Clinical Diagnosis Of Alzheimer's Disease Research Articles

Association between neuropsychological assessment and amyloid status in a clinical setting.

Large research cohorts show robust associations between neuropsychological tests and Alzheimer's disease (AD) biomarkers, but studies in clinical settings are limited. The increasing availability of AD biomarkers to the practicing clinician makes it important to understand the relationship between comprehensive clinical neuropsychological assessment and biomarker status. This study examined concordance between practicing clinical neuropsychologists' diagnostic impressions and AD biomarker status in patients seen at an outpatient medical center, with a secondary aim of defining the characteristics of discordant cases. Participants (N = 79) seen for clinical neuropsychological assessment who subsequently underwent lumbar puncture or amyloid positron emission tomography imaging were identified via retrospective chart review. Concordance between clinical neuropsychological diagnosis (non-AD, indeterminate, possible/probable AD) and AD biomarker status (negative, indeterminate, positive) was determined. Individual test score data were used to examine between-group differences based on amyloid status. AD biomarker positive and negative patients did not differ on individual neuropsychological tests after correcting for multiple comparisons, though the small number of AD biomarker indeterminate individuals performed better than biomarker positive patients. However, there was 76.7% concordance between neuropsychologists' diagnostic impressions and AD biomarker status (88% sensitivity and 55% specificity of neuropsychological assessment in detecting AD biomarker status). AD biomarker negative patients diagnosed as possible/probable AD (discordant) versus non-AD (concordant) had significantly lower Neuropsychological Assessment Battery Story Delayed Recall, higher Wechsler Adult Intelligence Scale-Fourth Edition Coding, and higher Trail-Making A (i.e., an amnestic memory profile). Comprehensive neuropsychological assessment showed modest concordance with AD biomarker status in patients seen in an outpatient medical center for routine clinical care. Low specificity for the clinical diagnosis of AD could be explained by the multiplicity of etiologies that cause memory impairment (i.e., TAR DNA-binding protein 43, suspected non-AD pathology). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Frontal Cortex Lipid Alterations During the Onset of Alzheimer's Disease.

Although sporadic Alzheimer's disease (AD) is a neurodegenerative disorder of unknown etiology, familial AD is associated with specific gene mutations. A commonality between these forms of AD is that both display multiple pathogenic events including cholinergic and lipid dysregulation. We aimed to identify the relevant lipids and the activity of their related receptors in the frontal cortex and correlating them with cognition during the progression of AD. MALDI-mass spectrometry imaging (MSI) and functional autoradiography was used to evaluate the distribution of phospholipids/sphingolipids and the activity of cannabinoid 1 (CB1), sphingosine 1-phosphate 1 (S1P1), and muscarinic M2/M4 receptors in the frontal cortex (FC) of people that come to autopsy with premortem clinical diagnosis of AD, mild cognitive impairment (MCI), and no cognitive impairment (NCI). MALDI-MSI revealed an increase in myelin-related lipids, such as diacylglycerol (DG) 36:1, DG 38:5, and phosphatidic acid (PA) 40:6 in the white matter (WM) in MCI compared to NCI, and a downregulation of WM phosphatidylinositol (PI) 38:4 and PI 38:5 levels in AD compared to NCI. Elevated levels of phosphatidylcholine (PC) 32:1, PC 34:0, and sphingomyelin 38:1 were observed in discrete lipid accumulations in the FC supragranular layers during disease progression. Muscarinic M2/M4 receptor activation in layers V-VI decreased in AD compared to MCI. CB1 receptor activity was upregulated in layers V-VI, while S1P1 was downregulated within WM in AD relative to NCI. FC WM lipidomic alterations are associated with myelin dyshomeostasis in prodromal AD, suggesting WM lipid maintenance as a potential therapeutic target for dementia.

Feasibility of Using Magnetic Resonance Spectroscopy Test Biomarkers to Diagnose Alzheimer's Disease: Systematic Evaluation and Meta-Analysis.

Alzheimer's disease (AD) is the leading cause of dementia, resulting in impairments in memory, cognition, decision-making, and social skills. Thus, accurate preclinical diagnosis of Alzheimer's disease is paramount. The identification of biomarkers for Alzheimer's disease through magnetic resonance spectroscopy (MRS) represents a novel adjunctive diagnostic approach. This study conducted a meta-analysis of the diagnostic results of this technology to explore its feasibility and accuracy. PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched without restrictions, with the search period extending up to July 31, 2022. The search strategy employed a combination of subject headings and keywords. All retrieved documents underwent screening by two researchers, who selected them for meta-analysis. The included literature was analyzed using Review Manager 5.4 software, with corresponding bias maps, forest plots, and summary receiver operating characteristic (SROC) curves generated and analyzed. A total of 344 articles were retrieved initially, with 11 articles meeting the criteria for inclusion in the analysis. The analysis encompassed data from approximately 1766 patients. In the forest plot, both sensitivity (95% CI) and specificity (95% CI) approached 1. Examining the true positive rate, false positive rate, true negative rate, and false negative rate, all studies on the summary receiver operating characteristic (SROC) curve clustered in the upper left quadrant, suggesting a very high accuracy of biomarkers detected by MRS for diagnosing Alzheimer's disease. The detection of biomarkers by MRS demonstrates feasibility and high accuracy in diagnosing AD. This technology holds promise for widespread adoption in the clinical diagnosis of AD in the future.

Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy.

To evaluate the effect of Alzheimer's disease (AD) -related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). Data from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4-R-Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD-positive (CBS/PSP-AD) and AD-negative (CBS/PSP-noAD) groups based on fluid biomarkers and amyloid PET scans. Cognitive, motor, and depression scores; AD fluid biomarkers (cerebrospinal p-tau, t-tau, and amyloid-beta, and plasma ptau-217); and neuroimaging data (amyloid PET, MRI and fMRI) were collected. Clinical features, whole-brain gray matter volume and functional networks connectivity were compared across groups. Data were analyzed from 87 CBS/PSP-noAD and 23 CBS/PSP-AD, 18 AD, and 30 healthy controls. CBS/PSP-noAD showed worse performance in comparison to CBS/PSP-AD in the PSPRS [mean(SD): 34.8(15.8) vs 23.3(11.6)] and the UPDRS scores [mean(SD): 34.2(17.0) vs 21.8(13.3)]. CBS/PSP-AD demonstrated atrophy in AD signature areas and brainstem, while CBS/PSP-noAD patients displayed atrophy in frontal and temporal areas, globus pallidus, and brainstem compared to healthy controls. The default mode network showed greatest disconnection in CBS/PSP-AD compared with CBS/PSP-no AD and controls. The thalamic network connectivity was most affected in CBS/PSP-noAD. AD biomarker positivity may modulate the clinical presentation of CBS/PSP, with evidence of distinctive structural and functional brain changes associated with the AD pathology/co-pathology. ANN NEUROL 2024.

Microvascular Perfusion Imaging in Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide and significantly impacts the essential functions of daily life and social activities. Research on AD has found that its pathogenesis is related to the extracellular accumulation of amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles in the cortical and limbic areas of the human brain, as well as cerebrovascular factors. The detection of Aβ or tau can be performed using various probes and methodologies. However, these modalities are expensive to implement and often require invasive procedures, limiting accessibility on a large scale. While magnetic resonance imaging (MRI) and computed tomography (CT) are generally used for morphological and structural brain imaging, they show wide variability in their accuracy for the clinical diagnosis of AD. Several novel imaging modalities have emerged as alternatives that can accurately and vividly display the changes in blood flow and metabolism in each brain area and enable physicians and researchers to gain insights into the generation and progression of the cerebro-microvascular pathologies of AD. In this review, we summarize the current knowledge on microvascular perfusion imaging modalities and their application in AD, including MRI (dynamic susceptibility contrast-MRI, arterial spin labeling-MRI), CT (cerebral CT perfusion imaging), emission computed tomography (positron emission tomography (PET), single-photon emission computed tomography (SPECT)), transcranial doppler ultrasonography (TCD), and retinal microvascular imaging (optical coherence tomography imaging, computer-assisted methods for evaluating retinal vasculature).

Constitutive NOS Production Is Modulated by Alzheimer's Disease Pathology Depending on APOE Genotype.

Both the endothelial (eNOS) and the neuronal (nNOS) isoforms of constitutive Nitric Oxide Synthase have been implicated in vascular dysfunctions in Alzheimer's disease (AD). We aimed to explore the relationship between amyloid pathology and NO dynamics by comparing the cerebrospinal fluid (CSF) levels of nNOS and eNOS of 8 healthy controls (HC) and 27 patients with a clinical diagnosis of Alzheimer's disease and isolated CSF amyloid changes, stratified according to APOE ε genotype (APOE ε3 = 13, APOE ε4 = 14). Moreover, we explored the associations between NOS isoforms, CSF AD biomarkers, age, sex, cognitive decline, and blood-brain barrier permeability. In our cohort, both eNOS and nNOS levels were increased in APOE ε3 with respect to HC and APOE ε4. CSF eNOS inversely correlated with CSF Amyloid-β42 selectively in carriers of APOE ε3; CSF nNOS was negatively associated with age and CSF p-tau only in the APOE ε4 subgroup. Increased eNOS could represent compensative vasodilation to face progressive Aβ-induced vasoconstriction in APOE ε3, while nNOS could represent the activation of NO-mediated plasticity strategies in the same group. Our results confirm previous findings that the APOE genotype is linked with different vascular responses to AD pathology.

Abstract P250: Vascular Contributions to Alzheimer's Disease

Introduction: Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that affects over 50 million people worldwide. The role of vascular risk factors have been described as a contributor to and a major comorbidity of AD pathogenesis; yet there is discordant evidence of this complex relationship between cardiovascular diseases (CVD) and its risk factors (like hypertension, hyperlipidemia, obesity, etc.) with AD pathophysiology and cognitive decline. AD associated Genome-wide association studies (GWAS) and derived polygenic risk scores (AD PRS) have uncovered some significant common genetic variants relating to CVD risk factors; however, we are still yet to unravel the comprehensive impact of these vascular genetic contributions to AD pathogenesis and cognitive decline. Method: In this study, we used 1800 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort spanning the full spectrum of clinical and pathological diagnoses of the AD spectrum, as our target dataset used for polygenic risk score calculation. Thereafter, we obtained GWAS summary statistics for cumulative cardiovascular risk by searching the Polygenic Score (PGS) GWAS Catalog using CVD as the ‘mapped trait” and then calculated cardiovascular-based PRS using HRS-based imputed GWAS data of the ADNI cohort. We conducted association analysis using a multivariate linear regression model with appropriate covariates (age, sex, APOE, education, etc.) between CVD-related polygenic risk score (CVD-PRS) with the different clinical AD diagnoses groups (Cognitively Normal/CN, Significant Memory Concerns/SMC, Mild Cognitive Impairment/MCI, Alzheimer's Disease/AD). We also performed association analysis of this CVD-PRS with white matter hyperintensity (WMHI) values, a vascular biomarker, at baseline using a linear regression model. Furthermore, we extended our analyses of CVD-related PRS with cognitive performance at baseline using composite scores for memory (MEM) and executive functioning (EF). Results and Conclusion: We found significantly strong correlation of CVD-related PRS with only certain AD Diagnoses groups (Significant Memory Concerns: SMC and Alzheimer's: AD) in the AD continuum. Additionally, we found strong associations (p < 0.05) of this cardiovascular based- polygenic risk score with baseline memory as well as White Matter Hyperintensity (WMH) in our sample, specifically the group with a clinical diagnosis of AD. Furthermore, we are performing longitudinal association analysis of CVD-related PRS with longitudinal cognitive decline using a linear mixed effects model. Our findings will help us understand 1) how a cumulative CVD-related PRS associates with different AD diagnoses subgroups as well as vascular biomarkers for AD and 2) how CVD-related PRS associates with cognitive performance and longitudinal cognitive decline.

Preliminary study on early diagnosis of Alzheimer's disease in APP/PS1 transgenic mice using multimodal magnetic resonance imaging.

Alzheimer's disease (AD) has an insidious onset and lacks clear early diagnostic markers, and by the time overt dementia symptoms appear, the disease is already in the mid-to-late stages. The search for early diagnostic markers of AD may open a critical window for Alzheimer's treatment and facilitate early intervention to slow the progression of AD. In this study, we aimed to explore the imaging markers for early diagnosis of AD through the combined application of structural magnetic resonance imaging (sMRI), resting-state functional magnetic resonance imaging (rs-fMRI), and 1H-magnetic resonance spectroscopy (1H-MRS) multimodal magnetic resonance imaging (MRI) techniques at the animal experimental level, with the aim to provide a certain reference for early clinical diagnosis of AD. First, sMRI scans were performed on 4-month-old amyloid beta precursor protein/presenilin 1 (APP/PS1) transgenic AD model mice and wild type mice of the same litter using a 7.0 T animal MRI scanner to analyze the differential brain regions with structural changes in the gray matter of the brain by voxel-based morphometry (VBM). Next, rs-fMRI scans were performed to analyze the differential brain regions between groups for local spontaneous brain activity and functional connectivity (FC) between brain regions. Finally, 1H-MRS scans were performed to quantify and analyze intergroup differences in the relative concentrations of different metabolites within regions of interest (cortex and hippocampus). Compared with wild type mice, the volume of the left hippocampus, and right olfactory bulb of APP/PS1 transgenic AD model mice were reduced, the functional activity of the bilateral hippocampus, right piriform cortex and right caudate putamen was reduced, the functional network connectivity of the hippocampus was impaired, and the relative content of N-acetylaspartate (NAA)in the hippocampus was decreased. In addition, this study found that imaging changes in olfactory-related brain regions were closely associated with AD diagnosis, and these findings may provide some reference for the early diagnosis of AD.

Awareness and cognitive rehabilitation in Alzheimer's disease and frontotemporal dementia.

Awareness influences the evolution of neurodegenerative dementias. We gathered participants' and caregivers assessments of dependence in daily activities and we studied how each score would be related to next year participant autonomy, independently of other explicative variables. We retrospectively analyzed data from mildly demented participants with a clinical diagnosis of Alzheimer's disease (AD, n = 186) and frontotemporal dementia (FTD, n = 29) and their relatives. A research tool was used to assess participant dependence in 98 daily activities and associated caregiver burden. A discrepancy score between the patient's and relative's judgment was calculated to evaluate awareness of dependence in activities at baseline. This dependence scores, as well as sex, age, education, and 1 year difference in Mini-Mental State Examination were taken as possible explicative variables for dependence in activities adapted by therapists during a 1-year cognitive rehabilitation program. Patients with FTD showed less awareness for daily dependence (discrepancy 20.9% vs. 11.8% in AD). Both groups benefited from cognitive rehabilitation (25% decrease in dependence) and subjective burden of relatives was decreased in both groups. In the AD group, there was a significant positive relationship between both caregiver (P < 0.001) and participant's (P < 0.02) evaluation of dependence in daily activities at inclusion and dependence of participants in adapted activities after 1 year. Awareness of impairment in daily activities is a clinical symptom that is more important at inclusion in FTD than in AD. However, in participants with AD who, as a group, significantly benefit from a cognitive rehabilitation program, not only caregiver's but also participant's assessment of dependence at baseline is correlated to subsequent, next year greater dependence in daily activities adapted by the therapists. Although discrepant, both caregiver and participant evaluations appear to be important variables to understand the evolution and the benefit of care in participants at early stages of dementia.

Connected speech features in non-English speakers with Alzheimer’s disease: protocol for scoping review

BackgroundA large body of literature indicates that connected speech profiles in patients with Alzheimer’s disease (AD) can be utilized for diagnosis, disease monitoring, and for developing communication strategies for patients. Most connected speech research has been conducted in English, with little work in some European languages. Therefore, significant drawback remains with respect to the diversity of languages studied, and how the fragmentation of linguistic features differs across languages in AD. Accordingly, existing reviews on connected speech in AD have focused on findings from English-speaking patients; none have specifically focused on the linguistic diversity of AD populations. This scoping review is undertaken to provide the currently reported characteristics of connected speech in AD in languages other than English. It also seeks to identify the type of assessments, methods to elicit speech samples, type of analysis and linguistic frameworks used, and micro- and macro-linguistic features of speech reported in non-English speakers with AD.MethodWe will conduct a scoping review of published studies that have quantitively assessed connected speech in AD in languages other than English. The inclusion criteria for the studies would be subject/s with a clinical diagnosis of AD. The search will include the electronic databases PubMed, Ovid-Embase, PsycINFO, Linguistic and Language Behaviour s (LLBA), and Web of Science up until March 2023. Findings will be mapped and described according to the languages studied, the methodology employed (e.g., patient characteristics, tasks used, linguistic analysis framework utilized), and connected speech profiles derived (e.g., micro- and macro-linguistic reported).DiscussionThe scoping review will provide an overview of languages studied in connected speech research in AD with variation in linguistic features across languages, thus allowing comparison with the established key features that distinguish AD patients from healthy controls. The findings will inform future research in connected speech in different languages to facilitate robust connected speech research in linguistically and ethnically diverse populations.

Odor Identification Across Time in Mutation Carriers and Non-Carriers in Autosomal-Dominant Alzheimer's Disease.

Impaired odor identification is a characteristic of sporadic Alzheimer'sdisease(AD), but its presence in autosomal-dominantAD (adAD) remains uncertain. To investigate odor identification ability in mutation carriers (MC) and non-carriers (NC) of adAD in relation to years to estimated clinical onset clinical onset (YECO) of disease. Participants from six families with autosomal-dominant mutations (APP Swedish, APP Arctic, and PSEN1 mutations) included 20 MC and 20 NC. The groups were comparable in age, gender, education, number of APOE ɛ4 alleles, and YECO, but differed in global cognition (Mini-Mental State Examination). The MC group included individuals in asymptomatic, symptomatic cognitively unimpaired, mild cognitive impairment, and dementia stages of disease, spanning approximately 40 years of the AD continuum. All NC were asymptomatic. Olfactory function was assessed by means of free and cued identification of common odors summarized as total identification. MC performed poorer than NC in free and total identification. Four MC and none of the NC were anosmic. Olfactory functions in MC and NC were significantly and inversely related to time course (YECO) for both free and total identification. The decline in free identification began approximately 10 years prior to the estimated clinical onset of AD in MC. Odor identification proficiency was associated with episodic memory and executive function in MC and NC. Impaired odor identification is present well before the clinical diagnosis of AD in MC and is associated with disease progression. Odor identification ability may be a useful early biomarker for adAD.

Potential Utility of Plasma Biomarker Panels in Differential Diagnosis of Alzheimer's Disease.

Blood tests are in need, in the clinical diagnosis of Alzheimer's disease (AD) as minimally invasive and less expensive alternatives to cerebrospinal fluid and neuroimaging methods. On these lines, single molecule array (Simoa) analysis of amyloid-β (Aβ42), total tau (t-tau), phospho-tau (p-tau 181), and neurofilament L (NfL) in the plasma samples of AD subjects, healthy controls (HC), and non-AD subjects was conducted. Findings from this study suggest that a panel of multiple plasma biomarkers (NfL, Aβ42, t-tau, and p-tau 181) combined with the clinical assessments could support differential diagnosis of AD and other dementias from healthy controls.

Use of modern classification systems for complex diagnostics of Alzheimer's disease

To compare the content of β-amyloid (Aβ) peptides Aβ40, Aβ42, total and threonine phosphorylated 181 tau-protein in cerebrospinal fluid (CSF) of patients with the clinical diagnosis of Alzheimer's disease (AD). The study was performed on 64 patients with a diagnosis of dementia and MMSE scores of 24 or lower. All patients underwent lumbar puncture. Aβ40, Aβ42, Aβ42/40 ratio, total tau, phosphorylated tau at threonine 181 were determined in the CSF using a multiplex assay according to the manufacturer's protocol, the concentration was determined in pkg/ml. The preliminary diagnosis of AD was made in 3 patients (5%). As a result of the study of protein content in the CSF, signs of AD were detected in 48 (75%) people. The findings suggest that the diagnosis of AD is made 10-14 times less frequently than it should be according to the World Health Organization data. The discrepancy between clinical diagnosis and laboratory findings is confirmed by our study. Differences in the therapy of dementias and the development of new drugs targeting specific links in the pathogenesis of different types of dementias require accurate and complete diagnosis of dementias, especially AD, as the most common type of dementia.

Cerebrospinal fluid biomarker profiling of diverse pathophysiological domains in Alzheimer's disease.

While Alzheimer's disease (AD) is defined by amyloid-β plaques and tau tangles in the brain, it is evident that many other pathophysiological processes such as inflammation, neurovascular dysfunction, oxidative stress, and metabolic derangements also contribute to the disease process and that varying contributions of these pathways may reflect the heterogeneity of AD. Here, we used a previously validated panel of cerebrospinal fluid (CSF) biomarkers to explore the degree to which different pathophysiological domains are dysregulated in AD and how they relate to each other. Twenty-five CSF biomarkers were analyzed in individuals with a clinical diagnosis of AD verified by positive CSF AD biomarkers (AD, n = 54) and cognitively unimpaired controls negative for CSF AD biomarkers (CU-N, n = 26) using commercial single- and multi-plex immunoassays. We noted that while AD was associated with increased levels of only three biomarkers (MMP-10, FABP3, and 8OHdG) on a group level, half of all AD participants had increased levels of biomarkers belonging to at least two pathophysiological domains reflecting the diversity in AD. LASSO modeling showed that a panel of FABP3, 24OHC, MMP-10, MMP-2, and 8OHdG constituted the most relevant and minimally correlated set of variables differentiating AD from CU-N. Interestingly, factor analysis showed that two markers of metabolism and oxidative stress (24OHC and 8OHdG) contributed independent information separate from MMP-10 and FABP3 suggestive of two independent pathophysiological pathways in AD, one reflecting neurodegeneration and vascular pathology, and the other associated with metabolism and oxidative stress. Better understanding of the heterogeneity among individuals with AD and the different contributions of pathophysiological processes besides amyloid-β and tau will be crucial for optimizing personalized treatment strategies. A panel of 25 highly validated biomarker assays were measured in CSF.MMP10, FABP3, and 8OHdG were increased in AD in univariate analysis.Many individuals with AD had increased levels of more than one biomarker.Markers of metabolism and oxidative stress contributed to an AD multianalyte profile.Assessing multiple biomarker domains is important to understand disease heterogeneity.

DMA-HPCNet: Dual Multi-level Attention Hybrid Pyramid Convolution Neural Network for Alzheimer's Disease Classification.

Computer-aided diagnosis (CAD) plays a crucial role in the clinical application of Alzheimer's disease (AD). In particular, convolutional neural network (CNN)-based methods are highly sensitive to subtle changes caused by brain atrophy in medical images (e.g., magnetic resonance imaging, MRI). Due to computational resource constraints, most CAD methods focus on quantitative features in specific regions, neglecting the holistic nature of the images, which poses a challenge for a comprehensive understanding of pathological changes in AD. To address this issue, we propose a lightweight dual multi-level hybrid pyramid convolutional neural network (DMA-HPCNet) to aid clinical diagnosis of AD. Specifically, we introduced ResNet as the backbone network and modularly extended the hybrid pyramid convolution (HPC) block and the dual multi-level attention (DMA) module. Among them, the HPC block is designed to enhance the acquisition of information at different scales, and the DMA module is proposed to sequentially extract different local and global representations from the channel and spatial domains. Our proposed DMA-HPCNet method was evaluated on baseline MRI slices of 443 subjects from the ADNI dataset. Experimental results show that our proposed DMA-HPCNet model performs efficiently in AD-related classification tasks with low computational cost.

Alzheimers disease course prediction methods based on deep learning methods

Alzheimer 's disease (AD) is a primary disease of the nervous system with memory and cognitive impairment as the main symptoms. It is the most common type of senile dementia and seriously threatens the quality of life and life safety of the elderly. Due to the pathological characteristics of AD and the limitations of medical technology, there is currently no very effective treatment worldwide. Therefore, early prediction and diagnosis of AD has always been a research hotspot worldwide. Deep learning may finish the joint classification of several stages by mining the abundant information implicit in the visual data collected from patients. It is a hub for computer-assisted diagnosis research. Therefore, many studies have applied computer-aided methods such as deep learning to the medical image data of Alzheimer 's disease, so as to provide ideas and help for prediction and diagnosis of diseases. This paper analyzes and compares various network structures, summarizes the use of the current, comparatively new deep learning network models applied in the classification of Alzheimer's disease course, and discusses the difficulties and potential future research directions for deep learning in the field of AD diagnosis. Thus, it is very important to raise the efficiency of the clinical diagnosis of AD and the accuracy of early forecasts.

Striatal Amyloid deposition in sporadic Alzheimer’s Disease

AbstractBackgroundIt has been shown that disorders associated with early‐life alterations in amyloid production or processing such as in autosomal dominant Alzheimer’s disease (AD) and down syndrome‐associated dementia have a different pattern of Aβ deposition, with early striatal accumulation, as compared to sporadic late‐onset cases, in which striatal deposition has been suggested to be a marker of late and advanced amyloidosis. It is not clear, however, if the pattern of amyloid accumulation is related to any other factors or if it has any impact on brain metabolism. We aimed to determine if there are any clinical or demographic predictors of striatal tau accumulation in sporadic AD and whether its presence affects the subjects´ brain metabolism.MethodSubjects that underwent positron emission tomography (PET) scans with 18F‐FDG and 11C‐PIB were analyzed retrospectively. Only those with clinical diagnosis of AD and mild cognitive impairment (MCI) due to AD were considered for the analysis. Visual analyses were performed to exclude subjects without cortical amyloid accumulation. Mean values from cortical volumes of interest (VOIs) and striatum were obtained. Amyloid deposition was correlated with age and disease duration via Pearson’s correlations. Amyloid deposition was also correlated to brain metabolism as assessed by FDG PET.Result150 subjects were included in this study. Neither age nor disease duration was correlated with striatal amyloid accumulation. Subjects with striatal Pib accumulation showed higher cortical amyloid burden. Moreover, higher striatal amyloid burden was positively correlated with higher frontal amyloid burden specifically. Amyloid burden in the striatum did not seem to have an impact on the glucose metabolism in the striatum itself. However, variations in cortical glucose metabolism could be observed. A higher striatal amyloid burden was correlated with cortical glucose hypometabolism, specifically in the precuneus and temporal areas (Figure 1).ConclusionThere seems to be a stage of sporadic Alzheimer’s disease in which amyloid accumulates in the striatum. This, in turn, appears to have an impact on brain functioning. Whether this has a real impact on cognitive performance remains to be elucidated.

Time‐encoded ASL shows higher sensitivity to detect cerebral blood flow reductions in AD

AbstractBackgroundPseudo continuous arterial spin labelling (pcASL) is an MRI technique to quantify cerebral blood flow (CBF). Time encoded ASL (te‐ASL) is a multiple time‐point pcASL variant that by acquiring several post‐label delays (PLD) to have more accurate CBF estimation allowing to measure arterial‐transit time (ATT). The aim of this study was to assess the performance of te‐ASL in detecting CBF and ATT changes in the Alzheimer’s disease (AD) continuum.MethodThe sample consisted of 59 subjects: 25 healthy controls (HC), 17 cognitively unimpaired individuals with positive cerebrospinal fluid (CSF) biomarkers (Ab42&lt;1.098pg/mL; p‐Tau181&gt;19pg/mL; Elecsys® ‐Roche Diagnostics) (preAD) and 17 patients with clinical diagnosis of AD (Ab42/p‐Tau181 ratio &lt;10.25; Lumipulse‐Fujirebio). The MRI protocol comprised of anatomical T1, and ASL sequences (M0 and te‐ASL). CBF and ATT maps were calculated in the oxford_asl toolbox in FSL. CBF and ATT maps were spatially normalized to the MNI, smoothed (12mm FWHM) and intensity normalized to the cerebellar gray matter. To detect patterns of lower CBF, voxel‐wise one way 3‐group ANOVA and post‐hoc paired t‐tests were performed using age and sex as confounders (SPM12; statistical threshold: p&lt;0.001 uncorrected; k&gt;100 voxels (∼0.33cm3) in all analyses). We compared results with those obtained using a single PLD by computing CBF from the last PLD (perfusion block, nominal PLD time of 2000ms) of the te‐ASL schema.ResultTable 1 displays the descriptive statistics of the sample. Figure 1 shows that, with te‐ASL, AD patients displayed lower CBF (yellow) in extensive bilateral pareto‐temporal, cingulate and occipital areas. Preclinical AD participants showed an overlapping pattern (green), albeit reduced in extension. When using pcASL, the detected pattern of lower CBF in the AD group was less extended and did not overlap with that of the PreAD groups. No ATT differences were found associated to AD.Conclusionte‐ASL was more sensitive to detect CBF differences across the AD continuum than single PLD ASL. The pattern of lower CBF in the AD group covered expected areas, and that in the preclinical AD group partially overlapped.

CSF Abeta 3‐42/1‐42 ratio and neurogranin as biomarkers of interest in dementia with Lewy bodies

AbstractBackgroundDementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are the among the most common neuropathologies. Amyloid and tau biomarker changes are often incorporated in the clinical diagnosis of AD. The current DLB criteria does not include robust biofluid biomarkers. However differences in amyloid plaque and CSF neurogranin in DLB has been of interest based on neuropathology and prior CSF reports. Our objective was to determine if Abeta modifications Abeta 3‐42 and Abeta 1‐42 along with neurogranin could be used to differentiate DLB from AD.MethodThis cohort study among 45 MCI stage of AD meeting NIA/AA 2011 criteria and 15 DLB participants meeting the 2017 Mc Keith criteria. We evaluated the CSF levels of Abeta 3‐42, Abeta 1‐42 by Liquid chromatography‐mass spectrometry (LC‐MS/MS) techniques and CSF neurogranin by standard ELISA to explore the differences between groups. Two sample t‐tests both without and with data imputation for samples not meeting lower levels of detection and linear regression models by considering the confounding variables of age, sex and education were assessed.ResultMean age 67.67 (SD5.13) years, 33% Female. Mean neurogranin levels in DLB 325.9 (SD 200.34 were lower than in MCI‐AD 707.7 (SD 489.94) pg/ml, (p = 0.0006 from two‐sample t‐test). Mean levels of Abeta 3‐42 were 51.63(SD = 19.6) and 43.63(SD = 13.5)fmol/l, and Abeta 1‐42 848.7 (SD = 248.4) fmol/l and 981.5(SD = 265.0) in DLB and MCI‐AD, respectively and were not significantly different. The ratio of Abeta 3‐42/Abeta 1‐42 was higher in DLB 0.06 (SD = 0.02) than MCI‐AD 0.04 (SD = 0.01) (p = 0.008 from two‐sample t‐test). In the multivariable regression models after adjusting for confounding variables the ratio of Abeta 3‐42/Abeta 1‐42 (Est = 67.19,SE = 29.62, p = 0.02) and neurogranin (Est = ‐0.0069,SE = 0.0026,p = 0.009) were significant discriminators between DLB and MCI‐AD .ConclusionHigher ratio of CSF Abeta 3‐42/Abeta 1‐42 and lower CSF levels of neurogranin were noted in the DLB group compared to MCI‐AD. Lower levels of CSF neurogranin in DLB has been reported, while higher ratio of CSF Abeta 3‐42/Abeta 1‐42 in DLB is a novel biomarker finding. Differences in Abeta species in DLB could be potential biomarkers in separating DLB from AD.

Usefulness of R2 maps to detect GM changes in AD continuum: a pilot study

AbstractBackgroundMRI multi‐echo sequences can be used to compute quantitative R2 maps (1/T2). This pilot study aimed to determine whether R2 maps might offer relevant information on GM changes in AD continuum.MethodThe sample consisted of 60 subjects: 20 healthy controls (HC), 20 cognitively unimpaired individuals with CSF Aβ42/40&lt;0.071 (preAD) and 20 subjects with clinical diagnosis of Alzheimer disease (AD) validated by biomarkers (Ab42/p‐Tau181 ratio &lt;10.25; Lumipulse‐Fujirebio). The MRI protocol included 3D T1W (voxel size: 1.2×1.2×1.2mm3, TR = 9.8ms, TE = 3ms, TI = 900ms) and multi‐echo (GRASE, voxel size: 2×2.2×2 mm3, TR = 2000ms, 32 echoes, TE: successive multiples of 9.3ms). R2 maps were obtained through linear regression of the logarithm of multi‐echo images. GM and R2 maps were spatially normalized to the MNI and smoothed (8mm FWHM). Voxel‐wise one‐way 3‐group ANOVA and post‐hoc paired t‐tests were performed on modulated GM (GMv) and R2 maps using age and sex as confounders and applying a common GM mask (SPM12, statistical threshold: p&lt;0.001 uncorrected; k&gt;100 voxels (∼0.33cm3) in all analyses).ResultTable 1 displays the descriptive statistics of the sample. Figure 1 shows the results from post‐hoc two‐sample t‐tests between HC and AD for GMv and R2 maps. GMv decrements were mostly located in temporal and parietal regions, as expected. Differences in R2 maps covered those regions but also others such anterior cingulate. No differences were found between HC and preAD neither in R2 maps nor in GMv.ConclusionResults might indicate that changes in R2 are not only reflecting atrophy but other undetermined tissular changes. Further research is warranted to further determine the mechanisms underlying R2 maps changes and the potential usefulness of R2 maps in AD characterization and diagnosis.