Medial Temporal Lobe Atrophy Scores Research Articles

Incidence of cerebral small vessel disease-related MR markers in the Swedish general population 'Good Aging in Skåne'(GÅS) study.

Cerebral small vessel disease (CSVD) is associated to cognitive decline and dementia. Neuroimaging changes of CSVD are highly prevalent above 80years. Only few studies report on incidence of CSVD in high age. We have investigated the incidence and prevalence of magnetic resonance imaging (MRI) markers of CSVD and risk factors in the general older population. As part of the general population Good Aging in Skåne cohort study (GÅS), 241 persons (mean age 76.3years) underwent two brain MRI, 3-T scanner with a mean interval of 5.9years. The incidence of white matter hyperintensities (WMH), lacunar infarction, cerebral atrophies and cerebral microbleeds (CMB) were calculated and the relationship to risk factors analysed by a multivariate regression analysis. Medial temporal lobe atrophy (MTA) was graded according to Scheltens'18 scale and CMB were defined as having > 1 small (0.2-0.5cm) hypointense lesion. The 6-year incidence of CMB, WMH and MTA were, 19%, 17% and 13% respectively, corresponding to 170/1,000 py., 172/1,000 py., and respectively 167/1,000 py. The incidence of CSVD according to the modified STRIVE score was 33%, 169/1,000 py and the prevalence at baseline was 73%. Moderate to high intake of alcohol was related to increased incidence of MTA and higher STRIVE score. Exposure to smoking was related to higher incidence of CMB and higher STRIVE score, adjusted for other known risk factors. CSVD is highly prevalent in the general older population and the 6-year incidence of WMH, CMB and MTA ranges from 13 to 19 percent. The modifiable lifestyle factors: smoking, and moderate alcohol intake are related to incident CSVD.

Dynamic functional network connectivity in patients with a mismatch between white matter hyperintensity and cognitive function.

White matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective. The resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system. The 149 CSVD patients included 20 cases of "Type I mismatch," 51 cases of Type I match, 38 cases of "Type II mismatch," and 40 cases of "Type II match." Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between "Type I match" and "Type I mismatch"; the FT of States 1 and 4 differed significantly between "Type II match" and "Type II mismatch." Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between "Type I match" and "Type I mismatch," while the left MTA score differed between "Type II match" and "Type II mismatch." Different mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education.

Prestroke Cognitive Impairment: Frequency and Association With Premorbid Neuropsychiatric, Functional, and Neuroimaging Features.

Some patients with stroke have prestroke cognitive impairment (pre-SCI), but its etiology is not clear. The aim of this cross-sectional study was to assess the frequency of pre-SCI and its association with premorbid neuropsychiatric, functional, and neuroimaging features. Patients hospitalized in stroke unit with an informant who could complete IQCODE (Informant Questionnaire for Cognitive Decline in the Elderly) were included. Pre-SCI was diagnosed if the IQCODE score was >3.3. Prestroke assessment also included NPI-Q (Neuropsychiatric Inventory Questionnaire), the basic Activities of Daily Living and Instrumental Activities of Daily Living scales, and the Clinical Dementia Rating scale. A multivariate logistic regression model was used to evaluate the association of pre-SCI with age, sex, education, arterial hypertension, atrial fibrillation, white matter lesions, cerebral microbleeds, and pathological medial temporal lobe atrophy. IQCODE was available in 474 of 520 patients (91.2%; 45% women; mean age 75.5±13.3 years). Pre-SCI had a prevalence of 32.5% and was associated with prestroke NPI-Q (pre-SCI absent versus present, 1.7±2.3 versus 5.5±4.9; P<0.001), Activities of Daily Living scale (0.3±0.8 versus 1.8±1.9; P<0.001), Instrumental Activities of Daily Living scale (0.6±1.3 versus 3.8±4.0; P<0.001), and Clinical Dementia Rating scale score (0.7±1.7 versus 7.2±6.2; P<0.001). In the 271 patients with a magnetic resonance imaging available, the multivariate logistic regression showed that age (odds ratio [OR], 1.05 [95% CI, 1.62-9.73]), white matter lesions (OR, 1.26 [95% CI, 1.003-1.58]), and a pathological medial temporal lobe atrophy score (OR, 3.97 [95% CI, 1.62-9.73]) were independently associated with pre-SCI. In the 218 patients with ischemic stroke, white matter lesions (OR, 1.34 [95% CI, 1.04-1.72]) and medial temporal lobe atrophy (OR, 3.56 [95% CI, 1.38-9.19]), but not age, were associated with pre-SCI. One-third of patients admitted to a stroke unit have pre-SCI that is associated with preexisting neuropsychiatric symptoms and functional performance. White matter lesions and medial temporal lobe atrophy are associated with pre-SCI, suggesting that both small vessel disease and neurodegeneration might be involved in its etiology.

Olfactory Dysfunction as a Marker for Cognitive Impairment in General Paresis of the Insane: A Clinical Study.

BACKGROUND General paresis of the insane (GPI) is characterized by cognitive impairment, neuropsychiatric symptoms, and brain structural abnormalities, mimicking many neuropsychiatric diseases. Olfactory dysfunction has been linked to cognitive decline and neuropsychiatric symptoms in numerous neuropsychiatric diseases. Nevertheless, it remains unclear whether patients with GPI experience olfactory dysfunction and whether olfactory dysfunction is associated with their clinical manifestations. MATERIAL AND METHODS Forty patients with GPI and 37 healthy controls (HCs) underwent the "Sniffin Sticks" test battery, Mini-Mental State Examination, and Neuropsychiatric Inventory to measure olfactory function, cognitive function, and neuropsychiatric symptoms, respectively. Brain structural abnormalities were evaluated using visual assessment scales including the medial temporal lobe atrophy (MTA) visual rating scale and Fazekas scale. RESULTS Compared with HCs, patients with GPI exhibited significant olfactory dysfunction, as indicated by deficits in the odor threshold (OT) (P=0.001), odor discrimination (OD) (P<0.001), and odor identification (OI) (P<0.001). In patients with GPI, the OI was positively correlated with cognitive function (r=0.57, P<0.001), but no significant correlation was found between olfactory function and neuropsychiatric symptoms, blood, or cerebrospinal fluid biomarkers (rapid plasma reagin circle card test and Treponema pallidum particle agglutination test), or brain structural abnormalities (MTA and Fazekas scale scores). Mediation analysis indicated that the impaired OI in patients with GPI was mediated by cognitive impairment and impaired OT respectively. CONCLUSIONS Patients with GPI exhibited overall olfactory dysfunction. OI is correlated with cognitive function and the impaired OI is mediated by cognitive impairment in patients with GPI. Thus, OI may serve as a marker for reflecting cognitive function in patients with GPI.

Delivering synaptic protein mRNAs via extracellular vesicles ameliorates cognitive impairment in a mouse model of Alzheimer’s disease

BackgroundSynaptic dysfunction with reduced synaptic protein levels is a core feature of Alzheimer’s disease (AD). Synaptic proteins play a central role in memory processing, learning, and AD pathogenesis. Evidence suggests that synaptic proteins in plasma neuronal-derived extracellular vesicles (EVs) are reduced in patients with AD. However, it remains unclear whether levels of synaptic proteins in EVs are associated with hippocampal atrophy of AD and whether upregulating the expression of these synaptic proteins has a beneficial effect on AD.MethodsIn this study, we included 57 patients with AD and 56 healthy controls. We evaluated their brain atrophy through magnetic resonance imaging using the medial temporal lobe atrophy score. We measured the levels of four synaptic proteins, including synaptosome-associated protein 25 (SNAP25), growth-associated protein 43 (GAP43), neurogranin, and synaptotagmin 1 in both plasma neuronal-derived EVs and cerebrospinal fluid (CSF). We further examined the association of synaptic protein levels with brain atrophy. We also evaluated the levels of these synaptic proteins in the brains of 5×FAD mice. Then, we loaded rabies virus glycoprotein-engineered EVs with messenger RNAs (mRNAs) encoding GAP43 and SNAP25 and administered these EVs to 5×FAD mice. After treatment, synaptic proteins, dendritic density, and cognitive function were evaluated.ResultsThe results showed that GAP43, SNAP25, neurogranin, and synaptotagmin 1 were decreased in neuronal-derived EVs but increased in CSF in patients with AD, and the changes corresponded to the severity of brain atrophy. GAP43 and SNAP25 were decreased in the brains of 5×FAD mice. The engineered EVs efficiently and stably delivered these synaptic proteins to the brain, where synaptic protein levels were markedly upregulated. Upregulation of synaptic protein expression could ameliorate cognitive impairment in AD by promoting dendritic density. This marks the first successful delivery of synaptic protein mRNAs via EVs in AD mice, yielding remarkable therapeutic effects.ConclusionsSynaptic proteins are closely related to AD processes. Delivery of synaptic protein mRNAs via EVs stands as a promising effective precision treatment strategy for AD, which significantly advances the current understanding of therapeutic approaches for the disease.

Visual associative learning to detect early episodic memory deficits and distinguish Alzheimer's disease from other types of dementia.

We investigated how well a visual associative learning task discriminates Alzheimer's disease (AD) dementia from other types of dementia and how it relates to AD pathology. 3,599 patients (63.9 ± 8.9 years old, 41% female) from the Amsterdam Dementia Cohort completed two sets of the Visual Association Test (VAT) in a single test session and underwent magnetic resonance imaging. We performed receiver operating curve analysis to investigate the VAT's discriminatory ability between AD dementia and other diagnoses and compared it to that of other episodic memory tests. We tested associations between VAT performance and medial temporal lobe atrophy (MTA), and amyloid status (n = 2,769, 77%). Patients with AD dementia performed worse on the VAT than all other patients. The VAT discriminated well between AD and other types of dementia (area under the curve range 0.70-0.86), better than other episodic memory tests. Six-hundred forty patients (17.8%) learned all associations on VAT-A, but not on VAT-B, and they were more likely to have higher MTA scores (odds ratios range 1.63 (MTA 0.5) through 5.13 for MTA ≥ 3, all p < .001) and to be amyloid positive (odds ratio = 3.38, 95%CI = [2.71, 4.22], p < .001) than patients who learned all associations on both sets. Performance on the VAT, especially on a second set administered immediately after the first, discriminates AD from other types of dementia and is associated with MTA and amyloid positivity. The VAT might be a useful, simple tool to assess early episodic memory deficits in the presence of AD pathology.

Towards validation in clinical routine: a comparative analysis of visual MTA ratings versus the automated ratio between inferior lateral ventricle and hippocampal volumes in Alzheimer’s disease diagnosis

PurposeTo assess the performance of the inferior lateral ventricle (ILV) to hippocampal (Hip) volume ratio on brain MRI, for Alzheimer’s disease (AD) diagnostics, comparing it to individual automated ILV and hippocampal volumes, and visual medial temporal lobe atrophy (MTA) consensus ratings.MethodsOne-hundred-twelve subjects (mean age ± SD, 66.85 ± 13.64 years) with varying degrees of cognitive decline underwent MRI using a Philips Ingenia 3T. The MTA scale by Scheltens, rated on coronal 3D T1-weighted images, was determined by three experienced radiologists, blinded to diagnosis and sex. Automated volumetry was computed by icobrain dm (v. 5.10) for total, left, right hippocampal, and ILV volumes. The ILV/Hip ratio, defined as the percentage ratio between ILV and hippocampal volumes, was calculated and compared against a normative reference population (n = 1903). Inter-rater agreement, association, classification accuracy, and clinical interpretability on patient level were reported.ResultsVisual MTA scores showed excellent inter-rater agreement. Ordinal logistic regression and correlation analyses demonstrated robust associations between automated brain segmentations and visual MTA ratings, with the ILV/Hip ratio consistently outperforming individual hippocampal and ILV volumes. Pairwise classification accuracy showed good performance without statistically significant differences between the ILV/Hip ratio and visual MTA across disease stages, indicating potential interchangeability. Comparison to the normative population and clinical interpretability assessments showed commensurability in classifying MTA “severity” between visual MTA and ILV/Hip ratio measurements.ConclusionThe ILV/Hip ratio shows the highest correlation to visual MTA, in comparison to automated individual ILV and hippocampal volumes, offering standardized measures for diagnostic support in different stages of cognitive decline.

Reduced visual associative learning is linked to Alzheimer’s disease pathology

AbstractBackgroundReduced learning is an early sign of memory impairment and relevant in the context of Alzheimer’s disease. The Visual Association Test (VAT) is a brief visual associative memory task comprising two sets (A and B) of six interactive pictures (e.g., a monkey holding an umbrella). We hypothesized that the VAT may be able to elicit learning deficits on set B when administered directly following set A, particularly in patients with Alzheimer’s disease‐related episodic memory deficits. We related learning on the VAT to medial temporal lobe atrophy (MTA) and amyloid‐β positivity.MethodWe selected 3,599 patients (63.9±8.9 years, 41% female) who completed two VAT sets. Patients had subjective cognitive decline (n = 1,369, 38%), mild cognitive impairment (n = 756, 21%), Alzheimer’s disease dementia (n = 856, 24%), or other types of dementia (n = 618, 17%). Average MTA scores of both hemispheres from magnetic resonance imaging were available for all; amyloid‐β status was obtained from cerebrospinal fluid or positron emission tomography for n = 2,769 (77%). We modeled learning curves on both VAT sets using linear mixed models, including an interaction with amyloid‐β status. Using logistic regressions, we analyzed the relationship between learning of associations on both sets (either all associations on both sets, or all associations on the first, but not the second set) and MTA, as well as amyloid‐β status.ResultMost patients learned all associations on both sets (n = 2,442, 68%). Patients who learned all associations on the first, but not the second set (n = 640, 18%) were more likely to have higher MTA scores and to be amyloid‐β positive than those who learned all associations (Table 1). Figure 1 shows learning curves on both sets of the VAT, stratified by amyloid‐β status. Less steep learning curves seem to suggest that amyloid‐β positive patients benefited less from completing a first set than amyloid‐β negative patients.ConclusionWe observed reduced learning on the second set, with those who did not learn all associations on both sets having more medial temporal lobe atrophy and more often being amyloid‐β positive. The VAT may be a useful, simple tool to assess early episodic memory deficits in the presence of Alzheimer’s disease pathology.

Executive function deficits and medial temporal lobe atrophy in late-life depression and Alzheimer's disease: a comparative study.

Alzheimer's disease (AD) and late-life depression (LLD) frequently exhibit executive function deficits (EFD) and medial temporal lobe atrophy (MTA) as shared characteristics. The objective of this research was to examine the utility of the Trail Making Test (TMT) and the MTA scale in distinguishing between LLD and AD. A study of 100 patients, 50 with AD and 50 with LLD, was conducted using a cross-sectional design. The individuals were subjected to clinical evaluations to assess their level of depression and overall cognitive abilities, which included the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). We evaluated executive function deficits (EFD) through the use of the TMT, which includes both TMT-A and TMT-B. MTA was measured using magnetic resonance imaging. To evaluate the ability of TMT and MTA scale to distinguish between the two groups, a receiver operating characteristic (ROC) curve was utilized. To investigate the connections between MTA and neuropsychological measures, a correlation analysis was performed. AD patients exhibited notably reduced MMSE, MoCA, and GDS scores, as well as an increased MTA total scores, time spent on TMT-A, and TMT-B compared to LLD patients (p < 0.05). TMT-A and TMT-B both exhibited excellent discriminatory power between AD and LLD, achieving area under curve (AUC) values of 92.2 and 94.2%, respectively. In AD patients, there was a negative correlation between MMSE and MoCA scores and MTA scores, while in LLD patients, there was a positive correlation between time spent on TMT-A and GDS scores and MTA scores. AD patients experience more severe EFD and MTA than LLD patients. The differential diagnosis of AD and LLD can be aided by the useful tool known as TMT. It is important to acknowledge that TMT is capable of capturing only a fraction of the executive function, thus necessitating a cautious interpretation of research findings.

Artificial intelligence and radiation effects on brain tissue in glioblastoma patient: preliminary data using a quantitative tool.

The quantification of radiotherapy (RT)-induced functional and morphological brain alterations is fundamental to guide therapeutic decisions in patients with brain tumors. The magnetic resonance imaging (MRI) allows to define structural RT-brain changes, but it is unable to evaluate early injuries and to objectively quantify the volume tissue loss. Artificial intelligence (AI) tools extract accurate measurements that permit an objective brain different region quantification. In this study, we assessed the consistency between an AI software (Quibim Precision® 2.9) and qualitative neruroradiologist evaluation, and its ability to quantify the brain tissue changes during RT treatment in patients with glioblastoma multiforme (GBM). GBM patients treated with RT and subjected to MRI assessment were enrolled. Each patient, pre- and post-RT, undergoes to a qualitative evaluation with global cerebral atrophy (GCA) and medial temporal lobe atrophy (MTA) and a quantitative assessment with Quibim Brain screening and hippocampal atrophy and asymmetry modules on 19 extracted brain structures features. A statistically significant strong negative association between the percentage value of the left temporal lobe and the GCA score and the left temporal lobe and the MTA score was found, while a moderate negative association between the percentage value of the right hippocampus and the GCA score and the right hippocampus and the MTA score was assessed. A statistically significant strong positive association between the CSF percentage value and the GCA score and a moderate positive association between the CSF percentage value and the MTA score was found. Finally, quantitative feature values showed that the percentage value of the cerebro-spinal fluid (CSF) statistically differences between pre- and post-RT. AI tools can support a correct evaluation of RT-induced brain injuries, allowing an objective and earlier assessment of the brain tissue modifications.

Relationship between MTA visual scale scores and hippocampal volume measured by a medical device in patients from a multicentric memory clinic population

AbstractBackgroundThe medial temporal lobe (MTL), including the hippocampus, undergoes atrophy in patients with Alzheimer’s disease (AD). Visual rating of medial temporal lobe atrophy (MTA) is often performed in the assessment of patients with cognitive impairment. Calculation of hippocampal volumes (HV) can also be achieved by multiple automated and semi‐automated methods using T1‐weighted MR images. The current study investigated the relationship between HV and z‐scores calculated by an automated method, included in the QyScore® medical device, and visual MTA rating scores using Scheltens’ scale in a multicentric memory clinic population at baseline.Method1959 participants from the MEMENTO cohort (Age 71.02 +/‐ 8.61, 1218 Female, MMSE 27.95 +/‐ 1.91) had 3DT1 MRI scans analyzed with QyScore®, an FDA‐approved and CE‐marked image analysis software. HV are reported in mL, corrected for % Intra Cranial Volume (ICV), and in z‐scores calculated relative to a cognitively normal population. 814 had amyloid status from CSF or PET, of which 216 were Amyloid+. Correlation between MTA scores and quantitative HV measurements was ascertained by Spearman’s rank correlation.ResultThere was a significant negative correlation between MTA scores and HV in %ICV (Left ‐0.62, p&lt;0.001; Right ‐0.59, p&lt;0.001) and z‐scores (Left ‐0.47, p&lt;0.001; Right ‐0.43 p&lt;0.001) for the total sample, as well as in Amyloid+ individuals HV in %ICV (Left ‐0.63 p&lt;0.001, Right ‐0.58 p&lt;0.001) and z‐scores (Left ‐0.50 p&lt;0.001, Right ‐0.47 p&lt;0.001). The correlation was also strong when separated by clinical diagnosis: patients with Subjective Cognitive Complaint (SCC, N = 306, AGE: 69.82 +/‐ 8.03, 196 female, MMSE: 28.86 +/‐ 1.17) and MCI (N = 1646, Age: 71.23 +/‐ 8.71, 1018 Female, MMSE: 27.79 +/‐ 1.95) presented MTA scores correlated both with HV in %ICV (Right = ‐0.47 p&lt;0.001, Left = ‐0.50 p&lt;0.001 for SCC; Right = ‐0.60 p&lt;0.001, Left = ‐0.63 p&lt;0.001 for MCI) and z‐scores (Right = ‐0.26 p&lt;0.001, Left = ‐0.33 p&lt;0.001 for SCC; Right = 0.44 p&lt;0.001, Left = ‐0.49 p&lt;0.001 for MCI).ConclusionThe automated quantification of ICV‐corrected HV and z‐scores were well‐correlated to MTA scores. QyScore® z‐scores may improve specificity in patients with cognitive impairment, by providing automated quantification of hippocampal atrophy directly compared with healthy ageing.

Brain MRI findings in patients with bullous pemphigoid: A case-control study.

Evidence suggests that bullous pemphigoid (BP) is associated with multiple neurological disorders. We aimed to compare brain magnetic resonance (MRI) findings between BP patients and a control group. This case-control study included patients with BP referred to two dermatology clinics during a two-year period. A group of individuals attending the same clinics for cosmetic procedures were selected as controls. First, participants' general information including age, gender, education, weight and underlying disease was recorded. For BP patients, the drugs and the BP Disease Area Index (BPDAI) were recorded as well. Then, all participants underwent brain MRI without contrast. The Fazekas scale, the general cerebral atrophy (GCA) score, and the Medial Temporal lobe Atrophy (MTA) score were used to assess MRI images. Overall, 24 BP patients and 24 controls were evaluated in this study. Both groups were comparable regarding age, gender and education. However, diabetes and hypertension were more frequent in the control group. The mean BPDAI total score was 51.39 ± 68.92 in BP patients and most of them used rituximab (41.7%). None of the participants had MS or Alzheimer MRI patterns. There was no difference between groups in terms of GCA and MTA scores. Furthermore, the frequency of partially empty sella did not differ significantly between BP patients and controls (p= 0.461); nevertheless, grade-3 Fazekas was significantly higher in BP patients compared to controls (25% vs. 0%, p= 0.019). Of note, one BP patient had an epidermoid cyst and another had moderate enlargement of three ventricles. Also, new infarcts were observed in two and old infarcts in four BP patients. Although the majority of abnormal brain MRI findings were more frequent in BP patients compared to controls, only grade-3 Fazekas was significantly higher and acute infarcts were exclusively observed in BP patients.

Combination of Cerebral Computed Tomography and Simplified Cardiac Arrest Hospital Prognosis (sCAHP) Score for Predicting Neurological Recovery in Cardiac Arrest Survivors.

Cerebral computed tomography (CT) and various severity scoring systems have been developed for the early prediction of the neurological outcomes of cardiac arrest survivors. However, few studies have combined these approaches. Therefore, we evaluated the value of the combination of cerebral CT and severity score for neuroprognostication. This single-center, retrospective observational study included consecutive patients surviving nontraumatic cardiac arrest (January 2016 and December 2020). Gray-to-white ratio (GWR), third and fourth ventricle characteristics, and medial temporal lobe atrophy scores were evaluated on noncontrast cerebral CT. Simplified cardiac arrest hospital prognosis (sCAHP) score was calculated for severity assessment. The associations between the CT characteristics, sCAHP score and neurological outcomes were analyzed. This study enrolled 559 patients. Of them, 194 (34.7%) were discharged with favorable neurological outcomes. Patients with favorable neurological outcome had a higher GWR (1.37 vs 1.25, p 0.001), area of fourth ventricle (461 vs 413 , p 0.001), anteroposterior diameter of fourth ventricle (0.95 vs 0.86 cm , p 0.001) and a lower sCAHP score (146 vs 190, p 0.001) than those with poor recovery. Patients with higher sCAHP score had lower GWR (p trend 0.001), area of fourth ventricle (p trend = 0.019) and anteroposterior diameter of fourth ventricle (p trend = 0.014). The predictive ability by using area under receiver operating characteristic curve (AUC) for the combination of sCAHP score and GWR was significantly higher than that calculated for sCAHP (0.86 vs 0.76, p 0.001) or GWR (0.86 vs 0.81, p = 0.001) alone. The combination of GWR and sCAHP score can be used to effectively predict the neurological outcomes of cardiac arrest survivors and thus ensure timely intervention for those at high risk of poor recovery.

Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of cognitively impaired patients with concomitant cerebral small vessel disease.

Plasma neurofilament light chain (NfL) is a potential biomarker for neurodegeneration in Alzheimer's disease (AD), ischemic stroke, and non-dementia cohorts with cerebral small vessel disease (CSVD). However, studies of AD in populations with high prevalence of concomitant CSVD to evaluate associations of brain atrophy, CSVD, and amyloid beta (Aβ) burden on plasma NfL are lacking. Associations were tested between plasma NfL and brain Aβ, medial temporal lobe atrophy (MTA) as well as neuroimaging features of CSVD, including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds. We found that participants with either MTA (defined as MTA score ≥2; neurodegeneration [N]+WMH-) or WMH (cut-off for log-transformed WMH volume at 50th percentile; N-WMH+) manifested increased plasma NfL levels. Participants with both pathologies (N+WMH+) showed the highest NfL compared to N+WMH-, N-WMH+, and N-WMH- individuals. Plasma NfL has potential utility in stratifying individual and combined contributions of AD pathology and CSVD to cognitive impairment.

Relationship between MTA visual scale scores and hippocampal volume measured by a medicaldevice in patients from a multicentric memory clinic population

AbstractBackgroundThe medial temporal lobe (MTL), including the hippocampus, undergoes atrophy in patients with Alzheimer's disease (AD). Visual rating of medial temporal lobe atrophy (MTA) is often performed in the assessment of patients with cognitive impairment. Calculation of hippocampal volumes (HV) can also be achieved by multiple automated and semi‐automated methods using T1‐weighted MR images. The current study investigated the relationship between HV and z‐scores calculated by an automated method, included in the QyScore® medical device, and visual MTA rating scores using Scheltens’ scale in a multicentric memory clinic population at baseline.Method1959 participants from the MEMENTO cohort (Age 71.02 +/‐ 8.61, 1218 Female, MMSE 27.95 +/‐ 1.91) had 3DT1 MRI scans analyzed with QyScore®, an FDA‐approved and CE‐marked image analysis software. HV are reported in mL, corrected for % Intra Cranial Volume (ICV), and in z‐scores calculated relative to a cognitively normal population. 814 had amyloid status from CSF or PET, of which 216 were Amyloid+. Correlation between MTA scores and quantitative HV measurements was ascertained by Spearman’s rank correlation.ResultThere was a significant negative correlation between MTA scores and HV in %ICV (Left ‐0.62, p&lt;0.001; Right ‐0.59, p&lt;0.001) and z‐scores (Left ‐0.47, p&lt;0.001; Right ‐0.43 p&lt;0.001) for the total sample, as well as in Amyloid+ individuals HV in %ICV (Left ‐0.63 p&lt;0.001, Right ‐0.58 p&lt;0.001) and z‐scores (Left ‐0.50 p&lt;0.001, Right ‐0.47 p&lt;0.001). The correlation was also strong when separated by clinical diagnosis: patients with Subjective Cognitive Complaint (SCC, N= 306, AGE: 69.82 +/‐ 8.03, 196 female, MMSE: 28.86 +/‐ 1.17) and MCI (N = 1646, Age: 71.23 +/‐ 8.71, 1018 Female, MMSE: 27.79 +/‐ 1.95) presented MTA scores correlated both with HV in %ICV (Right= ‐0.47 p&lt;0.001, Left= ‐0.50 p&lt;0.001 for SCC; Right= ‐0.60 p&lt;0.001, Left= ‐0.63 p&lt;0.001 for MCI) and z‐scores (Right= ‐0.26 p&lt;0.001, Left= ‐0.33 p&lt;0.001 for SCC; Right= 0.44 p&lt;0.001, Left= ‐0.49 p&lt;0.001 for MCI).ConclusionThe automated quantification of ICV‐corrected HV and z‐scores were well‐correlated to MTA scores. QyScore® z‐scores may improve specificity in patients with cognitive impairment, by providing automated quantification of hippocampal atrophy directly compared with healthy ageing

Microvascular Changes in the Retina Correlate with MRI Markers in Patients with Early-Onset Dementia.

Background and Aims: Recent reports suggest that results from imaging retinal microvascular changes with optical coherence tomography angiography (OCTA) in dementia patients reflect cerebral microcirculation changes that occur during dementia. Macula microvascular impairment has been shown in dementia patients compared to controls, but very little is known about its correlation with radiological visual rating scores associated with dementia. We aimed to explore the association between retinal microvasculature and radiological visual rating in early-onset dementia (EOD) patients. Methods: Swept-source OCTA (SS-OCTA) was used to image the retinal microvasculature of all EOD patients. Automated software in the OCTA tool segmented and measured the densities in the superficial vascular plexus (SVC) and deep vascular plexus (DVC) and foveal avascular zone (FAZ) areas. Radiological visual rating scores were evaluated on all MR images. Results: Medial temporal lobe atrophy (MTA) scores significantly correlated with FAZ area (p = 0.031) in EOD patients after adjusting for risk factors. PWMH correlated with SVC (p = 0.032) while DWMH significantly correlated with SVC (p = 0.007), DVC (p = 0.018) and FAZ (p = 0.001) in EOD patients. Discussion: FAZ changes correlated with MTA scores in EOD patients, while retinal microvasculature correlated with white matter hyperintensity. Our report suggests that microvascular changes in the retina may reflect cortical changes in the brain of EOD patients.

Correlation of muscle strength with cognitive function and medial temporal lobe atrophy in patients with mild to moderate Alzheimer's disease

Objective: To analyze the correlation of muscle strength with cognitive function and medial temporal lobe atrophy (MTA) in patients with mild to moderate Alzheimer's disease (AD). Methods: General information, sarcopenia-related indicators, neuropsychological tests and MTA score were collected in 80 confirmed AD patients (41 mild and 39 moderate patients) and 43 normal controls (NC) from the Memory Disorders Clinic of Department Of Neurology in the Second Affiliated Hospital of Soochow University between January and December 2021. Appendicular skeletal muscle mass index (ASMI), grip strength and 5-times sit-to-stand time and 6-m gait speed were used for assessing muscle mass, muscle strength and physical function, respectively. Cognitive function was assessed by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Memory and Executive Screening Scale (MES), Digit Symbol Substitution Test (DSST), Digital Span Test (DST) and Verbal Fluency Task (VFT), respectively. DST included Forward Digit Span Test (FDST) and Backward Digit Span Test (BDST). All the subjects underwent 3.0T coronal three-dimensional gradient echo sequence MRI. MTA scale was performed to evaluate the degree of medial temporal lobe atrophy. The differences in the sarcopenia-related indicators, cognitive score and MTA score were analyzed among the three groups, and the partial correlation analysis was performed between the inter-groups. Results: Eighty AD patients (24 males and 56 females) were included, aged (72±7) years old, with 41 mild and 39 moderate patients. Meanwhile, 43 NC included 19 males and 24 females, with a mean age of (70±6) years old. The disease duration in moderate AD patients was longer than that of mild AD patients [34.0 (25.0, 43.5) months vs 24.0 (11.0, 34.0) months, P<0.001]. The differences of sarcopenia-related indicators and MTA score among the three groups were statistically significant (all P<0.001), including 5-times sit-to-stand time [(13.6±1.8) s vs (11.5±1.7) s vs (10.3±1.9) s, P<0.001] and MTA score [2.0 (2.0, 3.0) vs 1.0 (1.0, 2.0) vs 0 (0, 0), P<0.001]. In neuropsychological tests, compared to the NC group, MMSE, MoCA, MES and VFT scores in mild and moderate AD groups were lower (all P<0.001); meanwhile, compared to the mild AD group, the moderate group had lower MMSE, MoCA, MES, DSST and VFT scores (all P<0.001). In sarcopenia-related indicators, muscle strength in particular was correlated with widespread cognitive functioning domains and MTA score in AD patients. Grip strength was positively correlated with MMSE, MoCA , MES, FDST (r=0.387, 0.418, 0.522 and 0.484, respectively, all P<0.001), DSST (r=0.327, P=0.006) and VFT score (r=0.354, P=0.003), and negatively correlated with MTA score (r=-0.631, P<0.001). 5-times sit-to-stand time was negatively correlated with MMSE, MoCA, MES, DSST, FDST, VFT score (r=-0.583, -0.587, -0.814, -0.591, -0.552 and -0.485, respectively, all P<0.001), and BDST (r=-0.355, P=0.003) strongly positively correlated with MTA score (r=0.836, P<0.001). ASMI was positively correlated with MMSE, MoCA, MES, DSST, FDST score (r=0.257, 0.238, 0.428, 0.282 and 0.364, respectively, all P<0.05), and negatively correlated with MTA score (r=-0.377, P=0.001). 6-m gait speed was positively correlated with MMSE, MoCA, MES, DSST, FDST score (r=0.419, 0.486, 0.699, 0.559 and 0.500, respectively, all P<0.001), BDST and VFT score (r=0.384、0.377, respectively, both P=0.001), and strongly negatively correlated with MTA score (r=-0.803, P<0.001). Conclusions: Patients with mild to moderate AD have widespread cognitive impairment. Muscle mass, muscle strength and physical function are all significantly impaired. Compared to muscle mass and physical function, decreased muscle strength is significantly associated with widespread cognitive decline and increased degree of medial temporal lobe atrophy.

The Clinical Use of Alzheimer's Disease Biomarkers in Patients with Mild Cognitive Impairment: A European Alzheimer's Disease Consortium Survey.

Background:Recent advances occurred in the field of Alzheimer’s disease (AD) biomarkers and the introduction of a research framework grounded on a biomarker-based definition of AD might have fostered an increased clinical use of AD biomarkers. For this reason, an up-to-date depiction of the clinical use of AD biomarkers is needed.Objective:To investigate the clinical use of the main AD biomarkers in patients with mild cognitive impairment (MCI) by examining the beliefs and preferences of professionals (clinicians and biomarker experts) of the European Alzheimer’s Disease Consortium (EADC).Methods:150 professionals filled in an online survey from May to September 2020. The investigated biomarkers were medial temporal lobe atrophy score (MTA) on structural MRI, typical AD (i.e., temporoparietal and posterior cingulate) hypometabolism on FDG-PET, CSF (Aβ42, p-tau, t-tau), amyloid-PET and tau-PET.Results:The frequency of responders reporting a frequent-to-constant use of MTA (77%) is higher than that of those reporting a frequent-to-constant use of the other AD biomarkers (i.e., CSF: 45%, p = 0.014; FDG-PET: 32%, p < 0.001; amyloid-PET: 8%, p < 0.001; and tau-PET: 2%, p < 0.001). CSF is considered the most valuable biomarker in terms of additional diagnostic value, followed by amyloid-PET, tau-PET, and typical AD hypometabolism on FDG-PET.Conclusion:AD biomarkers are widely used across European memory clinics with a clinical research background for the diagnosis of MCI. Overall, we observed that CSF is currently considered as the most useful biomarker, followed by amyloid-PET.

Machine learning based on Optical Coherence Tomography images as a diagnostic tool for Alzheimer's disease.

We mainly evaluate retinal alterations in Alzheimer's disease (AD) patients, investigate the associations between retinal changes with AD biomarkers, and explore an optimal machine learning (ML) model for AD diagnosis based on retinal thickness. A total of 159 AD patients and 299 healthy controls were enrolled. The retinal parameters of each participant were measured using optical coherence tomography (OCT). Additionally, cognitive impairment severity, brain atrophy, and cerebrospinal fluid (CSF) biomarkers were measured in AD patients. AD patients demonstrated a significant decrease in the average, superior, and inferior quadrant peripapillary retinal nerve fiber layer, macular retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL) thicknesses, as well as total macular volume (TMV) (all p < 0.05). Moreover, TMV was positively associated with Mini-Mental State Examination and Montreal Cognitive Assessment scores, IPL thickness was correlated negatively with the medial temporal lobe atrophy score, and the GCL thickness was positively correlated with CSF Aβ42 /Aβ40 and negatively associated with p-tau level. Based on the significantly decreased OCT variables between both groups, the XGBoost algorithm exhibited the best diagnostic performance for AD, whose four references, including accuracy, area under the curve, f1 score, and recall, ranged from 0.69 to 0.74. Moreover, the macular retinal thickness exhibited an absolute superiority for AD diagnosis compared with other enrolled variables in all ML models. We identified the retinal alterations in AD patients and found that macular thickness and volume were associated with AD severity and biomarkers. Furthermore, we confirmed that OCT combined with ML could serve as a potential diagnostic tool for AD.

Combining visual rating scales to identify prodromal Alzheimer's disease and Alzheimer's disease dementia in a population from a low and middle-income country.

BackgroundMany low- and middle-income countries, including Latin America, lack access to biomarkers for the diagnosis of prodromal Alzheimer's Disease (AD; mild cognitive impairment due to AD) and AD dementia. MRI visual rating scales may serve as an ancillary diagnostic tool for identifying prodromal AD or AD in Latin America. We investigated the ability of brain MRI visual rating scales to distinguish between cognitively healthy controls, prodromal AD and AD.MethodsA cross-sectional study was conducted from a multidisciplinary neurology clinic in Lima, Peru using neuropsychological assessments, brain MRI and cerebrospinal fluid amyloid and tau levels. Medial temporal lobe atrophy (MTA), posterior atrophy (PA), white matter hyperintensity (WMH), and MTA+PA composite MRI scores were compared. Sensitivity, specificity, and area under the curve (AUC) were determined.ResultsFifty-three patients with prodromal AD, 69 with AD, and 63 cognitively healthy elderly individuals were enrolled. The median age was 75 (8) and 42.7% were men. Neither sex, mean age, nor years of education were significantly different between groups. The MTA was higher in patients with AD (p < 0.0001) compared with prodromal AD and controls, and MTA scores adjusted by age range (p < 0.0001) and PA scores (p < 0.0001) were each significantly associated with AD diagnosis (p < 0.0001) but not the WMH score (p=0.426). The MTA had better performance among ages <75 years (AUC 0.90 [0.85–0.95]), while adjusted MTA+PA scores performed better among ages>75 years (AUC 0.85 [0.79–0.92]). For AD diagnosis, MTA+PA had the best performance (AUC 1.00) for all age groups.ConclusionsCombining MTA and PA scores demonstrates greater discriminative ability to differentiate controls from prodromal AD and AD, highlighting the diagnostic value of visual rating scales in daily clinical practice, particularly in Latin America where access to advanced neuroimaging and CSF biomarkers is limited in the clinical setting.