Application of survival analysis to the inception of dementia

SynopsisThe age at onset of dementia of the Alzheimer, Pick or senile type in relatives of probands with early onset dementia was examined using survival analytical techniques applied to data collected by Sjögren et al. (1952). Female relatives were found to have a higher risk of dementia than males, and there was a deficit of affected brothers compared with fathers of probands. In these comparisons due allowance was made for age at the last observation of each relative. Relatives of probable and definite Pick probands had a higher risk than relatives of probable and definite Alzheimer probands, but the difference was not significant and dementia did not occur at an earlier age to the former group.For the relatives as a whole, and for subgroups of relatives, the risk of dementia increased with age, at least up to age 80. It is hypothesized that the pattern of the age-related hazard of dementia is due to the nature of the dementing process; that this slow degenerative process is widespread; and that individual differences in the rate of the process are under the influence of genes. The statistical methods are explained in detail as they have rarely been applied to dementia before, though Chase et al. (1983) have used life tables and survival analysis in testing genetic hypotheses, with an application to Alzheimer's disease.

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Early-Onset Parkinson Disease Screening in Patients From Nigeria

Frontiers in Neurology ◽

10.3389/fneur.2020.594927 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lukasz M. Milanowski ◽

Olajumoke Oshinaike ◽

Benjamin J. Broadway ◽

Jennifer A. Lindemann ◽

Alexandra I. Soto-Beasley ◽

...

Keyword(s):

Functional Analysis ◽

Parkinson Disease ◽

Neurodegenerative Diseases ◽

Early Onset ◽

Local Population ◽

Age At Onset ◽

Compound Heterozygous ◽

Loss Of Function ◽

African Countries ◽

Age Related

Introduction: Nigeria is one of the most populated countries in the world; however, there is a scarcity of studies in patients with age-related neurodegenerative diseases, such as Parkinson disease (PD). The aim of this study was to screen patients with PD including a small cohort of early-onset PD (EOPD) cases from Nigeria for PRKN, PINK1, DJ1, SNCA multiplication, and LRRK2 p.G2019S.Methods: We assembled a cohort of 109 Nigerian patients with PD from the four main Nigerian tribes: Yoruba, Igbo, Edo, and Hausa. Fifteen cases [14 from the Yoruba tribe (93.3%)] had EOPD (defined as age-at-onset <50 years). All patients with EOPD were sequenced for the coding regions of PRKN, PINK1, and DJ1. Exon dosage analysis was performed with a multiplex ligation-dependent probe amplification assay, which also included a SNCA probe and LRRK2 p.G2019S. We screened for LRRK2 p.G2019S in the entire PD cohort using a genotyping assay. The PINK1 p.R501Q functional analysis was conducted.Results: In 15 patients with EOPD, 22 variants were observed [PRKN, 9 (40.9%); PINK1, 10 (45.5%); and DJ1, 3 (13.6%)]. Three (13.6%) rare, nonsynonymous variants were identified, but no homozygous or compound heterozygous carriers were found. No exonic rearrangements were present in the three genes, and no carriers of SNCA genomic multiplications or LRRK2 p.G2019S were identified. The PINK1 p.R501Q functional analysis revealed pathogenic loss of function.Conclusion: More studies on age-related neurodegenerative diseases are needed in sub-Saharan African countries, including Nigeria. Population-specific variation may provide insight into the genes involved in PD in the local population but may also contribute to larger studiesperformed in White and Asian populations.

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Novel Rare SORL1 Variants in Early-Onset Dementia

Journal of Alzheimer s Disease ◽

10.3233/jad-210207 ◽

2021 ◽

pp. 1-10

Author(s):

Anita Korpioja ◽

Johanna Krüger ◽

Susanna Koivuluoma ◽

Katri Pylkäs ◽

Virpi Moilanen ◽

...

Keyword(s):

Exome Sequencing ◽

Early Onset ◽

Rare Variants ◽

Late Onset ◽

Age At Onset ◽

Early Onset Dementia ◽

Missense Variants ◽

Whole Exome ◽

Increased Risk

Background: Rare variants of SORL1 have been associated with an increased risk of early-onset or late-onset Alzheimer’s disease (AD). However, a lot remains to be clarified about their significance in the pathogenesis of the disease. Objective: To evaluate the role of SORL1 variants among Finnish patients with early-onset AD (EOAD). Methods: The rare SORL1variants were screened in a cohort of 115 Finnish EOAD patients (mean age at onset 58.3 years, range 46–65 years) by using the whole-exome sequencing. Results: We found one novel nonsense variant (p.Gln290 *) and eight missense variants in SORL1. This is the first study reporting the SORL1 variants p.Lys80Arg, p.Ala789Val and p.Arg866Gln in EOAD patients. Furthermore, two of these three missense variants were overrepresented in EOAD patients compared to gnomAD non-neuro Finnish samples. Conclusion: This study strengthens the earlier findings, that the rare variants in SORL1 are associated with EOAD.

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THE ASSOCIATION OF MILD TBI WITH EARLY ONSET DEMENTIA IN POST-9/11 VETERANS

Innovation in Aging ◽

10.1093/geroni/igz038.2435 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S657-S657

Author(s):

Mary Jo Pugh ◽

Hari Krishna Raju Sagiraju ◽

Blessen Eapen ◽

Alicia A Swan ◽

Margaret Wells ◽

...

Keyword(s):

Early Onset ◽

Conditional Logistic Regression ◽

Steering Committee ◽

Post Traumatic Stress ◽

Mild Tbi ◽

Early Onset Dementia ◽

Age Related ◽

Severe Tbi ◽

The Individual ◽

The Impact

Abstract Evidence produced by studies using ICD-9 codes to identify dementia suggests that mild traumatic brain injury (mTBI) can accelerate age-related neurodegeneration and dementia risk. However, ICD-9 codes are unreliable in identifying early onset dementia (<65 years; EOD) in civilian (positive predictive value [PPV]=58%) and VA (PPV=28%). From 1,724 Veterans <65years of age with 2 or more dementia diagnoses based on ICD-9 codes recommended by VA Dementia Steering Committee, we validated dementia diagnoses in 153 randomly selected cases using medical chart abstractions and reviews by a neuropsychologist panel. We matched valid cases based on age, sex, race/ethnicity, year of entry to VA care, and branch of service to 2490 controls with no indicators of dementia or cognitive impairment. TBI severity was defined using multiple DoD and VA data sources. We also identified diagnoses for mental (e.g., depression, post-traumatic stress disorder, substance use disorders) and other medical conditions (e.g., stroke) associated with dementia. We used conditional logistic regression to examine the association of TBI severity with EOD controlling for comorbidity. After controlling for mental health and other comorbid conditions mild TBI (mTBI) was significantly associated with validated EOD [aOR( 95%CI): mTBI-4.5(2.4-8.9), moderate/severe TBI-21.3(8.4-54.3)]. Stroke, depression, PTSD, and headache were also associated with higher odds of EOD. These findings suggest that Veterans with mTBI are at risk for dementia, and clinicians should consider brief screening for cognitive dysfunction to ensure that they receive timely treatment to mitigate and address the impact of dementia on the individual, caregiver, family, and health care system

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Effect of Age at Onset on Disease Characteristics in Vitiligo

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2013.12075 ◽

2013 ◽

Vol 17 (4) ◽

pp. 253-258 ◽

Cited By ~ 7

Author(s):

Amrinder J. Kanwar ◽

Rahul Mahajan ◽

Davinder Parsad

Keyword(s):

Early Onset ◽

Late Onset ◽

Statistical Significance ◽

Age At Onset ◽

Positive Family History ◽

Disease Onset ◽

Disease Characteristics ◽

The Difference ◽

Trauma Stress ◽

Distinguishing Features

Background: Vitiligo is a multifactorial disease in which genetic, immunologic, and environmental factors play an important part. Late-onset vitiligo is a poorly defined entity. Materials and Methods: Case records of patients who attended the pigmentary clinic at our institute from January 2001 to December 2010 were reviewed. Patients with a diagnosis of vitiligo were analyzed with respect to their demographic characteristics with special reference to their age at onset. Results: Patients with disease onset after 30 years had a significantly higher association with precipitating factors such as trauma, stress, and drugs in comparison with early-onset vitiligo ( p < .004). However, the difference did not reach statistical significance when these factors were analyzed individually. There was a significantly higher association with other nonautoimmune diseases ( p = .05), a higher incidence of positive family history ( p < .0001), and a higher association with leukotrichia ( p < .002) in late-onset disease. Early-onset nonsegmental vitiligo was associated with a higher incidence of photosensitivity and pruritus compared to early-onset segmental vitiligo. Conclusion: Late-onset vitiligo has certain distinguishing features compared to early-onset vitiligo.

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Characteristics of Early-Onset Dementia in Chiba Prefecture, Japan: A Multicenter Survey

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000518294 ◽

2021 ◽

pp. 1-6

Author(s):

Shigeki Hirano ◽

Ryuji Sakakibara ◽

Naoya Komatsu ◽

Keisuke Shimizu ◽

Moeno Ishikawa ◽

...

Keyword(s):

Family History ◽

Early Onset ◽

Neuropsychological Test ◽

Age At Onset ◽

Positive Family History ◽

Lewy Bodies ◽

Lewy Body Dementia ◽

Early Onset Dementia ◽

Chiba Prefecture ◽

Multicenter Survey

Introduction: Early-onset dementia (EOD), defined as dementia onset before the age of 65 years, is relatively rare, but its social impacts are significant. This study aimed to characterize the diagnosis and clinical and social status of EOD subjects in the 11 dementia centers in Chiba Prefecture, Japan. Methods: A retrospective 1-year survey was conducted. Collected data included clinical diagnosis, age at onset, age at survey, neuropsychological test, family history, employment, and living status. Results: We identified 208 EOD subjects, including 123 (59.4%), 24 (11.6%), 21 (10.1%), 17 (8.2%), and 10 (4.8%) with Alzheimer’s disease (AD), vascular dementia, frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies/Parkinson’s disease dementia, and alcohol-related dementia, respectively. The Mini-Mental State Examination (MMSE) score <24 was observed in 50–75% of patients and was not correlated with disease duration. Twenty-four (16.4%) subjects had positive family history of EOD. EOD subjects were at risk of early retirement, and 133 subjects lived with their family, in whom 64 (30.8%) lived with their child. Conclusion: In dementia centers, AD, FTLD, and Lewy body dementia had relatively large proportion. Employment, economy, and social supports are urgently needed for EOD subjects and their family.

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Inter-individual differences in the foraging behavior of breeding Adélie penguins are driven by individual quality and sex

Marine Ecology Progress Series ◽

10.3354/meps13208 ◽

2020 ◽

Vol 636 ◽

pp. 189-205

Author(s):

A Lescroël ◽

PO’B Lyver ◽

D Jongsomjit ◽

S Veloz ◽

KM Dugger ◽

...

Keyword(s):

Individual Differences ◽

Foraging Behavior ◽

Ross Sea ◽

Individual Quality ◽

High Quality ◽

Breeding Experience ◽

Age Related ◽

Demographic Traits ◽

Iteroparous Species ◽

Adélie Penguins

Inter-individual differences in demographic traits of iteroparous species can arise through learning and maturation, as well as from permanent differences in individual ‘quality’ and sex-specific constraints. As the ability to acquire energy determines the resources an individual can allocate to reproduction and self-maintenance, foraging behavior is a key trait to study to better understand the mechanisms underlying these differences. So far, most seabird studies have focused on the effect of maturation and learning processes on foraging performance, while only a few have included measures of individual quality. Here, we investigated the effects of age, breeding experience, sex, and individual breeding quality on the foraging behavior and location of 83 known-age Adélie penguins at Cape Bird, Ross Sea, Antarctica. Over a 2 yr period, we showed that (1) high-quality birds dived deeper than lower quality ones, apparently catching a higher number of prey per dive and targeting different foraging locations; (2) females performed longer foraging trips and a higher number of dives compared to males; (3) there were no significant age-related differences in foraging behavior; and (4) breeding experience had a weak influence on foraging behavior. We suggest that high-quality individuals have higher physiological ability, enabling them to dive deeper and forage more effectively. Further inquiry should focus on determining the physiological differences among penguins of different quality.

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Health Among Sexual Minority Older Adults: Individual Differences and Implications for Improving Health

Innovation in Aging ◽

10.1093/geroni/igaa057.3170 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 860-860

Author(s):

Britney Wardecker ◽

Cara Exten

Keyword(s):

Older Adults ◽

Individual Differences ◽

Sexual Minority ◽

Health Care Access ◽

Psychological Health ◽

Negative Mood ◽

Health Problems ◽

Future Research ◽

Care Access ◽

Age Related

Abstract The number of sexual minority (SM) older adults is increasing rapidly, yet this population continues to be underrepresented in research (Fredriksen-Goldsen & Kim, 2017) and experiences significant disparities in health and health care access (Fredriksen-Goldsen, 2016; Wallace et al., 2011). In the current symposium, we analyze data from U.S. national probability samples of middle-aged and older adults (MIDUS, HRS, NESARC-III) to consider how age-related concerns and challenges may be experienced differently by SM individuals compared to their heterosexual counterparts. This symposium includes novel methods and statistical tools, such as daily diary assessments, multilevel modeling, and time-varying effects models. Individual presentations evaluate how: (1) SM women, compared to heterosexual women, may respond differently to menopause through norms and values surrounding womanhood; (2) midlife and older SM individuals use alcohol and cigarettes more frequently across a typical week than their heterosexual counterparts, though their substance use may not be tied to common triggers (e.g., negative mood, stress); (3) despite bisexual older adults reporting more health problems compared to lesbian and gay counterparts, they are less prepared for health concerns and crises (e.g., reporting a lower number of valid wills); and (4) the prevalence of depression and anxiety varies across age, such that older SM adults—especially women—are particularly vulnerable to psychological health problems. These presentations collectively examine complex issues facing older SM adults while emphasizing individual differences (i.e., women’s concerns, bisexual people’s issues). We discuss challenges in researching this growing at-risk population, and we highlight areas of future research and intervention.

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How Do We Choose Our Giants? Perceptions of Replicability in Psychological Science

Advances in Methods and Practices in Psychological Science ◽

10.1177/25152459211018199 ◽

2021 ◽

Vol 4 (2) ◽

pp. 251524592110181

Author(s):

Manikya Alister ◽

Raine Vickers-Jones ◽

David K. Sewell ◽

Timothy Ballard

Keyword(s):

Individual Differences ◽

Sample Size ◽

Statistical Methods ◽

Scientific Progress ◽

Research Practices ◽

Specific Study ◽

Psychological Science ◽

Average Confidence

Judgments regarding replicability are vital to scientific progress. The metaphor of “standing on the shoulders of giants” encapsulates the notion that progress is made when new discoveries build on previous findings. Yet attempts to build on findings that are not replicable could mean a great deal of time, effort, and money wasted. In light of the recent “crisis of confidence” in psychological science, the ability to accurately judge the replicability of findings may be more important than ever. In this Registered Report, we examine the factors that influence psychological scientists’ confidence in the replicability of findings. We recruited corresponding authors of articles published in psychology journals between 2014 and 2018 to complete a brief survey in which they were asked to consider 76 specific study attributes that might bear on the replicability of a finding (e.g., preregistration, sample size, statistical methods). Participants were asked to rate the extent to which information regarding each attribute increased or decreased their confidence in the finding being replicated. We examined the extent to which each research attribute influenced average confidence in replicability. We found evidence for six reasonably distinct underlying factors that influenced these judgments and individual differences in the degree to which people’s judgments were influenced by these factors. The conclusions reveal how certain research practices affect other researchers’ perceptions of robustness. We hope our findings will help encourage the use of practices that promote replicability and, by extension, the cumulative progress of psychological science.

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