Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 14 ( 2021-04-6), p. e1844-e1854
    Abstract: To determine whether a digital clock-drawing test, DCTclock, improves upon standard cognitive assessments for discriminating diagnostic groups and for detecting biomarker evidence of amyloid and tau pathology in clinically normal older adults (CN). Methods Participants from the Harvard Aging Brain Study and the PET laboratory at Massachusetts General Hospital were recruited to undergo the DCTclock, standard neuropsychological assessments including the Preclinical Alzheimer Cognitive Composite (PACC), and amyloid/tau PET imaging. Receiver operating curve analyses were used to assess diagnostic and biomarker discriminability. Logistic regression and partial correlations were used to assess DCTclock performance in relation to PACC and PET biomarkers. Results A total of 300 participants were studied. Among the 264 CN participants, 143 had amyloid and tau PET imaging (Clinical Dementia Rating [CDR] 0, Mini-Mental State Examination [MMSE] 28.9 ± 1.2). An additional 36 participants with a diagnosis of mild cognitive impairment or early Alzheimer dementia (CDR 0.5, MMSE 25.2 ± 3.9) were added to assess diagnostic discriminability. DCTclock showed excellent discrimination between diagnostic groups (area under the receiver operating characteristic curve 0.86). Among CN participants with biomarkers, the DCTclock summary score and spatial reasoning subscores were associated with greater amyloid and tau burden and showed better discrimination (Cohen d = 0.76) between Aβ± groups than the PACC (d = 0.30). Conclusion DCTclock discriminates between diagnostic groups and improves upon traditional cognitive tests for detecting biomarkers of amyloid and tau pathology in CN older adults. The validation of such digitized measures has the potential of providing an efficient tool for detecting early cognitive changes along the AD trajectory. Classification of Evidence This study provides Class II evidence that DCTclock results were associated with amyloid and tau burden in CN older adults.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S6 ( 2020-12)
    Abstract: Using a digital pen to record performance on neuropsychological tasks allows for the capture of much more subtle and nuanced aspects of cognitive performance. Previous research showed that lower DCTClock summary score was associated with greater entorhinal tau in clinically‐normal older adults (CN) (Rentz, AAIC 2019). Additionally, spatial reasoning was related to elevated entorhinal tau, inferior temporal tau, and neocortical amyloid. Given the observed cognitive heterogeneity in early stages of AD, we explored the relationship between different aspects of digital clock performance and amyloid and tau pathology across the cortical surface. Method CN from the Harvard Aging Brain Study completed both a spontaneous (COM) and copy (COP) clock drawing test using a digital pen. We used a summary score (DCTScore) and four main composite scores (drawing efficiency, simple motor, information processing and spatial reasoning) calculated by Digital Cognition Technologies. Participants also underwent [ 11 C]PiB‐PET (n = 112) and [ 18 F]T807‐PET (n = 116) acquisition within one year of cognitive testing. We utilized a vertex‐wise analysis with a cluster‐wise multiple comparison correction (minimum cluster extent=100mm 2 ) and a threshold of ‐log(p) 〉 2 to analyze relationships with clock scores across the vertices, adjusting for age, sex, and education. Result Lower DCTScore strongly correlated with greater amyloid signal in the frontal lobe, with some significant clusters also observed within the lateral temporal and inferior parietal cortices (Figure 1). Lower DCTScore also related to elevated tau signal in the right lateral temporal and inferior parietal lobes. Tau was most strongly associated with COM spatial reasoning score in the right lateral temporal lobe (Figure 2), reflecting known functional associations with this region; this was not reflected with COP spatial reasoning scores. Conclusion In clinically‐normal older adults, lower scores on clock drawing were associated with greater cortical amyloid and tau. Lower spatial reasoning scores were related to tauopathy, but only in spontaneous clock drawing, supporting the notion that more complex cognitive tasks are compromised earlier in the clinical continuum. More fine‐grained measurements of cognition using digital tasks in relation to neuroimaging markers has the potential to improve our understanding of the pathogenesis of early AD.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 24 ( 2021-06-15), p. e2933-e2943
    Abstract: To compare how structural MRI, fluorodeoxyglucose (FDG), and flortaucipir (FTP) PET signals predict cognitive decline in high-amyloid vs low-amyloid participants with the goal of determining which biomarker combination would result in the highest increase of statistical power for prevention trials. Methods In this prospective cohort study, we analyzed data from clinically normal adults from the Harvard Aging Brain Study with MRI, FDG, FTP, and Pittsburgh compound B (PiB)-PET acquired within a year and prospective cognitive evaluations over a mean 3-year follow-up. We focused analyses on predefined regions of interest: inferior temporal, isthmus cingulate, hippocampus, and entorhinal cortex. Cognition was assessed with the Preclinical Alzheimer's Cognitive Composite. We evaluated the association between biomarkers and cognitive decline using linear mixed-effect models with random intercepts and slopes, adjusting for demographics. We generated power curves simulating prevention trials. Results Data from 131 participants (52 women, age 73.98 ± 8.29 years) were analyzed in the study. In separate models, most biomarkers had a closer association with cognitive decline in the high-PiB compared to the low-PiB participants. A backward stepwise regression including all biomarkers demonstrated that only neocortical PiB, entorhinal FTP, and entorhinal FDG were independent predictors of subsequent cognitive decline. Power analyses revealed that using both high PiB and low entorhinal FDG as inclusion criteria reduced 3-fold the number of participants needed in a hypothetical trial compared to using only high PiB. Discussion In preclinical Alzheimer disease, entorhinal hypometabolism is a strong and independent predictor of subsequent cognitive decline, making FDG a potentially useful biomarker to increase power in clinical trials. Classification of Evidence This study provides Class II evidence that in people with preclinical Alzheimer disease, entorhinal hypometabolism identified by FDG-PET is predictive of subsequent cognitive decline.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 13 ( 2022-1-13)
    Abstract: Introduction: We investigated whether monthly assessments of a computerized cognitive composite (C3) could aid in the detection of differences in practice effects (PE) in clinically unimpaired (CU) older adults, and whether diminished PE were associated with Alzheimer's disease (AD) biomarkers and annual cognitive decline. Materials and Methods: N = 114 CU participants (age 77.6 ± 5.0, 61% female, MMSE 29 ± 1.2) from the Harvard Aging Brain Study completed the self-administered C3 monthly, at-home, on an iPad for one year. At baseline, participants underwent in-clinic Preclinical Alzheimer's Cognitive Composite-5 (PACC5) testing, and a subsample ( n = 72, age = 77.8 ± 4.9, 59% female, MMSE 29 ± 1.3) had 1-year follow-up in-clinic PACC5 testing available. Participants had undergone PIB-PET imaging (0.99 ± 1.6 years before at-home baseline) and Flortaucipir PET imaging ( n = 105, 0.62 ± 1.1 years before at-home baseline). Linear mixed models were used to investigate change over months on the C3 adjusting for age, sex, and years of education, and to extract individual covariate-adjusted slopes over the first 3 months. We investigated the association of 3-month C3 slopes with global amyloid burden and tau deposition in eight predefined regions of interest, and conducted Receiver Operating Characteristic analyses to examine how accurately 3-month C3 slopes could identify individuals that showed & gt;0.10 SD annual decline on the PACC-5. Results: Overall, individuals improved on all C3 measures over 12 months (β = 0.23, 95% CI [0.21–0.25], p & lt; 0.001), but improvement over the first 3 months was greatest (β = 0.68, 95% CI [0.59–0.77], p & lt; 0.001), suggesting stronger PE over initial repeated exposures. However, lower PE over 3 months were associated with more global amyloid burden ( r = −0.20, 95% CI [−0.38 – −0.01], p = 0.049) and tau deposition in the entorhinal cortex ( r = −0.38, 95% CI [−0.54 – −0.19], p & lt; 0.001) and inferior-temporal lobe ( r = −0.23, 95% CI [−0.41 – −0.02], p = 0.03). 3-month C3 slopes exhibited good discriminative ability to identify PACC-5 decliners (AUC 0.91, 95% CI [0.84–0.98]), which was better than baseline C3 ( p & lt; 0.001) and baseline PACC-5 scores ( p = 0.02). Conclusion: While PE are commonly observed among CU adults, diminished PE over monthly cognitive testing are associated with greater AD biomarker burden and cognitive decline. Our findings imply that unsupervised computerized testing using monthly retest paradigms can provide rapid detection of diminished PE indicative of future cognitive decline in preclinical AD.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2558898-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S4 ( 2020-12)
    Abstract: Recent work suggests regional tau burden is proximal to cortical thinning in clinically‐normal older adults. Clinically‐normal older females show higher levels of temporal tau burden than males, but it remains to be seen whether the association between tau pathology and cortical thinning is significantly impacted by biological sex. We hypothesized that females with higher tau burden would show faster cortical thinning than their male counterparts. Method 123 clinically‐normal older adults from the Harvard Aging Brain Study ( clinical dementia rating = 0; age (SD) = 73.6(6.1); female = 58%) underwent cross‐sectional Pittsburgh Compound‐B (PiB)‐PET, Flortaucipir (FTP)‐PET and longitudinal MRI (2.95 years; range = 1.3‐5.3 years post‐tau scan). FTP‐PET was introduced after onset of the study, so the first FTP‐PET scan was used as ‘baseline’. We selected temporal tau ROIs based on our previous results (HABS & ADNI) showing sex differences in tau signal (e.g. entorhinal, inferior temporal, fusiform, middle temporal). We conducted iterative linear mixed models examining the interaction of sex*time*tauROI on cortical thinning across 34 ROIs, covarying for baseline age*time. To assess the impact of PiB on this relationship, we also examined PiB+ and PiB− groups separately (based on HABS PiB DVR cut‐off = 1.186). Result Females with higher inferior temporal tau burden showed significantly faster cortical thinning than males in the entorhinal cortex only, t = −2.40, p = 0.02 (see Figure 1). This result was significant in the PiB+ group (n = 33: t = −2.28, p = 0.03), but not PiB− (n = 90: t = −1.60, p = 0.11), suggesting this relationship was driven by a sex effect in PiB+ individuals (see Figure 2). We also found a similar association using fusiform tau ( p = 0.03). Conclusion In the context of high inferior temporal tau burden, females exhibit significantly faster entorhinal cortical thinning than males. This result suggests that sex may moderate the effect of tau burden on cortical thinning, and for a given level of tau burden, females may be more susceptible to cortical atrophy in temporal lobe structures. We did not adjust for multiple comparisons, so replication is required in another cohort. This relationship between tau pathology and entorhinal neurodegeneration in females provides further insight into how sex‐related cortical structural vulnerability may correspond to pathology over time.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: Neuroimaging studies of autosomal dominant Alzheimer’s disease (ADAD) enable characterization of the trajectories of cerebral amyloid-β (Aβ) and tau accumulation in the decades prior to clinical symptom onset. Longitudinal rates of regional tau accumulation measured with positron emission tomography (PET) and their relationship with other biomarker and cognitive changes remain to be fully characterized in ADAD. Methods Fourteen ADAD mutation carriers ( Presenilin-1 E280A) and 15 age-matched non-carriers from the Colombian kindred underwent 2–3 sessions of Aβ (11C-Pittsburgh compound B) and tau (18F-flortaucipir) PET, structural magnetic resonance imaging, and neuropsychological evaluation over a 2–4-year follow-up period. Annualized rates of change for imaging and cognitive variables were compared between carriers and non-carriers, and relationships among baseline measurements and rates of change were assessed within carriers. Results Longitudinal measurements were consistent with a sequence of ADAD-related changes beginning with Aβ accumulation (16 years prior to expected symptom onset, EYO), followed by entorhinal cortex (EC) tau (9 EYO), neocortical tau (6 EYO), hippocampal atrophy (6 EYO), and cognitive decline (4 EYO). Rates of tau accumulation among carriers were most rapid in parietal neocortex (~ 9%/year). EC tau PET signal at baseline was a significant predictor of subsequent neocortical tau accumulation and cognitive decline within carriers. Conclusions Our results are consistent with the sequence of biological changes in ADAD implied by cross-sectional studies and highlight the importance of EC tau as an early biomarker and a potential link between Aβ burden and neocortical tau accumulation in ADAD.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2506521-X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S4 ( 2021-12)
    Abstract: Women’s Health Initiative Memory Study (WHIMS) findings suggest that hormone therapy increases risk of dementia. Conversely, evidence from the Kronos Early Estrogen Prevention Study (KEEPS) implicates estrogen hormone therapy (HT) as protective against ß‐amyloid (Aß) burden. We sought to explore if self‐reported HT use is associated with rates of Aß accumulation in an observational sample of clinically‐unimpaired older adults. Method 134 participants (Age=73yrs±5.8) underwent at least three timepoints of Pittsburgh compound‐B (PiB)‐PET scans over an average of 9.7 years. Longitudinal PiB‐PET was examined as aggregate neocortical DVR (composite reference region: whole cerebellum + eroded white matter). Concurrent with baseline PiB‐PET, female participants self‐reported if they ever took HT. Participants were thus identified as: females who never used HT (HT‐:n=36), females who have ever taken HT to any extent (HT+:n=42), and males (M:n=56). We examined the relationship between these three groups and longitudinal PiB‐PET using linear mixed models, adjusting for baseline age, and with random slopes and intercepts. Post‐hoc analyses adjusted for APOE ε4 status and examined interactions between HT and baseline PiB‐PET on change in PiB‐PET from baseline. Result While we found no significant sex (male/female) difference in PiB‐PET accumulation (t=1.5, p 〉 0.05,Fig 1A), we observed significant HT group differences with HT‐ exhibiting approximately half the PiB‐PET rate of change than M (t=2.3, p =0.02) and HT+ (t=1.8, p =0.07; Fig 1B). There was no significant slope difference between M and HT+ (t=0.32, p =0.75). These differences survived after covarying for APOE ε4. A three‐way interaction with baseline PiB‐PET revealed a greater slope difference between HT‐ and M (t=2.1, p =0.04) in those with higher baseline PiB‐PET relative to lower baseline PiB‐PET (Fig 2). Conclusion HT‐ showed significantly slower rates of Aß accumulation than males and a trend‐level slower rate compared to HT+; these differences appear heightened with greater baseline Aß burden. With similar ages across HT groups (p=0.20), these differences did not appear to be a function of chronological age. It remains unclear whether the introduction of estrogen, a mediating commonality, or collider bias is driving these results. Our findings, in conjunction with other studies, suggest the relationship between HT and Aß is complicated and necessitates examination of HT type and duration.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Annals of Neurology, Wiley, Vol. 88, No. 5 ( 2020-11), p. 921-932
    Abstract: The goal of this study was to examine sex differences in tau distribution across the brain of older adults, using positron emission tomography (PET), and investigate how these differences might associate with cognitive trajectories. Methods Participants were 343 clinically normal individuals (women, 58%; 73.8 [8.5] years) and 55 individuals with mild cognitive impairment (MCI; women, 38%; 76.9 [7.3] years) from the Harvard Aging Brain Study and the Alzheimer's Disease Neuroimaging Initiative. We examined 18 F‐Flortaucipir (FTP)‐positron emission tomography (PET) signal across 41 cortical and subcortical regions of interest (ROIs). Linear regression models estimated the effect of sex on FTP‐signal for each ROI after adjusting for age and cohort. We also examined interactions between sex*Aβ‐PET positive / negative (+ / −) and sex*apolipoprotein ε4 (APOEε4) status. Linear mixed models estimated the moderating effect of sex on the relationship between a composite of sex‐differentiated tau ROIs and cognitive decline. Results Women showed significantly higher FTP‐signals than men across multiple regions of the cortical mantle ( p 〈  0.007). β‐amyloid (Aβ)‐moderated sex differences in tau signal were localized to medial and inferio‐lateral temporal regions ( p 〈  0.007); Aβ + women exhibited greater FTP‐signal than other groups. APOEε4‐moderated sex differences in FTP‐signal were only found in the lateral occipital lobe. Women with higher FTP‐signals in composite ROI exhibited faster cognitive decline than men ( p = 0.04). Interpretation Tau vulnerability in women is not just limited to the medial temporal lobe and significantly contributed to greater risk of faster cognitive decline. Interactive effects of sex and Aβ were predominantly localized in the temporal lobe, however, sex differences in extra‐temporal tau highlights the possibility of accelerated tau proliferation in women with the onset of clinical symptomatology. ANN NEUROL 2020;88:921–932
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2037912-2
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S1 ( 2021-12)
    Abstract: Clinically normal females exhibit greater [18]F‐flortaucipir (FTP) PET signal than males in both temporal and neocortices. It remains unclear whether sex differences in neocortical regions are primarily explained by technical variability issues. We aimed to investigate the contribution of signal spillover/off‐target skull binding to sex differences in FTP‐PET. Next, we explored partial volume effects (PVE) by simulating sex differences in smoothed FTP‐PET signal. Discerning sex differences in tau signal versus noise is pivotal to understanding sex differences in the pathology of Alzheimer’s disease and associated tauopathies. Method 343 clinically normal (female=58%; mean[SD]=73.8[8.5] years) (female=38%; mean[SD]=76.9[7.3] years) participants from the Harvard Aging Brain Study and the Alzheimer’s Disease Neuroimaging Initiative underwent cross‐sectional FTP‐PET (standardized uptake value ratios [SUVrs]). For skull analyses, we created skull ROIs based on signal 12mm from the outer perimeter of voxels in FreeSurfer‐defined tau ROIs. Linear regression models estimated the main effects of sex across cortical tau ROIs while correcting for local skull binding. We simulated PVE by convolving group‐level SUVr means in each ROI with 6mm Gaussian kernels, and then compared the sexes with linear regression models post‐smoothing. Result Widespread sex differences in skull binding were observed (Table 1). Covarying for skull binding ameliorated weaker sex differences in cortical FTP signal but did not impact the largest effects. Sex differences in PVE were observed in both female and male directions; no clear sex‐related biases in PVE were found to impact cortical tau sex differences except for the rostral middle frontal region (Figure 1). Conclusion Our findings suggest that sex differences in FTP‐PET are not solely attributed to skull ‘clouding’ or PVE, but rather support hypotheses of female‐related tau vulnerability. Nevertheless, as only two potential confounds were investigated, and gross morphology/volumetric issues remain a key concern, further investigation is needed to fully elucidate this phenomenon. Investigations of sex differences in longitudinal tau accumulation (a few preliminary reports already suggest faster rates in females) will add further support to the argument that noise properties inherent in FTP‐PET do not significantly contribute to sex differences in cortical tau signal.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S4 ( 2021-12)
    Abstract: The Framingham Heart Study (FHS), a three‐generation community‐based cohort studying cardiovascular disease across the adult lifespan, has expanded to include positron emission tomography (PET) of beta‐amyloid (Aβ) and tau. Our aim is to characterize these pathologies in this unique sample and utilize the wide age range to assess the spatiotemporal ordering of emerging Aβ and tau. Method 211 clinically‐normal adults aged 33‐74 from FHS underwent Pittsburgh Compound B (PIB) and Flortaucipir (FTP) PET. PIB and FTP were regionally quantified in Desikan regions using distribution volume ratio (DVR) for PIB and standardized uptake volume ratio (SUVR) for FTP. Three approaches were used to identify early accumulating regions: 1. A series of Age*APOE linear models to identify regions accumulating earlier in the lifespan in ε4 carriers. 2. Identification of early regions as those more frequently elevated as previously used in older adults, with Gaussian mixture models (GMM) conducted to evaluate bimodality and set biomarker positivity thresholds for each region. 3. Applied the same frequency approach using well‐validated PIB GMM thresholds based on older adults from the Harvard Aging Brain Study (HABS). Result For PIB, significant Age*APOE interactions (Fig. 1) were seen across multiple regions previously implicated as early‐accumulating based on elevation frequencies from older adult samples, as well as the pars opercularis (p=0.005) and lateral parietal cortices (p 〈 0.04). PIB was significantly bimodal across all ROIs (LRT 〉 36.1, p 〈 0.001; Fig. 1). Application of GMM‐based regional positivity frequencies derived within FHS versus from HABS thresholds led to substantial discrepancies in the spatiotemporal ordering of PIB ( r s =0.30, p=0.17). Age*APOE effects were not detected for any tau regions, but inferior temporal (IT), middle temporal (MT), and amygdala (AM) increased with age (Fig. 2). Higher global Aβ was also associated with higher FTP SUVR in IT, MT, and a trend for AM, as well as inferior parietal and precuneus (Fig. 2). Conclusion Aβ and tau mainly follow spatiotemporal patterns consistent with prior evidence in older adult samples. GMM‐based methods used in older adult samples to dichotomize biomarker positivity may be suboptimal in younger samples. Continuous approaches may better capture early Aβ and tau in younger populations.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages