Is Parental Age Related to the Risk of Alzheimer's Disease?

Advanced maternal and paternal age were investigated as putative risk factors for AD in 198 clinically diagnosed Alzheimer patients and in 198 randomly selected healthy controls. No significant differences in average age of fathers and of mothers at birth of the subject were observed. The risk of AD was not significantly different across categories of maternal and paternal age. The association with parental age was not different for sporadic and familial AD. These findings do not support the view of a maternal or paternal age effect on AD.

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Parental Age and the Risk for Alzheimer’s Disease in Offspring: Systematic Review and Meta-Analysis

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000515523 ◽

2021 ◽

pp. 140-150

Author(s):

Natalia Szejko ◽

Pedro Macul Ferreira de Barros ◽

Victor J. Avila-Quintero ◽

Adam Lombroso ◽

Michael Howard Bloch

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Paternal Age ◽

Control Group ◽

Parental Age ◽

Older Parents ◽

Increased Risk

Background: Alzheimer’s disease (AD) is the most common cause of dementia worldwide, accounting for 50–75% of all cases. While older maternal and paternal age at childbirth are established risk factors for Down syndrome which is associated with later AD, it is still not entirely clear whether parental age is a risk factor for AD. Previous studies have suggested contradictory findings. Objectives: We conducted a systematic review and meta-analysis to examine whether parental (maternal and paternal) age at birth was associated with AD and whether individuals born to younger or older parents were at an increased risk for AD. Methods: Two reviewers searched the electronic database of PubMed for relevant studies. Eligibility for the meta-analysis was based on the following criteria: (1) studies involving patients with AD and an adequate control group, (2) case control or cohort studies, (3) studies investigating parental age. All statistical analyses were completed in STATA/IC version 16. Results: Eleven studies involving 4,371 participants were included in the systematic review and meta-analysis. Meta-analysis demonstrated no significant association between maternal (weighted mean difference [WMD] 0.49, 95% CI –0.52 to 1.49, p = 0.34) and paternal age and AD (WMD 1.00, 95% CI –0.55 to 2.56, p = 0.21). Similarly, individuals born to younger (<25 years) or older parents (>35 years) did not demonstrate a differential risk for AD. Conclusions: Overall, this meta-analysis did not demonstrate an association between parental age and the risk of AD in offspring. These findings should be interpreted with caution given the limited power of the overall meta-analysis and the methodological limitations of the underlying studies as in many cases no adjustment for potential confounders was included.

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Working Towards a Blood-Derived Gene Expression Biomarker Specific for Alzheimer’s Disease

10.1101/621987 ◽

2019 ◽

Author(s):

Hamel Patel ◽

Raquel Iniesta ◽

Daniel Stahl ◽

Richard J.B Dobson ◽

Stephen J Newhouse

Keyword(s):

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Classification Model ◽

Ageing Population ◽

Healthy Controls ◽

Classification Models ◽

Specific Expression ◽

Expression Signature ◽

Age Related

AbstractBackgroundA significant number of studies have investigated the use of blood-derived gene expression profiling as a biomarker for Alzheimer’s Disease (AD). However, the typical approach of developing classification models trained on subjects with AD and complimentary cognitive healthy controls may result in markers of general illness rather than being AD-specific. Incorporating additional related neurological and age-related disorders during the classification model development process may lead to the discovery of an AD-specific expression signature.MethodsTwo XGBoost classification models were developed and optimised. The first used the typical approach, training on 160 AD and 160 cognitively normal controls, while the second was trained in 6318 AD and 6318 mixed controls. Up-sampling was performed in each training set to the minority classes to avoid sampling bias, and both classification models were evaluated in an independent dataset consisting of 127 AD and 687 mixed controls. The mixed control group represents a heterogeneous ageing population consisting of Parkinson’s Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Bipolar Disorder, Schizophrenia, Coronary Artery Disease, Rheumatoid Arthritis, Chronic Obstructive Pulmonary Disease, and cognitively healthy subjects.ResultsThe typical approach resulted in a 74 gene classification model with a validation performance of 58.3% sensitivity, 30.3% specificity, 13.4% PPV and 79.7% NPV. In contrast, the second approach resulted in a 28 gene classification model with an overall improved validation performance of 46.5% sensitivity, 95.6% specificity, 66.3% PPV and 90.6% NPV.ConclusionsThe addition of related neurological and age-related disorders into the AD classification model developmental process identified a more AD-specific expression signature, with improved ability to distinguish AD from other related diseases and cognitively healthy controls. However, this was at the cost of sensitivity. Further improvement is still required to identify a robust blood transcriptomic signature specific to AD.

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[P3-524]: EXPLORING LATE-LIFE RISK FACTORS OF ALZHEIMER's DISEASE AND OTHER AGE-RELATED DEMENTIAS IN CPRD

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.06.1743 ◽

2017 ◽

Vol 13 (7S_Part_24) ◽

pp. P1178-P1179

Author(s):

Bowen Su ◽

Anita Kulatilake ◽

Roger Newson ◽

Ioanna Tzoulaki ◽

Michael Soljak ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Late Life ◽

Age Related

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Epigenetic inheritance of telomere length in wild birds

10.1101/284208 ◽

2018 ◽

Cited By ~ 1

Author(s):

Christina Bauch ◽

Jelle J. Boonekamp ◽

Peter Korsten ◽

Ellis Mulder ◽

Simon Verhulst

Keyword(s):

Telomere Length ◽

Early Development ◽

Paternal Care ◽

Protein Structures ◽

Epigenetic Inheritance ◽

Age Effect ◽

Paternal Age ◽

Parental Age ◽

Epigenetic Effect ◽

Paternal Age Effect

AbstractTelomere length (TL) predicts health and lifespan in humans and other organisms, making the identification of the causes of TL variation of interest. At conception, zygotes inherit genes that regulate TL during early development, but at the same time already express a phenotype, which is the TL of the parental gametes that formed the zygote. Whether the effect of gamete TL is transient or affects TL for life depends on the extent to which regulatory genes compensate for gamete TL variation during early development. A carry-over effect of parental TL, resulting in epigenetic inheritance, has been suggested to explain the observed relationship between parental age and offspring TL in humans and other species. However, reports of parental age effects are based on cross-sectional data, and age at reproduction has numerous confounds. Furthermore, parental age may affect offspring telomere dynamics between conception and sampling, which could also explain the paternal age effect. Using longitudinal telomere data of jackdaw parents and their chicks, we show that chicks hatched with shorter telomeres as individual fathers aged, whereas mother age had no effect. By cross-fostering eggs, we confirmed the paternal age effect to be independent of paternal care after conception. The epigenetic effect accounted for 34% of the variance in offspring TL that was explained by paternal telomere length; the remaining 66% we ascribe to a combination of environmental and additive genetic effects. Thus, our results strongly indicate epigenetic inheritance of TL, with potential consequences for offspring fitness prospects.Significance statementTelomeres are DNA-protein structures at chromosome ends and their length predicts remaining lifespan in humans and other organisms. Variation in telomere length is thought to be largely of genetic origin, but telomere inheritance may be unusual because a fertilised cell already has a telomere length (most traits are first expressed later in life). Telomeres shorten with age, and, using long-term individual-based data of jackdaw families, we show that as fathers aged, they produced chicks with shorter telomeres. This shows that paternal telomere length directly affects offspring telomere length, i.e. is inherited genetically but without the involvement of genes. This is known as an epigenetic effect and explained a large part (≥34%) of the telomere resemblance between fathers and their offspring.

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Epidemiology of Presenile Alzheimer's Disease in Scotland (1974–88)

The British Journal of Psychiatry ◽

10.1192/bjp.167.6.732 ◽

1995 ◽

Vol 167 (6) ◽

pp. 732-738 ◽

Cited By ~ 14

Author(s):

Lawrence J. Whalley ◽

Brenda M. Thomas ◽

John M. Starr

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Paternal Age ◽

Survival Times ◽

Coal Miners ◽

Geographical Differences ◽

Multifactorial Model ◽

Low Incidence ◽

Harmful Effects

Background and MethodWe related geographical variation of ‘probable’ presenile Alzheimer's disease (AD PSD) to exposures to possible risk factors for AD PSD and vascular dementia (VaD) and to geographical differences in survival times after presentation with AD PSD.ResultsWe found that an ecological measure of socio-economic deprivation was related to VaD but not to AD PSD. Among men with AD PSD and VaD, specific occupations conveyed no altered risk but having fathers who were coal miners was associated with AD PSD and VaD in offspring. Increased paternal age was associated with AD PSD but only in men. These factors acted independently of one another and did not distinguish between geographical areas of high and low incidence.ConclusionsThe length of survival after presentation with AD PSD distinguished between these areas, and when migration between these areas was taken into account, a plausible multifactorial model of the harmful effects of environment emerged, which acted independently of risk factors acting earlier in life.

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P4-127 Association of genetic risk factors for Alzheimer's disease and neurological soft-signs in individuals with subjective memory complaints and healthy controls

Neurobiology of Aging ◽

10.1016/s0197-4580(04)81685-3 ◽

2004 ◽

Vol 25 ◽

pp. S511

Author(s):

Nicola T. Lautenschlager ◽

Jing S. Wu ◽

Simon M. Laws ◽

Athena Paton ◽

Stefan Wagenpfeil ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genetic Risk ◽

Genetic Risk Factors ◽

Healthy Controls ◽

Subjective Memory Complaints ◽

Subjective Memory ◽

Neurological Soft Signs ◽

Memory Complaints

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Subject-specific multi-poroelastic model for exploring the risk factors associated with the early stages of Alzheimer's disease

Interface Focus ◽

10.1098/rsfs.2017.0019 ◽

2017 ◽

Vol 8 (1) ◽

pp. 20170019 ◽

Cited By ~ 15

Author(s):

Liwei Guo ◽

John C. Vardakis ◽

Toni Lassila ◽

Micaela Mitolo ◽

Nishant Ravikumar ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Exact Nature ◽

Vascular Disorder ◽

Prospective Data ◽

Parenchymal Tissue ◽

Subject Specific ◽

The Subject ◽

Poroelastic Model

There is emerging evidence suggesting that Alzheimer's disease is a vascular disorder, caused by impaired cerebral perfusion, which may be promoted by cardiovascular risk factors that are strongly influenced by lifestyle. In order to develop an understanding of the exact nature of such a hypothesis, a biomechanical understanding of the influence of lifestyle factors is pursued. An extended poroelastic model of perfused parenchymal tissue coupled with separate workflows concerning subject-specific meshes, permeability tensor maps and cerebral blood flow variability is used. The subject-specific datasets used in the modelling of this paper were collected as part of prospective data collection. Two cases were simulated involving male, non-smokers (control and mild cognitive impairment (MCI) case) during two states of activity (high and low). Results showed a marginally reduced clearance of cerebrospinal fluid (CSF)/interstitial fluid (ISF), elevated parenchymal tissue displacement and CSF/ISF accumulation and drainage in the MCI case. The peak perfusion remained at 8 mm s −1 between the two cases.

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Exploiting Common Aspects of Obesity and Alzheimer’s Disease

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2020.602360 ◽

2020 ◽

Vol 14 ◽

Author(s):

Sidra Tabassum ◽

Afzal Misrani ◽

Li Yang

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Brain Mitochondria ◽

Morphological Alterations ◽

Age Related ◽

Obesity And Overweight ◽

Age Related Cognitive Decline ◽

Brain Insulin Resistance

Alzheimer’s disease (AD) is an example of age-related dementia, and there are still no known preventive or curative measures for this disease. Obesity and associated metabolic changes are widely accepted as risk factors of age-related cognitive decline. Insulin is the prime mediator of metabolic homeostasis, which is impaired in obesity, and this impairment potentiates amyloid-β (Aβ) accumulation and the formation of neurofibrillary tangles (NFTs). Obesity is also linked with functional and morphological alterations in brain mitochondria leading to brain insulin resistance (IR) and memory deficits associated with AD. Also, increased peripheral inflammation and oxidative stress due to obesity are the main drivers that increase an individual’s susceptibility to cognitive deficits, thus doubling the risk of AD. This enhanced risk of AD is alarming in the context of a rapidly increasing global incidence of obesity and overweight in the general population. In this review, we summarize the risk factors that link obesity with AD and emphasize the point that the treatment and management of obesity may also provide a way to prevent AD.

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