Usefulness of medial temporal lobe atrophy visual rating scale in detecting Alzheimer's disease: Preliminary study

Background:

The Korean version of Mini-Mental Status Examination (K-MMSE) and the Korean version of Addenbrooke Cognitive Examination (K-ACE) have been validated as quick neuropsychological tests for screening dementia in various clinical settings. Medial temporal atrophy (MTA) is an early pathological characteristic of Alzheimer''s disease (AD). We aimed to assess the diagnostic validity of the fusion of the neuropsychological test and visual rating scale (VRS) of MTA in AD.

Materials and Methods:

A total of fifty subjects (25 AD, 25 controls) were included. The neuropsychological tests used were the K-MMSE and the K-ACE. T1 axial imaging visual rating scale (VRS) was applied for assessing the grade of MTA. We calculated the fusion score with the difference of neuropsychological test and VRS of MTA. The receiver operating characteristics (ROC) curve was used to determine optimal cut-off score, sensitivity and specificity of the fusion scores in screening AD.

Results:

No significant differences in age, gender and education were found between AD and control group. The values of K-MMSE, K-ACE, CDR, VRS and cognitive function test minus VRS were significantly lower in the AD group than control group. The AUC (Area under the curve), sensitivity and specificity for K-MMSE minus VRS were 0.857, 84% and 80% and for K-ACE minus VRS were 0.884, 80% and 88%, respectively. Those for K-MMSE only were 0.842, 76% and 72% and for K-ACE only were 0.868, 80% and 88%, respectively.

Conclusions:

The fusion of the neuropsychological test and VRS suggested clinical usefulness in their easy and superiority over neuropsychological test only. However, this study failed to find any difference. This may be because of small numbers in the study or because there is no true difference.     

Quantitative EEG and medial temporal lobe atrophy in Alzheimer's dementia: Preliminary study

Backgrounds:

The electroencephalogram (EEG) abnormalities in Alzheimer''s disease (AD) have been widely reported, and medial temporal lobe atrophy (MTLA) is one of the hallmarks in early stage of AD. We aimed to assess the relationship between EEG abnormalities and MTLA and its clinical validity.

Materials and Methods:

A total of 18 patients with AD were recruited (the mean age: 77.83 years). Baseline EEGs were analyzed with quantitative spectral analysis. MTLA was assessed by a T1-axial visual rating scale (VRS).

Results:

In relative power spectrum analysis according to the right MTLA severity, the power of theta waves in C4, T4, F4, F8, and T5 increased significantly and the power of beta waves in T6, C4, T4, F8, T5, P3, T3, and F7 decreased significantly in severe atrophy group. In relative power spectrum analysis according to the left MTLA severity, the power of theta waves in T3 increased significantly and that of beta waves in P4, T6, C4, F4, F8, T5, P3, C3, T3, F3, and F7 decreased significantly in severe atrophy group.

Conclusion:

The severe MTLA group, regardless of laterality, showed more severe quantitative EEG alterations. These results suggest that quantitative EEG abnormalities are correlated with the MTLA, which may play an important role in AD process.     

CT measurement of medial temporal lobe atrophy in Alzheimer's disease, vascular dementia, depression and paraphrenia

OBJECTIVE: Measurement of medial temporal lobe atrophy (MTL) by computerised tomography (CT) may be a useful adjunct to the diagnosis of AD. The aim of this study was to assess the sensitivity, specificity, predictive values and diagnostic accuracy of CT measurement of MTL thickness for patients with probable AD, compared with a 'diseased' control group, and to correlate the measure with neuropsychological test scores. DESIGN: Cross-sectional. METHODS: One hundred subjects were prospectively recruited: 60 with probable AD (mean age 73.7 years, mean Mini-Mental State Examination [MMSE] 19.6), 17 with probable vascular dementia (VaD) (mean age 77.9 years, mean MMSE 20.9), 14 with depression (mean age 73.2 years, mean MMSE 25.7) and nine with paraphrenia (mean age 74 years, mean MMSE 25.4). Axial and temporal lobe-oriented CT brain was performed and the minimum MTL thickness was measured electronically. RESULTS: The mean minimum MTL thickness was significantly smaller in AD subjects compared to VaD (p<0.0001) and psychiatric subjects (p<0.0001). For the clinical diagnosis of probable AD, the sensitivity of the measure was 0.75, specificity 0.9, and diagnostic accuracy 0.81. For the mildest cases of AD (CDR 0.5), the sensitivity of the measure was 0.61, specificity 0.91, and diagnostic accuracy 0.81. No significant correlations with neuropsychological test scores were found. CONCLUSIONS: Temporal lobe-oriented CT imaging is a non-invasive test with good discrimination for AD. Potential uses of this technique include as an aid to diagnosis and possibly as a means of monitoring disease progression.     

Relationship of medial temporal lobe atrophy,APOE genotype,and cognitive reserve in preclinical Alzheimer's disease

This study evaluated the utility of baseline and longitudinal magnetic resonance imaging (MRI) measures of medial temporal lobe brain regions collected when participants were cognitively normal and largely in middle age (mean age 57 years) to predict the time to onset of clinical symptoms associated with mild cognitive impairment (MCI). Furthermore, we examined whether the relationship between MRI measures and clinical symptom onset was modified by apolipoprotein E (ApoE) genotype and level of cognitive reserve (CR). MRI scans and measures of CR were obtained at baseline from 245 participants who had been followed for up to 18 years (mean follow‐up 11 years). A composite score based on reading, vocabulary, and years of education was used as an index of CR. Cox regression models showed that lower baseline volume of the right hippocampus and smaller baseline thickness of the right entorhinal cortex predicted the time to symptom onset independently of CR and ApoE‐?4 genotype, which also predicted the onset of symptoms. The atrophy rates of bilateral entorhinal cortex and amygdala volumes were also associated with time to symptom onset, independent of CR, ApoE genotype, and baseline volume. Only one measure, the left entorhinal cortex baseline volume, interacted with CR, such that smaller volumes predicted symptom onset only in individuals with lower CR. These results suggest that MRI measures of medial temporal atrophy, ApoE‐?4 genotype, and the protective effects of higher CR all predict the time to onset of symptoms associated with MCI in a largely independent, additive manner during the preclinical phase of Alzheimer's disease. Hum Brain Mapp 36:2826–2841, 2015. © 2015 Wiley Periodicals, Inc.     

Association between medial temporal lobe atrophy on CT and parietotemporal uptake decrease on SPECT in Alzheimer's disease

OBJECTIVES—Alzheimer's disease is the mostfrequent cause of degenerative dementia. Despite the availablediagnostic criteria, improvement of diagnosic accuracy is stillrequired. The aim of this prospective study was to assess in a largepopulation of patients referred to a memory clinic the diagnostic valueof the combination of medial temporal lobe atrophy on temporal orientedCT and decreased temporoparietal uptake on HMPAO single photon emissiontomography (SPECT).
METHODS—The study was conducted in 125 patientsaged 51-93: 64 with probable Alzheimer's disease (Mean (SD) minimental state examination (MMSE)=18.34 (6.93)), duration of disease=6.48(2.93) years, 13possible Alzheimer's disease (MMSE=21.58 (5.48),duration of disease=6.08 (2.56)), 48 patients with miscellaneous memorydisorders (MMSE=21.98 (6.10), duration the disease = 6.85 (3.91)).
RESULTS—For the diagnosis of probableAlzheimer's disease, the sensitivity of this association was 0.56, thespecificity 0.93, the positive predictive value 0.95, and the negativepredictive value 0.45. The diagnosic accuracy was 0.68. Both medialtemporal atrophy and parietotemporal decrease in uptake were present infour of 13 patients with possible Alzheimer's disease and 11 of 48 with miscellaneous memory disorders. The association was absent in 27 of 29 patients with frontotemporal dementia. In mild stages (MMSE>18;n = 32), the sensitivity of the association was 0.34,the specificity0.93, the positive predictive value 0.85, and the negative predictivevalue 0.57. The diagnosic accuracy was 0.53.
CONCLUSION—This association, although notsensitive, helps to select patients with high probability ofAlzheimer's disease at an early stage which can be of interest forclinical and research purposes.

     

Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease

Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia and Alzheimer's disease. Three groups of 10 subjects were studied: semantic dementia patients, Alzheimer's disease patients, and control subjects. The temporal lobe structures measured were the amygdala, hippocampus, entorhinal cortex, parahippocampal gyrus, fusiform gyrus, and superior, middle, and inferior temporal gyri. Semantic dementia and Alzheimer's disease groups did not differ significantly on global atrophy measures. In semantic dementia, there was asymmetrical temporal lobe atrophy, with greater left-sided damage. There was an anteroposterior gradient in the distribution of temporal lobe atrophy, with more marked atrophy anteriorly. All left anterior temporal lobe structures were affected in semantic dementia, with the entorhinal cortex, amygdala, middle and inferior temporal gyri, and fusiform gyrus the most severely damaged. Asymmetrical, predominantly anterior hippocampal atrophy was also present. In Alzheimer's disease, there was symmetrical atrophy of the entorhinal cortex, hippocampus, and amygdala, with no evidence of an anteroposterior gradient in the distribution of temporal lobe or hippocampal atrophy. These data demonstrate that there is a marked difference in the distribution of temporal lobe atrophy in semantic dementia and Alzheimer's disease. In addition, the pattern of atrophy in semantic dementia suggests that semantic memory is subserved by anterior temporal lobe structures, within which the middle and inferior temporal gyri may play a key role.     

Application of automated medial temporal lobe atrophy scale to Alzheimer disease

OBJECTIVE: To compare an automated intensity-based measure of medial temporal atrophy in Alzheimer disease (AD) with existing volumetric and visually based methods. DESIGN: Longitudinal study comparing a medial temporal atrophy measure with 2 criterion standards: (1) total hippocampal (HC) volume adjusted for total intracranial volume and (2) standard visual rating scale of medial temporal atrophy. SETTING: Cognitive disorders specialist clinic. PARTICIPANTS: Forty-seven patients with AD and 26 age- and sex-matched controls. INTERVENTION: Subjects were scanned using volumetric T1-weighted magnetic resonance imaging at baseline and 1 year later. MAIN OUTCOME MEASURE: Automated Medial Temporal Lobe Atrophy Scale (ATLAS) score, derived from dividing mean intensity of a standardized perihippocampal volume by that of a standardized pontine volume. RESULTS: Patients with AD had significantly reduced ATLAS scores and HC volumes and increased visual rating scores at baseline and repeat scanning. Rates of HC atrophy and decline in the ATLAS score were significantly higher in patients with AD compared with controls. The ATLAS scores were significantly correlated with HC volumes and visual rating scores. With specificity set at 85%, the sensitivities of HC volume and visual rating scale score were similar (84% and 86%, respectively), whereas ATLAS score had a lower sensitivity (73%). At repeat scanning, all 3 measures had similar sensitivities (86%-87%). Rate of decline in the ATLAS score required a similar sample size to HC atrophy rate to provide statistical power to clinical trials, but being automated, it is less labor intensive. CONCLUSIONS: Like the visual rating scale, ATLAS is a simple medial temporal atrophy measure, which has the additional advantage of being able to track AD progression on serial imaging.     

Distinct white matter injury associated with medial temporal lobe atrophy in Alzheimer's versus semantic dementia

This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty‐six AD patients, twenty‐one SD patients, and thirty‐nine controls underwent a high‐resolution T1‐MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe — essentially the uncinate and inferior longitudinal fasciculi — in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791–1800, 2017. © 2017 Wiley Periodicals, Inc.     

Behavioural and psychological symptoms are not related to white matter hyperintensities and medial temporal lobe atrophy in Alzheimer's disease

BACKGROUND: The neuropathology of behavioural and psychological symptoms is much less understood than the neuropathology of cognitive impairment in AD. On MRI, medial temporal lobe atrophy (MTA) is presumed to reflect Alzheimer- type pathology. White matter hyperintensities (WMH) are considered markers of vascular pathology. AIM: We investigated differences in prevalence of behavioural and psychological symptoms in AD according to the presence of MTA and WMH on MRI. METHODS: Behavioural and psychological symptoms of 111 consecutive AD patients were assessed using the Neuropsychatric Inventory (NPI). Symptoms were considered present when the score was > or =1. On MRI, MTA was rated using the five-point Scheltens-scale and WMH using the four-point Fazekas-scale. Both MRI measures were dichotomised (MTA: absent 0/1, present 2-4; WMH absent 0/1, present 2/3). RESULTS: Of the 111 AD patients, 60(55%) had MTA, and 32(29%) had WMH. The presence of MTA was associated with the presence of WMH (chi (2) = 11.8, p < 0.001). The prevalence of behavioural and psychological symptoms--defined as a NPI score of > or =1 on at least one symptom--was 74%.The median NPI score of the total study population was 6(0-41). There was no difference in prevalence according to MTA (p = 0.53) or WMH (p = 0.18). On inspection of individual NPI items, neither MTA, nor WMH was related to any of the symptoms. CONCLUSIONS: There were no differences in prevalence of behavioural and psychological symptoms according to MTA or WMH, as rated on MRI. This suggests that the occurrence of those symptoms depends on other determinants, such as coping style or genetic make-up.     

Medial temporal lobe atrophy predicts Alzheimer's disease in patients with minor cognitive impairment

OBJECTIVES: To investigate whether medial temporal lobe atrophy predicted outcome in patients with minor cognitive impairment and whether assessment of the medial temporal lobe could increase the predictive accuracy of age and delayed recall for outcome. Quantitative and qualitative methods of assessing the medial temporal lobe were also compared. METHODS: Patients with minor cognitive impairment older than 50 years (n=31) were selected from a memory clinic and were followed up for on average 1.9 years. The medial temporal lobe was assessed in three different ways: volumetry of the hippocampus, volumetry of the parahippocampal gyrus, and qualitative rating of medial temporal lobe atrophy (MTA). Outcome measures were Alzheimer type dementia or cognitive decline at follow up. Delayed recall was tested with a verbal learning test. RESULTS: Ten patients had experienced cognitive decline at follow up, of whom seven had probable Alzheimer type dementia. All medial temporal lobe measurements were associated with cognitive decline at follow up (p trend analysis between 0.001 (hippocampus) and 0.05 (parahippocampal gyrus)). Only the hippocampal volume and MTA score were associated with Alzheimer type dementia at follow up (p trend analysis respectively 0.003 and 0.01). All medial temporal lobe measurements increased the predictive accuracy of age and the delayed recall score for cognitive decline (p increase in predictive accuracy varied between <0.001 (hippocampus) and 0.02 (parahippocampal gyrus and MTA score)) and the hippocampal volume and the MTA score increased the predictive accuracy of age and the delayed recall score for Alzheimer type dementia (p= 0.02). CONCLUSIONS: The ability to detect patients at high risk for Alzheimer type dementia among those with minor cognitive impairment increases when data on age and memory function are combined with measures of medial temporal lobe atrophy. Volumetry of the hippocampus is preferred, but qualitative rating of medial temporal lobe atrophy is a good alternative.     

Callosal atrophy correlates with temporal lobe volume and mental status in Alzheimer's disease

BACKGROUND: Recent studies have reported significant atrophy of the corpus callosum (CC) in Alzheimer's Disease (AD). However, it is currently unknown whether CC atrophy is associated with specific cortical volume changes in AD. Moreover, possible atrophy in extra-callosal commissures has not been examined to date. The purpose of the present study was to quantify atrophy in two cerebral commissures [the CC and the anterior commissure (AC)], to correlate this measure with cognitive status, and to relate commissural size to independent measures of temporal lobe volume in AD patients. METHODS: A sample of AD patients and of age- and education-matched normal control subjects (NCs) underwent MRI and a cognitive test battery including the Dementia Rating Scale and Mini Mental State examination. Mid-sagittal regional areas within CC and AC were measured along with superior, middle and inferior temporal lobes volumes. RESULTS: Alzheimer's Disease patients had significantly smaller callosa than did NCs. The callosal regions most affected in AD included the midbody, isthmus and genu. The isthmus and midbody areas of the CC were positively correlated with cognitive performance and with superior temporal lobe volume in AD patients. The mid-sagittal area of the AC and the superior temporal volumes did not differ between AD patients and NCs. CONCLUSIONS: The study demonstrated that the regional morphology of the CC correlates with current cognitive status and temporal lobe atrophy in AD. As well, the lack of difference for the AC suggests that commissural atrophy in AD is regionally specific.     

Blood-brain barrier permeability correlates with medial temporal lobe atrophy but not with amyloid-beta protein transport across the blood-brain barrier in Alzheimer's disease

BACKGROUND/AIMS: Alterations in the blood-brain barrier (BBB) may play an important role in the pathogenesis and treatment of Alzheimer's disease (AD). We investigated BBB disturbance and its influence on the equilibrium of amyloid-beta protein (Abeta) between plasma and cerebrospinal fluid (CSF) in AD patients. METHODS: We analyzed albumin ratio as a marker of the BBB permeability and correlated it with the severity of dementia, brain atrophy on MRI, apolipoprotein E isoform, CSF levels of total tau, CSF and plasma levels of Abeta 1-40 (Abeta40) and 1-42 (Abeta42), and CSF/plasma ratios of Abeta40 and Abeta42 in 42 AD patients. RESULTS: The albumin ratio was positively correlated with the severity of medial temporal lobe atrophy but not with the other parameters including CSF/plasma ratios of Abeta40 or Abeta42. CONCLUSION: Our results suggest that progression of medial temporal lobe atrophy is associated with increased BBB permeability and that the transport of Abeta across the BBB is not influenced by the BBB alteration in AD.     

A comparative study of the different N-acetylaspartate measures of the medial temporal lobe in Alzheimer's disease

OBJECTIVE: To investigate group differences and correlations and to determine the sensitivity and specificity of different measures of the neuronal marker N-acetylaspartate (NAA) in the medial temporal lobe of Alzheimer's Disease (AD) patients. METHODS: The metabolic ratio NAA/creatine (Cr), the absolute concentration of NAA referenced against brain tissue (BT) water and NAA multiplied with the amount of BT in the proton magnetic resonance spectroscopy (1H-MRS) voxel were assessed in patients and healthy controls with a single-voxel 1H-MRS protocol. RESULTS: All measures were significantly lower in AD patients compared with controls. NAA/Cr and NAA correlated weakly, and there was no correlation of NAA with the amount of BT in the voxel. The highest specificity (87%) at a sensitivity of 80% was observed for NAA multiplied with the amount of BT in the voxel. There was no correlation of the MMSE with any of the NAA parameters. Conclusions: NAA/Cr does not reflect NAA concentration very well. NAA is not correlated with brain atrophy. The BT volume in the 1H-MRS voxel in combination with the concentration of NAA discriminates AD from healthy controls sufficiently.     

False positives to confusable objects predict medial temporal lobe atrophy

Animal models agree that the perirhinal cortex plays a critical role in object recognition memory, but qualitative aspects of this mnemonic function are still debated. A recent model claims that the perirhinal cortex is required to recognize the novelty of confusable distractor stimuli, and that damage here results in an increased propensity to judge confusable novel objects as familiar (i.e., false positives). We tested this model in healthy participants and patients with varying degrees of perirhinal cortex damage, i.e., amnestic mild cognitive impairment and very early Alzheimer's disease (AD), with a recognition memory task with confusable and less confusable realistic object pictures, and from whom we acquired high‐resolution anatomic MRI scans. Logistic mixed‐model behavioral analyses revealed that both patient groups committed more false positives with confusable than less confusable distractors, whereas healthy participants performed comparably in both conditions. A voxel‐based morphometry analysis demonstrated that this effect was associated with atrophy of the anteromedial temporal lobe, including the perirhinal cortex. These findings suggest that also the human perirhinal cortex recognizes the novelty of confusable objects, consistent with its border position between the hierarchical visual object processing and medial temporal lobe memory systems, and explains why AD patients exhibit a heightened propensity to commit false positive responses with inherently confusable stimuli. © The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

High resolution imaging of the medial temporal lobe in Alzheimer's disease and dementia with Lewy bodies

We used high resolution (0.3 mm in-plane) coronal 3T magnetic resonance (MR) imaging of the medial temporal lobe in 16 subjects with Alzheimer's disease (AD), 16 with dementia with Lewy bodies (DLB), and 16 similarly aged healthy subjects. On the anterior section of the hippocampus body, regions of interest were manually drawn blind to diagnosis on the CA1, CA2, and CA3/4 subregions, and the width of the subiculum and entorhinal cortex was measured. Controlling for intracranial volume, age, and years of education, we found the subiculum thickness was significantly reduced in AD (2.03 ± 0.29 mm) compared to both control (2.37 ± 0.28 mm, p = 0.008) and DLB (2.35 ± 0.24 mm, p = 0.001) subjects. The area of CA1 was likewise reduced in AD compared to controls and DLB. In the hippocampus images, a hypointense line is visible between CA1 and CA3/4. This line was significantly less distinct in AD, suggesting disease related changes to this region. Future studies should investigate whether subiculum thickness or the hypointense line could be a diagnostic feature to help discriminate AD from DLB.