Lewy Body Disease is a Contributor to Logopenic Progressive Aphasia Phenotype.

OBJECTIVE: The objective of this study was to describe clinical features, [18 F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) metabolism and digital pathology in patients with logopenic progressive aphasia (LPA) and pathologic diagnosis of diffuse Lewy body disease (DLBD) and compare to patients with LPA with other pathologies, as well as patients with classical features of probable dementia with Lewy bodies (pDLB). METHODS: This is a clinicopathologic case-control study of 45 patients, including 20 prospectively recruited patients with LPA among whom 6 were diagnosed with LPA-DLBD. We analyzed clinical features and compared FDG-PET metabolism in LPA-DLBD to an independent group of patients with clinical pDLB and regional α-synuclein burden on digital pathology to a second independent group of autopsied patients with DLBD pathology and antemortem pDLB (DLB-DLBD). RESULTS: All patients with LPA-DLBD were men. Neurological, speech, and neuropsychological characteristics were similar across LPA-DLBD, LPA-Alzheimer's disease (LPA-AD), and LPA-frontotemporal lobar degeneration (LPA-FTLD). Genetic screening of AD, DLBD, and FTLD linked genes were negative with the exception of APOE ε4 allele present in 83% of LPA-DLBD patients. Seventy-five percent of the patients with LPA-DLBD showed a parietal-dominant pattern of hy pometabolism; LPA-FTLD - temporal-dominant pattern, whereas LPA-AD showed heterogeneous patterns of hypometabolism. LPA-DLBD had more asymmetrical hypometabolism affecting frontal lobes, with relatively spared occipital lobe in the nondominantly affected hemisphere, compared to pDLB. LPA-DLBD had minimal atrophy on gross brain examination, higher cortical Lewy body counts, and higher α-synuclein burden in the middle frontal and inferior parietal cortices compared to DLB-DLBD. INTERPRETATION: Whereas AD is the most frequent underlying pathology of LPA, DLBD can also be present and may contribute to the LPA phenotype possibly due to α-synuclein-associated functional impairment of the dominant parietal lobe. ANN NEUROL 2021;89:520-533.

Hippocampal Volumes in Amnestic and Non-Amnestic Mild Cognitive Impairment Types Using Two Common Methods of MCI Classification.

OBJECTIVES: Mild cognitive impairment (MCI) types may have distinct neuropathological substrates with hippocampal atrophy particularly common in amnestic MCI (aMCI). However, depending on the MCI classification criteria applied to the sample (e.g., number of abnormal test scores considered or thresholds for impairment), volumetric findings between MCI types may change. Additionally, despite increased clinical use, no prior research has examined volumetric differences in MCI types using the automated volumetric software, Neuroreader™. METHODS: The present study separately applied the Petersen/Winblad and Jak/Bondi MCI criteria to a clinical sample of older adults (N = 82) who underwent neuropsychological testing and brain MRI. Volumetric data were analyzed using Neuroreader™ and hippocampal volumes were compared between aMCI and non-amnestic MCI (naMCI). RESULTS: T-tests revealed that regardless of MCI classification criteria, hippocampal volume z-scores were significantly lower in aMCI compared to naMCI (p's < .05), and hippocampal volume z-scores significantly differed from 0 (Neuroreader™ normative mean) in the aMCI group only (p's < .05). Additionally, significant, positive correlations were found between measures of delayed recall and hippocampal z-scores in aMCI using either MCI classification criteria (p's < .05). CONCLUSIONS: We provide evidence of correlated neuroanatomical changes associated with memory performance for two commonly used neuropsychological MCI classification criteria. Future research should investigate the clinical utility of hippocampal volumes analyzed via Neuroreader™ in MCI.

Memory Performance and Quantitative Neuroimaging Software in Mild Cognitive Impairment: A Concurrent Validity Study.

OBJECTIVE: This study examined the relationship between patient performance on multiple memory measures and regional brain volumes using an FDA-cleared quantitative volumetric analysis program - Neuroreader™. METHOD: Ninety-two patients diagnosed with mild cognitive impairment (MCI) by a clinical neuropsychologist completed cognitive evaluations and underwent MR Neuroreader™ within 1 year of testing. Select brain regions were correlated with three widely used memory tests. Regression analyses were conducted to determine if using more than one memory measures would better predict hippocampal z-scores and to explore the added value of recognition memory to prediction models. RESULTS: Memory performances were most strongly correlated with hippocampal volumes than other brain regions. After controlling for encoding/Immediate Recall standard scores, statistically significant correlations emerged between Delayed Recall and hippocampal volumes (rs ranging from .348 to .490). Regression analysis revealed that evaluating memory performance across multiple memory measures is a better predictor of hippocampal volume than individual memory performances. Recognition memory did not add further predictive utility to regression analyses. CONCLUSIONS: This study provides support for use of MR Neuroreader™ hippocampal volumes as a clinically informative biomarker associated with memory performance, which is a critical diagnostic feature of MCI phenotype.

Decreased Cerebrovascular Reactivity in Mild Cognitive Impairment Phenotypes.

BACKGROUND: Cerebrovascular health plays an important role in cognitive health in older adults. Cerebrovascular reactivity (CVR), a measure of cerebrovascular health, changes in both normal and pathological aging, and is increasingly being conceptualized as contributory to cognitive decline. Interrogation of this process will yield new insights into cerebrovascular correlates of cognition and neurodegeneration. OBJECTIVE: The current study examines CVR using advanced MRI in prodromal dementia states (amnestic and non-amnestic mild cognitive impairment phenotypes; aMCI and naMCI, respectively) and older adult controls. METHODS: CVR was assessed in 41 subjects (20 controls, 11 aMCI, 10 naMCI) using multiband multi-echo breath-holding task functional magnetic resonance imaging. Imaging data were preprocessed and analyzed using AFNI. All participants also completed a battery of neuropsychological tests. T-tests and ANOVA/ANCOVA analyses were conducted to compare controls to MCI groups on CVR and cognitive metrics. Partial correlation analyses between CVR derived from regions-of-interest (ROIs) and different cognitive functions were conducted. RESULTS: CVR was found to be significantly lower in aMCI and naMCI patients compared to controls. naMCI showed intermediate patterns between aMCI and controls (though aMCI and naMCI groups did not significantly differ). CVR of ROIs were positively correlated with neuropsychological measures of processing speed, executive functioning, and memory. CONCLUSION: The findings highlight regional CVR differences in MCI phenotypes compared to controls, where aMCI may have lower CVR than naMCI. Our results suggest possible cerebrovascular abnormalities associated with MCI phenotypes.

Changes in regional cerebral blood flow and functional connectivity in the cholinergic pathway associated with cognitive performance in subjects with mild Alzheimer's disease after 12-week donepezil treatment.

Acetylcholinesterase inhibitors (AChEIs), such as donepezil, have been shown to improve cognition in mild to moderate Alzheimer's disease (AD) patients. In this paper, our goal is to determine the relationship between altered cerebral blood flow (CBF) and intrinsic functional network connectivity changes in mild AD patients before and after 12-week donepezil treatment. An integrative neuroimaging approach was employed by combining pseudocontinuous arterial spin labeling (pCASL) MRI and resting-state functional MRI (R-fMRI) methods to determine the changes in CBF and functional connectivity (FC) in the cholinergic pathway. Linear regression analyses determined the correlations of the regional CBF alterations and functional connectivity changes with cognitive responses. These were measured with the Mini-Mental Status Examination (MMSE) scores and Alzheimer's disease Assessment Scale-Cognitive subscale (ADAS-cog) scores. Our results show that the regional CBF in mild AD subjects after donepezil treatment was significantly increased in the middle cingulate cortex (MCC) and posterior cingulate cortex (PCC), which are the neural substrates of the medial cholinergic pathway. In both brain regions, the baseline CBF and its changes after treatment were significantly correlated with the behavioral changes in ADAS-cog scores. The intrinsic FC was significantly enhanced in the medial cholinergic pathway network in the brain areas of the parahippocampal, temporal, parietal and prefrontal cortices. Finally, the FC changes in the medial prefrontal areas demonstrated an association with the CBF level in the MCC and the PCC, and also were correlated with ADAS-cog score changes. These findings indicate that regional CBF and FC network changes in the medial cholinergic pathway were associated with cognitive performance. It also is suggested that the combined pCASL-MRI and R-fMRI methods could be used to detect regional CBF and FC changes when using drug treatments in mild AD subjects.

Neural basis of the association between depressive symptoms and memory deficits in nondemented subjects: resting-state fMRI study.

Depressive symptoms often coexist with memory deficits in older adults and also are associated with incident cognitive decline in the elderly. However, little is known about the neural correlates of the association between depressive symptoms and memory deficits in nondemented elderly. Fifteen amnestic mild cognitive impairment (aMCI) and 20 cognitively normal (CN) subjects completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Multiple linear regression analysis was performed to test the main effects of the Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test delayed recall (RAVLT-DR) scores, and their interaction on the intrinsic amygdala functional connectivity (AFC) network activity. Severer depressive symptoms and memory deficits were found in the aMCI group than in the CN group. Partial correlation analysis identified that the RAVLT-DR scores were significantly correlated with the AFC network in the bilateral dorsolateral prefrontal cortex (DLPFC), dorsomedial and anterior prefrontal cortex, posterior cingulate cortex (PCC), middle occipital gyrus, right inferior parietal cortex, and left middle temporal gyrus (MTG). The GDS scores were positively correlated with the AFC network in the bilateral PCC and MTG, and left DLPFC. The interactive effects of the GDS and RAVLT-DR scores on the AFC network were seen in the bilateral PCC, MTG, and left DLPFC. These findings not only supported that there were interactive neural links between depressive symptoms and memory functions in nondemented elderly at the system level, but also demonstrated that R-fMRI has advantages in investigating the interactive nature of different neural networks involved in complex functions, such as emotion and cognition.

Influence of Water with Oxygen and Ozone Micro-Nano Bubbles on Concrete Physical Properties.

In this study, the possibility of using mixing water containing O2 and O3 micro-nano bubbles (M-NBs) in concrete technology was investigated. In particular, the effect of micro-nano bubbles on the durability and frost resistance of concrete was analyzed. Concretes with two types of micro-nano bubbles were studied. The physical properties of both the modified concretes and the reference concrete were determined, i.e., specific and apparent density, porosity, weight absorption and coefficient of water absorption. Mechanical parameters based on compressive and flexural strength were tested after 14 and 28 days of curing. Concrete durability was determined on the basis of frost resistance and resistance to salt crystallization. The pore distribution in the cement matrix was determined based on porosimetry studies. The use of water with micro-nano bubbles of O2 and O3, among others, contributed to a reduction in the water absorption coefficient from 42.7% to 52.3%, in comparison to the reference concrete. The strength characterizing the concrete with O3 increased by 61% after 28 days, and the frost resistance after 150 F-T cycles increased by 2.4 times. Resistance to salt crystallization improved by 11% when water with O3 was used.

Classification of Alzheimer disease, mild cognitive impairment, and normal cognitive status with large-scale network analysis based on resting-state functional MR imaging.

PURPOSE: To use large-scale network (LSN) analysis to classify subjects with Alzheimer disease (AD), those with amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) subjects. MATERIALS AND METHODS: The study was conducted with institutional review board approval and was in compliance with HIPAA regulations. Written informed consent was obtained from each participant. Resting-state functional magnetic resonance (MR) imaging was used to acquire the voxelwise time series in 55 subjects with clinically diagnosed AD (n = 20), aMCI (n =15), and normal cognitive function (n = 20). The brains were divided into 116 regions of interest (ROIs). The Pearson product moment correlation coefficients of pairwise ROIs were used to classify these subjects. Error estimation of the classifications was performed with the leave-one-out cross-validation method. Linear regression analysis was performed to analyze the relationship between changes in network connectivity strengths and behavioral scores. RESULTS: The area under the receiver operating characteristic curve (AUC) yielded 87% classification power, 85% sensitivity, and 80% specificity between the AD group and the non-AD group (subjects with aMCI and CN subjects) in the first-step classification. For differentiation between subjects with aMCI and CN subjects, AUC was 95%; sensitivity, 93%; and specificity, 90%. The decreased network indexes were significantly correlated with the Mini-Mental State Examination score in all tested subjects. Similarly, changes in network indexes significantly correlated with Rey Auditory Verbal Leaning Test delayed recall scores in subjects with aMCI and CN subjects. CONCLUSION: LSN analysis revealed that interconnectivity patterns of brain regions can be used to classify subjects with AD, those with aMCI, and CN subjects. In addition, the altered connectivity networks were significantly correlated with the results of cognitive tests.

Recovery of hippocampal network connectivity correlates with cognitive improvement in mild Alzheimer's disease patients treated with donepezil assessed by resting-state fMRI.

PURPOSE: To identify the neural correlates of cognitive improvement in mild Alzheimer's disease (AD) subjects following 12 weeks of donepezil treatment. MATERIALS AND METHODS: Resting-state functional connectivity magnetic resonance imaging (R-fMRI) was used to measure the hippocampal functional connectivity (HFC) in 14 mild AD and 18 age-matched normal (CN) subjects. AD subjects were scanned at baseline and after donepezil treatment. CN subjects were scanned only at baseline as a reference to identify regions correlated or anticorrelated to the hippocampus. Before each scan, participants underwent cognitive, behavioral, and functional assessments. RESULTS: After donepezil treatment, neural correlates of cognitive improvement measured by Mini-Mental State Examination scores were identified in the left parahippocampus, dorsolateral prefrontal cortex (DLPFC), and inferior frontal gyrus. Improvement in AD Assessment Scale-cognitive subscale scores correlated with the HFC changes in the left DLPFC and middle frontal gyrus. Stronger recovery in the network connectivity was associated with cognitive improvement. CONCLUSION: R-fMRI may provide novel insights into the brain's responses to AD treatment in clinical pharmacological trials, and also may predict clinical response.

Physical Properties and Durability of Lime-Cement Mortars Prepared with Water Containing Micro-Nano Bubbles of Various Gases.

The paper presents the experimental studies on the effect of the water containing micro-nano bubbles of various gases on the physico-mechanical properties of lime-cement mortars. In total, 7 types of mortars were prepared: with water containing the micro-nano bubbles of O2, O3 or CO2 as 50% or 100% substitute of ordinary mixing water (tap water) and the reference mortar prepared using tap water. In order to determine the influence of water with micro-nano bubbles of gases, the consistency of fresh mortar and the physical properties of hardened mortar, i.e., specific and apparent density, total porosity, water absorption by weight and capillary absorption, were established. The mechanical strength of the considered mortars was studied as well by conducting the tests for flexural and compressive strengths following 14, 28 and 56 days. Reduced workability and capillary absorption were observed in the modified mortars within the range of 0.9-8.5%. The mortars indicated an increase in the flexural strength after 28 days ranging from 3.4% to 23.5% and improved compressive strength in 1.2-31%, in comparison to the reference mortar. The conducted studies indicated increased flexural and compressive strengths along with the share of micro-nano bubbles of gases in the mixing water.

Surface Modification of Lightweight Mortars by Nanopolymers to Improve Their Water-Repellency and Durability.

The paper explores the possibility of covering the mortar with the lightweight aggregate by the nanopolymer silane and siloxane as surface hydrophobisation. The investigation involved the mortars with two types of hydrophobic agents diluted with water in a ratio of 1:4 and 1:8. Mortar wetting properties were determined by measuring the absorbability, water vapor diffusion, contact angle (CA) and surface free energy (SFE) of their structure. Surface micro-roughness and 2D topography were evaluated. Scanning electron microscopy (SEM) has shown the microstructure and distribution of pores in mortars. The reduction in absorbency after the first day of testing by 87% was shown. An improvement in frost resistance after 25 cycles by 97% and an 18-fold decrease in weight loss after the sulphate crystallization test were observed. The hydrophobic coating reduces the SFE of mortars and increases the CA. In the case of using silanes, a 9-fold increase CA was observed.

Effect of Eco-Friendly Cellulose Nanocrystals on Physical Properties of Cement Mortars.

Nanocellulose, being a material with nanodimensions, is characterized by high tensile strength, high modulus of elasticity, low thermal expansion, and relatively low density, as well as exhibiting very good electrical conductivity properties. The paper presents the results of research on cement mortars with the addition of nanocrystals cellulose, applied in three different amounts (0.5%, 1.0%, and 1.5%) by weight of cement, including: physical and mechanical properties, frost resistance and resistance against the detrimental effect of salt, and microstructure examination (SEM). Along with an increase in amount of admixture, the weight loss following frost resistance and salt crystallization tests is reduced. Studies have shown that the addition of nanocrystalline cellulose improves the compressive and flexural strength by 27.6% and 10.9%, respectively. After 50 freezing and thawing (F-T) cycles for the mortars with 1.5% nanocellulose admixture, an improvement in frost resistance by 98% was observed. In turn, the sulfate crystallization tests indicated a 35-fold decrease in weight loss following 1.5% nanopolymer addition to the mortar.

Medial temporal lobe activity for recognition of recent and remote famous names: an event-related fMRI study.

Previous neuroimaging studies examining recognition of famous faces have identified activation of an extensive bilateral neural network [Gorno Tempini, M. L., Price, C. J., Josephs, O., Vandenberghe, R., Cappa, S. F., Kapur, N. et al. (1998). The neural systems sustaining face and proper-name processing. Brain, 121, 2103-2118], including the medial temporal lobe (MTL) and specifically the hippocampal complex [Haist, F., Bowden, G. J., & Mao, H. (2001). Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature Neuroscience, 4, 1139-1145; Leveroni, C. L., Seidenberg, M., Mayer, A. R., Mead, L. A., Binder, J. R., & Rao, S. M. (2000). Neural systems underlying the recognition of familiar and newly learned faces. Journal of Neuroscience, 20, 878-886]. One model of hippocampal functioning in autobiographical, episodic memory retrieval argues that the hippocampal complex remains active in retrieval tasks regardless of time or age of memory (multiple trace theory, MTT), whereas another proposal posits that the hippocampal complex plays a time-limited role in retrieval of autobiographical memories. The current event-related fMRI study focused on the medial temporal lobe and its response to recognition judgments of famous names from two distinct time epochs (1990s and 1950s) in 15 right-handed healthy older adults (mean age=70 years). A pilot study with an independent sample of young and older subjects ensured that the stimuli were representative of a recent and remote time period. Increased MR signal activity was observed on a bilateral basis for both the hippocampus and parahippocampal gyrus (PHG) during recognition of familiar names from both the recent and remote time periods when compared to non-famous names. However, the impulse response functions in the right hippocampus and right PHG demonstrated a differential response to stimuli from different time epochs, with the 1990s names showing the greatest MR signal intensity change, followed by the 1950s names, followed by foils. The finding that recognition of famous names produced significant bilateral MTL activation regardless of time epoch relative to foils provides support for the MTT model. However, the finding of a temporal gradient in the right MTL also provides support for the HC model, given the greater MTL response associated with recently famous names relative to remotely famous names.

Effects of the coexistence of late-life depression and mild cognitive impairment on white matter microstructure.

BACKGROUND AND OBJECTIVE: Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are associated with white matter (WM) disruptions of the fronto-limbic and interhemispheric tracts implicated in mood regulation and episodic memory functions. This work investigates the extent of these WM abnormalities in patients LLD and aMCI when these diseases occur alone and when they coexist. MATERIALS AND METHODS: Eighty-four subjects separated into cognitively normal (n=33), LLD (n=20), aMCI (n=18), and comorbid aMCI and LLD (n=13) completed Diffusion Tensor Imaging (DTI) scans. Tract-based spatial statistics was employed to skeletonize multiple DTI indices of the cingulum, corpus callosum, fornix and uncinate fasciculus. Analysis of covariance and post-hoc tests compared group differences. Multiple linear regressions were performed between DTI and behavioral measures for the whole sample and within individual patient groups. RESULTS: Divergent microstructural disruptions were identified in LLD- and aMCI-only groups, whereas the comorbid group showed widespread abnormalities especially in the hippocampal cingulum and fornix tracts. The LLD groups also showed significant disruptions in the uncinate fasciculus and corpus callosal tracts. Higher depressive symptom and lower episodic memory scores were associated with increased diffusivity measures in the fornix and hippocampal cingulum across all subjects. CONCLUSIONS: Widespread WM microstructural disruptions are present when LLD and aMCI are comorbid -especially in the medial temporal lobe tracts. These WM disruptions may be a marker of disease severity. Also, multiple DTI parameters should be used when evaluating the WM fiber integrity in LLD and aMCI.

Aberrant functional connectivity in Papez circuit correlates with memory performance in cognitively intact middle-aged APOE4 carriers.

The main objective of this study is to detect the early changes in resting-state Papez circuit functional connectivity using the hippocampus as the seed, and to determine the associations between altered functional connectivity (FC) and the episodic memory performance in cognitively intact middle-aged apolipoprotein E4 (APOE4) carriers who are at risk of Alzheimer's disease (AD). Forty-six cognitively intact, middle-aged participants, including 20 APOE4 carriers and 26 age-, sex-, and education-matched noncarriers were studied. The resting-state FC of the hippocampus (HFC) was compared between APOE4 carriers and noncarriers. APOE4 carriers showed significantly decreased FC in brain areas that involve learning and memory functions, including the frontal, cingulate, thalamus and basal ganglia regions. Multiple linear regression analysis showed significant correlations between HFC and the episodic memory performance. Conjunction analysis between neural correlates of memory and altered HFC showed the overlapping regions, especially the subcortical regions such as thalamus, caudate nucleus, and cingulate cortices involved in the Papez circuit. Thus, changes in connectivity in the Papez circuit may be used as an early risk detection for AD.

Late-life depression, mild cognitive impairment and hippocampal functional network architecture.

Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are associated with medial temporal lobe structural abnormalities. However, the hippocampal functional connectivity (HFC) similarities and differences related to these syndromes when they occur alone or coexist are unclear. Resting-state functional connectivity MRI (R-fMRI) technique was used to measure left and right HFC in 72 elderly participants (LLD [n = 18], aMCI [n = 17], LLD with comorbid aMCI [n = 12], and healthy controls [n = 25]). The main and interactive relationships of LLD and aMCI on the HFC networks were determined, after controlling for age, gender, education and gray matter volumes. The effects of depressive symptoms and episodic memory deficits on the hippocampal functional connections also were assessed. While increased and decreased left and right HFC with several cortical and subcortical structures involved in mood regulation were related to LLD, aMCI was associated with globally diminished connectivity. Significant LLD-aMCI interactions on the right HFC networks were seen in the brain regions critical for emotion processing and higher-order cognitive functions. In the interactive brain regions, LLD and aMCI were associated with diminished hippocampal functional connections, whereas the comorbid group demonstrated enhanced connectivity. Main and interactive effects of depressive symptoms and episodic memory performance were also associated with bilateral HFC network abnormalities. In conclusion, these findings indicate that discrete hippocampal functional network abnormalities are associated with LLD and aMCI when they occur alone. However, when these conditions coexist, more pronounced vulnerabilities of the hippocampal networks occur, which may be a marker of disease severity and impending cognitive decline. By utilizing R-fMRI technique, this study provides novel insights into the neural mechanisms underlying LLD and aMCI in the functional network level.

Functional network endophenotypes unravel the effects of apolipoprotein E epsilon 4 in middle-aged adults.

Apolipoprotein E-ε4 (APOE-ε4) accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN), executive control (ECN) and salience (SN) networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc) in these networks. Resting-state functional connectivity MRI (R-fMRI) was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.

The co-existence of geriatric depression and amnestic mild cognitive impairment detrimentally affect gray matter volumes: voxel-based morphometry study.

While late-life depression (LLD) and amnestic mild cognitive impairment (aMCI), alone and in combination, is associated with an increased risk of incident Alzheimer's disease (AD), the neurobiological mechanisms of this link are unclear. We examined the main and interactive effects of LLD and aMCI on the gray matter (GM) volumes in 72 physically healthy participants aged 60 and older. Participants were separated into normal controls, cognitively normal depressed, non-depressed aMCI, and depressed aMCI groups. Optimized voxel-based morphometry estimated GM volumes. The main and interactive effects of LLD and aMCI, and of depressive symptoms and episodic memory deficits on the GM volumes were analyzed. While decreased GM volumes in the mood regulating circuitry structures were associated with depression, GM atrophy in regions essential for various cognitive performance were related to aMCI. LLD-aMCI interactions were associated with widespread subcortical and cortical GM volume loss of brain structures implicated in AD. The interactions between episodic memory deficits and depressive symptom severity are associated with volume loss in right inferior frontal gyrus/anterior insula and left medial frontal gyrus clusters. Our findings suggest that the co-existence of these clinical phenotypes is a potential marker for higher risk of AD.

Neural correlates of the interactive relationship between memory deficits and depressive symptoms in nondemented elderly: resting fMRI study.

Prospective studies have shown an association between depressive symptoms and cognitive impairment among older adults. However, the neural correlates of this relationship are poorly understood. Our aim was to examine whether interactive effects of memory deficits and depressive symptoms are present in the memory-associated functional networks, in nondemented elderly subjects. Fifteen subjects with amnestic mild cognitive impairment (aMCI) and 20 age-matched normal (CN) elderly subjects participated in this cross-sectional study. Resting-state functional connectivity MRI (R-fMRI) measured the hippocampal functional connectivity (HFC) alterations between the two groups. Voxelwise linear regression analysis was performed to correlate hippocampal network strength with the Rey Auditory Verbal Learning Test delayed recall and the Geriatric Depression Scale scores, after adjusting for age and group effects. Poorer memory performance was associated with decreased positively correlated HFC connectivity in the specific frontal lobe and default mode network (DMN) structures. Poorer memory performance also was associated with decreased anticorrelated HFC connectivity in the bilateral inferior parietal and right dorsolateral prefrontal cortices. In contrast, greater depressive symptom severity was associated with increased HFC connectivity in several frontal lobes and DMN regions. Depressive symptoms and memory functions had interactive effects on the HFC, in the frontal, temporal, and PCC structures. Our findings suggest that the R-fMRI technique can be used to examine the changes in functional neural networks where memory deficits and depressive symptoms coexist in the geriatric population.