Amygdala Atrophy Research Articles

Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer's Disease.

Very early Alzheimer’s disease (AD) – i.e., AD at stages of mild cognitive impairment (MCI) and mild dementia – is characterized by progressive structural and neuropathologic changes, such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex and also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC) patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n = 33) and patients with AD in the stages of MCI (AD-MCI, n = 38) and mild dementia (AD-D, n = 36). Outcome measures were voxel-based morphometry (VBM) values and region-of-interest-based iFC maps of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D). Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D), particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions, including that of amygdala.

Atrophy of amygdala and abnormal memory-related alpha oscillations over posterior cingulate predict conversion to Alzheimer's disease.

Synaptic dysfunction, a key pathophysiological hallmark of Alzheimer’s disease (AD), may account for abnormal memory-related EEG patterns in prodromal AD. Here, we investigate to what extent oscillatory EEG changes during memory encoding and/or retrieval enhance the accuracy of medial temporal lobe (MTL) atrophy in predicting conversion from amnestic mild cognitive impairment (aMCI) to AD. As expected, aMCI individuals that, within a 2-year follow-up period, developed dementia (N = 16) compared to healthy older (HO) (N = 26) and stable aMCI (N = 18) showed poorer associative memory, greater MTL atrophy, and lower capacity to recruit alpha oscillatory cortical networks. Interestingly, encoding-induced abnormal alpha desynchronized activity over the posterior cingulate cortex (PCC) at baseline showed significantly higher accuracy in predicting AD than the magnitude of amygdala atrophy. Nevertheless, the best accuracy was obtained when the two markers were fitted into the model (sensitivity = 78%, specificity = 82%). These results support the idea that synaptic integrity/function in the PCC is affected during prodromal AD and has the potential of improving early detection when combined with MRI biomarkers.

Amygdala atrophy affects emotion-related activity in face-responsive regions in frontotemporal degeneration

In the healthy brain, modulatory influences from the amygdala commonly explain enhanced activation in face-responsive areas by emotional facial expressions relative to neutral expressions. In the behavioral variant frontotemporal dementia (bvFTD) facial emotion recognition is impaired and has been associated with atrophy of the amygdala. By combining structural and functional MRI in 19 patients with bvFTD and 20 controls we investigated the neural effects of emotion in face-responsive cortex and its relationship with amygdalar gray matter (GM) volume in neurodegeneration. Voxel-based morphometry revealed decreased GM volume in anterior medio-temporal regions including amygdala in patients compared to controls. During fMRI, we presented dynamic facial expressions (fear and chewing) and their spatiotemporally scrambled versions. We found enhanced activation for fearful compared to neutral faces in ventral temporal cortex and superior temporal sulcus in controls, but not in patients. In the bvFTD group left amygdalar GM volume correlated positively with emotion-related activity in left fusiform face area (FFA). This correlation was amygdala-specific and driven by GM in superficial and basolateral (BLA) subnuclei, consistent with reported amygdalar-cortical networks. The data suggests that anterior medio-temporal atrophy in bvFTD affects emotion processing in distant posterior areas.

HLA-A2 Alleles Mediate Alzheimer's Disease by Altering Hippocampal Volume.

HLA-A is a locus of the major histocompatibility complex situated on chromosome 6p21.3. HLA-A has been shown to be associated with susceptibility to Alzheimer's disease (AD). In this study, we firstly investigated the association of gene variants in HLA-A and brain structures on MRI in a large sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to explore the effects of HLA-A on AD pathogenesis. We selected the hippocampus, parahippocampus, posterior cingulate, precuneus, middle temporal, entorhinal cortex, and amygdala as regions of interest (ROIs). In hybrid population analysis, our results showed a marginally significant association between rs9260168 and the atrophy of the left parahippocampus (P = 0.007, Pc = 0.054), rs3823342 and the atrophy of the left parahippocampus (P = 0.014, Pc = 0.054), rs76475517, which only exists in Caucasians with HLA-A23 or HLA-A24 alleles, and the atrophy of the right amygdala (P = 0.010, Pc = 0.085) at baseline. In particular, the haplotype (TGACAAGG), as a surrogate marker of HLA-A2, was founded to be positively associated with the atrophy of the right hippocampus (P = 0.047) at baseline. Furthermore, we detected the above four associations in mild cognitive impairment (MCI) subpopulation analysis. Our study provided preliminary evidences supporting HLA-A2 in Caucasians contribute to the risk of AD by modulating the alteration of hippocampal volume and HLA-A gene variants appear to play a role in altering AD-related brain structures on MRI.

The neurobehavioral phenotype in mucopolysaccharidosis Type IIIB: An exploratory study

ObjectivesOur goal was to describe the neurobehavioral phenotype in mucopolysaccharidosis Type IIIB (MPS IIIB). Parents report that behavioral abnormalities are a major problem in MPS III posing serious challenges to parenting and quality-of-life for both patient and parent. Our previous research on MPS IIIA identified autistic symptoms, and a Klüver-Bucy-type syndrome as indicated by reduced startle and loss of fear associated with amygdala atrophy. We hypothesized that MPS IIIB would manifest similar attributes when assessed with the same neurobehavioral protocol. MethodsTen patients with MPS IIIB were compared with 9 MPS IIIA patients, all older than 6. 8 younger children with Hurler syndrome (1H) were chosen as a comparison group for the Risk Room procedure; MPS IH does not directly affect social/emotional function and these younger children were closer to the developmental level of the MPS IIIB group. To examine disease severity, cognitive ability was assessed. Four evaluations were used: the Risk Room procedure (to measure social-emotional characteristics, especially fear and startle responses), the Autism Diagnostic Observation Schedule (ADOS), the Sanfilippo Behavior Rating Scale (SBRS), and amygdala brain volumes calculated from manually-traced MRI images. ResultsThe two groups are equivalent in severity and show severe cognitive impairment. On the ADOS, the MPS IIIB patients exhibited the same autistic features as IIIA. The IIIB means differed from MPS IH means on most measures. However, the IIIB group did not approach the Risk Room stranger, like the MPS IH group who kept their distance, but unlike the IIIA group who showed no fear of the stranger. On the SBRS, the MPS IIIB patients were described as more inattentive and more fearful, especially of new people than the MPS IIIA. Onsets of some disease characteristics appeared more closely spaced and slightly earlier in MPS IIIB than IIIA. ConclusionsOn most behavioral measures, MPS IIIB patients did not differ substantially from MPS IIIA patients over age six, demonstrating autistic features and a Klüver Bucy-like syndrome including lack of fear and poor attention. Delay in onset of behavioral symptoms was associated with later diagnosis in two patients. Lack of fear, poor attention, and autistic-like symptomatology are as characteristic of MPS IIIB as they are of MPS IIIA. A possible difference is that the some behavioral abnormalities develop more quickly in MPS IIIB. If this is so, these patients may become at risk for harm and present a challenge for parenting even earlier than do those with MPS IIIA. In future clinical trials of new treatments, especially with respect to quality of life and patient management, improvement of these behaviors will be an essential goal. Because very young patients were not studied, prospective natural history documentation of the early development of abnormal behaviors in MPS IIIB is needed.

MRI characterization of temporal lobe epilepsy using rapidly measurable spatial indices with hemisphere asymmetries and gender features

The paucity of morphometric markers for hemispheric asymmetries and gender variations in hippocampi and amygdalae in temporal lobe epilepsy (TLE) calls for better characterization of TLE by finding more useful prognostic MRI parameter(s). T1-weighted MRI (3 T) morphometry using multiple parameters of hippocampus-parahippocampus (angular and linear measures, volumetry) and amygdalae (volumetry) including their hemispheric asymmetry indices (AI) were evaluated in both genders. The cutoff values of parameters were statistically estimated from measurements of healthy subjects to characterize TLE (57 patients, 55% male) alterations. TLE had differential categories with hippocampal atrophy, parahippocampal angle (PHA) acuteness, and several other parametric changes. Bilateral TLE categories were much more prevalent compared to unilateral TLE categories. Female patients were considerably more disposed to bilateral TLE categories than male patients. Male patients displayed diverse categories of unilateral abnormalities. Few patients (both genders) had combined bilateral appearances of hippocampal atrophy, amygdala atrophy, PHA acuteness, and increase in hippocampal angle (HA) where medial distance ratio (MDR) varied among genders. TLE had gender-specific and hemispheric dominant alterations in AI of parameters. Maximum magnitude of parametric changes in TLE includes (a) AI increase in HA of both genders, (b) HA increase (bilateral) in female patients, and (c) increase in ratio of amygdale/hippocampal volume (unilateral, right hemispheric), and AI decrease in MDR, in male patients. Multiparametric MRI studies of hippocampus and amygdalae, including their hemispheric asymmetry, underscore better characterization of TLE. Rapidly measurable single-slice parameters (HA, PHA, MDR) can readily delineate TLE in a time-constrained clinical setting, which contrasts with customary three-dimensional hippocampal volumetry that requires many slice computation.

DOES CEREBRAL GLUCOSE METABOLISM AND BLOOD FLOW DISSOCIATE IN EARLY STAGES OF ALZHEIMER'S DISEASE?

Background: Mild cognitive impairment (MCI) patients with different biomarker profiles might be characterized by different patterns of cortical thinning and subcortical atrophy. Methods: 53 MCI patients (mean age 71, female 49%) were enrolled from 2 Italian Memory Clinics. Abeta42 and Tau CSF levels, temporo parietal hypometabolism and hippocampal volumes were measured. According to their biormarker profiles, patients were divided in two groups: (i) suspected n on-amyloid pathology (SNAP, N1⁄421) and (ii) patients with amyloid plus neurodegeneration (A+N, N1⁄432). Cortical thickness and sucortical volumes were quantified using the freesurfer pipeline. Comparisons were made at group level with 15 subjective memory complainers (SMC), considered as the control group. Results: SMC were cognitively intact, younger than SNAP and A+N patients (p<.006). Relative to SMC group, A+N showed cortical thinning in the left/right parietal inferior and superior regions (p<.028), temporal middle and superior temporo-lateral gyri (p1⁄4.05), left inferior frontal gyrus (p1⁄4.009), right lateral fusyform gyrus (p<.002), insula and precentral sulcus (p1⁄4.01). SNAP patients compared to SMC exhibited cortical thinning in the left central sulcus (p1⁄4.025), right superior and inferior tempro-lateral (p<.002) and parietal gyri (p1⁄4.04), and precentral sulcus (p1⁄4.011). The direct comparison between A+N and SNAP showed significant cortical thinning only in the A+N group in the right and left lateral fusyform gyrus (p<.039), left occipital middle and lingual gyri (p1⁄4.020 and p1⁄4.007), parietal regions (p<.049) and orbito-lateral sulcus (p1⁄4.041). Both SNAP and A+N groups compared to SMC showed substantial subcortical volume reductions bilaterally in the hippocampus (p<.05), the nucleus accumbens (p<.046), the right pallidum (p<.0401), the left amygdala (p<.005). The direct comparisons between the two patient groups revealed a significant right amygdala atrophy in A+N patients. Conclusions: Our results support the hypothesis that SNAP patients are characterized by a different cortical and subcortical involvement relative to A+N due to different underlying pathologic changes.

Shape abnormalities of subcortical and ventricular structures in mild cognitive impairment and Alzheimer's disease: Detecting, quantifying, and predicting

This article assesses the feasibility of using shape information to detect and quantify the subcortical and ventricular structural changes in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. We first demonstrate structural shape abnormalities in MCI and AD as compared with healthy controls (HC). Exploring the development to AD, we then divide the MCI participants into two subgroups based on longitudinal clinical information: (1) MCI patients who remained stable; (2) MCI patients who converted to AD over time. We focus on seven structures (amygdala, hippocampus, thalamus, caudate, putamen, globus pallidus, and lateral ventricles) in 754 MR scans (210 HC, 369 MCI of which 151 converted to AD over time, and 175 AD). The hippocampus and amygdala were further subsegmented based on high field 0.8 mm isotropic 7.0T scans for finer exploration. For MCI and AD, prominent ventricular expansions were detected and we found that these patients had strongest hippocampal atrophy occurring at CA1 and strongest amygdala atrophy at the basolateral complex. Mild atrophy in basal ganglia structures was also detected in MCI and AD. Stronger atrophy in the amygdala and hippocampus, and greater expansion in ventricles was observed in MCI converters, relative to those MCI who remained stable. Furthermore, we performed principal component analysis on a linear shape space of each structure. A subsequent linear discriminant analysis on the principal component values of hippocampus, amygdala, and ventricle leads to correct classification of 88% HC subjects and 86% AD subjects.

Brain atrophy rates in first degree relatives at risk for Alzheimer's

A positive family history (FH) raises the risk for late-onset Alzheimer's disease though, other than the known risk conferred by apolipoprotein ε4 (ApoE4), much of the genetic variance remains unexplained. We examined the effect of family history on longitudinal regional brain atrophy rates in 184 subjects (42% FH+, mean age 79.9) with mild cognitive impairment (MCI) enrolled in a national biomarker study. An automated image analysis method was applied to T1-weighted MR images to measure atrophy rates for 20 cortical and subcortical regions. Mixed-effects linear regression models incorporating repeated-measures to control for within-subject variation over multiple time points tested the effect of FH over a follow-up of up to 48 months. Most of the 20 regions showed significant atrophy over time. Adjusting for age and gender, subjects with a positive FH had greater atrophy of the amygdala (p < 0.01), entorhinal cortex (p < 0.01), hippocampus (p < 0.053) and cortical gray matter (p < 0.009). However, when E4 genotype was added as a covariate, none of the FH effects remained significant. Analyses by ApoE genotype showed that the effect of FH on amygdala atrophy rates was numerically greater in ε3 homozygotes than in E4 carriers, but this difference was not significant. FH+ subjects had numerically greater 4-year cognitive decline and conversion rates than FH− subjects but the difference was not statistically significant after adjusting for ApoE and other variables. We conclude that a positive family history of AD may influence cortical and temporal lobe atrophy in subjects with mild cognitive impairment, but it does not have a significant additional effect beyond the known effect of the E4 genotype.

MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies

To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy. Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, β-amyloid, and α-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala. pRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and β-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions. Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.

Non-beta-amyloid–related structural, metabolic and white matter fiber integrity changes in early-MCI

Background: According to the amyloid cascade hypothesis, b-amyloid (Ab) pathology is an early event in Alzheimer’s disease (AD), followed by structural, functional and finally cognitive changes. If Ab+ is essential for AD, Abcognitive decline is non-AD, whichmay involve changed structure and function compared to Abcognitively healthy persons (NL), but the changes should be different from those seen in Ab+ cognitive decline. In this study, we tested the specific hypothesis that there are differences in brain structure, metabolism, and white matter (WM) connectivity between AbNL and Abearly mild cognitive impairment (MCI). Furthermore, we assessed the relative importance of imaging modalities in classification of Abearly-MCI from AbNL in terms of effect size.Methods:Ab-negative status of NL and early-MCI subjects fromADNI-GO/2 studies was based on both their AV45-PETand CSF-Ab data, with cohort characteristics summarized in the table. Relative to NL, age-, sex-, and education-adjusted earlyMCI effect-size of regional cortical thickness, tissue volume,WM fractional anisotropy (FA), and regional metabolic PET uptake was estimate and corrected for multiple comparison at p1⁄40.05 significance level. Results: Compared to AbNL, Abearly-MCI had significant 1) cortical thinning in the left superior temporal (d1⁄4-0.49), right inferior temporal (d1⁄4-0.47), right posterior banks of the superior temporal sulcus (d1⁄4-0.46), and left caudal anterior cingulate (d1⁄4-0.46); 2) tissue volume loss in the left amygdala (d1⁄4-0.64), left hippocampus (d1⁄4-0.46), and increased third ventricle CSF (d1⁄40.55); 3) hypermetabolism in the bilateral paracentral (left: d1⁄41.05; right: d1⁄40.65); and 4) diffused WM integrity degradation including the left fornix (cres)/stria terminalis (d1⁄4-0.59), bilateral internal capsule (d1⁄40.36 -0.57), bilateral tapatum (d1⁄4-0.42 -0.54), right cerebral peduncle (d1⁄4-0.52), bilateral splenium and genu of corpus callosum (d1⁄4-0.38 -0.48), right external capsule (d1⁄4-0.42), and left posterior thalamic radiation (d1⁄4-0.37). Conclusions: Abcognitive decline at early-MCI stage involves both structural and functional brain changes. Althoughmetabolic and volumetric changes had greater effect size, impact on WM fiber integrity was more wide-spread. The involvement of hippocampal, amygdala, and temporal lobe atrophy, and WM degeneration at fornix/stria terminalis was surprising in these subjects without AD-related Ab pathology, suggesting a non-Ab-pathology-related cognitive decline mechanism.

Globular glial-like inclusions in a patient with advanced Alzheimer’s disease

disturbances and memory problems. During disease evolution, apraxia and agnosia completed the clinical picture. He was globally apathetic and presented only occasionally sprouts of aggressiveness, but no prominent behavioural alterations. There were no parkinsonism and no signs of MND. He had no family history of a neurological disorder. He died due to cardiac failure. Unfixed brain weight was 1,305 g. On gross examination, frontal and temporally accentuated brain atrophy with marked ventricular enlargement and severe atrophy of amygdala and hippocampus were observed. Basal ganglia appeared atrophic showing flattening of the head of caudate nucleus (similar to patient 2 of Ahmed’s description). Substantia nigra and locus coeruleus were unremarkable. Histologically, prominent neuronal loss, astrogliosis and microglial proliferation were observed in frontal and temporal cortices, in amygdala, hippocampus and entoand transentorhinal regions. Abundant mature, diffuse and primitive βA4-amyloid plaques (DAKO, Glostrup, Denmark, clone 6F/3D) were detected (Fig. 1a). These were distributed in all cortical areas, basal ganglia, brainstem nuclei and cerebellar cortex, corresponding to a phase 5 according to Thal et al. [6] and to an age-related plaque score C according to CERAD criteria [4]. There was mild, occipitally accentuated leptomeningeal amyloid angiopathy. Furthermore, abundant hyperphosphorylated tau (Thermo-Scientific, clone AT8) immunoreactive neuropil threads, tangles and dystrophic neurites surrounding senile plaques were observed in frontal, temporal (Fig. 1b) and parietal cortex, with no involvement of primary visual cortex. Extensive tau pathology was also detected in insula, cingulum, hippocampus and parahippocampal gyrus, basal ganglia, basal nucleus of Meynert and some brainstem nuclei. In hippocampus, abundant ghost-tangles, neuronal granulovacuolar degeneration and Hirano bodies were also We read with interest the article by Ahmed and colleagues [1] entitled “Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: an emerging group of 4-repeat tauopathies.” The authors present clinical, neuropathological and biochemical features of two patients, one with frontotemporal dementia (FTD) and the other with motor neuron disease (MND), both sharing the presence of characteristic globular glial 4-repeat tau positive inclusions (oligodendroglial and astrocytic) with different topographical distribution. Previously, Kovacs et al. [3] described in detail seven cases showing FTLD phenotype and abundant white matter globular glial inclusions. Both authors suggest grouping previous terms such as MSTD or FTD-P-MND/PSP-CST, in one encompassing term, as this pathology seems to represent a separate entity among tauopathies. We present the post-mortem neuropathologic study of an 82-year-old man, diagnosed with possible Alzheimer’s disease at the age of 73 years due to progressive word finding

Neural correlates of impaired emotion processing in manifest Huntington’s disease

The complex phenotype of Huntington's disease (HD) encompasses motor, psychiatric and cognitive dysfunctions, including early impairments in emotion recognition. In this first functional magnetic resonance imaging study, we investigated emotion-processing deficits in 14 manifest HD patients and matched controls. An emotion recognition task comprised short video clips displaying one of six basic facial expressions (sadness, happiness, disgust, fear, anger and neutral). Structural changes between patients and controls were assessed by means of voxel-based morphometry. Along with deficient recognition of negative emotions, patients exhibited predominantly lower neural response to stimuli of negative valences in the amygdala, hippocampus, striatum, insula, cingulate and prefrontal cortices, as well as in sensorimotor, temporal and visual areas. Most of the observed reduced activity patterns could not be explained merely by regional volume loss. Reduced activity in the thalamus during fear correlated with lower thalamic volumes. During the processing of sadness, patients exhibited enhanced amygdala and hippocampal activity along with reduced recruitment of the medial prefrontal cortex. Higher amygdala activity was related to more pronounced amygdala atrophy and disease burden. Overall, the observed emotion-related dysfunctions in the context of structural neurodegeneration suggest both disruptions of striatal-thalamo-cortical loops and potential compensation mechanism with greater disease severity in manifest HD.

Frontolimbic atrophy is associated with agitation and aggression in mild cognitive impairment and Alzheimer's disease

BackgroundThe neuroanatomy of agitation and aggression in Alzheimer's disease is not well understood. MethodsWe analyzed 24 months of Alzheimer's Disease Neuroimaging Initiative data for patients with Alzheimer's disease, mild cognitive impairment-stable, and mild cognitive impairment-converter (n = 462) using the Neuropsychiatric Inventory Questionnaire Agitation and Aggression subscale. Magnetic resonance imaging regions of interest that correlated with Neuropsychiatric Inventory Questionnaire Agitation and Aggression subscale raw scores were included in mixed-model, repeated-measures analyses of agitation and aggression over time with age, sex, apolipoprotein E ε4 status, education, and Mini-Mental State Examination score as covariates. ResultsNeuropsychiatric Inventory Questionnaire Agitation and Aggression subscale scores worsened in patients with Alzheimer's disease and in mild cognitive impairment-converter (P < .05; trend for mild cognitive impairment, P = .0518). Greater agitation and aggression severity was associated with greater atrophy of frontal, insular, amygdala, cingulate, and hippocampal regions of interest (P < .05). Mini-Mental State Examination score was significant in mixed-effect model repeated measures only in mild cognitive impairment-converters for posterior regions of interest. Demographics and apolipoprotein ε4 were not associated with agitation and aggression. ConclusionsAgitation and aggression in Alzheimer's disease and mild cognitive impairment is associated with neurodegeneration affecting the anterior salience network that may reduce capacity to process and regulate behaviors properly.

Ventromedial‐frontopolar prefrontal cortex atrophy correlates with insight loss in frontotemporal dementia and Alzheimer's disease

Loss in insight is a major feature of frontotemporal dementia (FTD) but has been investigated relatively little. More importantly, the neural basis of insight loss is still poorly understood. The current study investigated insight deficit profiles across a large cohort of neurodegenerative patients (n = 81), including FTD and Alzheimer's disease (AD) patients. We employed a novel insight questionnaire, which tapped into changes across different domains: social interaction, emotion, diagnosis/treatment, language, and motivation. FTD subtypes varied considerably for insight loss, with the behavioral variant worst and the progressive non-fluent variant least affected. All other subtypes and AD showed milder but consistent insight loss. Voxel-based morphometry analysis revealed that overall insight loss correlated with ventromedial and frontopolar prefrontal atrophy, with exception of social interaction and emotion insight loss, which additionally correlated with lateral temporal and amygdala atrophy, respectively. Our results show that patients with neurodegenerative conditions show variable loss of insight, with ventromedial and frontopolar cortex regions appearing to be particularly important for insight.

Intact limbic-prefrontal connections and reduced amygdala volumes in Parkinson's disease with mild depressive symptoms

BackgroundDepression is very common in Parkinson's disease (PD). The neuropathological basis for this remains unclear; however, dysfunction in prefrontal and limbic regions may play a role. MethodsWe examined non-demented PD patients with and without depression and healthy controls (n = 6 per group) for differences in limbic structures and connections between these structures and the prefrontal cortex. Depressed individuals were selected from a representative sample of 33 PD patients using scores from the 15 question Geriatric Depression Scale (GDS). Magnetic Resonance Diffusion Tensor Imaging (DTI) tractography was used to examine the structural integrity of the uncinate fasciculus (UF), a white matter tract that projects from the hippocampus, amygdala and temporal pole to the orbitofrontal cortex, and the corpus callosum. Integrity of the UF and corpus callosum was established through measures of mean diffusivity (MD), fractional anisotropy (FA) and tract length. A volumetric analysis of the hippocampal head, body and tail, as well as the amygdala was performed to determine whether volume differences in these structures in PD relate to depression. ResultsThe depressed PD group showed smaller amygdala volumes compared to healthy controls, but the groups did not differ on any other measure. ConclusionsThe present study found intact limbic connectivity but suggests that amygdala atrophy may be present in Parkinson's disease with depression. Further work is needed to replicate these findings.

Preserved and Impaired Emotional Memory in Alzheimer’s Disease

Patients with early atrophy of both limbic structures involved in memory and emotion processing in Alzheimer’s disease (AD) provide a unique clinical population for investigating how emotion is able to modulate retention processes. This review focuses on the emotional enhancement effect (EEE), defined as the improvement of memory for emotional events compared with neutral ones. The assessment of the EEE for different memory systems in AD suggests that the EEE could be preserved under specific retrieval instructions. The first part of this review examines these data in light of compelling evidence that the amygdala can modulate processes of hippocampus-dependent memory. We argue that the EEE could be a useful paradigm to reduce impairment in episodic memory tasks. In the second part, we discuss theoretical consequences of the findings in favor of an EEE, according to which a compensatory mechanism in patients with AD solicits greater amygdala functioning or additional networks, even when amygdala atrophy is present. These considerations emphasize the relevance of investigating patients with AD to understand the relationship between emotion and memory processes.

Amygdala atrophy is prominent in early Alzheimer's disease and relates to symptom severity

Despite numerous studies on the role of medial temporal lobe structures in Alzheimer's disease (AD), the magnitude and clinical significance of amygdala atrophy have been relatively sparsely investigated. In this study, we used magnetic resonance imaging (MRI) to compare the level of amygdala atrophy to that of the hippocampus in very mild and mild AD subjects in two large samples (Sample 1 n = 90; Sample 2 n = 174). Using a series of linear regression analyses, we investigated whether amygdala atrophy is related to global cognitive functioning (Clinical Dementia Rating Sum of Boxes: CDR-SB; Mini Mental State Examination: MMSE) and neuropsychiatric status. Results indicated that amygdala atrophy was comparable to hippocampal atrophy in both samples. MMSE and CDR-SB were strongly related to amygdala atrophy, with amygdala atrophy predicting MMSE scores as well as hippocampal atrophy, but predicting CDR-SB scores less robustly. Amygdala atrophy was related to aberrant motor behavior, with potential relationships to anxiety and irritability. These results suggest that the magnitude of amygdala atrophy is comparable to that of the hippocampus in the earliest clinical stages of AD, and is related to global illness severity. There also appear to be specific relationships between the level of amygdala atrophy and neuropsychiatric symptoms that deserve further investigation.

Morphometric characterization of Binswanger's disease: Comparison with Alzheimer's disease

Background and purposeDementia due to hypertensive vascular disease is a potential target to treat prophylactively before it progresses insidiously. Binswanger's disease (BD) is a type of subcortical vascular dementia, but its clinical features and pathophysiology are still obscure. We therefore tried to find a topographic distribution of brain atrophy in BD by morphometric analysis. MethodsTwenty patients with BD, 50 patients with AD, and 80 elderly controls were recruited. We contrasted the gray matter atrophy of BD to that of AD to identify a pathognomic pattern using magnetic resonance imaging. We used DARTEL (diffeomorphic anatomical registration through exponential Lie algebra) for voxel-based morphometry, expecting that its sophisticated algorithm would work well to deal with the subjects with brain atrophy. ResultsAtrophy of cortices was predominant in the posterior cortices in AD but was in the anterior cortices in BD. Atrophy of amygdala and hippocampus was similar in each disease. In contrast, thalamus, caudate nucleus, insula, anterior cingulate cortex, and frontal cortices were significantly more atrophied in BD than in AD (z-score >3). ConclusionsWe demonstrated topographic patterns of brain atrophy in BD. Since affected regions of BD match with the anatomical connections of frontal–subcortical circuits, it seems reasonable to suppose that BD pathology is the result of hypertensive vascular disease and subsequent regression from the white matter injuries.

La influencia de la emoción en la memoria como índice para el diagnóstico temprano del Alzheimer

Introduction: during non-pathological aging the modulatory effect of emotion on memory is impaired, being particularly sensitive to amygdala and hippocampus atrophy that occurs in Alzheimer's disease. Aim: the aim of this paper is to analyze how this affects the deterioration of affective states at the beginning and during development of the disease and how the difficulties in remembering emotional information could be used to study emotional valence and arousal levels, in order to develop a test capable of detecting these problems in early stages of the disease. Conclusions: in light of the studies consulted, we recommend the use of recognition instead free recall; multilevel emotional induction methods and greater sensitivity in the analysis of data using parameters based on Signal Detection Theory. The clinical implications of this approach focus on diagnosis, where emotion should be integrated at the same analysis level as memory and attention, and also in the experimental field, providing tools for neuroimaging studies with which to study biological bases of emotional dysfunction. (Alzheimer. Real Invest Demenc. 2011;48:33-38)