scholarly journals Brainstem Volumetric Integrity in Preclinical and Prodromal Alzheimer’s Disease

2020 ◽  
Vol 77 (4) ◽  
pp. 1579-1594 ◽  
Author(s):  
Shubir Dutt ◽  
Yanrong Li ◽  
Mara Mather ◽  
Daniel A. Nation ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Locus Coeruleus ◽  
Region Of Interest ◽  
Intracranial Volume ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Prodromal Ad ◽  
Brainstem Nuclei ◽  
Prodromal Alzheimer’S Disease

Background: Neuropathological studies have suggested the tau pathology observed in Alzheimer’s disease (AD) originates in brainstem nuclei, but no studies to date have quantified brainstem volumes in clinical populations with biomarker-confirmed mild cognitive impairment (MCI) or dementia due to AD or determined the value of brainstem volumetrics in predicting dementia. Objective: The present study examined whether MRI-based brainstem volumes differ among cognitively normal older adults and those with MCI or dementia due to AD and whether preclinical brainstem volumes predict future progression to dementia. Methods: Alzheimer’s Disease Neuroimaging Initiative participants (N = 1,629) underwent baseline MRI scanning with variable clinical follow-up (6–120 months). Region of interest and voxel-based morphometric methods assessed brainstem volume differences among cognitively normal (n = 814), MCI (n = 542), and AD (n = 273) participants, as well as subsets of cerebrospinal fluid biomarker-confirmed MCI (n = 203) and AD (n = 160) participants. Results: MCI and AD cases showed smaller midbrain volumes relative to cognitively normal participants when normalizing to whole brainstem volume, and showed smaller midbrain, locus coeruleus, pons, and whole brainstem volumes when normalizing to total intracranial volume. Cognitively normal individuals who later progressed to AD dementia diagnosis exhibited smaller baseline midbrain volumes than individuals who did not develop dementia, and voxel-wise analyses revealed specific volumetric reduction of the locus coeruleus. Conclusion: Findings are consistent with neuropathological observations of early AD-related pathology in brainstem nuclei and further suggest the clinical relevance of brainstem substructural volumes in preclinical and prodromal AD.

scholarly journals Brainstem substructures and cognition in prodromal Alzheimer’s disease

2021 ◽  
Author(s):  
Shubir Dutt ◽  
◽  
Yanrong Li ◽  
Mara Mather ◽  
Daniel A. Nation
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Locus Coeruleus ◽  
Carrier Status ◽  
Cognitively Normal ◽  
Brainstem Nuclei ◽  
Prodromal Alzheimer’S Disease ◽  
Executive Abilities

AbstractNeuropathological research suggests the tau pathology of Alzheimer’s disease may originate in brainstem nuclei, yet it remains unknown whether tau-mediated degeneration of brainstem nuclei influences cognitive impairment in prodromal Alzheimer’s disease. The present study examined cognitive domains impacted in prodromal Alzheimer’s disease and brainstem substructure volume in cognitively normal older adults (n = 814) and those with mild cognitive impairment (n = 542). Subsamples of cognitively normal (n = 112) and mild cognitive impairment (n = 202) also had cerebrospinal fluid Alzheimer’s disease biomarker characterization. Region-of-interest and voxel-level analyses related whole brainstem, midbrain, pons, and locus coeruleus volumes to cognition with multiple linear regression models corrected for age, sex, education, apolipoprotein-ε4 carrier status, and MRI magnet strength. Within mild cognitive impairment participants, smaller midbrain and locus coeruleus volumes were significantly related to poorer performance on tests of attention and executive function, and the relationship between locus coeruleus volume and executive abilities remained significant in the mild cognitive impairment subsample with biomarker-confirmed Alzheimer’s disease. A brainstem-masked voxel-wise regression further demonstrated an association between locus coeruleus volume and executive abilities. Brainstem volumes were not significantly related to memory processes. Study findings implicate midbrain and locus coeruleus volume in attention and executive deficits in mild cognitive impairment. Together with prior neuropathological studies, our data suggest a link between Alzheimer’s disease-related degeneration of brainstem nuclei and cognitive deficits in prodromal Alzheimer’s disease.

Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

2021 ◽  
pp. 1-11
Author(s):  
Fennie Choy Chin Wong ◽  
Seyed Ehsan Saffari ◽  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Nagaendran Kandiah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Intracranial Volume ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

scholarly journals Pre‐amyloid stage of Alzheimer's disease in cognitively normal individuals

2018 ◽  
Vol 5 (9) ◽  
pp. 1037-1047 ◽  
Author(s):  
Betty M. Tijms ◽  
Lisa Vermunt ◽  
Marissa D. Zwan ◽  
Argonde C. Harten ◽  
Wiesje M. Flier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitively Normal ◽  
Normal Individuals

scholarly journals Psychometric Properties of the Clinical Dementia Rating – Sum of Boxes and Other Cognitive and Functional Outcomes in a Prodromal Alzheimer’s Disease Population

2020 ◽  
pp. 1-10
Author(s):  
F. McDougall ◽  
C. Edgar ◽  
M. Mertes ◽  
P. Delmar ◽  
P. Fontoura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Psychometric Properties ◽  
Disease Assessment ◽  
Clinical Dementia Rating ◽  
Prodromal Ad ◽  
Ceiling Effects ◽  
Prodromal Alzheimer’S Disease ◽  
Selective Reminding Test

BACKGROUND: The Clinical Dementia Rating–Sum of Boxes (CDR-SB) has been proposed as a primary outcome for use in prodromal AD trials. However, the psychometric properties of this, and of other commonly used measures, have not been well-established in this patient population. OBJECTIVE: To describe the psychometric properties of commonly used efficacy measures in a clinical trial of prodromal AD. SETTING: Data were gathered as part of a two-year clinical trial. PARTICIPANTS: Patients had biomarker confirmed prodromal AD. MEASUREMENTS: Clinical Dementia Rating (CDR), Functional Activities Questionnaire (FAQ), Alzheimer’s Disease Assessment Scale – Cognition Subscale 11 and 13 (ADAS-Cog), Mini Mental State Exam (MMSE), and Free and Cued Selective Reminding Test (FCSRT-IR [words]). Assessments were conducted at least every 24 weeks. RESULTS: For the CDR-SB, test-retest reliability was good (intra-class correlation coefficient [ICC]=0.83); internal consistency was 0.65 at baseline but above 0.8 at later assessments. Relationships between the CDR-SB and other measures were as expected (higher correlations with more closely related constructs), and the CDR-SB differentiated between patients with different severities of dementia (-2.9 points difference between CDR-Global Score 0.5 and 1, P<.0001). Floor and ceiling effects on the CDR-SB total score were minimal; however, at baseline there were ceiling effects in the personal care domain. Further detail is provided on the psychometric properties of ADAS-Cog, MMSE, FCSRT-IR and FAQ in this population. CONCLUSION: The psychometric properties of the CDR-SB are adequate in prodromal AD and continued use is warranted in clinical trials. However, there remains scope for improvement in the assessment of functional constructs and development of novel measures should continue.

scholarly journals Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease

2019 ◽  
Vol 15 (6) ◽  
pp. 764-775 ◽  
Author(s):  
Andrea Vergallo ◽  
Lucile Mégret ◽  
Simone Lista ◽  
Enrica Cavedo ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Amyloid Β ◽  
Cognitively Normal ◽  
Cerebral Amyloidosis ◽  
Normal Individuals

P1-438: NEUROPSYCHIATRIC BURDEN IS RELATED TO INCREASED AMYLOID BUT NOT TAU DEPOSITION IN LATE-MIDDLE- AGED COGNITIVELY NORMAL INDIVIDUALS WITH A FAMILY HISTORY OF ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_8) ◽  
pp. P478-P479
Author(s):  
Alexa Pichet Binette ◽  
Etienne Vachon-Presseau ◽  
Julie Gonneaud ◽  
Natalie L. Marchant ◽  
Pierre Bellec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family History ◽  
Middle Aged ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
History Of

scholarly journals Alzheimer’s disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea

SLEEP ◽  
2020 ◽  
Author(s):  
Jessica E Owen ◽  
Bryndis Benediktsdottir ◽  
Elizabeth Cook ◽  
Isleifur Olafsson ◽  
Thorarinn Gislason ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Memory Deficits ◽  
Hippocampal Volume ◽  
Plaque Burden ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Obstructive Sleep

Abstract Obstructive sleep apnea (OSA) involves intermittent cessations of breathing during sleep. People with OSA can experience memory deficits and have reduced hippocampal volume; these features are also characteristic of Alzheimer’s disease (AD), where they are accompanied by neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques in the hippocampus and brainstem. We have recently shown reduced hippocampal volume to be related to OSA severity, and although OSA may be a risk factor for AD, the hippocampus and brainstems of clinically verified OSA cases have not yet been examined for NFTs and Aβ plaques. The present study used quantitative immunohistochemistry to investigate postmortem hippocampi of 34 people with OSA (18 females, 16 males; mean age 67 years) and brainstems of 24 people with OSA for the presence of NFTs and Aβ plaques. OSA severity was a significant predictor of Aβ plaque burden in the hippocampus after controlling for age, sex, body mass index (BMI), and continuous positive airway pressure (CPAP) use. OSA severity also predicted NFT burden in the hippocampus, but not after controlling for age. Although 71% of brainstems contained NFTs and 21% contained Aβ plaques, their burdens were not correlated with OSA severity. These results indicate that OSA accounts for some of the “cognitively normal” individuals who have been found to have substantial Aβ burdens, and are currently considered to be at a prodromal stage of AD.

Development, Spanish Normative Data, and Validation of a Social Cognition Battery in Prodromal Alzheimer’s Disease and Multiple Sclerosis

2020 ◽  
Author(s):  
Alfonso Delgado-Álvarez ◽  
Vanesa Pytel ◽  
Cristina Delgado-Alonso ◽  
Carmen María Olbrich-Guzmán ◽  
Ana Cortés-Martínez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Cognition ◽  
Neuropsychological Tests ◽  
Normative Data ◽  
Reactivity Index ◽  
Cognitive Domains ◽  
Prodromal Ad ◽  
Prodromal Alzheimer’S Disease

Abstract Objectives The assessment of social cognition changes may be challenging, especially in the earliest stages of some neurodegenerative diseases. Our objective was to validate a social cognition battery from a multidomain perspective. In this regard, we aimed to adapt several tests, collect normative data, and validate them in prodromal Alzheimer’s disease (AD) and multiple sclerosis (MS). Methods A total of 92 healthy controls, 25 prodromal AD, and 39 MS patients were enrolled. Age-, gender-, and education-matched control groups were created for comparisons. Social cognition battery was composed of an emotion-labeling task developed from FACES database, the Story-based Empathy test (SET), the Faux Pas test, and the Interpersonal Reactivity Index. Patients were also evaluated with a comprehensive cognitive battery to evaluate the other cognitive domains. Automatic linear modeling was used to predict each social cognition test’s performance using the neuropsychological tests examining other cognitive domains. Results The reliability of the battery was moderate-high. Significant intergroup differences were found with medium-large effect sizes. Moderate correlations were found between social cognition battery and neuropsychological tests. The emotion labeling task and SET showed moderate correlations with age and education, and age, respectively. Regression-based norms were created considering the relevant demographic variables. Linear regression models including other neuropsychological tests explained between 7.7% and 68.8% of the variance of the social cognition tests performance. Conclusions Our study provides a battery for the assessment of social cognition in prodromal AD and MS with Spanish normative data to improve the evaluation in clinical and research settings.

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