Quantitative MRI Brain Studies in Mild Cognitive Impairment and Alzheimer's disease: A Methodological Review

Classifying and predicting Alzheimer's disease (AD) in individuals with memory disorders through clinical and psychometric assessment is challenging especially in Mild Cognitive Impairment (MCI) subjects. Quantitative structural Magnetic Resonance Imaging (MRI) acquisition methods in combination with Computer-Aided Diagnosis (CAD) are currently being used for the assessment AD. These acquisitions methods include: i) Voxel-based Morphometry (VBM), ii) volumetric measurements in specific Regions of Interest (ROIs), iii) cortical thickness measurements, iv) shape analysis and v) texture analysis. This review evaluates the aforementioned methods in the classification of cases into one of the following 3 groups: Normal Controls (NC), MCI and AD subjects. Furthermore, the performance of the methods is assessed on the prediction of conversion from MCI to AD. In parallel, it is also assessed which ROIs are preferred in both classification and prognosis through the different states of the disease. Structural changes in the early stages of the disease are more pronounced in the Medial Temporal Lobe (MTL) especially in the entorhinal cortex, whereas with disease progression both entorhinal cortex and hippocampus offer similar discriminative power. However, for the conversion from MCI subjects to AD, entorhinal cortex provides better predictive accuracies rather than other structures, such as the hippocampus

Magnetic resonance imaging In Alzheimer’s disease, mild cognitive impairment and normal aging : Multi-template tensor-based morphometry and visual rating

Alzheimer's disease (AD) is the most common neurodegenerative disease preceded by a stage of mild cognitive impairment (MCI). The structural brain changes in AD can be detected more than 20 years before symptoms appear. If we are to reveal early brain changes in AD process, it is important to develop new diagnostic methods. Magnetic resonance imaging (MRI) is an imaging technique used in the diagnosis and monitoring of neurodegenerative diseases. Magnetic resonance imaging can detect the typical signs of brain atrophy of degenerative diseases, but similar changes can also be seen in normal aging. Visual rating methods (VRM) have been developed for visual evaluation of atrophy in dementia. A computer-based tensor-based morphometry (TBM) analysis is capable of assessing the brain volume changes typically encountered in AD. This study compared the VRM and TBM analysis in MCI and AD subjects by cross-sectional and longitudinal examination. The working hypothesis was that TBM analysis would be better than the visual methods in detecting atrophy in the brain. TBM was also used to analyze volume changes in the deep gray matter (DGM). Possible associations between TBM changes and neuropsychological tests performances were examined. This working hypothesis was that the structural DGM changes would be associated with impairments in cognitive functions. In the cross-sectional study, TBM distinguished the MCI from controls more sensitively than VRM, but the methods were equally effective in differentiating AD from MCI and controls. In the longitudinal study, both methods were equally good in the evaluation of atrophy in MCI, if the groups were sufficiently large and the disease progressed to AD. Volume changes were found in DGM structures, and the atrophy of DGM structures was related to cognitive impairment in AD. Based on these results, a TBM analysis is more sensitive in detecting brain changes in early AD as compared to VRM. In addition, the study produced information about the involvement of the deep gray matter in cognitive impairment in AD.Magneettikuvaus Alzheimerin taudissa, lievässä muistihäiriössä ja normaalissa ikääntymisessä: Tensoripohjainen muotoanalyysi ja visuaalinen arviointimenetelmä Alzheimerin tauti (AT) on yleisin dementoiva sairaus, jota edeltää yleensä lievä muistitoimintojen heikentyminen. AT:n aivomuutoksia voidaan todeta yli 20 vuotta ennen sairastumista. Jotta vielä varhaisempia AT:n aivomuutoksia voidaan todeta, on tärkeää kehittää uusia diagnostisia menetelmiä. Magneettikuvausta (MK) käytetään rappeuttavien aivosairauksien diagnostiikassa ja seurannassa. MK:lla voidaan havaita aivorappeumasairauksille tyypillistä kutistumista, mutta samanlaisia muutoksia voi esiintyä myös normaalissa ikääntymisessä. Aivorappeuman arviointiin on kehitetty silmämääräisiä arviointimenetelmiä. Tietokoneperusteinen tensoripohjainen muotoanalyysi (TPM) laskee esimerkiksi AT:lle tyypillisiä aivojen tilavuusmuutoksia. Tämä tutkimus vertaili silmämääräisiä arvioitimenetelmiä ja TPM:ä lievässä muistitoimintojen heikentymisessä ja AT:ssa poikittais- ja pitkittäistutkimuksella. TPM:n oletettiin olevan silmämääräisiä menetelmiä parempi tunnistamaan aivojen kutistumismuutoksia. Lisäksi TPM:llä tutkittiin AT:iin liittyviä aivojen syvän harmaan aiheen muutoksia, joita verrattiin neuropsykologisten testien tuloksiin. Syvän harmaan aineen kutistumisen oletettiin olevan yhteydessä tietojenkäsittelyn heikentymiseen. Tulosten perustella TPM tunnisti AT:iin liittyviä aivomuutoksia silmämääräistä menetelmää paremmin jo lievän muistitoimintojen heikentymisen vaiheessa. AT:iin liittyviä aivomuutoksia löytyi myös aivojen syvästä harmaasta aineesta ja ne olivat osittain yhteydessä neuropsykologisten testien tuloksiin. Tutkimuksen perusteella TPM voi parantaa AT:n varhaisdiagnostiikkaa verrattuna silmämääräisiin arviointimenetelmiin. Tutkimus antoi myös tietoa aivojen syvän harmaan aineen osallisuudesta ihmisen tietojenkäsittelyyn

Comparison of prefrontal atrophy and episodic memory performance in dysexecutive Alzheimer’s disease and behavioural-variant frontotemporal dementia

Alzheimer’s disease (AD) sometimes presents with prominent executive dysfunction and associated prefrontal cortex atrophy. The impact of such executive deficits on episodic memory performance as well as their neural correlates in AD, however, remains unclear. The aim of the current study was to investigate episodic memory and brain atrophy in AD patients with relatively spared executive functioning (SEF-AD; n = 12) and AD patients with relatively impaired executive functioning (IEF-AD; n = 23). We also compared the AD subgroups with a group of behavioral-variant frontotemporal dementia patients (bvFTD; n = 22), who typically exhibit significant executive deficits, and age-matched healthy controls (n = 38). On cognitive testing, the three patient groups showed comparable memory profiles on standard episodic memory tests, with significant impairment relative to controls. Voxel-based morphometry analyses revealed extensive prefrontal and medial temporal lobe atrophy in IEF-AD and bvFTD, whereas this was limited to the middle frontal gyrus and hippocampus in SEF-AD. Moreover, the additional prefrontal atrophy in IEF-AD and bvFTD correlated with memory performance, whereas this was not the case for SEF-AD. These findings indicate that IEF-AD patients show prefrontal atrophy in regions similar to bvFTD, and suggest that this contributes to episodic memory performance. This has implications for the differential diagnosis of bvFTD and subtypes of AD

Rates of lobar atrophy in asymptomatic MAPT mutation carriers.

IntroductionThe aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.MethodsMAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.ResultsThe rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.DiscussionAccelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers

Brain Alterations and Mini-Mental State Examination in Patients with Progressive Supranuclear Palsy: Voxel-Based Investigations Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Magnetic Resonance Imaging

Background/Aims: The aim of this study was to compare differences in morphological and functional changes in brain regions in individual patients with progressive supranuclear palsy (PSP) and correlate their Mini-Mental State Examination (MMSE) score with anatomy and function using magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: Sixteen PSP patients and 20 age-matched healthy volunteers underwent FDG-PET and 3-dimensional MRI. Gray matter, white matter and metabolic activity were compared between patients and normal controls. In addition, possible correlations between the MMSE score and brain function/anatomy were examined. Results: The PSP group had reduced cerebral glucose metabolism, and lower gray and white matter volumes in the frontal lobes and midbrain compared with normal controls. In PSP subjects, the metabolic changes observed in the PET scans were greater than the loss in gray and white matter observed in the MRI scans. The MMSE scores were positively correlated with volume and FDG uptake in the frontal lobe. Conclusion: FDG-PET is a more effective tool in the diagnosis of PSP than MRI. Atrophy and hypometabolism in the frontal lobe are as important as in the basal midbrain for differentiating PSP patients who primarily exhibit cognitive dysfunction from normal controls

MRI Morphometry of the Brain and Neurological Diseases

The diagnosis of diseases of the brain is based on additional methods, confirming the clinical diagnosis. One of the most objective methods is magnetic resonance imaging (MRI). A detailed quantitative evaluation became possible after the introduction of MRI voxel‐morphometry–statistical analysis of structural MRI images using a computerized segmentation matter of the brain gray and white matter. The decrease in the volume of the brain, as a manifestation of cerebral atrophy, is a common feature of many neurological diseases. We performed a study of brain structures in multiple sclerosis, Parkinson’s disease, and cerebrovascular diseases. In patients with multiple sclerosis the correlation was found between the score on a scale of Expanded Disability Status Scale and the total thickness of the cerebral cortex. In our study of the brain in Parkinson’s disease, the amount of the substantia nigra was slightly lower than in the control. In patients with long‐following Parkinson’s disease, the volume of substantia nigra was significantly higher than in patients with early stage. The increased volume was determined by the accumulation of organic iron compounds as a sign of neurodegeneration

Atrophy in Alzheimer’s disease and semantic dementia : an ALE meta-analysis of voxel-based morphometry studies

Background/Objectives: Alzheimer’s disease (AD) and semantic dementia (SD) have distinct episodic memory profiles despite the hippocampal atrophy that characterizes both diseases. The aim of this study was to delineate the pattern of gray matter (GM) atrophy associated with AD and SD as well as any differences in these patterns by pooling together the results of previous voxel-based morphometry (VBM) studies. Methods/Overview: We conducted a meta-analysis of VBM studies that investigated GM atrophy in AD patients versus controls (CTRLs) and in SD patients versus CTRLs using the activation likelihood estimation (ALE) approach. Our systematic review allowed us to identify 63 VBM studies. Results: The results confirmed that in addition to the classical cortical pattern of atrophy involving posterior medial and lateral regions in AD and the anterior lateral temporal lobes in SD, both AD and SD patients are characterized by bilateral atrophy of the hippocampus. Furthermore, in SD, the hippocampal atrophy was limited to the anterior portion of the hippocampus, while in AD, both the anterior and posterior parts of the hippocampus exhibited atrophy. When we compared the foci identified in the studies that compared AD patients versus CTRLs with those identified in the studies that compared SD patients versus CTRLs, we observed that the atrophy in the posterior hippocampus and precuneus was more severe in AD. Conclusion: These results support theories that propose that the deficits observed in AD result from damage to the episodic memory network, which involves the posterior hippocampus and posterior medial brain regions. However, sparing of the posterior hippocampus in SD could explain the absence of episodic memory deficits in this population

Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine