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Background: In clinical routine, cerebral computed tomography (cCT) is easily accessible and more commonly used than brain magnetic resonance imaging (cMRI). However, to the best of our knowledge a fully automated, validated regional specific volume estimation tool is lacking. Therefore, the aim of this study was to investigate the association between tissue classification for gray matter of both modalities. Method: Brain imaging segmentations of cCT and structural MRI of 37 healthy controls and 20 patients with mild cognitive impairment due to Alzheimer's disease were performed. The intensity and voxel count of normalized gray matter maps (MNI) in regions of interest using the Automated Anatomical Labelling Atlas (AAL3) were computed and compared between cCT and cMRI in both cohorts. Result: Brain Volume, measured by intensity and voxel count of gray matter, is associated between cortical regions acquired by cCT and cMRI. Although correlation coefficients varied between different brain areas, cortical compared to subcortical regions showed a relatively strong correlation. Conclusion: The evaluation of brain atrophy using segmented brain images acquired by cCT may be a simple, cost‐effective, and valuable addition to the clinical workflow, particularly in the context of socioeconomic and health disparities. [ABSTRACT FROM AUTHOR]

Background: Hippocampal volume atrophy is one of the most acknowledged supportive biomarkers for Alzheimer´s disease (AD). However, how hippocampal volumes along the anterior‐posterior axis mediate memory in aging and dementia is still subject of ongoing research. This study aimed to investigate the difference in volume of the hippocampus and its anterior and posterior subregions in a healthy young and senior control group as well as in mild cognitive impairment (MCI) due to AD and its ability to predict performance in spatial memory tasks. Method: Thirteen healthy young controls (24.9 ± 2.8 years), fourteen healthy senior controls (66.6 ± 8.2 years) as well as fifteen MCI patients (71.1 ± 6.0 years) with biomarkers typical for AD were included in this study. Subject‐specific manual tracing of hippocampi according to the EADC‐ADNI Harmonized Protocol for Hippocampal Segmentation (HarP) was performed on high‐resolution T1‐weighted MRI. Following the segmentation into anterior and posterior hippocampal parts, volumetry of anterior, posterior and total hippocampus was computed. Every subject performed a combined spatial memory and object recognition paradigm. Brain‐behavior correlations were conducted in order to explore prediction of spatial memory performance. Result: Volume measures of the hippocampi significantly differentiated healthy from pathological aging. Larger volume of posterior hippocampus in MCI patients correlated with higher performance scores in the spatial memory task (mean percentage of successfully retrieved object locations) whereas total and anterior hippocampal volume did not predict performance in the spatial memory task. Conclusion: These results support a functional hippocampal anterior‐posterior differentiation in memory processes and further stress the importance of integrating the dissociation of the hippocampus along its long‐axis concerning functional connectivity in memory processes and dementia. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is mainly associated with amnestic deficits. Imaging studies revealed a disruption of functional networks in AD, which plays a crucial role for the cognitive deficits. There is also evidence from resting‐state Electroencephalography (rsEEG) studies, which found altered functional connectivity measuring EEG coherence in AD (Babiloni et al., 2021; Wang et al., 2015). This was especially seen for the Alpha frequency band, which is known for its diagnostic potential in the disease. Furthermore, studies suggest that Alpha band marker correlate with cognitive decline in AD (Babiloni et al., 2010). The main aim of the current work is to gain a better understanding of the functional connectivity in Alzheimer's disease based on EEG given a very high temporal resolution. Method: The sample consisted of 15 patients (AD, 72.3 ± 8.28 years, 66.7% male) with mild cognitive impairment to mild dementia with a typical cerebrospinal fluid profile of Alzheimer's disease or pathological Amyloid‐PET and 15 age‐matched healthy controls (HC, 72.93 ± 7.17 years, 53.3% male). All participants underwent a neuropsychological examination and rsEEG. The rsEEG was recorded with the Neurowerk Amplifier using an elastic cap with 19 electrodes (10‐20 system). Raw data were preprocessed and further analyzed with regard to functional connectivity focusing on the Alpha frequency band (Brainstorm, SPSS, EEGlab). Functional connectivity was calculated by the magnitude squared coherence. Coherence was further clustered in global coherence and coherence per electrode. Finally, coherence scores were evaluated in relation to neuropsychological scores. Results: Centers of functional connectivity were found in frontal‐frontal and frontal‐parietal/occipital electrode pairs. Alpha frequency band (8 – 13 Hz), particularly Alpha1 frequency band (8 – 11 Hz), yielded the highest coherence scores. When comparing AD and HC, patients showed reduced coherence in Alpha2 (11 – 13 Hz) and Beta (13 – 20 Hz). Additionally, moderate correlations of global coherence and behavioral measures were found mainly for the Alpha1 frequency band. Conclusion: Alzheimer's disease can be associated with poorer functional connections of certain brain areas and rsEEG coherence might be a potential biomarker for AD. [ABSTRACT FROM AUTHOR]

Background: In clinical routine, cerebral computed tomography (cCT) is easily accessible and more commonly used than brain magnetic resonance imaging (cMRI). However, to the best of our knowledge a fully automated, validated regional specific volume estimation tool is lacking. Therefore, the aim of this study was to investigate the association between tissue classification for gray matter of both modalities. Method: Brain imaging segmentations of cCT and structural MRI of 37 healthy controls and 20 patients with mild cognitive impairment due to Alzheimer's disease were performed. The intensity and voxel count of normalized gray matter maps (MNI) in regions of interest using the Automated Anatomical Labelling Atlas (AAL3) were computed and compared between cCT and cMRI in both cohorts. Result: Brain Volume, measured by intensity and voxel count of gray matter, is associated between cortical regions acquired by cCT and cMRI. Although correlation coefficients varied between different brain areas, cortical compared to subcortical regions showed a relatively strong correlation. Conclusion: The evaluation of brain atrophy using segmented brain images acquired by cCT may be a simple, cost‐effective, and valuable addition to the clinical workflow, particularly in the context of socioeconomic and health disparities. [ABSTRACT FROM AUTHOR]

Background: Episodic memory decline characterizes "normal" aging but is also a core symptom of Alzheimer's disease. Therefore, considerable efforts have been undertaken to study this memory domain and its neural substrates. Recent studies have mainly focused on encoding‐ and retrieval‐ related processes. However, some findings suggest that episodic memory deficits are at least in part due to impaired consolidation processes. Methods: We investigated age effects on consolidation‐related functional network changes and their vulnerability to cognitive interference, using fMRI data of 13 young (20–30 years) and 16 senior (49–75 years) participants. FMRI scanning was performed prior to and during a spatial memory paradigm, consisting of encoding, consolidation, and retrieval phases. To ensure that the observed connectivity changes were due to consolidation processes, the consolidation phase was manipulated over two sessions: (1) no manipulation and (2) repeated stimulus‐presentation with interfering spatial context information. Results: We compared the fractional amplitude of low‐frequency fluctuations (fALFF) to analyze spontaneous brain activity changes from pre‐ to post‐encoding rest. In the control condition, fALFF decreased within left supramarginal gyrus (SMG), right middle temporal gyrus (MTL), and left precuneus (Pc), whereas, fALFF increased within parts of the occipital and inferior temporal cortex. To evaluate the integration in large‐scale brain networks, connectivity analyses between the fALFF‐derived seeds and network ROIs were performed. We observed significant coupling between consolidation‐related brain regions and large‐scale brain networks during consolidation, with connectivity between the SMG and large parts of the memory network modulated by aging. There was also a disruptive effect of interference on connectivity between the Pc and parts of the salience network. Of particular importance for successful consolidation, however, is the connectivity between parts of the occipital lobe, the inferior and middle temporal gyrus. Connectivity within this network, which corresponds to the ventral visual stream, may predict subsequent memory performance. The predictive value appears to be higher in young than in seniors. Conclusion: Our results support the assumption that age‐related memory decline is at least partly caused by impaired consolidation processes. We showed that consolidation requires a complex interplay between large‐scale brain networks, which is partially disrupted by aging and thus becomes insufficient. [ABSTRACT FROM AUTHOR]

Background: Plasma biomarkers as a new approach in Alzheimer's screening and diagnostics are time‐ and cost‐saving. Blood sampling is easier, less risky, and less invasive than other well‐established diagnostic tools, such as cerebrospinal fluid biomarkers (CSF), and is well tolerated by patients. The goal of this study was to test whether and to what extent plasma biomarkers are suitable for the differentiation between the clinical diagnostic groups dementia of Alzheimer's type (DAT), mild cognitive impairment (MCI) and subjective cognitive decline (SCD) in a routine care memory clinic. Method: We examined plasma samples of 144 memory clinic patients. Plasma biomarkers were measured through ultrasensitive Single molecule array (Simoa) immunoassay technology. The concentrations of amyloid‐beta42 (Aß42), amyloid‐beta40 (Aß40), phospho‐Tau181 (pTau181), total‐Tau (tTau) and neurofilament‐light (NF‐L) were determined. Statistical analysis, including receiver operating characteristics (ROC) analyses, were performed. Possible cut‐off values are discussed. Result: Through Aß40 a weak differentiation between SCD and DAT (AUC=0.64) and through Aß42/Aß40 a weak differentiation between SCD and MCI (AUC=0.64), SCD and MCI+DAT (AUC=0.66) and SCD and DAT (AUC=0.67) was possible. PTau181 was able to distinguish between diagnostic groups and showed a weak differentiation between MCI and DAT (AUC=0.69), a strong differentiation between SCD and MCI+DAT (AUC=0.78) and SCD and MCI (AUC=0.72) and an excellent differentiation between SCD and DAT (AUC=0.85). NF‐L weakly distinguished between SCD and MCI+DAT (AUC=0.70) and MCI and DAT (AUC=0.72), but strongly distinguished between SCD and DAT (AUC=0.81). At a cut‐off point of 10.2pg/ml pTau181 showed a sensitivity of 89% and a specificity of 73% to distinguish between SCD and DAT. Conclusion: Plasma Aß40, Aß42/Aß40, pTau181 and NF‐L analyzed with the Simoa technology proved to be promising future diagnostic and screening tools in a routine memory clinic setting outside of specific research studies. While amyloid markers showed only moderate discrimination between the groups, pTau181 and NF‐L clearly distinguished between SCD and the more progressed stages of MCI and DAT. These findings agree with the current model of amyloid build‐up already before significant clinical symptoms, and pTau and neurodegeneration correlating with symptomatic progression. In our data, pTau181 provided the best discrimination between the diagnostic groups. [ABSTRACT FROM AUTHOR]

Background: Impaired insight in cognitive deficits (anosognosia) in Alzheimer's disease (AD) is frequent and problematic, but pathophysiological mechanisms are not fully understood. So far, several regions such as the cingulate cortex or frontotemporal regions have been identified as crucial. The aim of the present study was to explore the neural substrates of anosognosia in AD by applying 18‐F fluorodeoxyglucose (FDG) and 18‐F‐AV‐1451 (Tau) positron emission tomography (PET). Method: Seventy‐four AD‐patients with mild cognitive impairment (MCI) or dementia were included in this study. Anosognosia was assessed by a clinician, based on a structured interview compared to patient's subjective cognitive impairment. Cognition was examined applying the Consortium to Establish a Registry for AD (CERAD‐Plus) neuropsychological assessment battery. All patients underwent FDG‐PET. Additionally, 29 patients received a Tau‐PET. Glucose metabolism and 18‐F‐AV‐1451 binding were analyzed in a whole brain approach by comparing patients with and without anosognosia. Imaging analyses were controlled for age and sex. Result: Of the 74 patients, 28 had anosognosia and 46 were aware of their deficits. Patients with anosognosia were significantly older and less depressed. The number of MCI/dementia patients was similar between groups (MCI+/‐anosognosia 11/25, dementia +/‐anosognosia 17/21, p=.209). Neuropsychological results showed a significantly more impaired verbal fluency in patients with anosognosia (p=.025). When FDG‐PET images were analyzed, patients with anosognosia had a significantly lower glucose metabolism in the inferior frontal gyrus, rectal gyrus and medial frontal gyrus including the anterior cingulate cortex (cluster level, p‐uncorrected<0.001, FWE‐corrected p=.006). Tau‐PET analyses showed a significant higher tracer binding in patients with anosognosia in the inferior and medial frontal gyrus (cluster level, p‐uncorrected=.003, FWE‐corrected p=.048). Conclusion: This is the first study examining FDG‐ and Tau‐PET in AD patients with and without anosognosia. Anosognosia was not only associated with reduced glucose metabolism but also with increased tau accumulation in inferior and medial frontal regions. We speculate that tau‐induced hypometabolism in regions related to self‐referential processes leads to anosognosia. [ABSTRACT FROM AUTHOR]

Background: In the last years, several voxel‐wise data‐driven metrics gained attention to study resting‐state connectivity in healthy aging and various pathological states. More recently, a new measure assessing the interaction between the commonly used metrics has been proposed and made widely available via the DPABI toolbox: the so‐called concordance index (CI). This index reflects the coupling of different metrics. The value of this new measure in Alzheimer's disease (AD) research is yet unclear. Method: Healthy young controls (YC, n=26), healthy senior controls (SC, n=29), and patients diagnosed with AD (n=35) underwent 3T resting‐state fMRI. First, the fractional amplitude of low frequency fluctuations (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated. Next, the CI among these measures was determined for each time window and each brain voxel across time by using Kendall's W. Differences in the CI between groups were examined on a whole brain, voxel‐wise, and network‐level using masks of seven of the most prominent intrinsic brain networks, with age, sex, head motion and gray matter volume as covariates. Result: The whole‐brain CI was significantly lower in AD patients as compared to YC and SC, which is in line with results from analyzing the single metrics. Reductions of the CI in AD was consistently observed in all networks investigated except for the limbic network. In SC compared to YC, no network‐level CI differences were detectable. On the voxel level, AD patients compared to SC showed lower CI in the right middle temporal gyrus, and SC compared to YC revealed lower CI in the left middle frontal gyrus. Analyzing the single metrics for their own, we observed a lower fALFF in the right angular gyrus in AD compared to SC, but no differences were detected for ReHo and DC. Conclusion: The newly proposed CI based on resting‐state connectivity may serve as a more sensitive imaging marker in AD than single metrics. The data suggest that this index distinguishes well between neurodegeneration and healthy aging. [ABSTRACT FROM AUTHOR]

Background: Impaired insight in cognitive deficits (anosognosia) in Alzheimer's disease (AD) is frequent and problematic, but pathophysiological mechanisms are not fully understood. So far, several regions such as the cingulate cortex or frontotemporal regions have been identified as crucial. The aim of the present study was to explore the neural substrates of anosognosia in AD by applying 18‐F fluorodeoxyglucose (FDG) and 18‐F‐AV‐1451 (Tau) positron emission tomography (PET). Method: Seventy‐four AD‐patients with mild cognitive impairment (MCI) or dementia were included in this study. Anosognosia was assessed by a clinician, based on a structured interview compared to patient's subjective cognitive impairment. Cognition was examined applying the Consortium to Establish a Registry for AD (CERAD‐Plus) neuropsychological assessment battery. All patients underwent FDG‐PET. Additionally, 29 patients received a Tau‐PET. Glucose metabolism and 18‐F‐AV‐1451 binding were analyzed in a whole brain approach by comparing patients with and without anosognosia. Imaging analyses were controlled for age and sex. Result: Of the 74 patients, 28 had anosognosia and 46 were aware of their deficits. Patients with anosognosia were significantly older and less depressed. The number of MCI/dementia patients was similar between groups (MCI+/‐anosognosia 11/25, dementia +/‐anosognosia 17/21, p=.209). Neuropsychological results showed a significantly more impaired verbal fluency in patients with anosognosia (p=.025). When FDG‐PET images were analyzed, patients with anosognosia had a significantly lower glucose metabolism in the inferior frontal gyrus, rectal gyrus and medial frontal gyrus including the anterior cingulate cortex (cluster level, p‐uncorrected<0.001, FWE‐corrected p=.006). Tau‐PET analyses showed a significant higher tracer binding in patients with anosognosia in the inferior and medial frontal gyrus (cluster level, p‐uncorrected=.003, FWE‐corrected p=.048). Conclusion: This is the first study examining FDG‐ and Tau‐PET in AD patients with and without anosognosia. Anosognosia was not only associated with reduced glucose metabolism but also with increased tau accumulation in inferior and medial frontal regions. We speculate that tau‐induced hypometabolism in regions related to self‐referential processes leads to anosognosia. [ABSTRACT FROM AUTHOR]

Background: To date, it remains unclear how the hallmark pathological changes of Alzheimer's disease (AD), amyloid plaques, and neurofibrillary tangles, affect neuronal activity and, consequently, cognition. In cognitively normal aging, it appears that tau accumulation may drive hippocampal hyperactivity, however, studies investigating this association in AD are sparse. Method: Patients with mild cognitive impairment (MCI) or mild dementia due to AD (n = 15) underwent positron emission tomography with the tracer [18F]‐AV‐1451, which binds to tau accumulation, and performed a visual item memory task during functional magnetic resonance imaging. Result: Entorhinal tau accumulation was highly correlated with memory‐related hippocampal activation. Greater tau accumulation and hippocampal activation were negatively correlated with memory performance. Neural activation in other task‐related structures was not correlated with local or global tau accumulation. Conclusion: Similar to observations in cognitively healthy aging, entorhinal tau accumulation is closely associated with hippocampal hyperactivity and impaired memory performance in MCI and mild dementia. Interestingly, this association is specific for medial temporal lobe structures. [ABSTRACT FROM AUTHOR]