Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, ...sex and gender have not yet been adequately integrated into many of these approaches.
The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD.
The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research.
The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.
With the use of publicly available software, reconstructed facial images from deidentified cranial MRI scans were matched to photographs of individual study participants 83% of the time as the first ...choice from a panel of photographs. This raises the possibility of identifying anonymous research participants.
Preeclampsia and cognitive impairment later in life Fields, Julie A., PhD; Garovic, Vesna D., MD; Mielke, Michelle M., PhD ...
American journal of obstetrics and gynecology,
07/2017, Letnik:
217, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background Hypertension is a risk factor for cerebrovascular disease and cognitive impairment. Women with hypertensive episodes during pregnancy report variable neurocognitive changes within the ...first decade following the affected pregnancy. However, long-term follow-up of these women into their postmenopausal years has not been conducted. Objective The aim of this study was to examine whether women with a history of preeclampsia were at increased risk of cognitive decline 35-40 years after the affected pregnancy. Study Design Women were identified and recruited through the medical linkage, population-based Rochester Epidemiologic Project. Forty women with a history of preeclampsia were age- and parity-matched to 40 women with a history of normotensive pregnancy. All women underwent comprehensive neuropsychological assessment and completed self-report inventories measuring mood, ie, depression, anxiety, and other symptoms related to emotional state. Scores were compared between groups. In addition, individual cognitive scores were examined by neuropsychologists and a neurologist blinded to pregnancy status, and a clinical consensus diagnosis of normal, mild cognitive impairment, or dementia for each participant was conferred. Results Age at time of consent did not differ between preeclampsia (59.2 range 50.9-71.5 years) and normotensive (59.6 range 52.1-72.2 years) groups, nor did time from index pregnancy (34.9 range 32.0-47.2 vs 34.5 range 32.0-46.4 years, respectively). There were no statistically significant differences in raw scores on tests of cognition and mood between women with histories of preeclampsia compared to women with histories of normotensive pregnancy. However, a consensus diagnosis of mild cognitive impairment or dementia trended toward greater frequency in women with histories of preeclampsia compared to those with normotensive pregnancies (20% vs 8%, P = .10) and affected more domains among the preeclampsia group ( P = .03), most strongly related to executive dysfunction ( d = 1.96) and verbal list learning impairment ( d = 1.93). Conclusion These findings suggest a trend for women with a history of preeclampsia to exhibit more cognitive impairment later in life than those with a history of normotensive pregnancy. Furthermore, the pattern of cognitive changes is consistent with that observed with vascular disease/white matter pathology.
Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder characterized by behavioral changes, language abnormality, as well as executive function deficits and motor impairment. In ...about 30-50% of FTLD patients, an autosomal dominant pattern of inheritance was found with major mutations in the
, and the
repeat expansion. These mutations could lead to neurodegenerative pathology years before clinical symptoms onset. With potential disease-modifying treatments that are under development, non-invasive biomarkers that help determine the early brain changes in presymptomatic FTLD patients will be critical for tracking disease progression and enrolling the right participants into the clinical trials at the right time during the disease course. In recent years, there is increasing evidence that a number of imaging biomarkers show the abnormalities during the presymptomatic stage. Imaging biomarkers of presymptomatic familial FTLD may provide insight into the underlying neurodegenerative process years before symptom onset. Structural magnetic resonance imaging (MRI) has demonstrated cortical degeneration with a mutation-specific neurodegeneration pattern years before onset of clinical symptoms in presymptomatic familial FTLD mutation carriers. In addition, diffusion tensor imaging (DTI) has shown the loss of white matter microstructural integrity in the presymptomatic stage of familial FTLD. Furthermore, proton magnetic resonance spectroscopy (
H MRS), which provides a non-invasive measurement of brain biochemistry, has identified early neurochemical abnormalities in presymptomatic
mutation carriers. Positron emission tomography (PET) imaging with
F-fluorodeoxyglucose (FDG) has demonstrated the glucose hypometabolism in the presymptomatic stage of familial FTLD. Also, a novel PET ligand,
F-AV-1451, has been used in this group to evaluate tau deposition in the brain. Promising imaging biomarkers for presymptomatic familial FTLD have been identified and assessed for specificity and sensitivity for accurate prediction of symptom onset and tracking disease progression during the presymptomatic stage when clinical measures are not useful. Furthermore, identifying imaging biomarkers for the presymptomatic stage is important for the design of disease-modifying trials. We review the recent progress in imaging biomarkers of the presymptomatic phase of familial FTLD and discuss the imaging techniques and analysis methods, with a focus on the potential implication of these imaging techniques and their utility in specific mutation types.
Abstract Introduction Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness. Methods We examined five ...methods for determining cut points. Results The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age-matched CN method labeled fewer people abnormal. Discussion In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age-matched CN method.
Objective:
A workgroup commissioned by the Alzheimer's Association (AA) and the National Institute on Aging (NIA) recently published research criteria for preclinical Alzheimer disease (AD). We ...performed a preliminary assessment of these guidelines.
Methods:
We employed Pittsburgh compound B positron emission tomography (PET) imaging as our biomarker of cerebral amyloidosis, and 18fluorodeoxyglucose PET imaging and hippocampal volume as biomarkers of neurodegeneration. A group of 42 clinically diagnosed AD subjects was used to create imaging biomarker cutpoints. A group of 450 cognitively normal (CN) subjects from a population‐based sample was used to develop cognitive cutpoints and to assess population frequencies of the different preclinical AD stages using different cutpoint criteria.
Results:
The new criteria subdivide the preclinical phase of AD into stages 1 to 3. To classify our CN subjects, 2 additional categories were needed. Stage 0 denotes subjects with normal AD biomarkers and no evidence of subtle cognitive impairment. Suspected non‐AD pathophysiology (SNAP) denotes subjects with normal amyloid PET imaging, but abnormal neurodegeneration biomarker studies. At fixed cutpoints corresponding to 90% sensitivity for diagnosing AD and the 10th percentile of CN cognitive scores, 43% of our sample was classified as stage 0, 16% stage 1, 12 % stage 2, 3% stage 3, and 23% SNAP.
Interpretation:
This cross‐sectional evaluation of the NIA‐AA criteria for preclinical AD indicates that the 1–3 staging criteria coupled with stage 0 and SNAP categories classify 97% of CN subjects from a population‐based sample, leaving only 3% unclassified. Future longitudinal validation of the criteria will be important ANN NEUROL 2012;
Development of radiopharmaceuticals for in vivo positron emission tomography imaging of alpha-synuclein aggregates has the potential to revolutionize Lewy body disease diagnosis and treatment. ...Reporting in this issue of Cell, Xiang et al. developed a high-affinity positron emission tomography tracer for alpha-synuclein.
Development of radiopharmaceuticals for in vivo positron emission tomography imaging of alpha-synuclein aggregates has the potential to revolutionize Lewy body disease diagnosis and treatment. Reporting in this issue of Cell, Xiang et al. developed a high-affinity positron emission tomography tracer for alpha-synuclein.
A reduction of CSF tau phosphorylated at threonine 217 (p-tau217) levels was observed in the treatment group compared with the placebo group, which was modulated by baseline p-tau217 levels, with ...those having higher p-tau217 at baseline responding better.4 After decades of research and development of biomarkers in the Alzheimer's disease field, biomarkers are now having a substantial impact on the development of disease-modifying therapies.5 Biomarkers were central to the approval process of aducanumab, and are being used in other phase 2 studies for patient selection and assessment of target engagement and treatment efficacy. Both plasma p-tau217 and p-tau181 had an excellent diagnostic performance in differentiating patients with Alzheimer's disease dementia from other neurodegenerative disorders.6 In a cohort from the Swedish BioFINDER study, p-tau217 showed stronger correlations with amyloid-β and tau PET than other p-tau variants, as well as higher accuracy in separating Alzheimer's disease dementia from other dementias.7 In 2021, molecular imaging biomarkers also contributed to our understanding of disease mechanisms associated with microglial activation and tau spreading. The APOE3-Jacksonville variant was found to reduce APOE aggregation and enhance lipidation, which has important implications in the design of APOE-targeted therapies.10 Finally, in the fields of Lewy body dementia, frontotemporal dementia, and vascular cognitive impairment, multisite consortia across the world were building on the findings of the Alzheimer's Disease Neuroimaging Initiative.
Clinical trials with anti-tau drugs will need to target individuals at risk of accumulating tau. Our objective was to identify variables available in a research setting that predict future rates of ...tau PET accumulation separately among individuals who were either cognitively unimpaired or cognitively impaired. All 337 participants had: a baseline study visit with MRI, amyloid PET, and tau PET exams, at least one follow-up tau PET exam; and met clinical criteria for membership in one of two clinical diagnostic groups: cognitively unimpaired (n = 203); or cognitively impaired (n = 134, a combined group of participants with either mild cognitive impairment or dementia with Alzheimer's clinical syndrome). Our primary analyses were in these two clinical groups; however, we also evaluated subgroups dividing the unimpaired group by normal/abnormal amyloid PET and the impaired group by clinical phenotype (mild cognitive impairment, amnestic dementia, and non-amnestic dementia). Linear mixed effects models were used to estimate associations between age, sex, education, APOE genotype, amyloid and tau PET standardized uptake value ratio (SUVR), cognitive performance, cortical thickness, and white matter hyperintensity volume at baseline, and the rate of subsequent tau PET accumulation. Log-transformed tau PET SUVR was used as the response and rates were summarized as annual per cent change. A temporal lobe tau PET meta-region of interest was used. In the cognitively unimpaired group, only higher baseline amyloid PET was a significant independent predictor of higher tau accumulation rates (P < 0.001). Higher rates of tau accumulation were associated with faster rates of cognitive decline in the cognitively unimpaired subgroup with abnormal amyloid PET (P = 0.03), but among the subgroup with normal amyloid PET. In the cognitively impaired group, younger age (P = 0.02), higher baseline amyloid PET (P = 0.05), APOE ε4 (P = 0.05), and better cognitive performance (P = 0.05) were significant independent predictors of higher tau accumulation rates. Among impaired individuals, faster cognitive decline was associated with faster rates of tau accumulation (P = 0.01). While we examined many possible predictor variables, our results indicate that screening of unimpaired individuals for potential inclusion in anti-tau trials may be straightforward because the only independent predictor of high tau rates was amyloidosis. In cognitively impaired individuals, imaging and clinical variables consistent with early onset Alzheimer's disease phenotype were associated with higher rates of tau PET accumulation suggesting this may be a highly advantageous group in which to conduct proof-of-concept clinical trials that target tau-related mechanisms. The nature of the dementia phenotype (amnestic versus non-amnestic) did not affect this conclusion.
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