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  • Oxford University Press (OUP)  (10)
  • McEvoy, Linda K  (10)
  • 1
    Online Resource
    Online Resource
    THE RANCHO BERNARDO STUDY (RBS) OF HEALTHY AGING: A RICH RESOURCE FOR STUDYING AGING IN WOMEN
    Oxford University Press (OUP) ; 2019
    In:  Innovation in Aging Vol. 3, No. Supplement_1 ( 2019-11-08), p. S355-S355
    Details
    In: Innovation in Aging, Oxford University Press (OUP), Vol. 3, No. Supplement_1 ( 2019-11-08), p. S355-S355
    Abstract: RBS is an ideal cohort to study healthy aging in women and to examine sex differences in aging. Initiated in 1972, RBS enrolled 82% of adult residents of Rancho Bernardo, a suburb of San Diego. Residents were white, and middle to upper-middle class. Participants have been followed via 12 research clinic visits at ~4 year intervals and 32 mailed surveys. RBS contains detailed assessment of cardiometabolic disease risk factors, bone health, biomarkers, physical ability, cognitive function, health and reproductive history, medications, behaviors (smoking, drinking, diet, exercise) and psychosocial measures. Of the 6726 participants, 54% are women and 65% were aged ≥50 at enrollment. Vital status is known for 91% of the cohort; overall mortality is 71%. Death certificates have been coded for cause of death for 91% of decedents. We will discuss contributors to healthy longevity in RBS women (average age of death 86.4 yrs; 29% lived to age ≥90).
    Type of Medium: Online Resource
    ISSN: 2399-5300
    URL: Article
    DOI: 10.1093/geroni/igz038.1289
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 2
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    Associations between MRI-assessed locus coeruleus integrity and cortical gray matter microstructure
    Oxford University Press (OUP) ; 2022
    In:  Cerebral Cortex Vol. 32, No. 19 ( 2022-09-19), p. 4191-4203
    Details
    In: Cerebral Cortex, Oxford University Press (OUP), Vol. 32, No. 19 ( 2022-09-19), p. 4191-4203
    Abstract: The locus coeruleus (LC) is one of the earliest sites of tau pathology, making it a key structure in early Alzheimer’s disease (AD) progression. As the primary source of norepinephrine for the brain, reduced LC integrity may have negative consequences for brain health, yet macrostructural brain measures (e.g. cortical thickness) may not be sensitive to early stages of neurodegeneration. We therefore examined whether LC integrity was associated with differences in cortical gray matter microstructure among 435 men (mean age = 67.5; range = 62–71.7). LC structural integrity was indexed by contrast-to-noise ratio (LCCNR) from a neuromelanin-sensitive MRI scan. Restriction spectrum imaging (RSI), an advanced multi-shell diffusion technique, was used to characterize cortical microstructure, modeling total diffusion in restricted, hindered, and free water compartments. Higher LCCNR (greater integrity) was associated with higher hindered and lower free water diffusion in multiple cortical regions. In contrast, no associations between LCCNR and cortical thickness survived correction. Results suggest lower LC integrity is associated with patterns of cortical microstructure that may reflect a reduction in cytoarchitectural barriers due to broader neurodegenerative processes. These findings highlight the potential utility for LC imaging and advanced diffusion measures of cortical microstructure in assessing brain health and early identification of neurodegenerative processes.
    Type of Medium: Online Resource
    ISSN: 1047-3211 , 1460-2199
    URL: Article
    DOI: 10.1093/cercor/bhab475
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 3
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    Sex-dependent autosomal effects on clinical progression of Alzheimer’s disease
    Oxford University Press (OUP) ; 2020
    In:  Brain Vol. 143, No. 7 ( 2020-07-01), p. 2272-2280
    Details
    In: Brain, Oxford University Press (OUP), Vol. 143, No. 7 ( 2020-07-01), p. 2272-2280
    Abstract: Sex differences in the manifestations of Alzheimer’s disease are under intense investigation. Despite the emerging importance of polygenic predictions for Alzheimer’s disease, sex-dependent polygenic effects have not been demonstrated. Here, using a sex crossover analysis, we show that sex-dependent autosomal genetic effects on Alzheimer’s disease can be revealed by characterizing disease progress via the hazard function. We first performed sex-stratified genome-wide associations, and then applied derived sex-dependent weights to two independent cohorts. Relative to sex-mismatched scores, sex-matched polygenic hazard scores showed significantly stronger associations with age-at-disease-onset, clinical progression, amyloid deposition, neurofibrillary tangles, and composite neuropathological scores, independent of apolipoprotein E. Models without using hazard weights, i.e. polygenic risk scores, showed lower predictive power than polygenic hazard scores with no evidence for sex differences. Our results indicate that revealing sex-dependent genetic architecture requires the consideration of temporal processes of Alzheimer’s disease. This has strong implications not only for the genetic underpinning of Alzheimer’s disease but also for how we estimate sex-dependent polygenic effects for clinical use.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awaa164
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 4
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    12-year prediction of mild cognitive impairment aided by Alzheimer’s brain signatures at mean age 56
    Oxford University Press (OUP) ; 2021
    In:  Brain Communications Vol. 3, No. 3 ( 2021-07-01)
    Details
    In: Brain Communications, Oxford University Press (OUP), Vol. 3, No. 3 ( 2021-07-01)
    Abstract: Neuroimaging signatures based on composite scores of cortical thickness and hippocampal volume predict progression from mild cognitive impairment to Alzheimer’s disease. However, little is known about the ability of these signatures among cognitively normal adults to predict progression to mild cognitive impairment. Towards that end, a signature sensitive to microstructural changes that may predate macrostructural atrophy should be useful. We hypothesized that: (i) a validated MRI-derived Alzheimer’s disease signature based on cortical thickness and hippocampal volume in cognitively normal middle-aged adults would predict progression to mild cognitive impairment; and (ii) a novel grey matter mean diffusivity signature would be a better predictor than the thickness/volume signature. This cohort study was part of the Vietnam Era Twin Study of Aging. Concurrent analyses compared cognitively normal and mild cognitive impairment groups at each of three study waves (ns = 246–367). Predictive analyses included 169 cognitively normal men at baseline (age = 56.1, range = 51–60). Our previously published thickness/volume signature derived from independent data, a novel mean diffusivity signature using the same regions and weights as the thickness/volume signature, age, and an Alzheimer’s disease polygenic risk score were used to predict incident mild cognitive impairment an average of 12 years after baseline (follow-up age = 67.2, range = 61–71). Additional analyses adjusted for predicted brain age difference scores (chronological age minus predicted brain age) to determine if signatures were Alzheimer-related and not simply ageing-related. In concurrent analyses, individuals with mild cognitive impairment had higher (worse) mean diffusivity signature scores than cognitively normal participants, but thickness/volume signature scores did not differ between groups. In predictive analyses, age and polygenic risk score yielded an area under the curve of 0.74 (sensitivity = 80.00%; specificity = 65.10%). Prediction was significantly improved with addition of the mean diffusivity signature (area under the curve = 0.83; sensitivity = 85.00%; specificity = 77.85%; P = 0.007), but not with addition of the thickness/volume signature. A model including both signatures did not improve prediction over a model with only the mean diffusivity signature. Results held up after adjusting for predicted brain age difference scores. The novel mean diffusivity signature was limited by being yoked to the thickness/volume signature weightings. An independently derived mean diffusivity signature may thus provide even stronger prediction. The young age of the sample at baseline is particularly notable. Given that the brain signatures were examined when participants were only in their 50 s, our results suggest a promising step towards improving very early identification of Alzheimer’s disease risk and the potential value of mean diffusivity and/or multimodal brain signatures.
    Type of Medium: Online Resource
    ISSN: 2632-1297
    URL: Article
    DOI: 10.1093/braincomms/fcab167
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 5
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    Association of Epigenetic Age Acceleration With Incident Mild Cognitive Impairment and Dementia Among Older Women
    Oxford University Press (OUP) ; 2022
    In:  The Journals of Gerontology: Series A Vol. 77, No. 6 ( 2022-06-01), p. 1239-1244
    Details
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 77, No. 6 ( 2022-06-01), p. 1239-1244
    Abstract: Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of 4 AgeAccel measures with incident MCI and dementia. Methods This prospective analysis included 578 older women from the Women’s Health Initiative Memory Study selected for a case–cohort study of coronary heart disease (CHD). Women were free of CHD and cognitive impairment at baseline. Associations of AgeAccel measures (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA] , AgeAccelPheno, and AgeAccelGrim) with risks for incident adjudicated diagnoses of MCI and dementia overall and stratified by incident CHD status were evaluated. Results IEAA was not significantly associated with MCI (HR, 1.23; 95% CI, 0.99–1.53), dementia (HR, 1.10; 95% CI, 0.88–1.38), or cognitive impairment (HR, 1.18; 95% CI, 0.99–1.40). In stratified analysis by incident CHD status, there was a 39% (HR, 1.39; 95% CI, 1.07–1.81) significantly higher risk of MCI for every 5-year increase in IEAA among women who developed CHD during follow-up. Other AgeAccel measures were not significantly associated with MCI or dementia. Conclusions IEAA was not significantly associated with cognitive impairment overall but was associated with impairment among women who developed CHD. Larger studies designed to examine associations of AgeAccel with cognitive impairment are needed, including exploration of whether associations are stronger in the setting of underlying vascular pathologies.
    Type of Medium: Online Resource
    ISSN: 1079-5006 , 1758-535X
    URL: Article
    DOI: 10.1093/gerona/glab245
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
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    Hearing Impairment and Cognitive Decline in Older, Community-Dwelling Adults
    Oxford University Press (OUP) ; 2020
    In:  The Journals of Gerontology: Series A Vol. 75, No. 3 ( 2020-02-14), p. 567-573
    Details
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 75, No. 3 ( 2020-02-14), p. 567-573
    Abstract: Hearing impairment is prevalent among older adults and has been identified as a risk factor for cognitive impairment and dementia. We evaluated the association of hearing impairment with long-term cognitive decline among community-dwelling older adults. Methods A population-based longitudinal study of adults not using hearing aids who had hearing acuity and cognitive function assessed in 1992–1996, and were followed for a maximum of 24 years with up to five additional cognitive assessments. Hearing acuity was categorized based on pure-tone average (PTA) thresholds: normal (PTA ≤ 25 dB), mild impairment (PTA & gt; 25–40 dB), moderate/severe impairment (PTA & gt; 40 dB). Results Of 1,164 participants (mean age 73.5 years, 64% women), 580 (49.8%) had mild hearing impairment and 196 (16.8%) had moderate/severe hearing impairment. In fully adjusted models, hearing impairment was associated with steeper decline on the Mini-Mental State Examination (MMSE) (mild impairment β = −0.04, p = .01; moderate/severe impairment β = −0.08, p = .002) and Trails B (mild impairment β = 1.21, p = .003; moderate/severe impairment β = 2.16, p = .003). Associations did not differ by sex or apolipoprotein E (APOE) ϵ4 status and were not influenced by social engagement. The MMSE-hearing association was modified by education: mild hearing impairment was associated with steeper decline on the MMSE among participants without college education but not among those with college education. Moderate/severe hearing impairment was associated with steeper MMSE decline regardless of education level. Conclusions Hearing impairment is associated with accelerated cognitive decline with age, and should be screened for routinely. Higher education may provide sufficient cognitive reserve to counter effects of mild, but not more severe, hearing impairment.
    Type of Medium: Online Resource
    ISSN: 1079-5006 , 1758-535X
    URL: Article
    DOI: 10.1093/gerona/glz035
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 7
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    HEAVY ALCOHOL CONSUMPTION IN MIDLIFE IS ASSOCIATED WITH ACCELERATED BRAIN AGING SIX YEARS LATER
    Oxford University Press (OUP) ; 2019
    In:  Innovation in Aging Vol. 3, No. Supplement_1 ( 2019-11-08), p. S911-S911
    Details
    In: Innovation in Aging, Oxford University Press (OUP), Vol. 3, No. Supplement_1 ( 2019-11-08), p. S911-S911
    Abstract: Excessive alcohol consumption is associated with cognitive decline, exacerbated brain atrophy, and dementia in older adults, but associations with midlife brain health are less well understood. We hypothesized that heavy drinkers would have older-looking brains in late midlife. We examined alcohol consumption at mean age 56 (range 51-59) in 364 men from the Vietnam Era Twin Study of Aging (VETSA) and their predicted brain age at mean age 62 (range 56-67). We created five midlife alcohol consumption groups based on drinks consumed over the past two weeks: never, former, light (1-14), moderate (15-28), and heavy ( & gt;28). Participants underwent structural magnetic resonance imaging at mean age 62. Predicted brain age was measured using the Brain-Age Regression Analysis and Computation Utility software (BARACUS). Models adjusted for age, scanner, race/ethnicity, SES, smoking, health, depressive symptoms, alcohol dependence, general cognitive ability at age 20, and non-independence of twins within pairs. Heavy drinkers had a significantly older predicted than chronological brain age (M= 5.93, SE= 0.88) compared to each of the other four groups (p’s & lt; 0.05). There were no significant differences among the never (M= 2.88, SE= 0.98), former (M= 2.76, SE= 0.74), light (M= 3.00, SE= 0.94), or moderate (M= 5.93, SE= 0.88) consumption groups. Heavy alcohol consumption at age 56 was associated with an approximately 3-year greater predicted brain age difference at age 62. There was no evidence of protective effects of light/moderate drinking over non-drinking. The neurotoxic effects of excessive alcohol may exacerbate brain aging in late midlife.
    Type of Medium: Online Resource
    ISSN: 2399-5300
    URL: Article
    DOI: 10.1093/geroni/igz038.3324
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2905697-4
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  • 8
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    Dual impairments in visual and hearing acuity and age-related cognitive decline in older adults from the Rancho Bernardo Study of Healthy Aging
    Oxford University Press (OUP) ; 2021
    In:  Age and Ageing Vol. 50, No. 4 ( 2021-06-28), p. 1268-1276
    Details
    In: Age and Ageing, Oxford University Press (OUP), Vol. 50, No. 4 ( 2021-06-28), p. 1268-1276
    Abstract: We examined the associations between dual impairments in visual and hearing acuity and aging-related cognitive decline. Methods This was a longitudinal study of adults who had visual and hearing acuity and cognitive function assessed in 1992–1996 and were followed for up to 24 years (mean = 7.3 years), with up to five additional cognitive assessments. Visual impairment was defined as vision worse than 20/40, hearing impairment as pure-tone average thresholds & gt;25 dB. Associations were tested using linear mixed-effects regressions. Results Of 1,383 participants, 293 had visual impairment, 990 had a hearing impairment and 251 had both deficits. In fully adjusted models, low visual acuity was associated with poorer Mini-Mental State Examination (MMSE; β = −0.29) and Trail-Making Test Part B (Trails B; β = 13.22) performance, and with faster declines in MMSE (β = −0.12) and Trails B (β = 1.84). The combination of low visual and low hearing acuity was associated with poorer MMSE (β = −0.44) and Trails B (β = 11.20) scores, and with faster declines in MMSE (β = −0.19), Trails B (β = 3.50), and Verbal Fluency Test (VFT; β = −0.14) performance. Associations were similar in men and women. Conclusion Impairments in both vision and hearing are associated with a more rapid decline in cognitive function with aging.
    Type of Medium: Online Resource
    ISSN: 0002-0729 , 1468-2834
    URL: Article
    DOI: 10.1093/ageing/afaa285
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2065766-3
    detail.hit.zdb_id: 186788-X
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  • 9
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    Lifetime physical activity and late-life cognitive function: the Rancho Bernardo study
    Oxford University Press (OUP) ; 2019
    In:  Age and Ageing Vol. 48, No. 2 ( 2019-03-01), p. 241-246
    Details
    In: Age and Ageing, Oxford University Press (OUP), Vol. 48, No. 2 ( 2019-03-01), p. 241-246
    Type of Medium: Online Resource
    ISSN: 0002-0729 , 1468-2834
    URL: Article
    DOI: 10.1093/ageing/afy188
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2065766-3
    detail.hit.zdb_id: 186788-X
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  • 10
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    Polygenic hazard score, amyloid deposition and Alzheimer’s neurodegeneration
    Oxford University Press (OUP) ; 2019
    In:  Brain Vol. 142, No. 2 ( 2019-02-01), p. 460-470
    Details
    In: Brain, Oxford University Press (OUP), Vol. 142, No. 2 ( 2019-02-01), p. 460-470
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awy327
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1474117-9
    detail.hit.zdb_id: 80072-7
    SSG: 12
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