The A/T/N biomarker scheme and patterns of brain atrophy assessed in mild cognitive impairment

A hierarchical clustering algorithm was applied to magnetic resonance images (MRI) of a cohort of 751 subjects having a mild cognitive impairment (MCI), 282 subjects having received Alzheimer’s disease (AD) diagnosis, and 428 normal controls (NC). MRIs were preprocessed to gray matter density maps and registered to a stereotactic space. By first rendering the gray matter density maps comparable by regressing out age, gender, and years of education, and then performing the hierarchical clustering, we found clusters displaying structural features of typical AD, cortically-driven atypical AD, limbic-predominant AD, and early-onset AD (EOAD). Among these clusters, EOAD subjects displayed marked cortical gray matter atrophy and atrophy of the precuneus. Furthermore, EOAD subjects had the highest progression rates as measured with ADAS slopes during the longitudinal follow-up of 36 months. Striking heterogeneities in brain atrophy patterns were observed with MCI subjects. We found clusters of stable MCI, clusters of diffuse brain atrophy with fast progression, and MCI subjects displaying similar atrophy patterns as the typical or atypical AD subjects. Bidirectional differences in structural phenotypes were found with MCI subjects involving the anterior cerebellum and the frontal cortex. The diversity of the MCI subjects suggests that the structural phenotypes of MCI subjects would deserve a more detailed investigation with a significantly larger cohort. Our results demonstrate that the hierarchical agglomerative clustering method is an efficient tool in dividing a cohort of subjects with gray matter atrophy into coherent clusters manifesting different structural phenotypes.

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Frontal White Matter Hyperintensity Is Associated with Verbal Aggressiveness in Elderly Women with Alzheimer Disease and Amnestic Mild Cognitive Impairment

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000486826 ◽

2018 ◽

Vol 8 (1) ◽

pp. 138-150 ◽

Cited By ~ 5

Author(s):

Noriko Ogama ◽

Takashi Sakurai ◽

Naoki Saji ◽

Toshiharu Nakai ◽

Shumpei Niida ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

White Matter ◽

Alzheimer Disease ◽

Frontal Lobe ◽

Brain Atrophy ◽

Amnestic Mild Cognitive Impairment ◽

White Matter Hyperintensity ◽

Verbal Aggressiveness ◽

The Impact

Background/Aims: Behavioral and psychological symptoms of dementia (BPSD) are exhibited in most patients with Alzheimer disease (AD). Although white matter hyperintensity (WMH) is often observed with AD, the precise role of WMH in BPSD remains unclear. The current study aimed to identify the impact of regional WMH on specific features of BPSD in persons with mild to moderate AD and amnestic mild cognitive impairment (aMCI). Methods: A sample of 256 female outpatients with AD (n = 217) and aMCI (n = 39) were recruited. We assessed BPSD using the Dementia Behavior Disturbance Scale. WMH and brain atrophy were evaluated using an automatic segmentation program. Regional WMH was evaluated as periventricular hyperintensity (PVH) and deep WMH in frontal, temporal, occipital, and parietal lobes. Results: Whole-brain WMH was associated with verbal aggressiveness. In multivariate analysis, PVH in the frontal lobe was independently associated with verbal aggressiveness after adjustment for brain atrophy and clinical confounders. Conclusion: The current results indicated that PVH in the frontal lobe was independently associated with verbal aggressiveness.

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Multivariate deformation-based analysis of brain atrophy to predict Alzheimer's disease in mild cognitive impairment

NeuroImage ◽

10.1016/j.neuroimage.2007.07.008 ◽

2007 ◽

Vol 38 (1) ◽

pp. 13-24 ◽

Cited By ~ 128

Author(s):

Stefan J. Teipel ◽

Christine Born ◽

Michael Ewers ◽

Arun L.W. Bokde ◽

Maximilian F. Reiser ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Brain Atrophy

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IC-P-050: Depression predicts progressive brain atrophy in mild cognitive impairment

Alzheimer s & Dementia ◽

10.1016/j.jalz.2011.05.119 ◽

2011 ◽

Vol 7 ◽

pp. S28-S29

Author(s):

Grace Lee ◽

Po-Haong Lu ◽

Xue Hua ◽

Suh Lee ◽

Alex Leow ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Brain Atrophy

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Surgery and Brain Atrophy in Cognitively Normal Elderly Subjects and Subjects Diagnosed with Mild Cognitive Impairment

Anesthesiology ◽

10.1097/aln.0b013e318246ec0b ◽

2012 ◽

Vol 116 (3) ◽

pp. 603-612 ◽

Cited By ~ 44

Author(s):

Richard P. Kline ◽

Elizabeth Pirraglia ◽

Hao Cheng ◽

Susan De Santi ◽

Yi Li ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Magnetic Resonance ◽

San Francisco ◽

Brain Atrophy ◽

Surgical Patients ◽

Elderly Subjects ◽

Resonance Imaging ◽

Regional Brain

Background Structural magnetic resonance imaging is used to longitudinally monitor the progression of Alzheimer disease from its presymptomatic to symptomatic phases. Using magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative, we tested the hypothesis that surgery would impact brain parameters associated with progression of dementia. Methods Brain images from the neuroimaging initiative database were used to study normal volunteer subjects and patients with mild cognitive impairment for the age group 55 to 90 inclusive. We compared changes in regional brain anatomy for three visits that defined two intervisit intervals for a surgical cohort (n = 41) and a propensity matched nonsurgical control cohort (n = 123). The first interval for the surgical cohort contained the surgical date. Regional brain volumes were determined with Freesurfer and quantitatively described with J-image software (University of California at San Francisco, San Francisco, California). Statistical analysis used Repeated Measures ANCOVA (SPSS, v.18.0; Chicago, IL). Results We found that surgical patients, during the first follow-up interval (5-9 months), but not subsequently, had increased rates of atrophy for cortical gray matter and hippocampus, and lateral ventricle enlargement, as compared with nonsurgical controls. A composite score of five cognitive tests during this interval showed reduced performance for surgical patients with mild cognitive impairment. Conclusions Elderly subjects after surgery experienced an increased rate of brain atrophy during the initial evaluation interval, a time associated with enhanced risk for postoperative cognitive dysfunction. Although there was no difference in atrophy rate by diagnosis, subjects with mild cognitive impairment suffered greater subsequent cognitive effects.

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Five-year outcomes after IVIG for mild cognitive impairment due to alzheimer disease

BMC Neuroscience ◽

10.1186/s12868-021-00651-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shawn Kile ◽

William Au ◽

Carol Parise ◽

Kimberley Rose ◽

Tammy Donnel ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Alzheimer Disease ◽

Brain Atrophy ◽

Ventricular Volume ◽

Cognitive Testing ◽

Percent Change ◽

Dosing Strategies ◽

One Year ◽

Double Blinded

Abstract Background The purpose of this study was to assess the five-year treatment effects of a short course of intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) due to Alzheimer disease (AD). Methods Fifty subjects 50 to 84 years of age with MCI due to AD were administered 0.4 g/kg 10% IVIG or 0.9% saline every two weeks x five doses in a randomized double-blinded design as part of a two-year study. Twenty-seven subjects completed an additional three-year extension study. MRI brain imaging, cognitive testing, and conversion to dementia were assessed annually. Participants were stratified into early MCI (E-MCI) and late MCI (L-MCI). The primary endpoint was brain atrophy measured as annualized percent change in ventricular volume (APCV) annually for five years. ANOVA was used to compare annualized percent change in ventricular volume from baseline between the groups adjusting for MCI status (E-MCI, L-MCI). Results Differences in brain atrophy between the groups, which were statistically significant after one year, were no longer significant after five years. IVIG-treated L-MCI subjects did demonstrate a delay in conversion to dementia of 21.4 weeks. Conclusion An eight-week course of IVIG totaling 2 g/kg in MCI is safe but is not sufficient to sustain an initial reduction in brain atrophy or a temporary delay in conversion to dementia at five years. Other dosing strategies of IVIG in the early stages of AD should be investigated to assess more sustainable disease-modifying effects. Trial registration ClinicalTrials.gov NCT01300728. Registered 23 February 2011.

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