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- Strikwerda-Brown, Cherie, et al.
(författare)
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Association of Elevated Amyloid and Tau Positron Emission Tomography Signal with Near-Term Development of Alzheimer Disease Symptoms in Older Adults Without Cognitive Impairment
- 2022
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 79:10, s. 975-985
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Tidskriftsartikel (refereegranskat)abstract
- Importance: National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD). Objective: To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD. Design, Setting, and Participants: This longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid β and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years. Exposures: Based on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+T+, A+T-, A-T+, A-T-). Presence (+) or absence (-) of neurodegeneration (N) was assessed using temporal cortical thickness. Main Outcomes and Measures: Each cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups. Results: Among 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable. Conclusions and Relevance: The clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years..
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| 2. |
- Baril, Andree-Ann, et al.
(författare)
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Day-to-day sleep variability with Alzheimer's biomarkers in at-risk elderly
- 2024
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Ingår i: ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING. - 2352-8729. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION Measuring day-to-day sleep variability might reveal unstable sleep-wake cycles reflecting neurodegenerative processes. We evaluated the association between Alzheimer's disease (AD) fluid biomarkers with day-to-day sleep variability. METHODS In the PREVENT-AD cohort, 203 dementia-free participants (age: 68.3 +/- 5.4; 78 males) with a parental history of sporadic AD were tested with actigraphy and fluid biomarkers. Day-to-day variability (standard deviations over a week) was assessed for sleep midpoint, duration, efficiency, and nighttime activity count. RESULTS Lower cerebrospinal fluid (CSF) ApoE, higher CSF p-tau181/amyloid-beta (A beta)(42), and higher plasma p-tau231/A beta(42) were associated with higher variability of sleep midpoint, sleep duration, and/or activity count. The associations between fluid biomarkers with greater sleep duration variability were especially observed in those that carried the APOE4 allele, mild cognitive impairment converters, or those with gray matter atrophy. DISCUSSION Day-to-day sleep variability were associated with biomarkers of AD in at-risk individuals, suggesting that unstable sleep promotes neurodegeneration or, conversely, that AD neuropathology disrupts sleep-wake cycles.
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| 3. |
- Hayden, Kathleen M, et al.
(författare)
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Effects of family history and apolipoprotein E epsilon4 status on cognitive decline in the absence of Alzheimer dementia: the Cache County Study.
- 2009
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Ingår i: Archives of neurology. - : American Medical Association (AMA). - 1538-3687 .- 0003-9942. ; 66:11, s. 1378-83
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the influences of a family history of Alzheimer dementia (FHxAD) and the apolipoprotein E epsilon4 genotype (APOE epsilon4) on cognitive decline. DESIGN, SETTING, AND PARTICIPANTS: Residents of Cache County, Utah, aged 65 years or older, were invited to participate. At baseline, 2957 participants provided DNA for genotyping of APOE and a detailed FHxAD. They also completed the Modified Mini-Mental State Examination. Cognitive status was reexamined after 3 and 7 years. We used mixed-effects models to examine the association among FHxAD, APOE epsilon4, and cognitive trajectories. MAIN OUTCOME MEASURE: Modified Mini-Mental State Examination score trajectories over time. RESULTS: Compared with participants who did not have APOE epsilon4 or an FHxAD, those with APOE epsilon4 scored lower on the Modified Mini-Mental State Examination at baseline (-0.70 points; 95% confidence interval [CI], -1.15 to -0.24). Participants with an FHxAD and APOE epsilon4 differed less, if at all, in baseline score (-0.46 points; 95% CI, -1.09 to 0.16) but declined faster during the 7-year study (-9.75 points [95% CI, -10.82 to -8.67] vs -2.91 points [95% CI, -3.37 to -2.44]). After exclusion of participants who developed prodromal AD or incident dementia, the group with an FHxAD and APOE epsilon4 declined much less during the 7-year study (-1.54; 95% CI, -2.59 to -0.50). CONCLUSIONS: Much of the association among FHxAD, APOE epsilon4, and cognitive decline may be attributed to undetected incipient (latent) disease. In the absence of latent disease, the 2 factors do not appear individually to be associated with cognitive decline, although they may be additive.
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| 5. |
- Meyer, Pierre-François, et al.
(författare)
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Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults.
- 2022
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 91:4, s. 548-560
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate novel plasma p-tau231 and p-tau181, as well as Aβ40 and Aβ42 assays as indicators of tau and Aβ pathologies measured with positron emission tomography (PET), and their association with cognitive change, in cognitively unimpaired older adults.In a cohort of 244 older adults at risk of Alzheimer's disease (AD) owing to a family history of AD dementia, we measured single molecule array (Simoa)-based plasma tau biomarkers (p-tau231 and p-tau181), Aβ40 and Aβ42 with immunoprecipitation mass spectrometry, and Simoa neurofilament light (NfL). A subset of 129 participants underwent amyloid-β (18 F-NAV4694) and tau (18 F-flortaucipir) PET assessments. We investigated plasma biomarker associations with Aβ and tau PET at the global and voxel level and tested plasma biomarker combinations for improved detection of Aβ-PET positivity. We also investigated associations with 8-year cognitive change.Plasma p-tau biomarkers correlated with flortaucipir binding in medial temporal, parietal, and inferior temporal regions. P-tau231 showed further associations in lateral parietal and occipital cortices. Plasma Aβ42/40 explained more variance in global Aβ-PET binding than Aβ42 alone. P-tau231 also showed strong and widespread associations with cortical Aβ-PET binding. Combining Aβ42/40 with p-tau231 or p-tau181 allowed for good distinction between Aβ-negative and -positive participants (area under the receiver operating characteristic curve [AUC] range=0.81-0.86). Individuals with low plasma Aβ42/40 and high p-tau experienced faster cognitive decline.Plasma p-tau231 showed more robust associations with PET biomarkers than p-tau181 in presymptomatic individuals. The combination of p-tau and Aβ42/40 biomarkers detected early AD pathology and cognitive decline. Such markers could be used as prescreening tools to reduce the cost of prevention trials. ANN NEUROL 2022.
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| 6. |
- Norton, Maria C, et al.
(författare)
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Church attendance and new episodes of major depression in a community study of older adults: the Cache County Study.
- 2008
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Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - 1079-5014. ; 63:3
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Tidskriftsartikel (refereegranskat)abstract
- We examined the relation between church attendance, membership in the Church of Jesus Christ of Latter-Day Saints (LDS), and major depressive episode, in a population-based study of aging and dementia in Cache County, Utah. Participants included 2,989 nondemented individuals aged between 65 and 100 years who were interviewed initially in 1995 to 1996 and again in 1998 to 1999. LDS church members reported twice the rate of major depression that non-LDS members did (odds ratio = 2.56, 95% confidence interval = 1.07-6.08). Individuals attending church weekly or more often had a significantly lower risk for major depression. After controlling for demographic and health variables and the strongest predictor of future episodes of depression, a prior depression history, we found that church attendance more often than weekly remained a significant protectant (odds ratio = 0.51, 95% confidence interval = 0.28-0.92). Results suggest that there may be a threshold of church attendance that is necessary for a person to garner long-term protection from depression. We discuss sociological factors relevant to LDS culture.
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| 10. |
- Norton, Maria C, et al.
(författare)
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Three-year incidence of first-onset depressive syndrome in a population sample of older adults: the Cache County study.
- 2006
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Ingår i: Am J Geriatr Psychiatry. - 1064-7481. ; 14:3, s. 237-45
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Estimates of incidence of late-life depression vary greatly with few studies excluding demented cases through in-depth evaluation and most studies failing to control for the effect of mortality and interval treatment. In a large population-based study, the authors examined the effect on incidence of first-onset depressive syndrome to determine whether any gender or age differences in incidence are attenuated with inclusion of these additional measures. METHOD: Incidence rates of depressive syndrome per 1,000 person-years are presented for 2,877 nondemented elderly (ages 65 to 100 years) residents of Cache County, Utah. Cases are identified by direct interview methods, by inference from prescription antidepressant medicine use, and by postmortem informant interview for decedents. RESULTS: In-person interviews yielded incidence rates of first-onset depressive disorder (any type) of 13.09 for men and 19.44 for women. Inclusion of antidepressant users increased these figures to 15.55 for men and 23.30 for women. Addition of postmortem interview data yielded rates of 20.66 for men and 26.29 for women. Individuals with no history of depression had rates for major depression of 7.88 for men and 8.75 for women; minor depression rates were 19.23 for men and 24.46 for women (p = 0.691; effect for minor depression p <0.0001). Age did not predict incidence. CONCLUSIONS: Incidence of first-onset major depression varies with data source and prior lifetime history of depression. Gender effects apparent in interview data are attenuated when postmortem information and pharmacotherapy were considered.
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