Apolipoprotein E and Functional Illness in the Elderly

Following on from the hypothesis of a role for the ApoE ε4 and ε2 alleles as risk and protective factors, respectively, for late-onset Alzheimer's disease (AD) came inevitable questions regarding other psychiatric conditions of late onset including depressive illness and schizophrenia. Is ApoE ε4 a risk factor in these diseases and do carriers have an earlier age of onset? Does ApoE ε2 have a protective role, with carriers of this allele having a later age of onset?

Download Full-text

Age, Age of Onset and Course of Primary Depressive Illness in the Elderly*

The Canadian Journal of Psychiatry ◽

10.1177/070674378302800204 ◽

1983 ◽

Vol 28 (2) ◽

pp. 102-104 ◽

Cited By ~ 32

Author(s):

Martin G. Cole

Keyword(s):

Elderly Patients ◽

Depressive Episode ◽

Early Onset ◽

Age Of Onset ◽

Late Onset ◽

The Elderly ◽

Depressive Illness ◽

Physical Illness ◽

Course Of Illness

Thirty-eight elderly patients with primary depressive illness (Feighner criteria) were followed up for 7–31 months. In the absence of persistent organic signs and severe physical illness, age of onset (first depressive episode after 60) but not age was significantly related to course of illness. Compared to early onset depressives, late onset depressives were more likely to remain completely well during the follow-up period and less likely to have frequent or disabling relapses.

Download Full-text

Apolipoprotein E ε4/4 genotype limits response to dietary induction of hyperhomocysteinemia and resulting inflammatory signaling

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211069006 ◽

2022 ◽

pp. 0271678X2110690

Author(s):

Charles E Seaks ◽

Erica M Weekman ◽

Tiffany L Sudduth ◽

Kevin Xie ◽

Brandi Wasek ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Apolipoprotein E ◽

Late Onset ◽

Apoe Ε4 ◽

Perivascular Inflammation ◽

Ε4 Allele ◽

Barrier Breakdown ◽

The Impact

Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia behind Alzheimer’s disease. Apolipoprotein E (ApoE) is a lipid transporting lipoprotein found within the brain and periphery. The APOE ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease and is a risk factor for VCID. Our lab has previously utilized a dietary model of hyperhomocysteinemia (HHcy) to induce VCID pathology and cognitive deficits in mice. This diet induces perivascular inflammation through cumulative oxidative damage leading to glial mediated inflammation and blood brain barrier breakdown. Here, we examine the impact of ApoE ε4 compared to ε3 alleles on the progression of VCID pathology and inflammation in our dietary model of HHcy. We report a significant resistance to HHcy induction in ε4 mice, accompanied by a number of related differences related to homocysteine (Hcy) metabolism and methylation cycle, or 1-C, metabolites. There were also significant differences in inflammatory profiles between ε3 and ε4 mice, as well as significant reduction in Serpina3n, a serine protease inhibitor associated with ApoE ε4, expression in ε4 HHcy mice relative to ε4 controls. Finally, we find evidence of pervasive sex differences within both genotypes in response to HHcy induction.

Download Full-text

Molecular Genetics of Early- and Late-Onset Alzheimer’s Disease

Current Gene Therapy ◽

10.2174/1566523220666201123112822 ◽

2020 ◽

Vol 20 ◽

Author(s):

Md. Sahab Uddin ◽

Sharifa Hasana ◽

Md. Farhad Hossain ◽

Md. Siddiqul Islam ◽

Tapan Behl ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Massively Parallel Sequencing ◽

Late Onset ◽

Current Knowledge ◽

The Elderly ◽

Apoe Ε4 ◽

Sequencing Technologies ◽

Genetic Components ◽

Ε4 Allele

: Alzheimer’s disease (AD) is the most common form of dementia in the elderly and this complex disorder is associated with environmental as well as genetic components. Early-onset AD (EOAD) and late-onset AD (LOAD, more common) are major identified types of AD. The genetics of EOAD is extensively understood with three genes variants such as APP, PSEN1, and PSEN2 leading to disease. On the other hand, some common alleles including APOE are effectively associated with LOAD identified but the genetics of LOAD is not clear to date. It has been accounted that about 5% to 10% of EOAD patients can be explained through mutations in the three familiar genes of EOAD. The APOE ε4 allele augmented the severity of EOAD risk in carriers, and APOE ε4 allele was considered as a hallmark of EOAD. A great number of EOAD patients, who are not genetically explained, indicate that it is not possible to identify disease- triggering genes yet. Although several genes have been identified through using the technology of next-generation sequencing in EOAD families including SORL1, TYROBP, and NOTCH3. A number of TYROBP variants were identified through exome sequencing in EOAD patients and these TYROBP variants may increase the pathogenesis of EOAD. The existence of ε4 allele is responsible for increasing the severity of EOAD. However, several ε4 allele carriers live into their 90s that propose the presence of other LOAD genetic as well as environmental risk factors that are not identified yet. It is urgent to find out missing genetics of EOAD and LOAD etiology to discover new potential genetics facets which will assist to understand the pathological mechanism of AD. These investigations should contribute to developing a new therapeutic candidate for alleviating, reversing and preventing AD. This article based on current knowledge represents the overview of the susceptible genes of EOAD, and LOAD. Next, we represent the probable molecular mechanism which might elucidate the genetic etiology of AD and highlight the role of massively parallel sequencing technologies for novel gene discoveries.

Download Full-text

Differences Between APOE Carriers and Non-APOE Carriers on Neurocognitive Tests: Jensen Effects?

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317518765895 ◽

2018 ◽

Vol 33 (6) ◽

pp. 353-361 ◽

Cited By ~ 4

Author(s):

Jan te Nijenhuis ◽

Kyu Yeong Choi ◽

Yu Yong Choi ◽

Jang Jae Lee ◽

Eun Hyun Seo ◽

...

Keyword(s):

Older Adults ◽

At Risk ◽

Risk Factor ◽

Apolipoprotein E ◽

Test Scores ◽

General Intelligence ◽

Apoe Ε4 ◽

Neurocognitive Tests ◽

Ε4 Allele ◽

The Difference

Background: Being a carrier of the apolipoprotein E (APOE) ε4 allele is a clear risk factor for development of Alzheimer’s disease (AD). On some neurocognitive tests, there are smaller differences between carriers and noncarriers, while other tests show larger differences. Aims: We explore whether the size of the difference between carriers and noncarriers is a function of how well the tests measure general intelligence, so whether there are Jensen effects. Methods: We used the method of correlated vectors on 441 Korean older adults at risk for AD and 44 with AD. Results: Correlations between APOE carriership and test scores ranged from −.05 to .11 (normal), and −.23 to .54 (AD). The differences between carriers and noncarriers were Jensen effects: r = .31 and r = .54, respectively. Conclusion: A composite neurocognitive score may show a clearer contrast between APOE carriers and noncarriers than a large number of scores of single neurocognitive tests.

Download Full-text

Protective Factors in Family Relationships

Contemporary Social Issues in East Asian Societies - Advances in Religious and Cultural Studies ◽

10.4018/978-1-4666-5031-2.ch004 ◽

2014 ◽

pp. 76-85 ◽

Cited By ~ 1

Author(s):

Ann Buchanan

Keyword(s):

Life Cycle ◽

Young People ◽

Protective Factors ◽

Family Relationships ◽

The Elderly ◽

Protective Role ◽

Care For The Elderly ◽

The Family ◽

The One ◽

Partnership Approach

This chapter analyzes the importance of protective factors in family relationships. In Confucian societies, where services for older people may be limited, intergenerational family relationships are crucial in providing care for the elderly. Confucian societies are better at recognizing the protective influence of the family, but scholars from these areas suggest that the culture may be changing. As the “One child” norm extends (not only in China) across many Asian societies, the challenges for young people in supporting their parents and grandparents may become overwhelming. This chapter suggests that at every stage of the life cycle, some families will need state support in order to carry out their protective role in mitigating the risks experienced by both the young and the old. A state/family partnership approach is likely to be more acceptable, more effective, and more economic than state care alone.

Download Full-text

Ozone and Particulate Matter Exposure and Alzheimer’s Disease: A Review of Human and Animal Studies

Advances in Alzheimer’s Disease - Alzheimer’s Disease and Air Pollution ◽

10.3233/aiad210034 ◽

2021 ◽

Author(s):

Rui-Ming Liu ◽

Zechen Chong ◽

Jiu-Chiuan Chen

Keyword(s):

Alzheimer’S Disease ◽

Risk Factor ◽

Particulate Matter ◽

Environmental Exposure ◽

Environmental Risk ◽

Genetic Risk ◽

The Elderly ◽

Genetic Risk Factor ◽

Apoe Ε4 ◽

Particulate Matter Exposure

Alzheimer’s disease (AD), an aging-related neurodegenerative disease, is a major cause of dementia in the elderly. Although the early-onset (familial) AD is attributed to mutations in the genes coding for amyloid-β protein precursor (AβPP) and presenilin 1/presenilin 2 (PS1/PS2), the cause for the late-onset AD (LOAD), which accounts for more than 95% of AD cases, remains unclear. Aging is the greatest risk factor for LOAD, whereas the apolipo protein E4 allele (APOEε4) is believed to be a major genetic risk factor in acquiring LOAD, with female APOE ε4 carriers at highest risk. Nonetheless, not all the elderly, even older female APOE ε4 carriers, develop LOAD, suggesting that other factors, including environmental exposure, must play a role. This review summarizes recent studies that show a potential role of environmental exposure, especially ozone and particulate matter exposure, in the development of AD. Interactions between environmental exposure, genetic risk factor (APOE ε4), and sex in AD pathophysiology are also discussed briefly. Identification of environmental risk factor(s) and elucidation of the complex interactions between genetic and environmental risk factors plus aging and female sex in the onset of AD will be a key to our understanding of the etiology and pathogenesis of AD and the development of the strategies for its prevention and treatment.

Download Full-text

Manic syndromes in old age

10.1093/med/9780199644957.003.0044 ◽

2013 ◽

Cited By ~ 1

Author(s):

Akshya Vasudev

Keyword(s):

Bipolar Disorder ◽

Clinical Presentation ◽

Age Of Onset ◽

Late Onset ◽

Epidemiological Data ◽

The Elderly ◽

Published Data ◽

Management Options ◽

Pharmacological Management ◽

Heterogenous Group

Manic syndromes in the elderly are different from those seen in the younger bipolar population. They are a heterogenous group but can probably be divided into two main groups based on age of onset of the illness: late onset bipolar disorder (LOB) and early onset bipolar disorder (EOB). This chapter elaborates on differences in these two groups based on epidemiological data findings, clinical presentation, aetiopathogenesis and management. Latest concepts with regards to the vascular mania hypothesis, neuroimaging findings, cognitive impairment in bipolar disorder are also dealt with. A critical review of pharmacological management options is also provided with reference to recently published data on mood stabilisers, antipsychotic and antidepressant usage for this age group.

Download Full-text

Late-onset bipolar disorder: What else?

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.147 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S121-S121

Author(s):

C.P. Ferreira ◽

S. Alves ◽

C. Oliveira ◽

M.J. Avelino

Keyword(s):

Elderly Patient ◽

Bipolar Disorder ◽

Treatment Guidelines ◽

Late Onset ◽

Mood Stabilizer ◽

The Elderly ◽

First Episode ◽

Therapeutic Implications ◽

Psychiatric Conditions ◽

New Onset

IntroductionGeriatric-onset of a first-episode mania is a rare psychiatric condition, which may be caused by a heterogeneous group of non-psychiatric conditions. To confirm late-onset bipolar disorder (LOBD) diagnosis, secondary-mania causes should be ruled out.ObjectivesTo provide a comprehensive review reporting prevalence, features, differential diagnosis, comorbidity and treatment of LOBD.MethodsThe literature was systematically reviewed by online searching using PubMed®. The authors selected review papers with the words “Late-onset mania” and/or “Late-onset bipolar” in the title and/or abstract published in the last 10 years.Results and discussionWith population ageing, LOBD is becoming a more prevalent disorder. Clinical presentation may be atypical and confounding, making the diagnosis not always obvious. Several non-psychiatric conditions must be considered in an elderly patient presenting with new-onset mania, namely stroke, dementia, hyperthyroidism or infection causing delirium. Only then LOBD diagnosis may be done, making that an exclusion diagnosis. Comorbidities, such as hypertension or renal insufficiency are often present in the elderly and must be taken into account when choosing a mood stabilizer.ConclusionsLOBD remains a complex and relatively understudied disorder with important diagnostic and therapeutic implications. This diagnosis must be kept in mind for every elderly patient presenting with new-onset mania. Further investigations could contribute to a better understanding of LOBD etiopathogenesis and to set out better treatment guidelines.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Download Full-text

Apolipoprotein E Allelic Frequency Altered in Women with Early-onset Breast Cancer

Breast Cancer Basic and Clinical Research ◽

10.1177/117822341000400005 ◽

2010 ◽

Vol 4 ◽

pp. 117822341000400 ◽

Cited By ~ 1

Author(s):

Tirtsa Porrata-Doria ◽

Jaime L. Matta ◽

Summer F. Acevedo

Keyword(s):

Breast Cancer ◽

Risk Factor ◽

Apolipoprotein E ◽

Potential Risk ◽

Tumor Size ◽

Early Onset ◽

Late Onset ◽

The United States ◽

The Body ◽

Early Onset Breast Cancer

Among women, the most prevalent type of cancer is breast cancer, affecting 1 out of every 8 women in the United States; in Puerto Rico, 70 out of every 100,000 will develop some type of breast cancer. Therefore, a better understanding of the potential risk factors for breast cancer could lead to the development of early detection tools. A gene that has been proposed as a risk factor in several populations around the world is Apolipoprotein E (apoE). ApoE functions as a mechanism of transport for lipoproteins and cholesterol throughout the body, with 3 main isoforms present in humans (apoE2, apoE3, and apoE4). Whether or not apoE4 is a risk factor for breast cancer remains controversial. Previous studies have either included test subjects of all ages (20–80) or have focused on late-onset (after age 50) breast cancer; none has concentrated specifically on early-onset (aged 50 and younger) breast cancer. The objectives of this study was to examine (in a Puerto Rican population) the differences in the relative frequency of occurrence of apoE4 in non-breast cancer versus breast cancer patients and to examine, as well, the potential differences of same in early- versus late-onset patients. We found an increased frequency of apoE4 (odds ratio 2.15) only in early-onset breast cancer survivors, which is similar to the findings of those studies that combined or adjusted for age as well as for an association between apoE4 and decreased tumor size. ApoE is also a potential risk factor for long-term cognitive effects after chemotherapy and affects response to hormone replacement. Our data supports the theory that knowing the apoE genotype of women who are at risk of developing breast cancer may be beneficial, as such knowledge would aid in the prediction of tumor size and the development of treatment regimens.

Download Full-text