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1.
medRxiv ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38798527

ABSTRACT

INTRODUCTION: We conducted a study within the Hispanic Community Health Study/Study of Latinos- Investigation of Neurocognitive Aging (HCHS/SOL-INCA) cohort to examine the association between gut microbiome and cognitive function. METHODS: We analyzed the fecal metagenomes of 2,471 HCHS/SOL-INCA participants to, cross-sectionally, identify microbial taxonomic and functional features associated with global cognitive function. Omnibus (PERMANOVA) and feature-wise analyses (MaAsLin2) were conducted to identify microbiome-cognition associations, and specific microbial species and pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG modules) associated with cognition. RESULTS: Eubacterium species( E. siraeum and E. eligens ), were associated with better cognition. Several KEGG modules, most strongly Ornithine, Serine biosynthesis and Urea Cycle, were associated with worse cognition. DISCUSSION: In a large Hispanic/Latino cohort, we identified several microbial taxa and KEGG pathways associated with cognition.

2.
J Neurol Neurosurg Psychiatry ; 95(1): 44-51, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-37558399

ABSTRACT

OBJECTIVES: Alzheimer's disease (AD) is characterised by amyloid-beta accumulation (A), tau aggregation (T) and neurodegeneration (N). Vascular (V) burden has been found concomitantly with AD pathology and has synergistic effects on cognitive decline with AD biomarkers. We determined whether cognitive trajectories of AT(N) categories differed according to vascular (V) burden. METHODS: We prospectively recruited 205 participants and classified them into groups based on the AT(N) system using neuroimaging markers. Abnormal V markers were identified based on the presence of severe white matter hyperintensities. RESULTS: In A+ category, compared with the frequency of Alzheimer's pathological change category (A+T-), the frequency of AD category (A+T+) was significantly lower in V+ group (31.8%) than in V- group (64.4%) (p=0.004). Each AT(N) biomarker was predictive of cognitive decline in the V+ group as well as in the V- group (p<0.001). Additionally, the V+ group showed more severe cognitive trajectories than the V- group in the non-Alzheimer's pathological changes (A-T+, A-N+; p=0.002) and Alzheimer's pathological changes (p<0.001) categories. CONCLUSION: The distribution and longitudinal outcomes of AT(N) system differed according to vascular burdens, suggesting the importance of incorporating a V biomarker into the AT(N) system.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/pathology , Amyloid beta-Peptides , Neuroimaging/methods , Cognitive Dysfunction/complications , Biomarkers , tau Proteins
3.
Alzheimers Dement ; 2022 Jun 29.
Article in English | MEDLINE | ID: mdl-35768339

ABSTRACT

INTRODUCTION: Epidemiological studies report an association between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and clinically diagnosed Alzheimer's disease (AD). We examined the association between TBI/PTSD and biomarker-defined AD. METHODS: We identified 289 non-demented veterans with TBI and/or PTSD and controls who underwent clinical evaluation, cerebrospinal fluid (CSF) collection, magnetic resonance imaging (MRI), amyloid beta (Aß) and tau positron emission tomography, and apolipoprotein E testing. Participants were followed for up to 5.2 years. RESULTS: Exposure groups (TBI, PTSD, and TBI + PTSD) had higher prevalence of mild cognitive impairment (MCI: P < .0001) and worse Mini-Mental State Examination scores (PTSD: P = .008; TBI & PTSD: P = .009) than controls. There were no significant differences in other cognitive scores, MRI volumes, Aß or tau accumulation, or in most longitudinal measures. DISCUSSION: TBI and/or PTSD were not associated with elevated AD biomarkers. The poorer cognitive status of exposed veterans may be due to other comorbid pathologies.

4.
Geroscience ; 42(1): 81-96, 2020 02.
Article in English | MEDLINE | ID: mdl-31811528

ABSTRACT

This third in a series of vascular cognitive impairment (VCI) workshops, supported by "The Leo and Anne Albert Charitable Trust," was held from February 8 to 12 at the Omni Resort in Carlsbad, CA. This workshop followed the information gathered from the earlier two workshops suggesting that we focus more specifically on brain white matter in age-related cognitive impairment. The Scientific Program Committee (Frank Barone, Shawn Whitehead, Eric Smith, and Rod Corriveau) assembled translational, clinical, and basic scientists with unique expertise in acute and chronic white matter injury at the intersection of cerebrovascular and neurodegenerative etiologies. As in previous Albert Trust workshops, invited participants addressed key topics related to mechanisms of white matter injury, biomarkers of white matter injury, and interventions to prevent white matter injury and age-related cognitive decline. This report provides a synopsis of the presentations and discussions by the participants, including the existing knowledge gaps and the delineation of the next steps towards advancing our understanding of white matter injury and age-related cognitive decline. Workshop discussions and consensus resulted in action by The Albert Trust to (1) increase support from biannual to annual "White Matter and Cognition" workshops; (2) provide funding for two collaborative, novel research grants annually submitted by meeting participants; and (3) coordinate the formation of the "Albert Research Institute for White Matter and Cognition." This institute will fill a gap in white matter science, providing white matter and cognition communications, including annual updates from workshops and the literature and interconnecting with other Albert Trust scientific endeavors in cognition and dementia, and providing support for newly established collaborations between seasoned investigators and to the development of talented young investigators in the VCI-dementia (VCID) and white matter cognition arena.


Subject(s)
Cognitive Dysfunction , Dementia, Vascular , White Matter , Aging , Cognition , Humans
5.
Acta Neuropathol ; 134(3): 459-473, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28638989

ABSTRACT

Cerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer's disease (AD) pathology, i.e. hyperphosphorylated tau (HPτ) and amyloid-beta (Aß) deposition. WML seen in AD have a posterior predominance compared to non-demented individuals but it is unclear whether the pathological and molecular signatures of WML differ between these two groups. We investigated differences in the composition and aetiology of parietal WML from AD and non-demented controls. Parietal WML tissue from 55 human post-mortem brains (AD, n = 27; non-demented controls, n = 28) were quantitatively assessed for axonal loss and demyelination, as well as for cortical HPτ and Aß burden and SVD. Biochemical assessment included Wallerian degeneration protease calpain and the myelin-associated glycoprotein (MAG) to proteolipid protein (PLP) ratio (MAG:PLP) as a measure of hypoperfusion. WML severity was associated with both axonal loss and demyelination in AD, but only with demyelination in controls. Calpain was significantly increased in WML tissue in AD, whereas MAG:PLP was significantly reduced in controls. Calpain levels were associated with increasing amounts of cortical AD-pathology but not SVD. We conclude that parietal WML seen in AD differ in their pathological composition and aetiology compared to WML seen in aged controls: WML seen in AD may be associated with Wallerian degeneration that is triggered by cortical AD-pathology, whereas WML in aged controls are due to ischaemia. Hence, parietal WML as seen on MRI should not invariably be interpreted as a surrogate biomarker for SVD as they may be indicative of cortical AD-pathology, and therefore, AD should also be considered as the main underlying cause for cognitive impairment in cases with parietal WML.


Subject(s)
Alzheimer Disease/pathology , Cerebral Small Vessel Diseases/pathology , Nerve Degeneration/pathology , Parietal Lobe/pathology , White Matter/pathology , Aged , Aged, 80 and over , Alzheimer Disease/complications , Cerebral Small Vessel Diseases/complications , Female , Humans , Male , Nerve Degeneration/complications
6.
J Alzheimers Dis ; 19(3): 859-71, 2010.
Article in English | MEDLINE | ID: mdl-20157242

ABSTRACT

We tested the hypothesis that global functional coupling of resting cortical electroencephalographic (EEG) rhythms is abnormal in amnesic mild cognitive impairment (MCI) patients with remarkable lesions along the cholinergic white-matter tracts. We used the eyes-closed resting EEG data (10-20 montage) of the same groups of 28 healthy elderly (Nold) and 57 MCI subjects of a previous reference study. The estimation of the cholinergic lesion was performed with a validated semi-automatic algorithm based on fluid-attenuated inversion recovery sequences on MRI. The MCI patients were divided into groups of high (MCI+; n=28) and low (MCI-; n=29) cholinergic damage. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30- 40 Hz). The global functional coupling of the EEG rhythms was indexed computing the spectral coherence between each electrode and the other 18 electrodes ("electrode" coherence) and then averaging the "electrode" coherence of all 19 electrodes (total coherence). Total coherence of alpha1 rhythms was highest in the Nold, intermediate in the MCI-, and lowest in the MCI+ groups. Furthermore, the alpha1 total coherence was negatively correlated to (moderate to high) cholinergic lesion across the MCI subjects. In conclusion, damage to the cholinergic system is associated with alterations of the functional global coupling of resting alpha rhythms.


Subject(s)
Amnesia , Brain/anatomy & histology , Brain/physiopathology , Cognition Disorders , Electroencephalography , Receptors, Cholinergic/physiology , Aged , Algorithms , Amnesia/diagnosis , Amnesia/epidemiology , Amnesia/physiopathology , Brain/pathology , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Cognition Disorders/physiopathology , Female , Humans , Magnetic Resonance Imaging , Male , Nerve Degeneration/metabolism , Nerve Degeneration/pathology , Nerve Degeneration/physiopathology , Neuropsychological Tests , Severity of Illness Index
7.
Hum Brain Mapp ; 30(5): 1431-43, 2009 May.
Article in English | MEDLINE | ID: mdl-19097164

ABSTRACT

Does impairment of cholinergic systems represent an important factor in the development of amnesic mild cognitive impairment (aMCI), as a preclinical stage of Alzheimer's disease (AD)? Here we tested the hypothesis that electroencephalographic (EEG) rhythms, known to be modulated by the cholinergic system, may be particularly affected in aMCI patients with lesions along the cholinergic white-matter tracts. Eyes-closed resting EEG data were recorded in 28 healthy elderly (Nold) and 57 aMCI patients. Lesions along the cholinergic white-matter tracts were detected with fluid-attenuated inversion recovery sequences on magnetic resonance imaging. The estimation of the cholinergic lesion was performed with a validated semi-automatic algorithm pipeline after registration to a stereotactic template, image integration with stereotactic masks of the cholinergic tracts, and normalization to intracranial volume. The aMCI patients were divided into two groups of high (MCI Ch+; N = 29; MMSE = 26.2) and low cholinergic damage (MCI Ch-; N = 28; MMSE = 26.6). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG generators were estimated by LORETA software. As main results, (i) power of occipital, parietal, temporal, and limbic alpha 1 sources was maximum in Nold, intermediate in MCI Ch-, and low in MCI Ch+ patients; (ii) the same trend was true in theta sources. These results are consistent with the hypothesis that damage to the cholinergic system is associated with alterations of EEG sources in aMCI subjects.


Subject(s)
Acetylcholine/metabolism , Alpha Rhythm , Amnesia/pathology , Cerebral Cortex , Cognition Disorders/pathology , Aged , Amnesia/complications , Analysis of Variance , Brain Mapping , Cerebral Cortex/injuries , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Cognition Disorders/complications , Female , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/pathology , Neuropsychological Tests , Spectrum Analysis
8.
J Alzheimers Dis ; 15(3): 357-72, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18997289

ABSTRACT

We evaluated changes of brain rhythmicity correlating with the cerebrovascular damage of long-range (capsular tract) and short-range (medial and perisylvian tracts) cholinergic pathways in subjects with mild cognitive impairment (MCI). Ninety-four MCI subjects underwent electroencephalographic (EEG) recordings and magnetic resonance imaging (MRI). The EEG relative power spectrum was computed in delta, theta, alpha1, alpha2, alpha3, beta1, beta2, gamma frequency bands. White matter hyperintensities along each cholinergic tract was segmented on MRI. Three MCI subgroups were identified based on increasing damage. A significant increase of delta and theta power band was found in patients with the highest total cholinergic burden as well as in patients with highest capsular pathway damage; total load of cholinergic damage was also associated with decreased gamma power band. Alpha frequency was differentially affected: decrease of alpha3 power band was associated with the greatest damage of the capsular pathway whereas increase of alpha3 power band was associated with the greatest damage of the perisylvian pathway. Multiple regression linear analysis showed independent association of cholinergic damage with delta, theta and gamma frequency, not with alpha frequency. In conclusion, the damage of long-range and short range cholinergic tracts has possible different implications for cognitive functions in MCI subjects.


Subject(s)
Autonomic Pathways/blood supply , Autonomic Pathways/pathology , Cerebrovascular Disorders/pathology , Cognition Disorders/pathology , Electroencephalography , Parasympathetic Nervous System/blood supply , Parasympathetic Nervous System/pathology , Aged , Cerebrovascular Circulation/physiology , Data Interpretation, Statistical , Female , Hippocampus/pathology , Humans , Image Processing, Computer-Assisted , Male , Models, Statistical , Neuropsychological Tests , Prospective Studies , Regression Analysis
9.
Lancet Neurol ; 1(1): 13-21, 2002 May.
Article in English | MEDLINE | ID: mdl-12849541

ABSTRACT

Neuroimaging is increasingly used to aid diagnosis in dementia. The traditional view that imaging is important solely as means of excluding treatable causes of dementia is maintained by many guidelines. These conditions however, account for a tiny proportion (<1%) of all causes of dementia. Over the past few years it has been recognised that a more accurate diagnosis and prognosis is important for patients and their families. The different pathological processes that produce cerebral dysfunction at a cellular level also produce macroscopic effects that can be detected in vivo with imaging. Clinically useful measures that distinguish between neurodegenerative disorders at an early stage are still awaited. The most likely future use of structural imaging will be the identification of patients at risk for Alzheimer's disease or with preclinical Alzheimer's disease. For magnetic resonance imaging (MRI) this will mean focusing on those areas that are affected earliest in the disease; ie, entorhinal cortex and hippocampus, using high resolution structural MRI or sophisticated brain mapping techniques. Imaging research is also likely to focus on measuring progression and detecting therapeutic effect. As such, MRI is already become an indispensable tool in clinical trials in dementia.


Subject(s)
Brain/pathology , Dementia/diagnosis , Magnetic Resonance Imaging/methods , Humans , Magnetic Resonance Imaging/trends
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