GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Shared genetic risk between eating disorder‐ and substance‐use‐related phenotypes: Evidence from genome‐wide association studies
    Wiley ; 2021
    In:  Addiction Biology Vol. 26, No. 1 ( 2021-01)
    Details
    In: Addiction Biology, Wiley, Vol. 26, No. 1 ( 2021-01)
    Abstract: Eating disorders and substance use disorders frequently co‐occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [ r g ], twin‐based = 0.23‐0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome‐wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN] , AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance‐use‐related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism‐based genetic correlations between eating disorder‐ and substance‐use‐related phenotypes. Significant positive genetic associations emerged between AUD and AN ( r g = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN ( r g = 0.23; q 〈 0.0001), and cannabis initiation and AN with binge eating ( r g = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating ( r gs = −0.19 to −0.23; qs 〈 0.04). The genetic correlation between AUD and AN was no longer significant after co‐varying for major depressive disorder loci. The patterns of association between eating disorder‐ and substance‐use‐related phenotypes highlights the potentially complex and substance‐specific relationships among these behaviors.
    Type of Medium: Online Resource
    ISSN: 1355-6215 , 1369-1600
    URL: Issue
    URL: Article
    DOI: 10.1111/adb.v26.1
    DOI: 10.1111/adb.12880
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1495537-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Performance on the graded naming test in a population‐based sample of 72‐year‐olds: Associations with life‐course predictors and β‐amyloid pathology : Neuropsychology/Early detection of cognitive decline with neuropsychological tests
    Wiley ; 2020
    In:  Alzheimer's & Dementia Vol. 16, No. S6 ( 2020-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S6 ( 2020-12)
    Abstract: Word‐finding difficulties are a common early feature of Alzheimer’s disease (AD) and may be detectable during the preclinical stage. However, the relationship between changes in naming ability and accumulation of β‐amyloid pathology is not fully understood, and questions remain about the role of factors such as sex and education. Method Participants in Insight 46, a sub‐study of the British 1946 birth cohort, completed baseline cognitive assessments and neuroimaging (combined MRI/ 18 F‐Florbetapir‐PET) at age 69‐71. Follow‐up assessments are currently underway (mean interval 28.9 months, SD 2.1) and include an audio‐recorded version of the 30‐item Graded Naming Test (GNT), which was not administered at baseline. Preliminary interim analyses have been conducted based on 211 cognitively‐normal individuals with complete neuroimaging data (see Table 1 for characteristics). A multivariable regression model was used to investigate predictors of picture naming accuracy, where the outcome was GNT score (max. 30) and predictors were sex, age at follow‐up assessment, β‐amyloid status at baseline (positive / negative), APOE genotype (ε4 carrier/non‐carrier), and prospectively‐collected measures of childhood cognitive ability, education and socioeconomic position (based on occupation). Due to the negatively‐skewed distribution of GNT scores, bootstrapping was used to produce bias‐corrected and accelerated 95% confidence intervals from 2,000 replications. Results will be updated to include the full sample before the conference. We also plan to include data on naming latency extracted from the audio‐recordings, which may be a more sensitive measure of early changes than naming accuracy. Result Higher childhood cognitive ability predicted higher GNT scores over 60 years later (Table 2 , Figure 1). Men scored 0.9 points higher than women on average. Amyloid‐positive participants scored 1.2 points lower than amyloid‐negative participants on average. These effects were all significant at the 5% level and were mutually independent. Conclusion Subtle changes in naming accuracy associated with β‐amyloid pathology are detectable in cognitively‐normal individuals as early as age 72. Performance is additionally influenced by sex and general cognitive ability, so these factors should be accounted for where possible in future studies and clinical trials that seek to detect and track the emergence of naming deficits.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v16.S6
    DOI: 10.1002/alz.040897
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Serum neurofilament light and whole brain volume associate with machine‐learning derived brain‐predicted age in the British 1946 birth cohort : Neuroimaging / New imaging methods
    Wiley ; 2020
    In:  Alzheimer's & Dementia Vol. 16, No. S4 ( 2020-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S4 ( 2020-12)
    Abstract: Age is the biggest risk factor for dementia, yet human brains do not age uniformly. The British 1946 birth cohort, the world’s longest continuously running birth cohort, provides a unique opportunity to assess these variations in biological ageing. So‐called ‘brain age’ is a biomarker of brain ageing, derived from machine‐learning analysis trained on a large sample of healthy brains (N=2001). Brain age has previously been related to cognitive ageing, physiological ageing and mortality risk (DOI: 10.1038/mp.2017.62), supporting the validity of this approach for assessing biological ageing. Method 502 participants in the Insight 46 study, all born during one week in 1946, completed baseline cognitive and neuroimaging assessments at age 69‐71. 468 underwent combined 18 florbetapir PET‐MRI scans, from which amyloid status (positive/negative), whole brain volume (WBV), total intracranial volume (TIV) and hippocampal volumes (HV) were derived. The T1‐weighted sequence was passed through the Brain‐age algorithm (https://github.com/james‐cole/brainageR), deriving brain predicted‐age (BPA) and brain‐predicted age difference (brain‐PAD; BPA minus chronological age). Serum neurofilament light (NFL) concentration was measured via Simoa immunoassay. A Preclinical Alzheimer’s Cognitive Composite Score (PACC) was calculated as a mean of z‐scores of the Mini‐mental state exam (MMSE), logical memory delayed recall, digit symbol substitution score and the Face‐Name test. Life course metrics (childhood cognitive scores, education level and Framingham Risk scores) were obtained from previous cohort assessments. Multivariate regression models were used to investigate whether life course metrics predict BPA, as well as whether NFL levels, brain volumes, or cognitive scores correlated with BPA, adjusting for chronological age. Result There was a significant difference between the 229 females assessed (mean BPA 65.2 years) compared with the 239 males assessed (mean BPA 70.7). BPA was independently associated with serum NFL concentration (p = 0.071) and inversely with whole brain volume (p 〈 0.001). Life course factors did not predict brain age. Conclusion The results showed a significant association of BPA, a cross‐sectional imaging metric, with a biochemical marker of neuronal damage (NFL) and sex. BPA has utility as an imaging metric that can integrate multiple modalities contributing to biological age, with potential as a predictive biomarker of cognitive decline.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v16.S4
    DOI: 10.1002/alz.045965
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Fixel‐based analysis of the effect of amyloid beta on white matter tracts in neurologically normal 70 year olds
    Wiley ; 2021
    In:  Alzheimer's & Dementia Vol. 17, No. S4 ( 2021-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S4 ( 2021-12)
    Abstract: Fixel‐based analysis (FBA) of diffusion MRI allows analysis of brain white matter (WM) tracts with greater specificity than voxel‐based approaches, including measures of microstructural fibre density (FD), macrostructural fibre cross section (FC), and representations of crossing fibres. We use FBA to explore early WM changes associated with amyloid‐β (Aβ) prior to manifestations of Alzheimer’s disease. We additionally explored global WM changes associated with increased cardiovascular risk. Method We performed FBA on 233 participants in the Insight 46 birth cohort study, all of whom have been followed prospectively since birth in a single week in 1946, including cardiovascular risk assessment using the Framingham Risk Score (FRS). At age 69‐71 participants underwent cognitive assessment and combined 18 F‐florbetapir PET‐MRI scans on a single scanner. Aβ positive status was defined using a Gaussian mixed model as a standardised uptake value ratio over 0.6103. Using Aβ positive (n=40) and negative (n=193) participants with no major brain disorders and excellent scan quality, we assessed FD and FC, as well as the combined FD and FC (FDC) metric across all white matter fixels. Subsequently we performed a tract‐of‐interest analysis of associations between Aβ and FDC in 13 selected white matter tracts, 7 defined a priori based on Alzheimer’s disease mechanisms, and 6 based on results of the global analysis. Result Aβ positivity was associated with changes in microstructural and macrostructural changes (FD, FC and FDC), throughout the right corticospinal tract inferior to the internal capsule, and microstructurally in the right inferior longitudinal fasciculus. Similar left sided corticospinal changes were seen in FC and FDC only. Increased FRS was associated with FD changes in the right superior longitudinal fasciculus. Tract‐of‐interest analyses showed no significant associations between FDC and Aβ after false discovery correction using the Benjamini‐Hochberg method. Conclusion We show Aβ associated changes in fixel‐based metrics in the corticospinal tracts, predominantly affecting the right hemisphere. These preliminary results raise the possibility of these fibres being predisposed to damage, perhaps in a length dependent manner, though longitudinal analysis based on further phases of Insight 46 may prove more powerful to detect change at this very early stage.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v17.S4
    DOI: 10.1002/alz.056187
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Accelerated forgetting is sensitive to β‐amyloid pathology and cerebral atrophy in cognitively normal 72‐year‐olds : Neuropsychology/Early detection of cognitive decline with neuropsychological tests
    Wiley ; 2020
    In:  Alzheimer's & Dementia Vol. 16, No. S6 ( 2020-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S6 ( 2020-12)
    Abstract: Accelerated Forgetting (AF) is the phenomenon whereby material is retained normally over short intervals (minutes or hours) but forgotten abnormally rapidly over longer periods (days or weeks). AF has been observed in presymptomatic carriers of mutations causing familial Alzheimer’s disease (AD) (doi:10.1016/S1474‐4422(17)30434‐9). To our knowledge, no studies have investigated whether AF is sensitive to preclinical AD pathology in cognitively‐normal older adults. Method Participants in the Insight 46 study, a sub‐study of the British 1946 birth cohort, completed baseline cognitive and neuroimaging assessments at age 69‐71. For the follow‐up visits (∼29 months later), we complemented the clinic visit assessments of Complex Figure Drawing and the Face‐Name test (FNAME‐12) with a 7‐day delay version administered by telephone (Figure 1). AF scores were calculated as the percentage of material retained after 7 days, relative to retention after 30 minutes. Cerebral atrophy between baseline and follow‐up was quantified from T1‐weighted MRI using the Brain Boundary Shift Integral (BBSI). β‐amyloid status at baseline (positive / negative) was determined from 18 F‐Florbetapir‐PET. As follow‐up assessments are still underway, preliminary interim analyses have been conducted based on 195 cognitively‐normal individuals with complete neuroimaging data (see Table 1 for characteristics). Multivariable regression models were used to investigate the effects of β‐amyloid status and BBSI on AF, and to explore interactions between these two predictors, adjusting for potential confounders including prospectively‐collected measures of childhood cognitive ability and education. Result Despite no statistically‐significant differences after a 30‐minute delay, β‐amyloid‐positive participants retained a lower percentage of Complex Figure material over 7 days (71.8% vs. 80.7%, p =0.010) and a trend to a lower percentage of FNAME‐12 material (69.4% vs. 77.2%, p = 0.083) (Table 2, Figure 2). Higher education predicted better retention of the Complex Figure. Among β‐amyloid‐positive participants only, greater cerebral atrophy predicted poorer retention of the Complex Figure (Table 2, Figure 3). Conclusion These results provide novel evidence of AF in cognitively‐normal β‐amyloid‐positive 72‐year‐olds. AF may be a sensitive outcome measure for therapeutic trials in preclinical AD, as it may reveal subtle memory decline at an earlier stage than traditional assessments. The interaction between β‐amyloid pathology and cerebral atrophy merits longitudinal investigation.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v16.S6
    DOI: 10.1002/alz.040987
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Longitudinal trajectories of self‐reported subjective cognitive decline in relation to objective cognitive performance in a population‐based cohort
    Wiley ; 2023
    In:  Alzheimer's & Dementia Vol. 19, No. S4 ( 2023-06)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. S4 ( 2023-06)
    Abstract: Subjective Cognitive Decline (SCD) may represent the onset of cognitive decline before impairment on standard cognitive tests occurs (Jessen et al., 2014). Previous cross‐sectional studies were shown to have limited ability to capture objective differences in cognitive performance between groups with and without SCD (Cacciamani et al., 2017). Understanding the interplay between changes in subjective memory ratings and objective cognitive function over time may have utility in identifying people at risk of dementia. Method 370 cognitively normal (CN) individuals with complete cognitive data ( Table 1 for characteristics) from Insight 46, a longitudinal neuroscience sub‐study of the MRC National Survey for Health and Development (the British 1946 Birth Cohort), underwent cognitive, clinical, and physical assessments, and neuroimaging (combined MRI/18F‐Florbetapir‐PET). SCD was measured using MyCog (Rami et al., 2014) a validated tool, from the SCD‐Questionnaire, where higher scores indicate greater subjective complaints. Linear regression models were used to test whether longitudinal cognitive change as measured using the Preclinical Alzheimer Cognitive Composite (PACC) and a visual short‐term memory binding task were influenced by baseline MyCog and whether there are parallel associations between rates of change in MyCog and longitudinal cognitive change. Covariates were sex, age at baseline visit, childhood cognitive ability, educational attainment, and adult socioeconomic position. Result Baseline MyCog scores did not predict rates of change in PACC or visual short‐term memory binding outcome measures ( Table 2 ). Rates of MyCog change alone did not predict rate of change in PACC, localisation error, total correct number of trials or proportion of misbinding errors ( Table 3 ). However, we observed an interaction effect with baseline amyloid‐b status, whereby greater rates of subjective memory concerns predicted faster rates of decline in the proportion of misbinding errors in amyloid‐b positive participants only ( Table 3; Figure 1 ). Conclusion These findings suggest that higher amyloid‐b burden in CN individuals with subjective memory complaints is associated with faster rates of decline in visual working memory. Corroborating previous reports that feature binding tasks can objectify subtle cognitive deficits found in SCD (Koppara et al., 2015) and serve as a promising tool for identifying people at risk of dementia.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v19.S4
    DOI: 10.1002/alz.067642
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Rates of cortical thinning in Alzheimer’s disease signature regions: pathological influences and cognitive consequences in members of the 1946 British birth cohort
    Wiley ; 2022
    In:  Alzheimer's & Dementia Vol. 18, No. S6 ( 2022-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S6 ( 2022-12)
    Abstract: Consistent patterns of reduced cortical thickness (so‐called signature regions) have been identified in early Alzheimer’s disease (AD), including in the pre‐dementia stages, but studies investigating the pathological underpinnings and cognitive consequences of longitudinal changes in these regions have been limited. Method 337 cognitively normal participants (mean [SD] age 70.5 [0.6] years) underwent 18F‐florbetapir amyloid‐ß PET, volumetric MRI, and cognitive assessment as part of Insight 46, a sub‐study of the 1946 British birth cohort (Table 1 for characteristics). Baseline and follow‐up T1‐weighted MRI (mean [SD] interval 2.4 [0.2] years) were processed using Freesurfer’s longitudinal stream (v.7.1.0) and cortical thickness was derived in two AD signatures (Table 2 footnote for details). Linear regression was used to test whether rates of change in AD signature cortical thickness were influenced by baseline amyloid‐ß deposition (positive/negative status or continuous SUVR) or white matter hyperintensity volume (WMHV; a marker of presumed cerebrovascular disease), and whether they were related to longitudinal cognitive change as measured using the Preclinical Alzheimer Cognitive Composite (PACC). Covariates included sex, age at baseline scan, childhood cognition, educational attainment, and socioeconomic position. Interaction terms were added to test whether associations with longitudinal cognitive change differed by baseline amyloid‐ß status. Result Higher baseline WMHV was associated with faster rates of cortical thinning in AD signature regions, but baseline amyloid‐ß status and SUVR were not (Table 2; Figure 1). There were differential effects of rates of change in AD signature cortical thickness by baseline amyloid‐ß status, whereby greater rates of AD signature cortical thinning predicted faster rates of PACC decline in amyloid‐ß positive participants only (Table 3; Figure 2). Conclusion Cortical thinning in AD signature regions may arise via non‐amyloid‐ß pathways in cognitively normal elderly. However, the presence of amyloid‐ß may make individuals more susceptible to the effects of faster rates of cortical thinning in these regions (or vice versa) since these factors interact to influence rates of cognitive decline. These findings provide insight into processes that might underlie progression to dementia in later life and have implications for the utility of AD signature cortical thickness as a biomarker in the preclinical phase of AD.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v18.S6
    DOI: 10.1002/alz.067336
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Associations between peripheral hearing ability at age 70, brain atrophy and cognitive decline in adults born in the same week of 1946
    Wiley ; 2023
    In:  Alzheimer's & Dementia Vol. 19, No. S8 ( 2023-06)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. S8 ( 2023-06)
    Abstract: Peripheral hearing impairment has been proposed as a risk factor for dementia. However, the relationship between hearing ability, neurodegeneration and cognitive decline, and the extent to which pathological processes associated with increased risk of specific causes of dementia, such as β‐amyloid and small vessel disease, influence these relationships, is unclear. Method Data were analysed from 287 cognitively normal adults born in the same week of 1946 who underwent pure tone audiometry testing at baseline (mean age = 70.6 years), with cognitive assessment and brain imaging at baseline and at follow‐up on average 2.4 years later. Peripheral hearing impairment was defined as a pure tone average of greater than 25 decibels in the best hearing ear. Rates of change for whole brain, hippocampal and ventricle volume were estimated from structural MRI using the Boundary Shift Integral. Cognition was assessed using the Pre‐clinical Alzheimer’s Cognitive Composite. Regression models were performed to evaluate how baseline hearing impairment associated with subsequent brain atrophy and cognitive decline after adjustment for a range of variables including baseline β‐amyloid deposition (assessed using florbetapir‐PET) and baseline small vessel disease burden (estimated using white matter hyperintensity volume). Results 111 out of 287 participants were defined as having peripheral hearing impairment. Hearing impaired individuals demonstrated faster rates of whole brain atrophy (p = 0.031 – figure/table 1) compared with those with normal hearing. Peripheral hearing impairment did not predict change in PACC performance, but there was evidence of an interaction between hearing impairment and whole brain atrophy rates in terms of effect on change in PACC performance. Specifically, faster rates of whole brain atrophy predicted greater cognitive decline in participants with hearing impairment (p = 0.004), whilst there was no evidence of an association between cognitive change and atrophy in participants with preserved hearing (figure/table 2). There was no evidence that β‐amyloid deposition or white matter hyperintensity volume modified these relationships. Conclusion We present evidence of associations between peripheral hearing ability at age 70, brain atrophy and cognitive decline independent of β‐amyloid and small vessel disease, suggesting hearing may associate with brain health via mechanisms distinct from those typically implicated in pre‐clinical Alzheimer’s disease and vascular cognitive impairment.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v19.S8
    DOI: 10.1002/alz.059498
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Lifetime cigarette smoking and later‐life brain health: The population‐based 1946 British Birth Cohort : Public health: ADRD risk and protective factors: Brain changes and mechanisms
    Wiley ; 2020
    In:  Alzheimer's & Dementia Vol. 16, No. S10 ( 2020-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S10 ( 2020-12)
    Abstract: Cigarette smoking is implicated as a risk factor for dementia, but the underlying mechanisms are poorly understood. In a population‐based sample free of dementia, we examine associations between smoking patterns over the life course and imaging markers associated with dementia. Method Dementia‐free participants from Insight 46 (n=458, 49% female, age 69‐71), a sub‐study of the 1946 British Birth Cohort, underwent 18 F‐florbetapir Aβ‐PET and multi‐modal MR imaging including T1, T2, FLAIR and multi‐shell diffusion‐weighted sequences. Information on smoking frequency and cessation (current/former/never) were obtained at multiple timepoints, spanning ages 15‐69 years. Pack‐years were calculated as number of cigarettes smoked/day divided by 20, multiplied by years of smoking. Age and sex adjusted regression analyses examined relationships between smoking metrics and later‐life imaging measures; including Aβ‐PET status, brain, hippocampal and white matter hyperintensity (WMH) volumes, normal appearing white matter (NAWM) fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI) and orientation dispersion index (ODI), and Alzheimer’s disease (AD)‐related cortical thickness. Result Increased smoking pack‐years was associated with alterations in NAWM microstructure metrics (lower FA and NDI; higher MD and ODI) and smaller brain and hippocampal volume (Figure 1). There was no significant relationship with Aβ‐PET status (OR=0.99 [95% CI 0.97,1.01]), WMH volume or AD‐related cortical thickness (Figure 1). Unlike current smokers (n=16, 3%), former smokers (n=285, 61%) had comparable NAWM microstructure metrics to those who had never smoked (n=163, 35%). Conclusion In a population‐based sample without dementia or other major neurological problems, increased smoking frequency and duration over 50 years was associated with altered white matter microstructural metrics, and smaller brain and hippocampal volumes. However, there was no evidence that smoking was associated with markers of AD pathology (amyloid‐PET, AD‐related cortical thickness) or cerebral small vessel disease (WMH). Former smokers were comparable to non‐smokers on measures of microstructural metrics, suggesting that smoking‐related microstructural changes may at least partly be reversible. Stopping or reducing smoking may help reduce risks to brain health via microstructural pathways.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v16.S10
    DOI: 10.1002/alz.041111
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Plasma phospho‐tau181 in over 400 cognitively healthy 69‐ to 71‐year‐olds: Associations with cerebral amyloid, structural imaging and cognition in the Insight 46 study : Biomarkers (non‐neuroimaging): Multimodal biomarker studies in cognitively unimpaired cohorts
    Wiley ; 2020
    In:  Alzheimer's & Dementia Vol. 16, No. S5 ( 2020-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S5 ( 2020-12)
    Abstract: We examined cross‐sectional associations between plasma phospho‐tau181 (p‐tau181) and amyloid PET, MRI and cognitive outcomes in Insight 46, a sub‐study of the British 1946 birth cohort. Method At age 69‐71, participants underwent blood sampling, neurocognitive assessment, and 3T‐MRI with simultaneous 18 F‐florbetapir‐PET (yielding amyloid status binarized at grey matter:eroded white matter SUVR 0.6104). Plasma p‐tau181 was measured by a homebrew Simoa immunoassay. ROC analyses were performed for amyloid status incorporating p‐tau181 into a model combining age, sex and APOE ε 4 carrier status ( APOE ε 4). Linear regression examined associations between p‐tau181 (predictor) and (A): cognitive measures (preclinical AD cognitive composite (PACC), digit‐symbol substitution (DSS), delayed logical memory (LMD), and 12‐item‐face‐name association memory (FNAME‐12)), adjusting for age, sex, APOE ε 4, childhood cognition, socioeconomic position and education; and (B): imaging biomarkers of neurodegeneration (whole brain, ventricular and hippocampal volumes (WBV,VV,HV) and AD‐signature cortical thickness (CTh)) and vascular disease (white matter hyperintensity volume (WMHV)), adjusting for age, sex, APOE ε 4, amyloid status and total intracranial volume as appropriate. Result After excluding those with prior neurological diagnoses, mild cognitive impairment or dementia, 444 individuals had complete plasma p‐tau181 data (Table 1); 410 had high‐quality amyloid PET data. An amyloid status ROC model using plasma p‐tau181 alone had an AUC of 0.720,95%CI[0.657,0.783]. This was not significantly different from the prediction of a base model incorporating age, sex and APOE ε 4 (0.692[0.622,0.761]), but adding plasma p‐tau181 to the base model improved it significantly (0.787[0.737,0.837] , 2 p 〈 0.001: figure 1). The numbers needed to pre‐screen for a pre‐symptomatic Alzheimer’s trial could be reduced by about 27% by using the latter compared to the base model (table 2). Higher p‐tau181 was associated with lower FNAME‐12 (z‐score‐change for 10% p‐tau181 rise: ‐0.020,95%CI[‐0.033,‐0.007], p =0.003) and lower PACC (‐0.013[‐0.022,‐0.005], p =0.002). Only the latter association was significantly attenuated by further adjustment for amyloid status. Higher p‐tau181 was associated with higher VV (ratio‐change for 10% p‐tau181 rise: 1.010, 95%CI[1.003,1.017], p =0.007) and lower CTh (0.999[0.998,1.000], p =0.007). DSS, LMD, HV, WBV and WMHV had no significant associations with p‐tau181. Conclusion In cognitively normal individuals, plasma p‐tau181 may contribute toward pre‐screening for amyloid PET positivity, and is associated with cognitive performance and imaging biomarkers of neurodegeneration.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v16.S5
    DOI: 10.1002/alz.037848
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...