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Background: Apathy is a common and early symptom in Alzheimer's disease (AD) and is linked to poorer prognosis. Theoretical interpretations of apathy implicate alterations of connections amongst fronto-striatal and limbic regions., Objective: To test the association between presence of apathy and patterns of brain functional connectivity in patients with clinically-established AD., Methods: Seventy AD patients were included. Thirty-five patients experienced apathy as defined by the screening question of the Neuropsychiatric Inventory, and thirty-five did not. All patients agreed to undergo an MRI protocol inclusive of resting-state acquisitions. The hemodynamic-dependent signal was extracted bilaterally from five regions of interest: ventromedial prefrontal cortices, anterior cingulate cortices, dorsolateral prefrontal cortices, insulae and amygdalae. t tests were run to compare connectivity maps of apathetic and non-apathetic patients. Age, education, Mini Mental State Examination score, gray matter volumes and gray matter fractions served as covariates., Results: At a p FWE < .05 threshold, apathetic patients had reduced connectivity between the left insula and right superior parietal cortex. Apathetic patients had also increased connectivity between the right dorsolateral prefrontal seed and the right superior parietal cortex. Patients with apathy were significantly more likely to experience other psychiatric symptoms., Conclusion: Our findings support a role of frontal and insular connections in coordinating value-based decisions in AD. Both down-regulation and maladaptive up-regulation mechanisms appear to be at play in these regions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

As quantitative susceptibility mapping (QSM) is maturing, more clinical applications are being explored. With this comes the question whether QSM is sufficiently robust and reproducible to be directly used in a clinical setting where patients are possibly not cooperative and/or unable to suppress involuntary movements sufficiently. Twenty-nine patients with Alzheimer's disease, 31 patients with mild cognitive impairment and 41 healthy controls were scanned on a 3 T scanner, including a multi-echo gradient-echo sequence for QSM and an inversion-prepared segmented gradient-echo sequence (T1-TFE, MPRAGE). The severity of motion artifacts (excessive/strong/noticeable/invisible) was categorized via visual inspection by two independent raters. Quantitative susceptibility was reconstructed using 'joint background-field removal and segmentation-enhanced dipole inversion', based on segmented subcortical gray-matter regions, as well as using 'morphology enabled dipole inversion'. Statistical analysis of the susceptibility maps was performed per region. A large fraction of the data showed motion artifacts, visible in both magnitude images and susceptibility maps. No statistically significant susceptibility differences were found between groups including motion-affected data. Considering only subjects without visible motion, significant susceptibility differences were observed in caudate nucleus as well as in putamen. Motion-effects can obscure statistically significant differences in QSM between patients and controls. Additional measures to restrict and/or compensate for subject motion should be taken for QSM in standard clinical settings to avoid risk of false findings.

The clock drawing (CD) task involves visual integration skills associated with parietal lobe function. Seven mild Alzheimer's Disease (AD) patients and 11 healthy elderly controls (EC) underwent functional magnetic resonance imaging (fMRI) scanning while viewing a radial motion (RM) task. This RM task in EC activated the bilateral secondary visual cortex and parietal regions, whereas AD patients activated only the right-sided secondary visual cortex. The magnitude of the fMRI signal in the left superior parietal lobe was positively correlated with performance on the CD task in AD patients. These findings suggest that complex visuospatial processing impairments reflect the underlying AD neuropathology in parietal regions.

Background/aims: Visuospatial impairments are known to occur in Alzheimer's disease (AD). We hypothesised that functional magnetic resonance imaging (fMRI) response in task-related brain regions would be impaired in patients with AD during the task and that treatment with acetyl cholinesterase inhibitors would enhance activations in brain regions concerned with this visual perceptual processing., Method: Ten AD subjects were neuropsychologically assessed and underwent fMRI imaging whilst performing a series of visuospatial perception tasks, before and after treatment with acetyl cholinesterase inhibitors. Eleven healthy elderly comparison subjects were also scanned twice., Results: Regions of increased brain activation in AD included the left precuneus, left cuneus, left supramarginal gyrus, right parieto-temporal cortex and right inferior parietal lobule. Further, increased activation in the left precuneus was found to correlate significantly with improved functioning of activities of daily living., Conclusions: We believe this to be the first fMRI study that, after controlling for the confound of repeat scanning, demonstrates altered patterns of brain activation associated with visuospatial processing following treatment in patients with AD. The treatment-related improvement of visual perception in AD may rely on enhanced attentional mechanisms, thereby possibly supporting independent living through improvement on activities of daily living.

The neural basis of visuospatial deficits in Alzheimer's disease is unclear. We wished to investigate the neural basis of visuospatial perception in patients with Alzheimer's disease compared with healthy elderly comparison subjects using functional magnetic resonance imaging (fMRI). Twelve patients with AD and thirteen elderly comparison subjects were investigated. The patients were recruited from the local clinic and comparison subjects were from spouses and community. All participants underwent fMRI whilst viewing visuospatial stimuli and structural MRI, and findings were analysed using voxel-based morphometry. The comparison group activated V5, superior parietal lobe, parieto-occipital cortex and premotor cortices. The AD group demonstrated hypoactivation in the above regions and instead showed greater activation in inferior parietal lobule and activated additional areas. There was no structural atrophy above and beyond that found globally in patients in the identified regions of BOLD activation. To our knowledge, this is the first study to explore the neuroanatomy of perception of depth and motion in Alzheimer's disease. These specific functional deficits in AD provide evidence for an underlying patho-physiological basis for the clinically important symptom of visuospatial disorientation in patients with AD.

Purpose: Objective quantification of brain structure can aid diagnosis and therapeutic monitoring in several neuropsychiatric disorders. In this study, we aimed to compare direct and indirect quantification approaches for hippocampal formation changes in patients with mild cognitive impairment and Alzheimer's disease (AD)., Methods and Materials: Twenty-one healthy volunteers (mean age: 66.2), 21 patients with mild cognitive impairment (mean age: 66.6), and 10 patients with AD (mean age: 65.1) were enrolled. All subjects underwent extensive neuropsychological testing and were imaged at 1.5T (Vision, Siemens, Germany; T1w coronal TR=4 ms, Flip=13 degrees , FOV=250 mm, Matrix=256 x 256, 128 contiguous slices, 1.8mm). Direct measurement of the hippocampal formation was performed on coronal slices using a standardized protocol, while indirect temporal horn volume (THV) was calculated using a watershed algorithm-based software package (MeVis, Germany). Manual tracing took about 30 min, semi-automated measurement less than 3 min time., Results: Successful direct and indirect quantification was performed in all subjects. A significant volume difference was found between controls and AD patients (p<0.001) with both the manual and the semi-automated approach. Group analysis showed a slight but not significant decrease of hippocampal volume and increase in temporal horn volume (THV) for subjects with mild cognitive impairment compared to volunteers (p<0.07). A significant correlation (p<0.001) of direct and indirect measurement was found., Conclusion: The presented indirect approach for hippocampus volumetry is equivalent to the direct approach and offers the advantages of observer independency, time reduction and thus usefulness for clinical routine.

Alzheimer's disease (AD) is associated with widespread brain atrophy including structures subserving memory. We applied an improved structural detection methodology to examine the less well known progression of atrophy in early-stage AD. We sought to i) longitudinally study volumetric differences in patients with early-stage AD and healthy volunteers; and ii) test the hypothesis that hippocampal volumes would be correlated with clinically relevant cognitive function. Seven patients and eleven healthy subjects underwent two structural MRI scans and neuropsychological assessments. Scans were normalised to a study-specific template and 'morphologically opened' to reduce tissue misclassification. Using brain-parcellation, patient atrophy was localised to left fusiform and parahippocampal gyri, whilst left hippocampal volumes were correlated with a cognitive performance measure. A whole-brain search methodology, showed that patients had reduced volumes including fronto-temporal regions bilaterally, in hippocampi and amygdalae and right cerebellum. Whole-brain correlational analyses revealed that cognitive performance was correlated with volumes of both hippocampi, superior temporal gyri and left insula. Neither group exhibited significant longitudinal volumetric changes. Utilising a novel methodology, we have shown that in early-stage AD, clinically relevant cognitive deficits are correlated with regionally specific grey-matter volumes, which are detectable at an early stage of the illness.