodsBaseline demographic, vascular risk factors, structural imaging and cognitive tests scores were compared between 103 Patients with TIA and 103 age-and-sex-matched controls from the Predementia Neuroimaging of Transient Ischaemic Attack (PREVENT) Study. MTA was assessed using the Schelten's Scale, and ISD was calculated as the distance between the septal nucleus of each hemisphere. Multiple linear regression models were used to evaluate how MTA and ISD related to cognitive change after adjusting for covariates. ResultsPatients with TIA had larger ISD measurements (1.4 mm [SD=1.2] vs. 0.9 mm [SD=1.0]); p < 0.001) and higher right/left MTA scores (both p < 0.05) compared to controls. At baseline, controls performed significantly better on the RAVLT (total recall), BVMT (total and delayed recall) and the Trail Making Task (A and B) compared to patients with TIA. However, at one-year follow-up there was no evidence of decline in the patients with TIA compared with controls. Higher MTA and ISD scores were not associated with cognitive decline. ConclusionsPatients with TIA had higher MTA scores and ISD measurements than controls, but neither were predictors of cognitive decline at one year. Future studies with longer follow-up periods will be required to determine whether higher MTA scores and ISD predict risk of cognitive decline in patients with TIA.

Medial temporal atrophy in posterior cortical atrophy and its relationship to the cingulate island sign

AbstractBackgroundPosterior cortical atrophy (PCA) is associated with hypometabolism on FDG‐PET and atrophy on MRI in the parietal and occipital lobes, and patients often show the cingulate island sign (CIS) whereby posterior cingulate metabolism is relatively spared compared to the precuneus and cuneus. It has been hypothesized that medial temporal sparing may be related to CIS in PCA. We aimed to assess the severity of medial temporal atrophy in PCA and determine whether the presence of a CIS is related to medial temporal sparing.MethodFifty‐five PCA patients underwent a 3T volumetric MRI and FDG‐PET. The degree and symmetry of medial temporal atrophy on MRI was visually assessed in both hemispheres using the five‐point Scheltens scale (0=normal; 1=mild; 2=moderate; 3=marked; 4=severe). Visual assessments of FDG‐PET coded the presence/absence of a CIS and whether the CIS was symmetric or asymmetric. Hippocampal volumes and a quantitative CIS were also measured. Associations between medial temporal atrophy scores and clinical measures were assessed using linear regression correcting for age.ResultMedial temporal atrophy was most commonly mild (38% on the right, 40% on the left), followed by moderate (35% on the right, 29% on the left), and then no atrophy (18% on right, 25% on left). Marked or severe atrophy was only observed in 9% of patients on the right and 5% of patients on the left. Atrophy was asymmetric in 55%, and when asymmetric was most commonly worse on the right (76%). Greater medial temporal atrophy was associated with older age (p&lt;0.001) and worse verbal episodic memory (p=0.008). The CIS was observed in 44% of the PCA patients and was asymmetric in 50% of these. The patients with a CIS showed greater medial temporal asymmetry (p=0.016), but did not show lower medial temporal atrophy scores, compared to those without a CIS. Hippocampal volumes were not associated with quantitative CIS.ConclusionMild to moderate medial temporal atrophy is a common finding in PCA and is associated with worse memory impairment and older age. However, medial temporal sparing was not related to the presence of a CIS in PCA.

Longitudinal change in ATN biomarkers in cognitively normal individuals

BackgroundBiomarkers for amyloid, tau, and neurodegeneration (ATN) have predictive value for clinical progression, but it is not clear how individuals move through these stages. We examined changes in ATN profiles over time, and investigated determinants of change in A status, in a sample of cognitively normal individuals presenting with subjective cognitive decline (SCD).MethodsWe included 92 individuals with SCD from the SCIENCe project with [18F]florbetapir PET (A) available at two time points (65 ± 8y, 42% female, MMSE 29 ± 1, follow-up 2.5 ± 0.7y). We additionally used [18F]flortaucipir PET for T and medial temporal atrophy score on MRI for N. Thirty-nine individuals had complete biomarker data at baseline and follow-up, enabling the construction of ATN profiles at two time points. All underwent extensive neuropsychological assessments (follow-up time 4.9 ± 2.8y, median number of visits n = 4). We investigated changes in biomarker status and ATN profiles over time. We assessed which factors predisposed for a change from A− to A+ using logistic regression. We additionally used linear mixed models to assess change from A− to A+, compared to the group that remained A− at follow-up, as predictor for cognitive decline.ResultsAt baseline, 62% had normal AD biomarkers (A−T−N− n = 24), 5% had non-AD pathologic change (A−T−N+ n = 2,) and 33% fell within the Alzheimer’s continuum (A+T−N− n = 9, A+T+N− n = 3, A+T+N+ n = 1). Seventeen subjects (44%) changed to another ATN profile over time. Only 6/17 followed the Alzheimer’s disease sequence of A → T → N, while 11/17 followed a different order (e.g., reverted back to negative biomarker status). APOE ε4 carriership inferred an increased risk of changing from A− to A+ (OR 5.2 (95% CI 1.2–22.8)). Individuals who changed from A− to A+, showed subtly steeper decline on Stroop I (β − 0.03 (SE 0.01)) and Stroop III (− 0.03 (0.01)), compared to individuals who remained A−.ConclusionWe observed considerable variability in the order of ATN biomarkers becoming abnormal. Individuals who became A+ at follow-up showed subtle decline on tests for attention and executive functioning, confirming clinical relevance of amyloid positivity.

The correlation between enlarged perivascular spaces and cognitive impairment in Parkinson’s disease and vascular parkinsonism

IntroductionThe widespread use of brain magnetic resonance imaging (MRI) has revealed the correlation between enlarged perivascular spaces (EPVS) and cognitive impairment (CI). However, few studies have examined the correlation between MRI-visible EPVS and CI in patients with Parkinson’s disease (PD) and vascular parkinsonism (VaP). This study explored how the number and main location of EPVS in PD and VaP are correlated with the occurrence of CI in these diseases to provide radiology markers and other evidence for early clinical diagnosis in a Chinese cohort.MethodsClinical data were prospectively collected from 77 patients: 26 patients clinically diagnosed with PD or probable PD, 19 patients clinically diagnosed with VaP, and 32 control subjects with normal cognitive function and no stroke or parkinsonism. The patients with PD and VaP were divided into a CI group and a no CI (NCI) group according to the Montreal Cognitive Assessment Beijing version (MoCA-BJ). The relevant clinical data were statistically analysed.ResultsThe centrum semiovale (CSO)-EPVS, lacunes, Fazekas scores, global cortical atrophy scale (GCA) scores, Koedam posterior atrophy visual scale (KS) scores, and medial temporal atrophy (MTA) scores were higher in the PD-CI and VaP-CI groups than in the control group (adjusted P < 0.017). The number of basal ganglia (BG)-EPVS in the VaP group was higher than that in the PD and control groups (adjusted P < 0.017). BG-EPVS, Fazekas scores, GCA scores, KS scores, and MTA scores were higher in the VaP-CI group than in the PD-CI group (adjusted P < 0.017). Multivariate logistic regression analysis showed that the differences in BG-EPVS and Fazekas scores were not significant between PD-CI and VaP-CI patients (P > 0.05).ConclusionVaP-CI results from multiple factors and is significantly associated with BG-EPVS, lacunes, white matter hyperintensities and brain atrophy. BG-EPVS can be used as an imaging marker to distinguish VaP-CI from PD-CI.

MO392: Mildly Impaired Kidney Function May Be Associated With the Risk of Hippocampal Atrophy in Young and Midlife Adults

Abstract BACKGROUND AND AIMS To date, associations between kidney function and brain structural abnormalities have been described in several studies [1]. Reports of renal function in relation to hippocampal atrophy have been scarce and the majority of studies have been focussed on older end-stage renal disease populations [2]. Particularly, with the ageing process, the hippocampus has a greater propensity to atrophy than other cerebral structures.The purpose of this study was to evaluate the relationship between kidney function assessed by estimated glomerular filtration rate (eGFR) and the degrees of hippocampal atrophy among young and midlife adults. METHOD In this cross-sectional study, the risk factors for hippocampal atrophy were evaluated in a cohort of 219 non-diabetic chronic kidney disease (CKD) patients, age ≤ 55 years, who had undergone magnetic resonance imaging (MRI) of the brain. The eGFR was calculated using the CKD-EPI formula. Hippocampal volume (HV) was assessed in brain MRIs with the Scheltens’ Medial Temporal Atrophy score, including a 5-stage escalation—0: no atrophy, 1: only widening of choroid fissure, 2: also widening of the temporal horn of lateral ventricle, 3: moderate loss of HV (decrease in height) and 4: severe loss of HV [3]. RESULTS In our group, the median and interquartile ranges (IQR) of age was 45 (14) years, 57.53% (126 patients) being males. The median eGFR was 100.6 (34.7) mL/min/1.73m2 and 46.75% (102 patients) presented with mild reduction in eGFR (eGFR between 60 to 89 mL/min/1.73m2). In univariable regression analysis, eGFR (R2 = 0.207, P &amp;lt; 0.001), arterial hypertension (R2 = 0.018, P = 0.045), dyslipidaemia (R2 = 0.044, P = 0.002), haematocrit (R2 = 0.021, P = 0.032), natrium levels (R2 = 0.018, P = 0.047), and potassium levels ( R2 = 0.019, P = 0.042) were associated with smaller HV. In multivariable regression analysis, eGFR [odds ratio (OR), 0.95; 95% confidence interval (CI), 0.94–0.97; P &amp;lt; 0.001) and serum natrium (OR, 0.91; 95% CI, 0.83–0.98; P = 0.027) were significantly associated with hippocampal atrophy. CONCLUSION This cross-sectional study shows that mild decrease in eGFR is independently associated with hippocampal atrophy. Our results suggest that brain imaging tests should be routinely performed in patients with mild reduction of eGFR, as the hippocampal atrophy process appears to be due, in part, to the mild renal dysfunction itself.

Medial Temporal Atrophy in Posterior Cortical Atrophy and Its Relationship to the Cingulate Island Sign.

It has been hypothesized that medial temporal sparing may be related to preserved posterior cingulate metabolism and the cingulate island sign (CIS) on [18F]fluorodeoxyglucose (FDG) PET in posterior cortical atrophy (PCA). To assess the severity of medial temporal atrophy in PCA and determine whether the presence of a CIS is related to medial temporal sparing. Fifty-five PCA patients underwent MRI and FDG-PET. The degree and symmetry of medial temporal atrophy on MRI was visually assessed using a five-point scale for both hemispheres. Visual assessments of FDG-PET coded the presence/absence of a CIS and whether the CIS was symmetric or asymmetric. Hippocampal volumes and a quantitative CIS were also measured. Medial temporal atrophy was most commonly mild or moderate, was symmetric in 55% of patients, and when asymmetric was most commonly worse on the right (76%). Older age and worse memory performance were associated with greater medial temporal atrophy. The CIS was observed in 44% of the PCA patients and was asymmetric in 50% of these. The patients with a CIS showed greater medial temporal asymmetry, but did not show lower medial temporal atrophy scores, compared to those without a CIS. Hippocampal volumes were not associated with quantitative CIS. Mild medial temporal atrophy is a common finding in PCA and is associated with memory impairment. However, medial temporal sparing was not related to the presence of a CIS in PCA.

MRI findings suggestive of Alzheimer's disease in patients with primary open angle glaucoma - a single sequence analysis using rapid 3D T1 spoiled gradient echo.

Primary open-angle glaucoma (POAG) is a degenerative optic neuropathy disease which has somewhat similar pathophysiology to Alzheimer's disease (AD). This study aims to determine the presence of medial temporal atrophy and parietal lobe atrophy in patients with POAG compared to normal controls using medial temporal atrophy (MTA) scoring and posterior cortical atrophy (PCA) scoring system on T1 magnetization-prepared rapid gradient-echo. 50 POAG patients and 50 normal subjects were recruited and an MRI brain with T1-magnetization-prepared rapid gradient-echo was performed. Medial temporal lobe and parietal lobe atrophy were by MTA and PCA/Koedam scoring. The score of the PCA and MTA were compared between the POAG group and the controls. There was a significant statistical difference between PCA score in POAG and the healthy control group (p-value = 0.026). There is no statistical difference between MTA score in POAG compared to the healthy control group (p-value = 0.58). This study suggests a correlation between POAG and PCA score. Potential application of this scoring method in clinical diagnosis and monitoring of POAG patients. The scoring method used in AD may also be applied in the diagnosis and monitoring of POAGMRI brain, specifically rapid volumetric T1 spoiled gradient echo sequence, may be applied in POAG assessment.

Association of the ATN Research Framework With Clinical Profile, Cognitive Decline, and Mortality in Patients With Dementia With Lewy Bodies.

The ATN framework has been developed to categorize biological processes within the Alzheimer disease (AD) continuum. Because AD pathology often coincides with dementia with Lewy bodies (DLB), we aimed to investigate the distribution of ATN profiles in DLB and associate ATN profiles in DLB with prognosis. We included 202 patients with DLB from the Amsterdam Dementia Cohort (68±7 years; 19% female; Mini-Mental State Examination 24 ± 3; abnormal DAT-SPECT 105/119). Patients were classified into 8 profiles according to the ATN framework, using CSF β-amyloid (Aβ)42 (A), CSF p-tau (T), and medial temporal atrophy scores (N). We compared presence of clinical symptoms in ATN profiles and used linear mixed models to analyze decline on cognitive tests (follow-up 3±2 years for n = 139). Mortality risk was assessed using Cox proportional hazards analysis. Analyses were performed on the 8 profiles as well as 3 clustered categories (normal AD biomarkers, non-AD pathologic change, and AD continuum). Fifty (25%) patients with DLB had normal AD biomarkers (A-T-N-), 37 (18%) had non-AD pathologic change (A-T+N- 10%, A-T-N+ 6%, A-T+N+ 3%), and 115 (57%) were classified within the AD continuum (A+T-N- 20%, A+T+N- 16%, A+T-N+ 10%, A+T+N+ 9%). A+T+N+ patients were older and least often had REM sleep behavior disorder symptoms. Parkinsonism was more often present in A+T- compared to A-T+ patients (independent of N). Compared to patients with normal AD biomarkers, patients in A+ categories showed steeper decline on memory tests and higher mortality risk. Cognitive decline and mortality did not differ between non-AD pathologic change and normal AD biomarkers. In our DLB cohort, we found clinically relevant associations between ATN categories and disease manifestation. Patients within the AD continuum had steeper cognitive decline and shorter survival. Implementing the ATN framework within patients with DLB aids in subtyping patients based on underlying biological processes and could provide targets for future treatment strategies (for example, AD-modifying treatment). Expanding the framework by incorporating markers for α-synucleinopathy would improve the use of the framework to characterize patients with dementia with mixed pathology, which could enhance proper stratification of patients for therapeutic trials.

Sloping Shoulders Sign: A Practical Radiological Sign for the Differentiation of Alzheimer’s Disease and Argyrophilic Grain Disease

Background: Although hippocampal atrophy is a well-known imaging biomarker of Alzheimer’s disease (AD), this finding is not useful to differentiate AD from argyrophilic grain disease (AGD) which is a common AD mimicker presenting with similar amnestic symptoms and medial temporal atrophy. Instead, we propose use of the “sloping shoulders sign”, defined as a distinct configuration of the bilateral hippocampal heads showing lateral and downward slopes on axial magnetic resonance imaging (MRI). Objective: We investigated the diagnostic utility of the “sloping shoulders sign” as a simple radiological discriminator of AD from AGD. Methods: Using axial and coronal three-dimensional MRI, our newly proposed “sloping shoulders sign”, other quantitative indices including the axial hippocampal head angle (AHHA), and well-known medial temporal atrophy (MTA) score were evaluated in pathologically-proven 24 AD and 11 AGD patients. Results: Detection rate of the “sloping shoulders sign” was significantly higher in all AD groups (83%; 20/24) and AD with Braak neurofibrillary tangle V/VI stage subgroup (88%; 15/17) than in AGD patients (18% – 2/11; p &lt; 0.001 and p &lt; 0.001, respectively). In contrast to the MTA score, this sign as well as AHHA demonstrated higher diagnostic performance and reproducibility, especially to differentiate all AD patients from AGD ones (accuracies of 71.4% , 82.9% and 82.9%; Cohen’s kappa of 0.70 and 0.81, and intraclass correlation coefficient of 0.96, respectively). Conclusion: The “sloping shoulders sign” is useful to differentiate advanced-stage AD from AGD. Its simplicity and reproducibility based on visual inspection using axial MRI make it suitable for routine clinical practice.

ATN classification in dementia with Lewy bodies: Association with clinical profile, cognitive decline and survival

AbstractBackgroundThe ATN framework has been developed to characterize biological processes within the Alzheimer’s disease (AD) continuum. Since AD pathology often coincides with dementia with Lewy Bodies (DLB), we aimed to examine the distribution of ATN profiles in DLB and associate ATN‐profiles in DLB to prognosis.MethodWe included 192 DLB patients from the Amsterdam Dementia Cohort (68±7yrs, 19%F, MMSE: 24±3, DAT‐SPECT abnormal: 104/114). Patients were classified according to the ATN framework, using CSF Aβ1‐42 (A), CSF p‐tau (T) and medial temporal atrophy scores (N). Categories were compared on presence of clinical symptoms and demographics. To yield sufficient power for longitudinal analyses, the eight profiles were combined into four categories: normal AD biomarkers (A‐T‐N‐, reference), non‐AD pathologic change (A–T–N+/A–T+N–/A–T+N+), amyloid‐only (A+T‐N‐) and amyloid‐plus (A+T–N+/A+T+N–/A+T+N+). We used linear mixed models to analyze decline in MMSE (follow‐up 3±2yrs for n=137). We assessed differences in mortality using Cox proportional‐hazards models.ResultFifty (26%) DLB patients had normal AD biomarkers (A‐T‐N‐), 36 (19%) had non‐AD pathologic change (A‐T+N‐: 10%/A‐T‐N+: 6%/A‐T+N+: 3%) and 106 (55%) were classified within the AD‐continuum (A+T‐N‐: 20%/A+T+N‐: 16%/A+T‐N+: 10%/A+T+N+: 9%)(figure 1). A+T+N+ patients were older and less often had RBD symptoms. Compared to patients with normal AD biomarkers, those with amyloid‐only had steeper decline in MMSE (β±SE=‐0.82±0.28, p=0.005), while amyloid‐plus was associated to higher mortality rate (HR: 1.85[1.09‐3.13]). Cognitive decline and mortality did not differ between non‐AD pathologic change and normal AD biomarkers (figure 2‐3).ConclusionIn our DLB cohort, we found clinically relevant associations between ATN categories and disease manifestation. Patients within the AD‐continuum had steeper cognitive decline (especially amyloid‐only) and shorter survival (amyloid‐plus). Individuals with non‐AD pathologic change did not differ from those with normal AD biomarkers in clinical presentation, decline or survival. Implementing the ATN framework within DLB patients could aid in subtyping patients based on underlying biological processes and provide targets for future treatment strategies, e.g. AD modifying treatment.

Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of patients with mixed pathology

AbstractBackgroundRecent studies on subjects with “pure” Alzheimer’s disease (AD) reported significant association between high blood neurofilament light chain (NfL) and AD‐related atrophy and poor cognition, but not with white matter hyperintensities (WMHs). In contrast, studies on non‐demented elderly with cerebral small vessel disease (CSVD) revealed a significant association between blood NfL and magnetic resonance imaging (MRI) markers of SVD including WMHs, lacunes and microbleeds. A major limitation of these studies is the lack of participants with mixed pathology to explore the potential independent and/or combined effects of brain atrophy, CSVD and amyloid burden (Aβ) on blood NfL.MethodThis study included 208 Singaporean participants of an ongoing longitudinal study, including non‐cognitively impaired controls (NCI; n=43), cognitively impaired no dementia (CIND; n=99), AD (n=44) and Vascular dementia (VaD; n=22). The presence of brain atrophy was defined by medial temporal atrophy scores ≥2. CSVD were determined by MRI markers. Brain Aβ was assessed by [11C]‐PiB PET SUVR. Plasma NfL (pNfL) was measured by Single molecule array (Simoa) immunoassay.ResultpNfL concentrations were significantly increased in AD and VaD. In the full cohort, stepwise regression including neuroimaging markers (brain atrophy, WMH, cerebral microbleeds, lacunes and brain Aβ), vascular risk factors (hypertension, hyperlipidemia, diabetes, smoking and APOE ε4 carriership) and demographics (age, gender, education) as independent variables showed that brain atrophy, WMH, age, gender and presence of diabetes to be independently associated with pNfL (all p&lt;0.05). Further univariate general linear models (Fig 1) showed that in the presence of brain atrophy (N+WMH‐) or high WMH (N‐WMH+) alone, pNfL was significantly increased after controlling for age, gender and presence of diabetes (p≤0.007). There was a trend of further increase in pNfL in the presence of both brain atrophy and high WMH burden.ConclusionThe independent associations and potential combined effects of brain atrophy and WMH on pNfL, together with the high prevalence of SVD burden in the elderly, suggests that SVD needs to be considered when interpreting elevated pNfL in elderly patients.

Correlation of frontal atrophy and CSF tau levels with neuropsychiatric symptoms in patients with cognitive impairment: A memory clinic experience

AbstractBackgroundBehavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy.MethodOne‐hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer’s disease; Lewy‐body disease, LBD; frontotemporal dementia; vascular dementia) underwent a complete diagnostic workup, including 3T‐MRI and/or CT and CSF. Cortical atrophy was assessed with medial temporal atrophy (MTA), posterior atrophy (PA) and global cortical atrophy‐frontal lobe (GCA‐F) scales. BPSD were rated using Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium.ResultDelusions, hallucinations and psychosis cluster were differently distributed among the diagnostic groups (p&lt;0.05, p&lt;0.001, and p&lt;0.05), with LBD patients showing higher scores for hallucinations (vs MCI, p&lt;0.001, and AD, p&lt;0.05) and psychosis cluster (vs MCI, p&lt;0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p=0.08), confirmed by beta regression (p&lt;0.01), while a positive non‐significant relationship was observed in MCI. Higher GCA‐F scores were associated with delusions and apathy (p&lt;0.05, on both hemispheres) and to hallucinations (left: p&lt;0.01, right: p&lt;0.05). GCA‐F scores were positively correlated with psychosis cluster (right: p&lt;0.05), and agitation/aggression (left: p&lt;0.05). Conversely, nighttime disturbances were positively correlated with both GCA‐F and MTA scores (left: p&lt;0.01; right: p&lt;0.05).ConclusionOur results suggest that psychotic symptoms are significantly more represented in LBD patients, and that CSF tau and frontal atrophy are associated with the occurrence and severity of BPSD in clinical practice. Longitudinal studies are however required to ascertain their actual predictive value.

Factors Associated with Cognitive Outcomes After First-Ever Ischemic Stroke: The Impact of Small Vessel Disease Burden and Neurodegeneration.

Differences exist regarding post-stroke cognitive outcomes. The aim of this study investigates the potential factors associated with post-stroke cognitive performance and trajectories. We performed a prospective cohort study using serial monitoring of cognitive function over a 1-year period after a first-ever ischemic stroke. Small vessel disease (SVD) burden and hippocampal atrophy (HA) were evaluated using the modified cerebral small vessel disease scores (mCSVD) and medial temporal atrophy score (MTA) scores. A generalized estimating equation (GEE) model and a group-based trajectory model (GBTM) was used to analyze the potential factors associated with post-stroke cognitive outcomes. A total of 112 patients were enrolled. The GEE model showed that all patients, regardless of initial cognitive performance, had a tendency to show an increase in the Montreal Cognitive Assessment over time. The cognitive performance was better in male patients with higher education levels (p = 0.046 and p < 0.001, respectively), but tended to be worse in patients with higher SVD burden and HA. The GBTM model grouped patients into low, intermediate, and high performance (LP, IP, and HP) after stroke. A higher SVD burden, rather than HA and initial stroke severity and location, independently predicted a higher odds of poor post-stroke cognitive trajectory (being in the LP group) after stroke (adjusted odds ratio 2.74, 95%CI 1.09-6.86). In patients with first-ever mild stroke, cognitive improvement over time was evident. The detrimental impact of the SVD burden may outweigh the effect of HA or acute stroke insult on the post-stroke cognitive trajectory during the 1-year follow-up.

Total Cerebral Small Vessel Disease Burden on MRI Correlates With Medial Temporal Lobe Atrophy and Cognitive Performance in Patients of a Memory Clinic.

Background: Cerebral small vessel disease (cSVD) and neurodegeneration are the two main causes of dementia and are considered distinct pathological processes, while studies have shown overlaps and interactions between the two pathological pathways. Medial temporal atrophy (MTA) is considered a classic marker of neurodegeneration. We aimed to investigate the relationship of total cSVD burden and MTA on MRI using a total cSVD score and to explore the impact of the two MRI features on cognition.Methods: Patients in a memory clinic were enrolled, who underwent brain MRI scan and cognitive evaluation within 7 days after the first visit. MTA and total cSVD score were rated using validated visual scales. Cognitive function was assessed by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales. Spearman's correlation and regression models were used to test (i) the association between MTA and total cSVD score as well as each cSVD marker and (ii) the correlation of the MRI features and cognitive status.Results: A total of 312 patients were finally enrolled, with a median age of 75.0 (66.0–80.0) years and 40.7% (127/312) males. All of them finished MRI and MMSE, and 293 subjects finished MoCA. Of note, 71.8% (224/312) of the patients had at least one of the cSVD markers, and 48.7% (152/312) of them had moderate–severe MTA. The total cSVD score was independently associated with MTA levels, after adjusting for age, gender, years of education, and other vascular risk factors (OR 1.191, 95% CI 1.071–1.324, P = 0.001). In regard to individual markers, a significant association existed only between white matter hyperintensities and MTA after adjusting for the factors mentioned above (OR 1.338, 95% CI 1.050–1.704, P = 0.018). Both MTA and total cSVD score were independent risk factors for MMSE ≤ 26 (MTA: OR 1.877, 95% CI 1.407–2.503, P < 0.001; total cSVD score: OR 1.474, 95% CI 1.132–1.921, P = 0.004), and MoCA < 26 (MTA: OR 1.629, 95% CI 1.112–2.388, P = 0.012; total cSVD score: OR 1.520, 95% CI 1.068–2.162, P = 0.020). Among all the cSVD markers, microbleed was found significantly associated with MMSE ≤ 26, while no marker was demonstrated a relationship with MoCA < 26.Conclusion: Cerebral small vessel disease was related to MTA in patients of a memory clinic, and both the MRI features had a significant association with cognitive impairment.