Amygdala In Patients Research Articles

The paramedian supracerebellar-transtentorial approach to the entire length of the mediobasal temporal region: an anatomical and clinical study

The exploration of lesions in the mediobasal temporal region (MTR) has challenged generations of neurosurgeons to achieve an appropriate approach. To address this challenge, the extensive use of the paramedian supracerebellar-transtentorial (PST) approach to expose the entire length of the MTR, as well as the fusiform gyrus, was investigated. The authors studied the microsurgical aspects of the PST approach in 20 cadaver brains and 5 cadaver heads under the operating microscope. They evaluated the features, advantages, difficulties, and limitations of the PST approach and refined the surgical technique. They then used the PST approach in 15 patients with large intrinsic MTR tumors (6 patients), tumor in the posterior fusiform gyrus with mediobasal temporal epilepsy (MTE) (1 patient), cavernous malformations in the posterior MTR including the fusiform gyrus (2 patients), or intractable MTE with hippocampal sclerosis (6 patients) from December 2007 to May 2010. Patients ranged in age from 11 to 63 years (mean 35.2 years), and in 9 patients (60%) the lesion was located on the left side. In all patients with neuroepithelial tumors or cavernous malformations, the lesions were completely and safely resected. In all patients with intractable MTE with hippocampal sclerosis, the anterior two-thirds of the parahippocampal gyrus and hippocampus, as well as the amygdala, were removed selectively through the PST approach. There was no surgical morbidity or mortality in this series. Three patients (20%) with high-grade neuroepithelial tumors underwent postoperative radiotherapy and chemotherapy but needed a second surgery for recurrence during the follow-up period. In all patients with MTE, antiepileptic medication could be decreased to a single drug at lower doses, and no seizure activity has occurred until this point. The PST approach provides the surgeon precise anatomical orientation when exposing the entire length of the MTR, as well as the fusiform gyrus, for removing any lesion. This is a novel technique especially for removing tumors involving the entire MTR in a single session without damaging neighboring neural or vascular structures. This approach can also be a viable alternative for selective removal of the parahippocampal gyrus, hippocampus, and amygdala in patients with MTE due to hippocampal sclerosis.

Common Abnormalities and Disorder-Specific Compensation During Implicit Regulation of Emotional Processing in Generalized Anxiety and Major Depressive Disorders

Anxiety and depressive disorders are both associated with abnormalities in the processing and regulation of emotion. However, little is known about the similarities and differences between anxiety and depression at the neural level. The authors examined emotional conflict processing using a salient stimulus associated with observable and interpretable behavioral outcomes and with activation in limbic and prefrontal regions implicated in anxiety and depression. Thirty-two healthy comparison subjects, 18 patients with generalized anxiety disorder only, 14 patients with major depression only, and 25 patients with comorbid generalized anxiety disorder and major depression were studied using functional MRI while they performed an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect label words. The authors used behavioral and neural measures to compare trial-by-trial changes in conflict regulation, a test of implicit regulation of emotional processing. Behavioral data indicated that only patients with generalized anxiety (i.e., the anxiety-only and comorbid groups) failed to implicitly regulate emotional conflict. By contrast, deficits in activation and connectivity of the ventral anterior cingulate and amygdala, areas previously implicated in regulating emotional conflict, were found in all patient groups. Depression-only patients, however, compensated for this deficit by also activating the left and right anterior lateral prefrontal cortices, in which activity was correlated with behavioral evidence of successful implicit regulation, thus mediating the disorder-specificity of the behavioral phenotype. These data support the existence of a common abnormality in anxiety and depression in the ventral cingulate and the amygdala, which may be related to a shared genetic etiology. Compensatory engagement of cognitive control circuitry in depression illustrates how the complex nature of psychopathology arises from the interaction of deficits and compensation, all of which can occur at an implicit level.

Abnormal amygdala connectivity in patients with primary insomnia: Evidence from resting state fMRI

Neurobiological mechanisms underlying insomnia are poorly understood. Previous findings indicated that dysfunction of the emotional circuit might contribute to the neurobiological mechanisms underlying insomnia. The present study will test this hypothesis by examining alterations in functional connectivity of the amygdala in patients with primary insomnia (PI). Resting-state functional connectivity analysis was used to examine the temporal correlation between the amygdala and whole-brain regions in 10 medication-naive PI patients and 10 age- and sex-matched healthy controls. Additionally, the relationship between the abnormal functional connectivity and insomnia severity was investigated. We found decreased functional connectivity mainly between the amygdala and insula, striatum and thalamus, and increased functional connectivity mainly between the amygdala and premotor cortex, sensorimotor cortex in PI patients as compared to healthy controls. The connectivity of the amygdala with the premotor cortex in PI patients showed significant positive correlation with the total score of the Pittsburgh Sleep Quality Index (PSQI). The decreased functional connectivity between the amygdala and insula, striatum, and thalamus suggests that dysfunction in the emotional circuit might contribute to the neurobiological mechanisms underlying PI. The increased functional connectivity of the amygdala with the premotor and sensorimotor cortex demonstrates a compensatory mechanism to overcome the negative effects of sleep deficits and maintain the psychomotor performances in PI patients.

Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder

Social anxiety disorder patients suffer from excessive anxious responses in social interaction leading to avoidance behavior and social impairment. Although the amygdala has a central role in perception and processing of threatening cues, little is known about the involved networks and corresponding dysfunctions in social anxiety. Therefore, this study aims to investigate the functional connectivity network of the amygdala in patients with social anxiety disorder and to identify regions that might influence amygdalar reactivity via modulatory pathways.Ten patients with anxiety disorders (social and/or panic) and 27 healthy controls underwent a facial emotion processing task as well as 6-min functional MRI at resting state. Individual voxel-wise functional connectivity maps were calculated using the amygdala as seed region. Group comparisons were done by random-effects analysis in SPM.Patients exhibited an amygdala hyperactivation during the emotional task and decreased functional coupling of the left amygdala with the medial orbitofrontal cortex and the posterior cingulate cortex/precuneus. The strength of this functional connectivity showed a negative association with the severity of state anxiety. In addition, an exploratory analysis revealed further reduced functional connectivity and a marked functional separation between the medial orbitofrontal and anterior cingulate cortices in the patient group.Our results suggest alterations within the amygdalar functional connectivity network in social anxiety disorder. Combined with the amygdalar hyperactivation our findings corroborate the proposed dysfunction of the fronto-amygdalar inhibition in anxiety disorders and indicate a modulatory influence of the anterior and posterior cingulate cortices on threat perception and processing.

Local amygdala structural differences with 3T MRI in patients with Alzheimer disease

Histologic studies show that the amygdala is affected by Alzheimer disease (AD) pathology, and its medial aspect is the most involved. We aimed to assess in vivo local structural differences in the amygdala of patients with AD using high-field MRI. A total of 19 patients with AD (mean age 76, SD 6 years, mean Mini-Mental State Examination score [MMSE] 13, SD 4) and 19 healthy elderly controls (age 74, SD 5, MMSE 29, SD 1) were enrolled. The radial atrophy mapping technique was used to reconstruct the 3-dimensional surface of the amygdala. Maps of surface tissue loss in patients with AD vs controls were computed and statistically tested with permutation tests thresholded at p < 0.05, to correct for multiple comparisons. A digital atlas of the amygdalar nuclei was used to infer which nuclei were involved. Both amygdalar volumes were significantly smaller in patients with AD (right 1,508 mm³, SD 418; left 1,646, SD 419) than controls (right 2,129 mm³, SD 316; left 2,077, SD 376; p < 0.002). In the dorsomedial part, significant local tissue loss (20%-30%) was mapped in the medial and central nuclei. Ventrally, the lateral nucleus (La) and the basolateral ventral medial nucleus (BLVM) were also involved (20%-30% loss). We found in vivo local structural differences in the amygdala of patients with AD. The nuclei involved have known connections to the hippocampus (BLVM, La) and olfactory system (medial nucleus) and with cholinergic pathways (central nucleus). This pattern is consistent with the known pathophysiology of neural systems affected by AD.

Suicidal attempts and increased right amygdala volume in schizophrenia

Suicide is a major cause of death in schizophrenia. Neurobiological studies suggest that suicidality is associated with abnormal brain structure and connectivity in fronto-temporo-limbic regions. However, it is still unclear whether suicidality in schizophrenia is related to volumetric abnormalities in subcortical structures that play a key role in emotion regulation, aggression and impulse control. Therefore, we aimed to examine whether the volume of selected subcortical regions is associated with previous suicidal attempts and self-aggression in schizophrenia. For this cross-sectional study, we recruited 50 outpatients with schizophrenia and 50 healthy controls (HC) matched for age and gender. Fourteen patients had a history of one or more suicide attempts. Different forms of aggression were assessed using the Modified Overt Aggression Scale. All participants underwent structural MR imaging at 3 Tesla. Physical volumetric measures were calculated for the lateral ventricles, thalamus, hippocampus, amygdala, caudate, putamen, pallidum and accumbens using an automatic segmentation method on T1-weighted high-resolution (voxel size 1 × 1 × 1 mm 3) images. Multivariate and follow-up univariate ANOVAs revealed a selective increase in volume in the right amygdala of patients with a history of suicidality compared both to patients without such a history and HC. Moreover, in the entire patient group increased right amygdala volume was related to increased self-aggression. Our findings suggest that right amygdala hypertrophy may be a risk factor for suicide attempts in patients with schizophrenia and this could be relevant for suicide prevention.

Association between structural abnormalities and fMRI response in the amygdala in patients with temporal lobe epilepsy

The goal of this study was to investigate whether dysplastic amygdalae show an impaired response as revealed by functional MRI (fMRI). A fearful face fMRI paradigm using video sequences, as we have recently applied, was used in 25 patients with temporal lobe epilepsy (TLE): 24 had mesial TLE (14 right-, nine left-sided, one bilateral); one left lateral neocortical TLE. T1-, T2-weighted and fluid attenuated inversion recovery (FLAIR) MRI sequences were assessed for the detection and categorisation of structural amygdalar abnormalities according to size and MR signal intensity. Of the 25 patients, five patients had probable dysplastic amygdala (pDA): two right- and three left-sided. A fearful face paradigm led to significant amygdalar activation in all but one patient (p<0.05). In 15 (60%) of the patients amygdalar activation was found contralateral and in four (16%) ipsilateral to the side of seizure onset. Bilateral amygdalar activation was registered in five (20%) patients. In two patients with right-sided and one with left-sided pDA, fMRI activation was observed only in the contralateral amygdala. In two out of three patients with left-sided pDA we found significant ipsilateral amygdalar fMRI-responses. Unilateral pDA does not necessarily affect the amygdalar fMRI BOLD-response.

Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: A magnetic resonance spectroscopy study

Fibromyalgia (FM) has been defined as a systemic disorder that is clinically characterized by pain, cognitive deficit, and the presence of associated psychopathology, all of which are suggestive of a primary brain dysfunction. This study was undertaken to identify the nature of this cerebral dysfunction by assessing the brain metabolite patterns in patients with FM through magnetic resonance spectroscopy (MRS) techniques. A cohort of 28 female patients with FM and a control group of 24 healthy women of the same age were studied. MRS techniques were used to study brain metabolites in the amygdala, thalami, and prefrontal cortex of these women. In comparison with healthy controls, patients with FM showed higher levels of glutamate/glutamine (Glx) compounds (mean +/- SD 11.9 +/- 1.6 arbitrary units [AU] versus 13.4 +/- 1.7 AU in controls and patients, respectively; t = 2.517, 35 df, corrected P = 0.03) and a higher Glx:creatine ratio (mean +/- SD 2.1 +/- 0.4 versus 2.4 +/- 1.4, respectively; t = 2.373, 35 df, corrected P = 0.04) in the right amygdala. In FM patients with increased levels of pain intensity, greater fatigue, and more symptoms of depression, inositol levels in the right amygdala and right thalamus were significantly higher. The distinctive metabolic features found in the right amygdala of patients with FM suggest the possible existence of a neural dysfunction in emotional processing. The results appear to extend previous findings regarding the dysfunction in pain processing observed in patients with FM.

Chronic Stress Causes Amygdala Hyperexcitability in Rodents

Chronic stress is a major health concern, often leading to depression, anxiety, or when severe enough, posttraumatic stress disorder. While many studies demonstrate that the amygdala is hyperresponsive in patients with these disorders, the cellular neurophysiological effects of chronic stress on the systems that underlie psychiatric disorders, such as the amygdala, are relatively unknown. In this study, we examined the effects of chronic stress on the activity and excitability of amygdala neurons in vivo in rats. We used in vivo intracellular recordings from single neurons of the lateral amygdala (LAT) to measure neuronal properties and determine the cellular mechanism for the effects of chronic stress on LAT neurons. We found a mechanism for the effects of chronic stress on amygdala activity, specifically that chronic stress increased excitability of LAT pyramidal neurons recorded in vivo. This hyperexcitability was caused by a reduction of a regulatory influence during action potential firing, facilitating LAT neuronal activity. The effects of stress on excitability were occluded by agents that block calcium-activated potassium channels and reversed by pharmacological enhancement of calcium-activated potassium channels. These data demonstrate a specific channelopathy that occurs in the amygdala after chronic stress. This enhanced excitability of amygdala neurons after chronic stress may explain the observed hyperresponsiveness of the amygdala in patients with posttraumatic stress disorder and may facilitate the emergence of depression or anxiety in other patients.

112. fMRI response of dysplastic amygdala in patients with temporal lobe epilepsy

112. fMRI response of dysplastic amygdala in patients with temporal lobe epilepsy

Volumes of the Hippocampus and Amygdala in Patients With Borderline Personality Disorder: A Meta-Analysis

Individuals with borderline personality disorder (BPD) often exhibit impulsive and aggressive behavior. The hippocampus and amygdala form part of the limbic system, which plays a central role in controlling such expressions of emotional reactivity. There are mixed results in the literature regarding whether patients with BPD have smaller hippocampal and amygdalar volume relative to healthy controls. To clarify the precise nature of these mixed results, we performed a meta-analysis to aggregate data on the size of the hippocampus and amygdala in patients with BPD. Seven publications involving six studies and a total of 104 patients with BPD and 122 healthy controls were included. A significantly smaller volume was found in both the right and left hippocampi and amygdala of patients with BPD compared to healthy controls. These findings raise the possibility that reduced hippocampal and amygdalar volumes are biological substrates of some symptoms of BPD.

Decreased Gray Matter Volumes in the Cingulo-Frontal Cortex and the Amygdala in Patients With Fibromyalgia

Studies in fibromyalgia syndrome with functional neuroimaging support the hypothesis of central pain augmentation. To determine whether structural changes in areas of the pain system are additional preconditions for the central sensitization in fibromyalgia we performed voxel based morphometry in patients with fibromyalgia and healthy controls. We performed 3 Tesla magnetic resonance imaging of the brain in 14 patients with fibromyalgia and 14 healthy controls. Regional differences of the segmented and normalized gray matter volumes in brain areas of the pain system between both groups were determined. In those areas in which patients structurally differed from healthy controls, the correlation of disease-related factors with gray matter volumes was analyzed. Patients presented a decrease in gray matter volume in the prefrontal cortex, the amygdala, and the anterior cingulate cortex (ACC). The duration of pain or functional pain disability did not correlate with gray matter volumes. A trend of inverse correlation of gray matter volume reduction in the ACC with the duration of pain medication intake has been detected. Our results suggest that structural changes in the pain system are associated with fibromyalgia. As disease factors do not correlate with reduced gray matter volume in areas of the cingulo-frontal cortex and the amygdala in patients, one possible interpretation is that volume reductions might be a precondition for central sensitization in fibromyalgia.

Facial Emotion Processing in Schizophrenia: A Meta-analysis of Functional Neuroimaging Data

People with schizophrenia have difficulty with emotion perception. Functional imaging studies indicate regional brain activation abnormalities in patients with schizophrenia when processing facial emotion. However, findings have not been entirely consistent across different studies. Activation likelihood estimation (ALE) meta-analyses were conducted to examine brain activation during facial emotion processing in patients with schizophrenia, controls, and patients compared with controls. Secondary meta-analyses were performed to assess the contribution of task design and illness chronicity to the results reported. When processing facial expressions of emotions, both patients with schizophrenia and healthy controls activated the bilateral amygdala and right fusiform gyri. However, the extent of activation in these regions was generally much more limited in the schizophrenia samples. When directly compared with controls, the extent of activation in bilateral amygdala, parahippocampal gyrus and fusiform gyrus, right superior frontal gyrus, and lentiform nucleus was significantly less in patients. Patients with schizophrenia, but not controls, activated the left insula. A relative failure to recruit the amygdala in patients occurred regardless of whether the task design was explicit or implicit, while differences in fusiform activation were evident in explicit, not implicit, tasks. Restricting the analysis to patients with chronic illness did not substantially change the results. A marked underrecruitment of the amygdala, accompanied by a substantial limitation in activation throughout a ventral temporal-basal ganglia-prefrontal cortex "social brain" system may be central to the difficulties patients experience when processing facial emotion.

TDP‐43 Neuronal Cytoplasmic Inclusions in the Amygdala of Patients with Advanced Alzheimer Disease

TAR DNA binding protein‐43 (TDP‐43)‐immunoreactive neuronal cytoplasmic inclusions (NCIs), characteristically associated with frontotemporal lobar degenerations (FTLD‐U and FTLD‐MND), have been found in the hippocampal dentate granule cells of about 20% of cases with advanced Alzheimer disease (AD). The extent and distribution of TDP‐43 pathology in brain regions other than hippocampus in AD is not known, especially in AD cases without hippocampal NCIs.Sections of hippocampus, amygdala, neocortex, and medulla from patients with clinical dementia and pathologic features of AD were analyzed for the presence of TDP‐43‐immunoreactive NCIs.22 cases of advanced AD (Braak Stage V‐VI) without hippocampal NCIs and 23 cases of advanced AD with hippocampal NCIs were included. 6 hippocampal‐negative cases (27%) had TDP‐43 positive NCIs in the amygdala. All 23 cases of hippocampal‐positive cases had numerous TDP‐43 NCIs in the amygdala, with decreasing density of NCIs in the other brain regions.In summary, TDP‐43 immunoreactive NCIs are found predominantly in the medial temporal structures in advanced AD, and the amygdala appears to be the area most vulnerable.

5‐HT1A receptor gene C −1019 G polymorphism and amygdala volume in borderline personality disorder

Alterations of amygdala structure and function have been repeatedly described in patients with borderline personality disorder (BPD). The aim of our study was to determine whether a functional polymorphism of the 5-hydroxytryptamine(1A) receptor (5-HTR(1A)) gene C -1019 G (identity number: rs6295 G/C) is associated with structural changes of the amygdala in patients with BPD. Twenty-five right-handed female inpatients with BPD according to DSM IV and 25 healthy controls matched for age, sex, handedness and educational status were enrolled. Brain volumetry of the amygdala was performed with a 1.5-T Magnetom Vision apparatus (Siemens, Erlangen, Germany) and analyzed by the software program 'BRAINS'. Patients who have the 5-HTR(1A) gene G allele had significantly smaller amygdala volumes than C/C genotype carriers (P = 0.02). While no difference of allelic distribution between patients and controls was detected, the described effect of 5-HTR(1A) genotype on amygdala volume was found for the whole group of patients, as well as in the subgroup of patients with comorbid major depression (P = 0.004) but not in controls. In contrast to these subgroups of BPD patients who had significant amygdala volume differences, the mean amygdala volume of the whole group of BPD patients was not significantly different from that of controls. In summary, our study provides first evidence that 5-HTR(1A) gene C -1019 G polymorphism is associated with structural changes in the limbic system of BPD patients, a finding that might be disease related and might contribute to explanation of previous discrepant results regarding amygdala volume changes in BPD. Future research is recommended to clarify possible interactions between this functional polymorphism and symptoms, course and treatment responses in this disorder.

A Functional Magnetic Resonance Imaging Study of Amygdala Responses to Human Faces in Aging and Mild Alzheimer’s Disease

Neuropsychiatric symptoms are very common even in mild stages of Alzheimer's disease (AD). The amygdala exhibits very early pathology in AD, but amygdala function in mild AD has received relatively little attention. The current study investigates functional alterations in the amygdala in aging and mild AD, and their relationships with neuropsychiatric symptoms. Functional magnetic resonance imaging (fMRI) was used to examine and compare amygdala responses in 12 young and elderly controls and in 12 mild AD patients during viewing of neutral and emotional human facial expressions. Amygdala responses in the young and elderly did not significantly differ from each other. However, the AD group had significantly greater amygdala responses to both neutral and emotional faces relative to elderly controls. This group effect was maintained when amygdala volume, sex and age were included as covariates in the analysis. Furthermore, amygdala activity correlated with the severity of irritability and agitation symptoms in AD. The amygdala in patients with mild AD is excessively responsive to human faces relative to elderly controls. These amygdala functional alterations may represent a physiologic marker for certain neuropsychiatric manifestations of AD.

Selective Involvement of the Amygdala in Systemic Lupus Erythematosus

BackgroundAntibodies specifically affect the amygdala in a mouse model of systemic lupus erythematosus (SLE). The aim of our study was to investigate whether there is also specific involvement of the amygdala in human SLE.Methods and FindingsWe analyzed a group of 37 patients with neuropsychiatric SLE (NP-SLE), 21 patients with SLE, and a group of 12 healthy control participants with diffusion weighted imaging (DWI). In addition, in a subset of eight patients, plasma was available to determine their anti-NMDAR antibody status. From the structural magnetic resonance imaging data, the amygdala and the hippocampus were segmented, as well as the white and gray matter, and the apparent diffusion coefficient (ADC) was retrieved. ADC values between controls, patients with SLE, and patients with NP-SLE were tested using analysis of variance with post-hoc Bonferroni correction. No differences were found in the gray or white matter segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 × 10−6 mm2/s; p = 0.006 and 949 × 10−6 mm2/s; p = 0.019, respectively) was lower than in healthy control participants (1152 × 10−6 mm2/s). Mann-Whitney analysis revealed that the average ADC in the amygdala of patients with anti-NMDAR antibodies (n = 4; 802 × 10−6 mm2/s) was lower (p = 0.029) than the average ADC of patients without anti-NMDAR antibodies (n = 4; 979 × 10−6 mm2/s) and also lower (p = 0.001) than in healthy control participants.ConclusionsThis is the first study to our knowledge to observe damage in the amygdala in patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies.

Neural Correlates of Antinociception in Borderline Personality Disorder

A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain. To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD. Case-control study. A university hospital. Twelve women with BPD and self-injurious behavior and 12 age-matched control subjects. Psychophysical assessment and blood oxygen level-dependent functional magnetic resonance imaging during heat stimulation with fixed-temperature heat stimuli and individual-temperature stimuli adjusted for equal subjective pain in all the participants. Blood oxygen level-dependent functional magnetic resonance imaging signal changes during heat pain stimulation. Patients with BPD had higher pain thresholds and smaller overall volumes of activity than controls in response to identical heat stimuli. When the stimulus temperature was individually adjusted for equal subjective pain level, overall volumes of activity were similar, although regional patterns differed significantly. Patient response was greater in the dorsolateral prefrontal cortex and smaller in the posterior parietal cortex. Pain also produced neural deactivation in the perigenual anterior cingulate gyrus and the amygdala in patients with BPD. The interaction between increased pain-induced response in the dorsolateral prefrontal cortex and deactivation in the anterior cingulate and the amygdala is associated with an antinociceptive mechanism in patients with BPD.

Convergence of Heat Shock Protein 90 with Ubiquitin in Filamentous α-Synuclein Inclusions of α-Synucleinopathies

Convergence of Heat Shock Protein 90 with Ubiquitin in Filamentous α-Synuclein Inclusions of α-Synucleinopathies

Morphometry of the amygdala in patients with questionable dementia and mild dementia

The volume of the amygdala is reduced in advanced Alzheimer's disease (AD). However, there is controversy whether amygdala atrophy is present in mild AD and in the transitional phase between health and the onset of dementia. The aim of this prospective longitudinal study was to investigate whether amygdala atrophy is present in subjects with questionable dementia and mild dementia and whether amygdala volume is associated with the future rate of cognitive change, that is the annual change in the Mini Mental State Examination (MMSE). At baseline, volumes of the amygdala were measured in 97 participants aged 70–87 years (40 controls, 33 patients with questionable dementia, 24 patients with mild AD) using magnetic resonance imaging. Eighty-six participants were clinically re-examined after 2.3 years on average. At baseline, significant differences in mean amygdala volume were found between controls and participants with mild AD. There was no significant correlation between the longitudinal annual change in MMSE and the baseline amygdala volume in any of the three groups.