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1.
Sirwan K.L. Darweesh Frank J. Wolters M. Arfan Ikram Frank de Wolf Daniel Bos Albert Hofman 《Alzheimer's & dementia》2018,14(11):1450-1459
Introduction
Inflammatory markers are often elevated in patients with dementia, including Alzheimer's disease (AD). However, it remains unclear whether inflammatory markers are associated with the risk of developing dementia.Methods
We searched PubMed, Embase, and Cochrane library for prospective population-based studies reporting associations between inflammatory markers and all-cause dementia or AD. We used random effects meta-analyses to obtain pooled hazard ratios (HRs) and 95% confidence intervals of inflammatory markers (highest vs. lowest quantile) for all-cause dementia and AD.Results
Fifteen articles from 13 studies in six countries reported data that could be meta-analyzed. C-reactive protein (HR = 1.37 [1.05; 1.78]), interleukin-6 (HR = 1.40 [1.13; 1.73]), α1-antichymotrypsin (HR = 1.54 [1.14; 2.80]), lipoprotein-associated phospholipase A2 activity (HR = 1.40 [1.03; 1.90]), and fibrinogen were each associated with all-cause dementia, but neither was significantly associated with AD.Discussion
Several inflammatory markers are associated with an increased risk of all-cause dementia; however, these markers are not specific for AD. Whether inflammatory markers closely involved in AD pathology are associated with the risk of AD remains to be elucidated. 相似文献2.
Elżbieta Kuźma Ilianna Lourida Sarah F. Moore Deborah A. Levine Obioha C. Ukoumunne David J. Llewellyn 《Alzheimer's & dementia》2018,14(11):1416-1426
Introduction
Stroke is an established risk factor for all-cause dementia, though meta-analyses are needed to quantify this risk.Methods
We searched Medline, PsycINFO, and Embase for studies assessing prevalent or incident stroke versus a no-stroke comparison group and the risk of all-cause dementia. Random effects meta-analysis was used to pool adjusted estimates across studies, and meta-regression was used to investigate potential effect modifiers.Results
We identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69 (95% confidence interval: 1.49–1.92; P < .00001; I2 = 87%). For incident stroke, the pooled risk ratio was 2.18 (95% confidence interval: 1.90–2.50; P < .00001; I2 = 88%). Study characteristics did not modify these associations, with the exception of sex which explained 50.2% of between-study heterogeneity for prevalent stroke.Discussion
Stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia. 相似文献3.
Vincent Chouraki Sarah R. Preis Qiong Yang Alexa Beiser Shuo Li Martin G. Larson Galit Weinstein Thomas J. Wang Robert E. Gerszten Ramachandran S. Vasan Sudha Seshadri 《Alzheimer's & dementia》2017,13(12):1327-1336
Introduction
The identification of novel biomarkers associated with Alzheimer's disease (AD) could provide key biological insights and permit targeted preclinical prevention. We investigated circulating metabolites associated with incident dementia and AD using metabolomics.Methods
Plasma levels of 217 metabolites were assessed in 2067 dementia-free Framingham Offspring Cohort participants (mean age = 55.9 ± 9.7 years; 52.4% women). We studied their associations with future dementia and AD risk in multivariate Cox models.Results
Ninety-three participants developed incident dementia (mean follow-up = 15.6 ± 5.2 years). Higher plasma anthranilic acid levels were associated with greater risk of dementia (hazard ratio [HR] = 1.40; 95% confidence interval [CI] = [1.15–1.70]; P = 8.08 × 10?4). Glutamic acid (HR = 1.38; 95% CI = [1.11–1.72]), taurine (HR = 0.74; 95% CI = [0.60–0.92]), and hypoxanthine (HR = 0.74; 95% CI = [0.60–0.92]) levels also showed suggestive associations with dementia risk.Discussion
We identified four biologically plausible, candidate plasma biomarkers for dementia. Association of anthranilic acid implicates the kynurenine pathway, which modulates glutamate excitotoxicity. The associations with hypoxanthine and taurine strengthen evidence that uric acid and taurine may be neuroprotective. 相似文献4.
Catherine Feart Catherine Helmer Bénédicte Merle François R. Herrmann Cédric Annweiler Jean-François Dartigues Cécile Delcourt Cécilia Samieri 《Alzheimer's & dementia》2017,13(11):1207-1216
Introduction
Hypovitaminosis D has been associated with several chronic conditions; yet, its association with cognitive decline and the risk of dementia and Alzheimer's disease (AD) has been inconsistent.Methods
The study population consisted of 916 participants from the Three-City Bordeaux cohort aged 65+, nondemented at baseline, with assessment of vitamin D status and who were followed for up to 12 years.Results
In multivariate analysis, compared with individuals with 25(OH)D sufficiency (n = 151), participants with 25(OH)D deficiency (n = 218) exhibited a faster cognitive decline. A total of 177 dementia cases (124 AD) occurred: 25(OH)D deficiency was associated with a nearly three-fold increased risk of AD (hazard ratio = 2.85, 95% confidence interval 1.37–5.97).Discussion
This large prospective study of French older adults suggests that maintaining adequate vitamin D status in older age could contribute to slow down cognitive decline and to delay or prevent the onset of dementia, especially of AD etiology. 相似文献5.
Tobias Skillbäck Ronald Lautner Niklas Mattsson Jonathan M. Schott Ingmar Skoog Katarina Nägga Lena Kilander Anders Wimo Bengt Winblad Maria Eriksdotter Kaj Blennow Henrik Zetterberg 《Alzheimer's & dementia》2018,14(7):895-901
Introduction
The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied.Methods
We used a data set on 2858 subjects (1098 AD, 260 vascular dementia [VaD], 145 mixed AD and VaD, 90 other dementia diagnoses, and 1265 controls) to examine the association of APOE polymorphisms with clinical dementia diagnoses, biomarker profiles, and longevity.Results
The ε4 allele was associated with reduced longevity as ε4 versus ε3 homozygotes lived on average 2.6 years shorter (P = .006). In AD, ε4 carriers lived 1.0 years shorter than noncarriers (P = .028). The ε4 allele was more prevalent in AD, mixed AD and VaD, and VaD patients compared to controls, but not in other dementia disorders.Discussion
The APOE ε4 allele is influential in AD but might also be of importance in VaD and in mixed AD and VaD, diseases in which concomitant AD pathology is common. 相似文献6.
Lana Fani Frank J. Wolters M. Kamran Ikram Marco J. Bruno Albert Hofman Peter J. Koudstaal Sarwa Darwish Murad M. Arfan Ikram 《Alzheimer's & dementia》2018,14(10):1377-1382
Introduction
Helicobacter pylori infection might increase risk of dementia, but available evidence is inconsistent, and longitudinal studies are sparse. We investigated the association between H. pylori serology and dementia risk in a population-based cohort.Methods
Between 1997 and 2002, we measured H. pylori serum IgG titers in 4215 nondemented participants of the Rotterdam Study with a mean age of 69 years. We determined the association between H. pylori at baseline and dementia incidence until 2015, per natural log (U/mL) increase in titer, and for seropositive/seronegative, using Cox models adjusting for cohort, sex, age, education, and cardiovascular risk factors.Results
During a median follow-up of 13.3 years, 529 participants developed dementia, of which 463 had Alzheimer's disease. H. pylori was not associated with risk of dementia (hazard ratio [95% confidence interval] for antibody titer: 1.04 [0.90–1.21]; for seropositivity 1.03 [0.86–1.22]), or Alzheimer's disease.Discussion
In this community-dwelling population, H. pylori was not associated with dementia risk. 相似文献7.
Thanh G.N. Ton Thomas DeLeire Suepattra G. May Ningqi Hou Mahlet G. Tebeka Er Chen Joshua Chodosh 《Alzheimer's & dementia》2017,13(3):217-224
Introduction
Individuals with amnestic mild cognitive impairment (aMCI) are at elevated risk of developing Alzheimer's disease (AD) dementia.Methods
With data from the Aging, Demographics, and Memory Study, we used the Clinical Dementia Rating Sum of Boxes classifications to conduct a cross-sectional analysis assessing the relationship between cognitive state and various direct and indirect costs and health care utilization patterns.Results
Patients with aMCI had less medical expenditures than patients with moderate and severe AD dementia (P < .001) and were also significantly less likely to have been hospitalized (P = .04) and admitted to nursing home (P < .001). Compared to individuals with normal cognition, patients with aMCI had significantly less household income (P = .018).Discussion
Patients with aMCI had lower medical expenditures than patients with AD dementia. Poor cognitive status was linearly associated with lower household income, higher medical expenditures, higher likelihood of nursing and home care services, and lower likelihood of outpatient visits. 相似文献8.
Introduction
The etiologies of dementia are complex and influenced by genetic and environmental factors including medical conditions.Methods
We used Cox regression model to estimate the individual and joint effects of physical activity (PA), apolipoprotein E (APOE) ε4, and diabetes status on risk of dementia and cognitive impairment without dementia (CIND) among 1438 cognitively intact Mexican American elderly who were followed up to 10 years.Results
The risk of developing dementia/CIND was increased more than threefold in APOE ε4 carriers or diabetics with low levels of PA compared with ε4 noncarriers or nondiabetics who engaged in high PA (ε4: hazard ratio [HR] = 3.44, 95% confidence interval [CI] = 1.85–6.39; diabetes: HR = 3.11, 95% CI = 1.87–5.18); the presence of all three risk factors increased risk by nearly 10-fold (HR = 9.49, 95% CI = 3.57–25.3).Discussion
PA in elderly Hispanics protects strongly against the onset of dementia/CIND, especially in APOE ε4 carriers and those who have diabetes. 相似文献9.
Kumar B. Rajan Jennifer Weuve Lisa L. Barnes Robert S. Wilson Denis A. Evans 《Alzheimer's & dementia》2019,15(1):1-7
Introduction
The trends in prevalence and incidence of Alzheimer's disease (AD) dementia remain uncertain.Methods
A sample of 2794 participants with a clinical diagnosis for AD dementia were included.Results
The 2010 census standardized prevalence of AD dementia was 14.5% (95% CI = 13.7–15.3), and annual incidence was 2.3% (1.7–2.9). Both prevalence and incidence showed substantial variation over time, but no secular trends. The prevalence of AD dementia did not change significantly from 14.6% (95% CI = 13.0, 16.2) in 1994–1997 to 14.7% (95% CI = 13.2, 16.2) in 2010–2012 (P = .84). The annual incidence of AD dementia was 2.8% (95% CI = 2.2, 3.2) in 1998–2000 and 2.2% (95% CI = 1.6, 2.8) in 2004–2006 (P = .20) and remained steady in 2010–2012. The prevalence and incidence among African Americans were approximately twice than those among European Americans.Conclusions
The prevalence and incidence of AD dementia showed substantial variation between 1994 and 2012, but no secular trend. 相似文献10.
Kathleen M. Hayden Daniel P. Beavers Susan E. Steck James R. Hebert Fred K. Tabung Nitin Shivappa Ramon Casanova JoAnn E. Manson Claudia B. Padula Elena Salmoirago-Blotcher Linda G. Snetselaar Oleg Zaslavsky Stephen R. Rapp 《Alzheimer's & dementia》2017,13(11):1187-1196
Introduction
The Mediterranean and Dietary Approaches to Stop Hypertension diets have been associated with lower dementia risk. We evaluated dietary inflammatory potential in relation to mild cognitive impairment (MCI)/dementia risk.Methods
Baseline food frequency questionnaires from n = 7085 women (aged 65–79 years) were used to calculate Dietary Inflammatory Index (DII) scores that were categorized into four groups. Cognitive function was evaluated annually, and MCI and all-cause dementia cases were adjudicated centrally. Mixed effect models evaluated cognitive decline on over time; Cox models evaluated the risk of MCI or dementia across DII groups.Results
Over an average of 9.7 years, there were 1081 incident cases of cognitive impairment. Higher DII scores were associated with greater cognitive decline and earlier onset of cognitive impairment. Adjusted hazard ratios (HRs) comparing lower (anti-inflammatory; group 1 referent) DII scores to the higher scores were group 2-HR: 1.01 (0.86–1.20); group 3-HR: 0.99 (0.82–1.18); and group 4-HR: 1.27 (1.06–1.52).Conclusions
Diets with the highest pro-inflammatory potential were associated with higher risk of MCI or dementia. 相似文献11.
Pamela L. Lutsey Jeffrey R. Misialek Thomas H. Mosley Rebecca F. Gottesman Naresh M. Punjabi Eyal Shahar Richard MacLehose Rachel P. Ogilvie David Knopman Alvaro Alonso 《Alzheimer's & dementia》2018,14(2):157-166
Introduction
This study tested the hypotheses that late-midlife obstructive sleep apnea (OSA) and short and long sleep duration are associated with dementia over 15 years of follow-up.Methods
A total of 1667 Atherosclerosis Risk in Communities Study participants underwent in-home polysomnography (1996–1998) and were followed for dementia. Dementia was defined by (1) hospitalization diagnosis codes (1996–2012) and (2) a comprehensive neurocognitive examination (2011–2013) with adjudication.Results
OSA and sleep duration were not associated with risk of incident dementia. When using adjudicated outcomes, severe OSA (≥30 vs. <5 apnea-hypopnea events/hour) was associated with higher risk of all-cause dementia (risk ratio [95% confidence interval], 2.35 [1.06–5.18]) and Alzheimer's disease dementia (1.66 [1.03–2.68]); associations were attenuated with cardiovascular risk factor adjustment. Sleeping <7 versus 8 to ≤9 hours was associated with higher risk of all-cause dementia (2.00 [1.03–3.86]).Discussion
When adjudicated outcome definitions were used, late-midlife OSA and short sleep duration were associated with all-cause and Alzheimer's disease dementia in later life. 相似文献12.
Archana Singh-Manoux Aline Dugravot Martin Shipley Eric J. Brunner Alexis Elbaz Séverine Sabia Mika Kivimaki 《Alzheimer's & dementia》2018,14(2):178-186
Introduction
We examined whether obesity at ages 50, 60, and 70 years is associated with subsequent dementia. Changes in body mass index (BMI) for more than 28 years before dementia diagnosis were compared with changes in BMI in those free of dementia.Methods
A total of 10,308 adults (33% women) aged 35 to 55 years in 1985 were followed up until 2015. BMI was assessed six times and 329 cases of dementia were recorded.Results
Obesity (BMI ≥30 kg/m2) at age 50 years (hazard ratio = 1.93; 1.35–2.75) but not at 60 or 70 years was associated with risk of dementia. Trajectories of BMI differed in those with dementia compared with all others (P < .0001) or to matched control subjects (P < .0001) such that BMI in dementia cases was higher from 28 years (P = .001) to 16 years (P = .05) and lower starting 8 years before diagnosis.Discussion
Obesity in midlife and weight loss in the preclinical phase characterizes dementia; the current obesity epidemic may affect future dementia rates. 相似文献13.
Olivier Hanon Jean-Sébastien Vidal Sylvain Lehmann Stéphanie Bombois Bernadette Allinquant Jean-Marc Tréluyer Patrick Gelé Christine Delmaire Fredéric Blanc Jean-François Mangin Luc Buée Jacques Touchon Jacques Hugon Bruno Vellas Evelyne Galbrun Athanase Benetos Gilles Berrut Elèna Paillaud Suzanna Schraen-Maschke 《Alzheimer's & dementia》2018,14(7):858-868
Introduction
Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aβ42 and Aβ40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers.Methods
One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included.Results
Plasma Aβ1–42 and Aβ1–40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aβ1–42 and P = .04 for Aβ1–40). Globally, plasma Aβ1–42 correlated with age, Mini–Mental State Examination, and APOE ε4 allele. Plasma Aβ1–42 correlated with all CSF biomarkers in MCI but only with CSF Aβ42 in AD.Discussion
Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose. 相似文献14.
Shireen Sindi Ingemar Kåreholt Lena Johansson Johan Skoog Linnea Sjöberg Hui-Xin Wang Boo Johansson Laura Fratiglioni Hilkka Soininen Alina Solomon Ingmar Skoog Miia Kivipelto 《Alzheimer's & dementia》2018,14(10):1235-1242
Introduction
Few longitudinal studies assessed whether sleep disturbances are associated with dementia risk.Methods
Sleep disturbances were assessed in three population-based studies (H70 study and Kungsholmen Project [Sweden]; Cardiovascular Risk Factors, Aging and Dementia study [Finland]). Late-life baseline analyses (3–10 years follow-up) used all three studies (N = 1446). Baseline ages ≈ 70 years (Cardiovascular Risk Factors, Aging and Dementia, H70), and ≈84 years (Kungsholmen Project). Midlife baseline (age ≈ 50 years) analyses used Cardiovascular Risk Factors, Aging and Dementia (21 and 32 years follow-up) (N = 1407).Results
Midlife insomnia (fully adjusted hazard ratio = 1.24, 95% confidence interval = 1.02–1.50) and late-life terminal insomnia (fully adjusted odds ratio = 1.94, 95% confidence interval = 1.08–3.49) were associated with a higher dementia risk. Late-life long sleep duration (>9 hours) was also associated with an increased dementia risk (adjusted odds ratio = 3.98, 95% confidence interval = 1.87–8.48).Discussion
Midlife insomnia and late-life terminal insomnia or long sleep duration were associated with a higher late-life dementia risk. 相似文献15.
Karen Ritchie Isabelle Carrière Li Su John T. O&#x;Brien Simon Lovestone Katie Wells Craig W. Ritchie 《Alzheimer's & dementia》2017,13(10):1089-1097
Introduction
Although biomarker studies of late-onset Alzheimer's disease suggest pathology to be present decades before diagnosis, little is known about cognitive performance at this stage.Methods
A sample of 210 adults (aged 40–59) of whom 103 have a parent diagnosed with dementia (family history subgroup) underwent computerized cognitive testing. Apolipoprotein E (apoE) status was determined, and 193 subjects had magnetic resonance imaging. Distance from dementia onset was estimated in relation to age of parental diagnosis, and Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Scores were calculated.Results
Lower hippocampal volumes (P = .04) were associated with poorer spatial location recall and higher Dementia Risk Scores with poorer visual recognition (P = .0005), and lower brain and hippocampal volume (P < .0001, P = .04, respectively). Family history subgroup participants closer to dementia onset had lower scores on visual working memory (P = .05), whereas those with an APOE ε4 allele performed better on form perception (P = .005).Discussion
Middle-aged adults at risk of dementia show evidence of poorer cognitive performance, principally in visuospatial functions. 相似文献16.
María M. Corrada Kathleen M. Hayden Annlia Paganini-Hill Szofia S. Bullain Jaime DeMoss Colette Aguirre Ron Brookmeyer Claudia H. Kawas 《Alzheimer's & dementia》2017,13(2):103-110
Introduction
We investigated the association between age of onset of hypertension and dementia risk in an oldest-old cohort.Methods
Participants are from The 90+ Study, a population-based longitudinal study of people aged 90+ who are survivors from the Leisure World Cohort Study. We estimated hypertension onset age using self-reported information from The 90+ Study and Leisure World Cohort Study, collected about 20 years earlier. A total of 559 participants without dementia were followed every 6 months for up to 10 years.Results
A total of 224 participants developed dementia during follow-up (mean = 2.8 years). Compared with those without hypertension, participants whose hypertension onset age was 80 to 89 years had a lower dementia risk (hazard ratio = 0.58, P = .04) and participants with an onset age of 90+ years had the lowest risk (hazard ratio = 0.37, P = .004).Discussion
Developing hypertension at older ages may protect against dementia. Understanding the mechanisms for this lower risk is important for determining ways to prevent dementia in the very elderly. 相似文献17.
Jason D. Flatt Paola Gilsanz Charles P. Quesenberry Kathleen B. Albers Rachel A. Whitmer 《Alzheimer's & dementia》2018,14(1):28-34
Introduction
Post-traumatic stress disorder (PTSD) is associated with an increased risk of dementia in male veterans, but little is known in females and civilians.Methods
PTSD and comorbidities were abstracted from medical records from 1/1/1996 to 12/31/2001. Dementia incidence from 1/1/2002 to 12/31/2014 in 499,844 health care members aged 60+ years over an average of 8.2 years. Cox proportional hazard models were adjusted for age, demographics, and comorbidities.Results
PTSD was associated with increased risk of dementia over an average of 8 years of follow-up (females: hazard ratio [HR] = 1.59, 95% confidence interval [CI] = 1.30–1.95; males: HR = 1.96, 95% CI = 1.51–2.55). There was a two-fold risk of dementia in those with both PTSD and depression (females: HR = 2.08; 95% CI = 1.66–2.59; males: HR = 2.06; 95% CI = 1.47–2.91) versus those without.Discussion
PTSD was a risk factor for dementia in both sexes, with a heightened risk in those with comorbid depression. 相似文献18.
Lidia Sarro Nirubol Tosakulwong Christopher G. Schwarz Jonathan Graff-Radford Scott A. Przybelski Timothy G. Lesnick Samantha M. Zuk Robert I. Reid Mekala R. Raman Bradley F. Boeve Tanis J. Ferman David S. Knopman Giancarlo Comi Massimo Filippi Melissa E. Murray Joseph E. Parisi Dennis W. Dickson Ronald C. Petersen Kejal Kantarci 《Alzheimer's & dementia》2017,13(3):257-266
Introduction
Cerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB).Methods
White-matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age-matched and sex-matched cognitively normal subjects (CN) from a population-based cohort.Results
DLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia.Discussion
In DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease. 相似文献19.
Carlos Cruchaga Jorge L. Del-Aguila Benjamin Saef Kathleen Black Maria Victoria Fernandez John Budde Laura Ibanez Yuetiva Deming Manav Kapoor Giuseppe Tosto Richard P. Mayeux David M. Holtzman Anne M. Fagan John C. Morris Randall J. Bateman Alison M. Goate Oscar Harari 《Alzheimer's & dementia》2018,14(2):205-214
Objective
To determine whether the extent of overlap of the genetic architecture among the sporadic late-onset Alzheimer's Disease (sLOAD), familial late-onset AD (fLOAD), sporadic early-onset AD (sEOAD), and autosomal dominant early-onset AD (eADAD).Methods
Polygenic risk scores (PRSs) were constructed using previously identified 21 genome-wide significant loci for LOAD risk.Results
We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. The highest association of the PRS and risk (odds ratio [OR] = 2.27; P = 1.29 × 10?7) was observed in sEOAD, followed by fLOAD (OR = 1.75; P = 1.12 × 10?7) and sLOAD (OR = 1.40; P = 1.21 × 10?3). The PRS was associated with cerebrospinal fluid ptau181-Aβ42 on eADAD (P = 4.36 × 10?2).Conclusion
Our analysis confirms that the genetic factors identified for LOAD modulate risk in sLOAD and fLOAD and also sEOAD cohorts. Specifically, our results suggest that the burden of these risk variants is associated with familial clustering and earlier onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset. 相似文献20.
James D. Stefaniak Li Su Elijah Mak Nasim Sheikh-Bahaei Katie Wells Karen Ritchie Adam Waldman Craig W. Ritchie John T. O&#x;Brien 《Alzheimer's & dementia》2018,14(2):253-258