Your search for: 'author:("Lowe, Val J.")' has returned 21 results. (0.038s) Save search

Authors: Josephs, Kennedy A. | Pham, Nha Trang Thu | Graff-Radford, Jonathan | Machulda, Mary M. | Lowe, Val J. | Whitwell, Jennifer L.

Article Type: Research Article

Abstract: Background: It has been hypothesized that medial temporal sparing may be related to preserved posterior cingulate metabolism and the cingulate island sign (CIS) on [18 F]fluorodeoxyglucose (FDG) PET in posterior cortical atrophy (PCA). Objective: To assess the severity of medial temporal atrophy in PCA and determine whether the presence of a CIS is related to medial temporal sparing. Methods: Fifty-five PCA patients underwent MRI and FDG-PET. The degree and symmetry of medial temporal atrophy on MRI was visually assessed using a five-point scale for both hemispheres. Visual assessments of FDG-PET coded the presence/absence of a CIS and whether the CIS …was symmetric or asymmetric. Hippocampal volumes and a quantitative CIS were also measured. Results: Medial temporal atrophy was most commonly mild or moderate, was symmetric in 55% of patients, and when asymmetric was most commonly worse on the right (76%). Older age and worse memory performance were associated with greater medial temporal atrophy. The CIS was observed in 44% of the PCA patients and was asymmetric in 50% of these. The patients with a CIS showed greater medial temporal asymmetry, but did not show lower medial temporal atrophy scores, compared to those without a CIS. Hippocampal volumes were not associated with quantitative CIS. Conclusion: Mild medial temporal atrophy is a common finding in PCA and is associated with memory impairment. However, medial temporal sparing was not related to the presence of a CIS in PCA. Show more

Keywords: Cingulate island sign, FDG-PET, hippocampus, MRI, visual assessment

DOI: 10.3233/JAD-215263

Citation: Journal of Alzheimer's Disease, vol. 86, no. 1, pp. 491-498, 2022

Authors: Jayachandran, Muthuvel | Miller, Virginia M. | Lahr, Brian D. | Bailey, Kent R. | Lowe, Val J. | Fields, Julie A. | Mielke, Michelle M. | Kantarci, Kejal

Article Type: Research Article

Abstract: Background: The identification of blood-borne biomarkers for the diagnosis and prognosis of Alzheimer’s disease and related dementias is more feasible at the population level than obtaining cerebrospinal fluid or neuroimaging markers. Objective: This study determined the association of blood microvesicles, derived from cells of the neurovascular unit, with brain amyloid-β deposition in menopausal women. Methods: A subset of women from the Kronos Early Estrogen Prevention Study underwent brain amyloid-β positron emission tomography three years following cessation of study treatment with placebo (PL, n  = 29), transdermal 17β-estradiol (tE2; n  = 21), or oral conjugated equine estrogen (oCEE; n  = 17). Isolated peripheral venous …blood microvesicles were analyzed by digital flow cytometry using fluorophore conjugated antibodies directed toward total tau, amyloid-β 1–42 (Aβ1–42 ), neuron specific class III β-tubulin (Tuj1), microglia ionized calcium -binding adaptor molecule 1(Iba1), glial fibrillary acid protein (GFAP), and low density lipoprotein receptor-related protein1 (LRP1). Principal components analysis reduced the dimensionality of these selected six markers to two principal components (PCs). Proportional odds ordinal logistic regression analysis was used with amyloid-β deposition regressed on these PCs. Results: Only the number of microvesicles positive for Aβ1–42 differed statistically among prior treatment groups (median [IQR]: 6.06 [2.11, 12.55] in PL; 2.49 [0.73, 3.59] in tE2; and 4.96 [0.83, 10.31] in oCEE; p  = 0.032). The joint association between the 2 PCs and brain amyloid-β deposition was significant (p  = 0.045). Conclusion: Six selected markers expressing peripheral blood microvesicles derived from cells of the neurovascular unit, when summarized into two principal components, were associated with brain amyloid-β deposition. Show more

Keywords: Alzheimer’s disease, 17β-estradiol, conjugated equine estrogen, extracellular vesicles, KEEPS, PET imaging

DOI: 10.3233/JAD-201410

Citation: Journal of Alzheimer's Disease, vol. 80, no. 1, pp. 397-405, 2021

Authors: Schwarz, Christopher G. | Gunter, Jeffrey L. | Lowe, Val J. | Weigand, Stephen | Vemuri, Prashanthi | Senjem, Matthew L. | Petersen, Ronald C. | Knopman, David S. | Jack Jr, Clifford R.

Article Type: Research Article

Abstract: Longitudinal PET studies in aging and Alzheimer’s disease populations rely on accurate and precise measurements of change over time from serial PET scans. Various methods for partial volume correction (PVC) are commonly applied to such studies, but existing comparisons and validations of these PVC methods have focused on cross-sectional measurements. Rate of change measurements inherently have smaller magnitudes than cross-sectional measurements, so levels of noise amplification due to PVC must be smaller, and it is necessary to re-evaluate methods in this context. Here we compare the relative precision in longitudinal measurements from serial amyloid PET scans when using geometric transfer …matrix (GTM) PVC versus the traditional two-compartment (Meltzer-style), three-compartment (Müller-Gärtner-style), and no-PVC approaches. We used two independent implementations of standardized uptake value ratio (SUVR) measurement and PVC (one in-house pipeline based on SPM12 and ANTs, and one using FreeSurfer 6.0). For each approach, we also tested longitudinal-specific variants. Overall, we found that measurements using GTM PVC had significantly worse relative precision (unexplained within-subject variability ≈4–8%) than those using two-compartment, three-compartment, or no PVC (≈2–4%). Longitudinally-stabilized approaches did not improve these properties. This data suggests that GTM PVC methods may be less suitable than traditional approaches when measuring within-person change over time in longitudinal amyloid PET. Show more

Keywords: Amyloid PET, change over time, geometric transfer matrix, partial volume correction, Pittsburgh Compound B, precision, SUVR

DOI: 10.3233/JAD-180749

Citation: Journal of Alzheimer's Disease, vol. 67, no. 1, pp. 181-195, 2019

Authors: Zhou, Andrew L. | Sharda, Nidhi | Sarma, Vidur V. | Ahlschwede, Kristen M. | Curran, Geoffry L. | Tang, Xiaojia | Poduslo, Joseph F. | Kalari, Krishna R. | Lowe, Val J. | Kandimalla, Karunya K.

Article Type: Research Article

Abstract: Background: Age is the most common risk factor for Alzheimer’s disease (AD), a neurodegenerative disorder characterized by the hallmarks of toxic amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles. Moreover, sub-physiological brain insulin levels have emerged as a pathological manifestation of AD. Objective: Identify age-related changes in the plasma disposition and blood-brain barrier (BBB) trafficking of Aβ peptides and insulin in mice. Methods: Upon systemic injection of 125 I-Aβ40 , 125 I-Aβ42 , or 125 I-insulin, the plasma pharmacokinetics and brain influx were assessed in wild-type (WT) or AD transgenic (APP/PS1) mice at various ages. Additionally, publicly available single-cell RNA-Seq data …[GSE129788] was employed to investigate pathways regulating BBB transport in WT mice at different ages. Results: The brain influx of 125 I-Aβ40 , estimated as the permeability-surface area product, decreased with age, accompanied by an increase in plasma AUC. In contrast, the brain influx of 125 I-Aβ42 increased with age, accompanied by a decrease in plasma AUC. The age-dependent changes observed in WT mice were accelerated in APP/PS1 mice. As seen with 125 I-Aβ40 , the brain influx of 125 I-insulin decreased with age in WT mice, accompanied by an increase in plasma AUC. This finding was further supported by dynamic single-photon emission computed tomography (SPECT/CT) imaging studies. RAGE and PI3K/AKT signaling pathways at the BBB, which are implicated in Aβ and insulin transcytosis, respectively, were upregulated with age in WT mice, indicating BBB insulin resistance. Conclusion: Aging differentially affects the plasma pharmacokinetics and brain influx of Aβ isoforms and insulin in a manner that could potentially augment AD risk. Show more

Keywords: Aging, amyloid-β, blood-brain barrier, insulin, pharmacokinetics

DOI: 10.3233/JAD-215128

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1031-1044, 2022

Authors: Schwarz, Christopher G. | Knopman, David S. | Ramanan, Vijay K. | Lowe, Val J. | Wiste, Heather J. | Cogswell, Petrice M. | Utianski, Rene L. | Senjem, Matthew L. | Gunter, Jeffrey R. | Vemuri, Prashanthi | Petersen, Ronald C. | Jack Jr., Clifford R.

Article Type: Short Communication

Abstract: We present the case of a cognitively unimpaired 77-year-old man with elevated, asymmetric, and longitudinally increasing Flortaucipir tau PET despite normal (visually negative) amyloid PET. His atypical tau PET signal persisted and globally increased in a follow-up scan five years later. Across eight years of observations, temporoparietal atrophy was observed consistent with tau PET patterns, but he retained the cognitively unimpaired classification. Altogether, his atypical tau PET signal is not explained by any known risk factors or alternative pathologies, and other imaging findings were not remarkable. He remains enrolled for further observation.

Keywords: Alzheimer’s disease, AV-1451, case reports, Flortaucipir, PET imaging, tau proteins

DOI: 10.3233/JAD-215052

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 59-64, 2022

Authors: Tetzloff, Katerina A. | Duffy, Joseph R. | Clark, Heather M. | Pham, Nha Trang Thu | Machulda, Mary M. | Botha, Hugo | Jack Jr., Clifford R. | Dickson, Dennis W. | Lowe, Val J. | Josephs, Keith A. | Whitwell, Jennifer L. | Utianski, Rene L.

Article Type: Research Article

Abstract: Background: The agrammatic variant of primary progressive aphasia (PAA), primary progressive apraxia of speech (PPAOS), or a combination of both (AOS-PAA) are neurodegenerative disorders characterized by speech-language impairments and together compose the AOS-PAA spectrum disorders. These patients typically have an underlying 4-repeat tauopathy, although they sometimes show evidence of amyloid-β and tau deposition on PET, suggesting Alzheimer’s disease (AD). Given the growing number of pharmacologic treatment options for AD, it is important to better understand the incidence of AD pathology in these patients. Objective: This study aimed to evaluate the frequency of amyloid-β and tau positivity in AOS-PAA spectrum disorders. …Sixty-five patients with AOS-PAA underwent a clinical speech-language battery and PiB PET and flortaucipir PET imaging. Methods: Global PiB PET standardized uptake value ratios (SUVRs) and flortaucipir PET SUVRs from the temporal meta region of interest were compared between patient groups. For 19 patients who had died and undergone autopsy, their PET and pathology findings were also compared. Results: The results showed that although roughly half of the patients are positive for at least one biomarker, their clinical symptoms and biomarker status were not related, suggesting that AD is not the primary cause of their neurodegeneration. All but one patient in the autopsy subset had a Braak stage of IV or less, despite four being positive on tau PET imaging. Conclusions: Inclusion criteria for clinical trials should specify clinical presentation or adjust the evaluation of such treatments to be specific to disease diagnosis beyond the presence of certain imaging biomarkers. Show more

Keywords: Alzheimer’s disease, biomarkers, amyloid-β protein, tau protein

DOI: 10.3233/JAD-230912

Citation: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1759-1765, 2023

Authors: Ramanan, Vijay K. | Przybelski, Scott A. | Graff-Radford, Jonathan | Castillo, Anna M. | Lowe, Val J. | Mielke, Michelle M. | Roberts, Rosebud O. | Reid, Robert I. | Knopman, David S. | Jack Jr., Clifford R. | Petersen, Ronald C. | Vemuri, Prashanthi

Article Type: Research Article

Abstract: Background: Statins have been proposed to reduce the risk of Alzheimer’s disease (AD). Objective: Assess whether long-term statin use was associated with neuroimaging biomarkers of aging and dementia. Methods: Methods: We analyzed neuroimaging biomarkers in 1,160 individuals aged 65+ from the Mayo Clinic Study of Aging, a population-based prospective longitudinal study of cognitive aging. Results: Statin-treated (5+ years of therapy) individuals had greater burden of mid-and late-life cardiovascular disease (p  < 0.001) than statin-untreated (≤3 months) individuals. Lower fractional anisotropy in the genu of the corpus callosum, an early marker of cerebrovascular disease, was associated with long-term statin exposure (p  < 0.035). …No significant associations were identified between long-term statin exposure and cerebral amyloid or tau burden, AD pattern neurodegeneration, or white matter hyperintensity burden. Conclusions: Long-term statin therapy was not associated with differences in AD biomarkers. Individuals with long-term statin exposure had worse white matter integrity in the genu of the corpus callosum, consistent with the coexistence of higher cerebrovascular risk factor burden in this group. Show more

Keywords: Alzheimer’s disease, amyloid, neurodegeneration, cerebrovascular disease, biomarkers, magnetic resonance imaging, positron emission tomography, statins, tau, white matter

DOI: 10.3233/JAD-180446

Citation: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1345-1352, 2018

Authors: Kantarci, Kejal | Lowe, Val J. | Lesnick, Timothy G. | Tosakulwong, Nirubol | Bailey, Kent R. | Fields, Julie A. | Shuster, Lynne T. | Zuk, Samantha M. | Senjem, Matthew L. | Mielke, Michelle M. | Gleason, Carey | Jack Jr, Clifford R. | Rocca, Walter A. | Miller, Virginia M.

Article Type: Research Article

Abstract: Background: It remains controversial whether hormone therapy in recently postmenopausal women modifies the risk of Alzheimer’s disease (AD). Objective: To investigate the effects of hormone therapy on amyloid-β deposition in recently postmenopausal women. Methods: Participants within 5–36 months past menopause in the Kronos Early Estrogen Prevention Study, a randomized, double blinded placebo-controlled clinical trial, were randomized to: 1) 0.45 mg/day oral conjugated equine estrogens (CEE); 2) 50μg/day transdermal 17β-estradiol; or 3) placebo pills and patch for four years. Oral progesterone (200 mg/day) was given to active treatment groups for 12 days each month. 11 C Pittsburgh compound B (PiB) PET imaging was …performed in 68 of the 118 participants at Mayo Clinic approximately seven years post randomization and three years after stopping randomized treatment. PiB Standard unit value ratio (SUVR) was calculated. Results: Women (age = 52–65) randomized to transdermal 17β-estradiol (n  = 21) had lower PiB SUVR compared to placebo (n  = 30) after adjusting for age [odds ratio (95% CI) = 0.31(0.11–0.83)]. In the APOE ɛ 4 carriers, transdermal 17β-estradiol treated women (n  = 10) had lower PiB SUVR compared to either placebo (n  = 5) [odds ratio (95% CI) = 0.04(0.004–0.44)], or the oral CEE treated group (n  = 3) [odds ratio (95% CI) = 0.01(0.0006–0.23)] after adjusting for age. Hormone therapy was not associated with PiB SUVR in the APOE ɛ 4 non-carriers. Conclusion: In this pilot study, transdermal 17β-estradiol therapy in recently postmenopausal women was associated with a reduced amyloid-β deposition, particularly in APOE ɛ 4 carriers. This finding may have important implications for the prevention of AD in postmenopausal women, and needs to be confirmed in a larger sample. Show more

Keywords: Alzheimer’s disease, amyloid-β, cognitive function, estrogen, hormone therapy, menopause, PET, prevention

DOI: 10.3233/JAD-160258

Citation: Journal of Alzheimer's Disease, vol. 53, no. 2, pp. 547-556, 2016

Authors: Krishnan, Kamini | Machulda, Mary M. | Whitwell, Jennifer L. | Butts, Alissa M. | Duffy, Joseph R. | Strand, Edythe A. | Senjem, Matthew L. | Spychalla, Anthony J. | Jack Jr., Clifford R. | Lowe, Val J. | Josephs, Keith A.

Article Type: Research Article

Abstract: Background: The logopenic variant of primary progressive aphasia (lvPPA) manifests due to a breakdown of the language network with prominent hypometabolism of the left temporoparietal region. LvPPA is strongly associated with amyloid deposition, yet there is question as to whether it is a homogeneous clinical entity. Objective: This study investigated whether differences in temporoparietal metabolic patterns on 18 F fludeoxyglucose positron emission tomography (FDG-PET) could elucidate brain regions preferentially affected in lvPPA. Method: We used differences in FDG-PET metabolic z-scores relative to controls for means of left lateral temporal, left inferior parietal, and left superior parietal regions to classify 53 amyloid-positive lvPPA …patients into temporal, parietal, or temporoparietal predominate groups. Clinical features and FDG-PET regions of hypometabolism outside of the temporoparietal region were then compared across the three groups; the latter using statistical parametric mapping. Results: Of the 53 lvPPA patients, 15 were classified as temporal, 14 as temporoparietal, and 22 as parietal predominate. There were no significant differences between the groups on demographic measures, language evaluation, or apolipoprotein E genotype. Compared to the other two groups, individuals with the parietal predominate pattern had extensive hypometabolism in left frontal lobe and the precuneus. Furthermore, this group had greater behavioral dyscontrol and deficits in executive function, visuospatial skills, visual memory retention, working memory, and cognitive flexibility (Bonferronip  < 0.05). Conclusions: This study demonstrates that there is clinical heterogeneity within amyloid-positive lvPPA. Patients with lvPPA with predominant parietal hypometabolism, unlike those with temporal or temporoparietal predominant hypometabolism, demonstrated widespread cognitive and behavioral changes. Show more

Keywords: Amyloid-β, executive function, 18F fludeoxyglucose, positron emission tomography, primary progressiveaphasia, visuospatial deficit, working memory

DOI: 10.3233/JAD-160614

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 1019-1029, 2017

Authors: Krell-Roesch, Janina | Ruider, Hanna | Lowe, Val J. | Stokin, Gorazd B. | Pink, Anna | Roberts, Rosebud O. | Mielke, Michelle M. | Knopman, David S. | Christianson, Teresa J. | Machulda, Mary M. | Jack, Clifford R. | Petersen, Ronald C. | Geda, Yonas E.

Article Type: Research Article

Abstract: One of the key research agenda of the field of aging is investigation of presymptomatic Alzheimer’s disease (AD). Furthermore, abnormalities in brain glucose metabolism (as measured by FDG-PET) have been reported among cognitively normal elderly persons. However, little is known about the association of FDG-PET abnormalities with neuropsychiatric symptoms (NPS) in a population-based setting. Thus, we conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging in order to examine the association between brain glucose metabolism and NPS among cognitively normal (CN) persons aged > 70 years. Participants underwent FDG-PET and completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), Beck …Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Cognitive classification was made by an expert consensus panel. We conducted multivariable logistic regression analyses to compute odds ratios (OR) and 95% confidence intervals after adjusting for age, sex, and education. For continuous variables, we used linear regression and Spearman rank-order correlations. Of 668 CN participants (median 78.1 years, 55.4% males), 205 had an abnormal FDG-PET (i.e., standardized uptake value ratio < 1.32 in AD-related regions). Abnormal FDG-PET was associated with depression as measured by NPI-Q (OR = 2.12; 1.23–3.64); the point estimate was further elevated for APOE ɛ 4 carriers (OR = 2.59; 1.00–6.69), though marginally significant. Additionally, we observed a significant association between abnormal FDG-PET and depressive and anxiety symptoms when treated as continuous measures. These findings indicate that NPS, even in community-based samples, can be an important additional tool to the biomarker-based investigation of presymptomatic AD. Show more

Keywords: Agitation, Alzheimer’s disease, anxiety, apathy, cognitively normal persons, depression, FDG-PET, neuroimaging, neuropsychiatric symptoms

DOI: 10.3233/JAD-160326

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1609-1616, 2016