Medial Temporal Lobe Atrophy Scores Research Articles

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.

Comparison of brain microstructure alterations on diffusion kurtosis imaging among Alzheimer's disease, mild cognitive impairment, and cognitively normal individuals.

ObjectiveOur study aimed to explore the differences in brain microstructure in patients with Alzheimer’s disease (AD) and with mild cognitive impairment (MCI) and in individuals with normal cognition using diffusion kurtosis imaging (DKI) to identify a potential non-invasive biomarker of AD.Materials and methodsA total of 61 subjects were included in our study, including 20 subjects diagnosed with AD, 21 patients diagnosed with amnestic MCI, and 20 cognitively normal individuals. We acquired magnetic resonance imaging (MRI) scans, and DKI images were processed. Twelve regions of interest were drawn, and various parameters were measured and analyzed using SPSS version 11.0 software.ResultsComparative analysis showed that differences in brain regions in terms of mean diffusion (MD) and mean kurtosis (MK) between groups were the most marked. Precuneus MD, temporal MK, precuneus MK, and hippocampal MK were significantly correlated with neuropsychological test scores. Hippocampal MK showed the strongest correlation with the medial temporal lobe atrophy score (r = −0.510), and precuneus MD had the strongest correlation with the Koedam score (r = 0.463). The receiver operating curve analysis revealed that hippocampal MK exhibited better diagnostic efficacy than precuneus MD for comparisons between any group pair.ConclusionDKI is capable of detecting differences in brain microstructure between patients with AD, patients with MCI, and cognitively normal individuals. Moreover, it compensates for the deficiencies of conventional MRI in detecting pathological changes in microstructure before the appearance of macroscopic atrophy. Hippocampus MK was the most sensitive single parameter map for differentiating patients with AD, patients with MCI, and cognitively normal individuals.

Associations of multiple visual rating scales based on structural magnetic resonance imaging with disease severity and cerebrospinal fluid biomarkers in patients with Alzheimer’s disease

The relationships between multiple visual rating scales based on structural magnetic resonance imaging (sMRI) with disease severity and cerebrospinal fluid (CSF) biomarkers in patients with Alzheimer’s disease (AD) were ambiguous. In this study, a total of 438 patients with clinically diagnosed AD were recruited. All participants underwent brain sMRI scan, and medial temporal lobe atrophy (MTA), posterior atrophy (PA), global cerebral atrophy-frontal sub-scale (GCA-F), and Fazekas rating scores were visually evaluated. Meanwhile, disease severity was assessed by neuropsychological tests such as the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating (CDR). Among them, 95 patients were tested for CSF core biomarkers, including Aβ1–42, Aβ1–40, Aβ1–42/Aβ1–40, p-tau, and t-tau. As a result, the GCA-F and Fazekas scales showed positively significant correlations with onset age (r = 0.181, p < 0.001; r = 0.411, p < 0.001, respectively). Patients with late-onset AD (LOAD) showed higher GCA-F and Fazekas scores (p < 0.001, p < 0.001). With regard to the disease duration, the MTA and GCA-F were positively correlated (r = 0.137, p < 0.05; r = 0.106, p < 0.05, respectively). In terms of disease severity, a positively significant association emerged between disease severity and the MTA, PA GCA-F, and Fazekas scores (p < 0.001, p < 0.001, p < 0.001, p < 0.05, respectively). Moreover, after adjusting for age, gender, and APOE alleles, the MTA scale contributed to moderate to severe AD in statistical significance independently by multivariate logistic regression analysis (p < 0.05). The model combining visual rating scales, age, gender, and APOE alleles showed the best performance for the prediction of moderate to severe AD significantly (AUC = 0.712, sensitivity = 51.5%, specificity = 84.6%). In addition, we observed that the MTA and Fazekas scores were associated with a lower concentration of Aβ1–42 (p < 0.031, p < 0.022, respectively). In summary, we systematically analyzed the benefits of multiple visual rating scales in predicting the clinical status of AD. The visual rating scales combined with age, gender, and APOE alleles showed best performance in predicting the severity of AD. MRI biomarkers in combination with CSF biomarkers can be used in clinical practice.

CT-Detected MTA Score Related to Disability and Behavior in Older People with Cognitive Impairment.

Our study aims to investigate the relationship between medial temporal lobe atrophy (MTA) score, assessed by computed tomography (CT) scans, and functional impairment, cognitive deficit, and psycho-behavioral disorder severity. Overall, 239 (M = 92, F = 147; mean age of 79.3 ± 6.8 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. MTA was evaluated from 0 (no atrophy) to 4 (severe atrophy). The homocysteine serum was set to two levels: between 0 and 10 µmol/L, and >10 µmol/L. The cholesterol and glycemia blood concentrations were measured. Hypertension and atrial fibrillation presence/absence were collected. A total of 14 patients were MTA 0, 44 patients were MTA 1, 63 patients were MTA 2, 79 patients were MTA 3, and 39 patients were MTA 4. Cognitive (p < 0.0001) and functional (p < 0.0001) parameters decreased according to the MTA severity. According to the diagnosis distribution, AD patient percentages increased by MTA severity (p < 0.0001). In addition, the homocysteine levels increased according to MTA severity (p < 0.0001). Depression (p < 0.0001) and anxiety (p = 0.001) increased according to MTA severity. This study encourages and supports the potential role of MTA score and CT scan in the field of neurodegenerative disorder research and diagnosis.

Association of Homocysteine Levels With Medial Temporal Lobe Atrophy Among Carriers and Non-carriers of APOE ε4 in MCI Subjects.

BackgroundDifferent clinical subtypes of mild cognitive impairment (MCI) involve heterogeneous underlying etiologies. This study investigated the association between demographics, neuropsychological performance, apolipoprotein E (APOE) genotype and magnetic resonance imaging (MRI) measures in patients with MCI (amnestic [aMCI] and non-amnestic [naMCI]).MethodsThis case–control study included 130 aMCI patients, 58 naMCI patients, and 1,106 healthy controls (HCs). APOE genotypes, medial temporal lobe atrophy (MTA), neurological evaluation results, and white matter hyperintensities (WMH) were investigated. Serum folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and plasma hyperhomocysteinemia (Hcy) was assessed by a high-performance liquid chromatography-fluorescence method.ResultsSerum folate levels were significantly lower, but plasma Hcy levels were higher, in patients with aMCI and naMCI than in healthy controls. There were significantly higher MTA scores in the aMCI group than the healthy control group. Multiple linear regression showed that serum Hcy and folate concentrations were positively associated with MTA (p < 0.05), while APOE4 showed a significant negative association with MTA in the aMCI group (p < 0.01). In addition, moderate/severe WMH showed a significant negative association with MTA in the naMCI and HC groups (p < 0.01).ConclusionThe combined presence of APOE4 and Hcy is associated with aMCI in elderly individuals, while moderate/severe WMH is related to naMCI, which suggests etiological differences across MCI subtypes.

Third ventricle width measured by transcranial ultrasound and its diagnostic value in patients with Alzheimer's disease

Objective: To explore the diagnostic value of third ventricle width (TVW) measured by transcranial ultrasound (TCS) in the clinical diagnosis of Alzheimer's disease (AD) by analyzing and comparing the image characteristics of TVW in AD patients and healthy controls, and its correlation with cranial magnetic resonance medial temporal lobe atrophy (MTA) visual score and neuropsychological characteristics. Methods: TCS examination, MTA score and neuropsychological tests were performed in 39 confirmed AD and 41 normal controls from the Second Affiliated Hospital of Soochow University between January and July 2021. The correlation of TVW with MTA score and neuropsychological characteristics was analyzed and compared between the two groups. Results: A total of thirty-nine AD patients were enrolled, with 28 males and 11 females, aged (73±9) years, including 18 mild, 20 moderate, and 1 severe AD patient. Meanwhile, 41 healthy controls were also included, with 24 males and 17 females, aged (69±6) years old. TVW in AD patients was significantly wider than that in normal controls [0.76(0.66, 0.87) cm vs 0.50(0.44, 0.56) cm, P<0.001]. In neuropsychological tests, compared with normal controls, AD patients showed impaired performances in several cognitive functions, and there were statistically significant differences in delayed memory [0(0, 0) vs 4.0(4.0, 5.0), P<0.001], naming [2.0(1.0, 3.0) vs 3.0(2.0, 3.0), P<0.001], executive function [2.0(2.0, 3.0) vs 3.0(2.5, 3.0), P<0.001], language [0.0(0.0, 2.0) vs 3.0(2.0, 3.0), P<0.001] and other aspects between AD patients and normal controls (all P<0.05). TVW was negatively correlated with immediate memory (r=-0.339, P=0.035), delayed recall (r=-0.523, P<0.001), attention and computing power (r=-0.409, P=0.045), visual space and executive function (r=-0.333, P=0.039), but positively correlated with the atrophy of the medial temporal lobe (r= 0.552, P<0.001). Conclusions: TCS can be used to measure TVW in AD patients. When combined with MTA score and neuropsychological tests, it can provide a reliable objective basis for the clinical diagnosis of AD.

Qualitative and Quantitative Comparison of Hippocampal Volumetric Software Applications: Do All Roads Lead to Rome?

Brain volumetric software is increasingly suggested for clinical routine. The present study quantifies the agreement across different software applications. Ten cases with and ten gender- and age-adjusted healthy controls without hippocampal atrophy (median age: 70; 25–75% range: 64–77 years and 74; 66–78 years) were retrospectively selected from a previously published cohort of Alzheimer’s dementia patients and normal ageing controls. Hippocampal volumes were computed based on 3 Tesla T1-MPRAGE-sequences with FreeSurfer (FS), Statistical-Parametric-Mapping (SPM; Neuromorphometrics and Hammers atlases), Geodesic-Information-Flows (GIF), Similarity-and-Truth-Estimation-for-Propagated-Segmentations (STEPS), and Quantib™. MTA (medial temporal lobe atrophy) scores were manually rated. Volumetric measures of each individual were compared against the mean of all applications with intraclass correlation coefficients (ICC) and Bland–Altman plots. Comparing against the mean of all methods, moderate to low agreement was present considering categorization of hippocampal volumes into quartiles. ICCs ranged noticeably between applications (left hippocampus (LH): from 0.42 (STEPS) to 0.88 (FS); right hippocampus (RH): from 0.36 (Quantib™) to 0.86 (FS). Mean differences between individual methods and the mean of all methods [mm3] were considerable (LH: FS −209, SPM-Neuromorphometrics −820; SPM-Hammers −1474; Quantib™ −680; GIF 891; STEPS 2218; RH: FS −232, SPM-Neuromorphometrics −745; SPM-Hammers −1547; Quantib™ −723; GIF 982; STEPS 2188). In this clinically relevant sample size with large spread in data ranging from normal aging to severe atrophy, hippocampal volumes derived by well-accepted applications were quantitatively different. Thus, interchangeable use is not recommended.

Characteristics of Cortical Atrophy and White Matter Lesions Between Dementia With Lewy Bodies and Alzheimer's Disease: A Case-Control Study.

Introduction: Currently, there is still clinical overlap between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients, which may affect the accuracy of the early diagnosis of DLB. For better diagnosis and prognosis, further exploration of local cortical atrophy patterns and white matter lesions is needed.Methods: We reviewed the outpatient medical records of 97 DLB patients and 173 AD patients from January 2018 to September 2020 along with 30 matched outpatient clinic normal elderly people. MRI visual rating scales, including medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale (GCA-F), posterior atrophy (PA), Fazekas scale, Evans Index and cerebral microbleeds were evaluated and analyzed in DLB and AD patients with different severities and normal controls.Results: Overall, patients with DLB had higher scores on all visual rating scales than the normal controls. Meanwhile, compared with AD, DLB had lower MTA scores in the mild to moderate groups (both p ≤ 0.001), but the GCA-F and PA scores were similar (all p > 0.05). The Fazekas scores in the moderate to severe DLB group were lower than those in the AD group (p = 0.024 and p = 0.027, respectively). In addition, the diagnostic performance and sensitivity of multiple imaging indicators for DLB were better than that of MTA alone (the combination of MTA, GCA-F, PA, Fazekas visual rating scales, AUC = 0.756, 95%CI: 0.700–0.813, sensitivity = 0.647, specificity = 0.804 and MTA visual rating scale, AUC = 0.726, 95%CI: 0.667–0.785, sensitivity = 0.497, specificity = 0.876, respectively).Conclusion: The medial temporal lobe of DLB patients was relatively preserved, the frontal and parietal lobes were similarly atrophied to AD patients, and the white matter hyperintensity was lighter than that in AD patients. Combined multiple visual rating scales may provide a novel idea for the diagnosis of early DLB.

Cortical Atrophy, White Matter Lesions, and Bulb Configuration in Patients with Idiopathic Olfactory Loss and Other Causes of Olfactory Loss

Introduction: While magnetic resonance imaging (MRI) is not included in the current guidelines for diagnosing olfactory disorders in the most recent position paper on olfactory dysfunction, both 1.5T and 3T MRI are commonly used in the diagnostic workup of many patients with olfactory loss. Often, MRI is used to rule out intracranial tumours, but other useful information may be obtained from MRI scans in these patients. The potential of MRI in olfactory loss depends on sufficient knowledge of structural changes in different aetiologies of olfactory loss. We present common clinical MRI findings in olfactory loss and evaluate the usefulness of structural integrity scores in differentiating between aetiologies. Methods: In this study, we investigated if white matter hyperintensities (WMHs, measured by Fazekas score), global cortical atrophy (GCA), and medial temporal lobe atrophy (MTA) are more common in patients with idiopathic olfactory loss than in patients with acquired olfactory loss due to other aetiologies. Furthermore, we compared olfactory bulb (OB) configurations in different olfactory loss aetiologies. Results: In 88 patients with olfactory loss, WMHs, GCA, and MTA were not more significant findings on MRI in idiopathic olfactory loss (n = 51) compared with other causes of acquired olfactory loss (Fazekas score p = 0.2977; GCA score p = 0.6748; MTA score p = 0.7851). Bulb configurations differed in patients suffering from post-traumatic olfactory loss and may aid in identifying the underlying aetiology in patients where trauma is among the suspected causes of olfactory loss. Conclusion: We recommend that structural MRI with an OB sequence is included in the diagnostic evaluation of olfactory loss with suspected congenital and post-traumatic aetiology and should be considered in idiopathic olfactory loss with suspected central aetiology (e.g., tumour).

Cognitive decline in possible vascular cognitive impairment (VCI): Does the form of vascular brain injury matter?

AbstractBackgroundPatients presenting at a memory clinic with possible VCI include a heterogeneous population in terms of cognitive profile, vascular brain injury and prognosis. Little is known about the trajectories of cognitive decline on cognitive test performance in relation to the different forms of vascular brain injury.MethodWe included 474 memory clinic patients(age 68(±8.2) years, 44% female, mean MMSE 25.9(±2.9), 212(44.7%) patients with dementia) from the prospective TRACE‐VCI cohort study with possible VCI; cognitive complaints and vascular brain injury on MRI. We assessed cognitive functioning at baseline and follow‐up(mean follow‐up time 2.5(±1.4) years, total of 1176 neuropsychological tests) including the Rey Auditory Verbal Learning Test(RAVLT) immediate and delayed recall(memory), the Trail Making Test(TMT) A and B(attention and executive functioning, respectively), category fluency(language) and MMSE. Linear mixed models were used to evaluate the effect of different forms of vascular brain injury on cognitive decline. Models included(dichotomized) terms for vascular brain injury(infarct(s), lacune(s), white matter hyperintensities(WMH), microbleed(s)), time and vascular brain injury*time. All models were adjusted for sex, age, diagnosis (dementia versus no dementia), education and medial temporal lobe atrophy(MTA) score(dichotomized as ≥1.5). Also, the models were evaluated in patients with a positive(+CSF‐AD) and negative(‐CSF‐AD) biomarker CSF Alzheimer profile.ResultVascular brain injury(multiple forms in one patient possible) consisted of infarct(s) in 54(11.4%), lacune(s) in 108(22.8%), moderate/severe WMH in 212(44.7%) and microbleed(s) in 203(42.8%) patients. In 164(54.3%) patients the MTA score was ≥1.5. We found no association between any form of vascular brain injury and baseline cognition. Infarct(s) showed an association with worsening on the TMTB(β;30.19,p=.00), especially in patients with a –CSF‐AD(β;65.93,p=.00). This effect was not found in patients with a +CSF‐AD(β;‐25.24,p=.18). Lacune(s) were associated with a rate of decline in immediate memory(β;1.62), delayed recall(β;.33), category fluency(β;.44) and MMSE(β;.46;all p&lt;0.05). Infarct(s) were associated with a slower rate of decline on category fluency(β;.96,p=.01). We found no association between WMH, microbleed(s) and rate of cognitive decline.ConclusionIn patients with possible VCI, infarct(s) were associated with steeper decline in executive functioning, especially in patients with a –CSF‐AD. Counterintuitively, the presence of lacune(s) and infarct(s) predisposed for a more favorable trajectory in memory.

Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer's disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial

SummaryBackgroundDrugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease.MethodsIn this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012–003641–15), and is completed.FindingsBetween July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or placebo (n=106). Of 197 (93%) participants who completed the study, 171 (81%) had complete primary outcome data. The mean brain volume (BSI) reduction was 19·1 mL (SD 10·3) in the losartan group and 20·0 mL (10·8) in the placebo group. The difference in total volume reduction between groups was –2·29 mL (95% CI –6·46 to 0·89; p=0·14). The number of adverse events was low (22 in the losartan group and 20 in the placebo group) with no differences between treatment groups. There was one treatment-related death per treatment group.Interpretation12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. Further research is needed to assess the potential therapeutic benefit from earlier treatment in patients with milder cognitive impairment or from longer treatment periods.FundingEfficacy and Mechanism Evaluation Programme (UK Medical Research Council and National Institute for Health Research).

The sex‐specific effect of the apolipoprotein E allele and methylenetetrahydrofolate reductase gene polymorphism on the biochemical, anatomical, and cognitive profiles of patients clinically diagnosed with probable Alzheimer's disease

We aimed to evaluate the sex-specific effect of apolipoprotein E (APOE) alleles and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on the biochemical, anatomical, and cognitive profiles of Alzheimer's disease (AD) patients. The patient (followed-up for at least 2 years) medical records, which comprised of data on plasma homocysteine and folate levels, lipid profile, HbA1c, MTHFR C677T genotype, APOE allele type, mini-mental state examination (MMSE) and clinical dementia rating (CDR) scores, and brain scans, were retrospectively analyzed. Two trained neurologists scored the white matter lesions (Fazekas scale), medial temporal lobe atrophy (MTA), and microbleeds using brain magnetic resonance imaging scans. This study included 574 patients clinically diagnosed with probable AD (average age, 73.2 years; mean MMSE score, 10.05). The effect of sex on all parameters was evaluated. The triglyceride (TG) and homocysteine levels and the MTA and Fazekas scores were higher in female APOE-ε4/ε4 carriers than in women without APOE-ε4. The TG and homocysteine levels were lower in men with the MTHFR CC allele than in those with the MTHFR TT allele. In contrast, MTHFR polymorphism and APOE-ε4 alleles were not significantly correlated with anatomical lesions and rate of decline in the MMSE and CDR scores. We demonstrated the sex-specific effect of the APOE allele and MTHFR polymorphism on the serological and anatomical biomarkers in AD patients. The APOE allele and MTHFR mutations did not directly affect cognitive progression, but differentially affected other biochemical factors, between the sexes. These findings will aid in devising novel preventive and therapeutic strategies.

Evaluation of MR Visual Rating Scales in Major Forms of Dementia.

Objective The aim of the study is to visually rate major forms of dementia using global cortical atrophy (GCA), medial temporal lobe atrophy (MTA), and Fazeka’s scales and Koedam’s score using magnetic resonance imaging (MRI). The purpose is to correlate the visual rating scales (VRS) with severity of dementia. Materials and Methods Thirty patients fulfilling DSM 5 (Diagnostic and Statistical Manual of Mental Disorders) criteria for Alzheimer’s dementia (AD), vascular dementia (VaD), and frontotemporal dementia (FTD) underwent MRI brain. Cortical atrophy, medial temporal, and parietal lobe atrophy were assessed using GCA and MTA scales and Koedam’s score, respectively. White matter hyperintensities were assessed using Fazeka’s scale. Correlation between VRS and mini-mental state exam (MMSE) scores was done using Pearson correlation coefficient. Results 70% of patients had Grade 2 GCA. More patients with AD had higher MTA scores as compared with others with 57% of AD patients showing abnormal for age MTA scores. Fazeka’s scale was abnormal for age in 58.33% of VaD and 57% AD patients. Majority (75%) showing severe parietal atrophy (Grade 3 Koedam’s score) were AD patients. Disproportionate frontal lobe atrophy was seen in all four (100%) FTD patients. Significant negative correlation was seen between MMSE and GCA scores of all patients ( p -value = 0.003) as well as between MTA and MMSE scores in AD patients ( p -value = 0.00095). Conclusion Visual rating of MTA is a reliable method for detecting AD and correlates strongly with memory scores. Atrophy of specific regions is seen more commonly in some conditions, for instance, where MTA and parietal atrophy are specific for AD while asymmetric frontal lobe and temporal pole atrophy favor FTD.

Transcranial Sonography Findings in Alzheimer's Disease: A New Imaging Biomarker.

To validate transcranial sonography (TCS) as a novel imaging tool for the assessment of medial temporal lobe (MTL) atrophy (MTA). Participants with Alzheimer's disease (AD, n = 30) and age-sex-matched controls (n = 30) underwent TCS and MRI. On TCS, MTL structures (choroidal fissure (CF) and temporal horn (TH)) were measured and combined to create an MTA score in sonography (MTA-S). Furthermore, both THs and the third ventricle were combined to form the ventricle enlargement score in sonography (VES-S). On MRI, the MTL was evaluated by linear measurements, MTA scale and hippocampal volumetry. Validation was performed by comparing imaging methods and the patient group. Intraclass correlations for CF and TH showed substantial intra/inter-rater reliability (> 0.80). TCS and MRI showed strong to moderate correlation regarding TH (right = 0.88, left = 0.89) and CF (right = 0.70, left = 0.47). MTA-S correlated significantly with the hippocampal volume (right = -0.51, left = -0.47), predicted group membership in logistic regression (Exp(B) right = 3.0, left = 2.7), and could separate AD patients from controls (AUC = 0.93). An MTA-S of 6 mm and 10 mm discriminated MRI MTA scores 0-1 (from 2-4) and MTA score 4 (from 0-3) with 100 % specificity, respectively. VES-S also showed a moderate correlation with the hippocampal volume (r = -0.66) and could differentiate AD patients from controls (AUC = 0.93). Our results suggest that TCS may be an alternative imaging tool for the assessment of MTL atrophy and ventricular enlargement for patients in whom MRI scanning is not possible. Additionally, TCS offers a practical, patient-friendly and inexpensive option for the screening and follow-up of individuals with AD.

The Entorhinal Cortex Atrophy Score Is Diagnostic and Prognostic in Mild Cognitive Impairment.

Structural magnetic resonance imaging (MRI) is routinely performed in patients with mild cognitive impairment (MCI), but diagnostic accuracy to detect early cerebral atrophy is limited. To validate the visual entorhinal cortex atrophy (ERICA) rating scale regarding diagnosis, biomarker status, neuropsychological profile, and dementia risk in MCI. The ERICA score was retrospectively assessed regarding its discrimination of MCI (n = 80) from subjective cognitive decline and Alzheimer's disease (AD) dementia (n = 60, respectively), its prediction of conversion to dementia (median follow-up 28 months) and amyloid/tau biomarker status, and its association with neuropsychological tests. The ERICA score achieved 97% positive predictive value (PPV) for the presence of MCI. Discrimination between MCI and AD dementia (area under the curve: 0.71) was comparable to volumetry, and superior to the medial temporal lobe atrophy (MTA) score (p = 0.006). The PPV of the ERICA score for conversion to dementia was 83%, equivalent to tau status. It achieved 90% PPV for conversion when combined with tau, and 100% negative predictive value with verbal recall. While no measure predicted the predominantly positive amyloid status, the ERICA score was at least comparable to volumetry, and superior to the MTA score in predicting tau positivity (92% PPV for phospho-tau). The ERICA score was associated with verbal learning and memory, and, unlike the MTA score, also with AD-specific deficits in cued verbal recall. The ERICA score is a simple and valuable tool to exploit structural MRI for diagnosis and prognosis in MCI and is non-inferior to volumetry.

The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies

BackgroundAlzheimer’s disease (AD)-related pathology is frequently found in patients with dementia with Lewy bodies (DLB). However, it is unknown how amyloid-β and tau-related pathologies influence neurodegeneration in DLB. Understanding the mechanisms underlying brain atrophy in DLB can improve our knowledge about disease progression, differential diagnosis, drug development and testing of anti-amyloid and anti-tau therapies in DLB. ObjectivesWe aimed at investigating the combined effect of CSF amyloid-β42, phosphorylated tau and total tau on regional brain atrophy in DLB in the European DLB (E-DLB) cohort. Methods86 probable DLB patients from the E-DLB cohort with CSF and MRI data were included. Random forest was used to analyze the association of CSF biomarkers (predictors) with visual rating scales for medial temporal lobe atrophy (MTA), posterior atrophy (PA) and global cortical atrophy scale-frontal subscale (GCA-F) (outcomes), including age, sex, education and disease duration as extra predictors. ResultsDLB patients with abnormal MTA scores had abnormal CSF Aβ42, shorter disease duration and older age. DLB patients with abnormal PA scores had abnormal levels of CSF Aβ42 and p-tau, older age, lower education and shorter disease duration. Abnormal GCA-F scores were associated with lower education, male sex, and older age, but not with any AD-related CSF biomarker. ConclusionsThis study shows preliminary data on the potential combined effect of amyloid-β and tau-related pathologies on the integrity of posterior brain cortices in DLB patients, whereas only amyloid-β seems to be related to MTA. Future availability of α-synuclein biomarkers will help us to understand the effect of α-synuclein and AD-related pathologies on brain integrity in DLB.

Quantification of medial temporal lobe atrophy score in patients with vascular dementia

Vascular dementia (VD) is the second most common cause of dementia in older people. It is a chronic progressive disease of the brain bringing about cognitive impairment. The loss of brain parenchyma is caused by cerebrovascular diseases. Dementia rates are growing at alarming proportion in several regions of the world and is related to population aging. This study aimed to determine the influence of medial temporal lobe atrophy on the Mini-Mental State Examination-Philippines (MMSE-P) and Clock Drawing Test (CDT) scores in patients diagnosed with VD. This study utilized a cross-sectional design. We included elderly Filipinos > 60 years old diagnosed with VD from 2013 – 2018. Subjects were derived from in- and out-patient referrals in a tertiary hospital in Metro Manila. Schelten’s visual scale was utilized to evaluate medial temporal lobe atrophy (MTA). The mean age of subjects in the study was 73.54 years old (mean SD + 8.63), mostly females and completed tertiary education. Linear regression analysis was used to measure the influence of medial temporal lobe atrophy in MMSE-P and CDT scores. Results showed inverse relation for MTA on both MMSE-P and CDT scores. Hence, for every 1-unit increase in MTA, there is a 0.58-unit decrease in CDT and 0.66-unit decrease in MMSE-P scores. MTA significantly decreased MMSE-P and CDT scores in patients with VD. So, as the medial temporal lobe atrophy score is higher, a corresponding decrease in both the MMSE-P and CDT scores.

Medial temporal lobe atrophy and posterior atrophy scales normative values.

ObjectivesThe medial temporal lobe atrophy (MTA) and the posterior atrophy (PA) scales allow to assess the degree hippocampal and parietal atrophy from magnetic resonance imaging (MRI) scans. Despite reliable, easy and widespread employment, appropriate normative values are still missing. We aim to provide norms for the Italian population.MethodsTwo independent raters assigned the highest MTA and PA score between hemispheres, based on 3D T1-weighted MRI of 936 Italian Brain Normative Archive subjects (age: mean ± SD: 50.2 ± 14.7, range: 20–84; MMSE>26 or CDR = 0). The inter-rater agreement was assessed with the absolute intraclass correlation coefficient (aICC). We assessed the association between MTA and PA scores and sociodemographic features and APOE status, and normative data were established by age decade based on percentile distributions.ResultsRaters agreed in 90% of cases for MTA (aICC = 0.86; 95% CI = 0.69–0.98) and in 86% for PA (aICC = 0.82; 95% CI = 0.58–0.98). For both rating scales, score distribution was skewed, with MTA = 0 in 38% of the population and PA = 0 in 52%, while a score ≥ 2 was only observed in 12% for MTA and in 10% for PA. Median denoted overall hippocampal (MTA: median = 1, IQR = 0–1) and parietal (PA: median = 0, IQR = 0–1) integrity. The 90th percentile of the age-specific distributions increased from 1 (at age 20–59) for both scales, to 2 for PA over age 60, and up to 4 for MTA over age 80. Gender, education and APOE status did not significantly affect the percentile distributions in the whole sample, nor in the subset over age 60.ConclusionsOur normative data for the MTA and PA scales are consistent with previous studies and overcome their main limitations (in particular uneven representation of ages and missing percentile distributions), defining the age-specific norms to be considered for proper brain atrophy assessment.

Cognitive Profiles and Atrophy Ratings on MRI in Senior Patients With Mild Cognitive Impairment.

In this cross-sectional study, we sought to describe cognitive and neuroimaging profiles of Memory clinic patients with Mild Cognitive Impairment (MCI). 51 MCI patients and 51 controls, matched on age, sex, and socio-economic status (SES), were assessed with an extensive neuropsychological test battery that included a measure of intelligence (General Ability Index, “GAI,” from WAIS-IV), and structural magnetic resonance imaging (MRI). MCI subtypes were determined after inclusion, and z-scores normalized to our control group were generated for each cognitive domain in each MCI participant. MR-images were scored by visual rating scales. MCI patients performed significantly worse than controls on 23 of 31 cognitive measures (Bonferroni corrected p = 0.001), and on 8 of 31 measures after covarying for intelligence (GAI). Compared to nonamnestic MCI patients, amnestic MCI patients had lower test results in 13 of 31 measures, and 5 of 31 measures after co-varying for GAI. Compared to controls, the MCI patients had greater atrophy on Schelten's Medial temporal lobe atrophy score (MTA), especially in those with amnestic MCI. The only structure-function correlation that remained significant after correction for multiple comparisons was the MTA—long delay recall domain. Intelligence operationalized as GAI appears to be an important moderator of the neuropsychological outcomes. Atrophy of the medial temporal lobe, based on MTA scores, may be a sensitive biomarker for the functional episodic memory deficits associated with MCI.

Modified Visual Magnetic Resonance Rating Scale for Evaluation of Patients with Forgetfulness.

As cognitive impairment increases with age, sulcal atrophy (SA) and the enlargement of the ventricles also increase. Considering the measurements on the previously proposed visual scales, a new scale is proposed in this study that allows us to evaluate the atrophy, white matter hyperintensities (WMHs), basal ganglia infarct (BGI), and infratentorial infarct (ITI) together. Our aim of this study is to propose a practical and standardized MRI for the clinicians to be used in daily practice. A total of 97 patients older than 60 years and diagnosed with depression or Alzheimer's disease (AD) are included. Cranial MRI, Mini Mental State Examination (MMSE), detailed neuropsychometric tests, and depression scales are applied to all patients. The SA, ventricular atrophy (VA), medial temporal lobe atrophy (MTA), periventricular WMH (PWMH), subcortical WMH (SCWMH), BGI, and ITI are scored according to the scale. The total score is also recorded. The average age of the patients was 74.53, and the mean MMSE score was 22.7 in the degenerative group and 27.8 in the non-degenerative group. Among the patients, 50 were diagnosed with AD. All parameters significantly increased with age. In the degenerative group, SA, VA, MTA, PWMH, SCWMH, and total scores were found to be significantly higher. Sensitivities of VA, PWMH, SCWMH, and total scores, as well as both sensitivity and specificities of MTA score, were observed to be high. When they were combined, sensitivities and specificities were found to be high. The scale is observed to be predictive in discriminating degenerative and non-degenerative processes. This discrimination is important, particularly in depressive patients complaining of forgetfulness.