Mixed Brain Pathology Is the Most Common Cause of Cognitive Impairment in the Elderly

2020 ◽  
Vol 78 (1) ◽  
pp. 453-465
Author(s):  
Irina Alafuzoff ◽  
Sylwia Libard
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
The Elderly ◽  
Systemic Diseases ◽  
Brain Pathology ◽  
Cerebrovascular Lesions ◽  
Peripheral Organs ◽  
Age Related

Background: Systemic diseases, diabetes mellitus (DM), and cardiovascular disease (CaVD) have been suggested being risk factors for cognitive impairment (CI) and/or influence Alzheimer’s disease neuropathologic change (ADNC). Objective: The purpose was to assess the type and the extent of neuropathological alterations in the brain and to assess whether brain pathology was associated with CaVD or DM related alterations in peripheral organs, i.e., vessels, heart, and kidney. Methods: 119 subjects, 15% with DM and 24% with CI, age range 80 to 89 years, were chosen and neuropathological alterations were assessed applying immunohistochemistry. Results: Hyperphosphorylated τ (HPτ) was seen in 99%, amyloid-β (Aβ) in 71%, transactive DNA binding protein 43 (TDP43) in 62%, and α-synuclein (αS) in 21% of the subjects. Primary age related tauopathy was diagnosed in 29% (more common in females), limbic predominant age-related TDP encephalopathy in 4% (14% of subjects with CI), and dementia with Lewy bodies in 3% (14% of subjects with CI) of the subjects. High/intermediate level of ADNC was seen in 47% and the extent of HPτ increased with age. The extent of ADNC was not associated with the extent of pathology observed in peripheral organs, i.e., DM or CaVD. Contrary, brain alterations such as pTDP43 and cerebrovascular lesions (CeVL) were influenced by DM, and CeVL correlated significantly with the extent of vessel pathology. Conclusion: In most (66%) subjects with CI, the cause of impairment was “mixed pathology”, i.e., ADNC combined with TDP43, αS, or vascular brain lesions. Furthermore, our results suggest that systemic diseases, DM and CaVD, are risk factors for CI but not related to ADNC.

Different Sides of Depression in the Elderly: An In-depth View on the Role of Aβ Peptides

2021 ◽  
Vol 28 ◽  
Author(s):  
Giovann Pagni ◽  
Claudia Tagliarini ◽  
Manuel Glauco Carbone ◽  
Bruno Pietro Imbimbo ◽  
Donatella Marazziti ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Late Onset ◽  
Amyloid Β ◽  
The Elderly ◽  
High Plasma ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Prodromal Phase ◽  
Aβ Peptides

Background: Late-onset depression (LOD) is the most common neuropsychiatric disorder associated with Alzheimer's disease (AD), often associated with structural and functional brain changes, neuropsychological impairments and negative family history for affective disorders. LOD could be a risk factor or a prodromal phase of AD; this has led to the investigation of the link between depression and amyloid-β (Aβ) peptides by measuring Aβ levels in plasma, cerebrospinal fluid (CSF) and brains of elderly depressed subjects. Objective: Clarify the complex relationship between depression, Aβ peptides and AD. Method: We evaluated all articles published up to 2019 in PubMed in which Aβ was measured in serum (or plasma), CSF or brain in elderly with Major Depressive Disorder or depressive symptoms evaluated with standard scales. Results: Low plasma Aβ42 levels are strongly associated with depression severity. Plasma Aβ40 levels are higher in younger depressed, drug-resistant and those with more severe symptoms. CSF Aβ42 levels are lower in depressed than controls. PET-detected global and region-specific increases in Aβ deposition are sometimes associated with LOD, cognitive impairment, anxiety but not with Cardiovascular Diseases (CVDs)/CVD risk factors. Elderly depressed with CVDs/CVD risk factors have more frequently high plasma Aβ40 levels and drug-resistance; those without these co-morbidities have low plasma Aβ42 levels and a greater cognitive impairment. Conclusion: Two specific Aβ profiles emerge in elderly depressed. One is associated with Aβ42 reductions in plasma and CSF, possibly reflecting increased brain amyloid deposition and prodromal AD. The other one is characterized by high plasma Aβ40 levels, cerebrovascular disease and clinically associated with increased AD risk.

scholarly journals Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

2021 ◽  
Vol 22 (3) ◽  
pp. 1170
Author(s):  
Arunbalaji Pugazhendhi ◽  
Margaret Hubbell ◽  
Pooja Jairam ◽  
Balamurali Ambati
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Rho Kinase Inhibitors ◽  
Age Related ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.

Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stroke Risk ◽  
Multivariable Analysis ◽  
The Elderly ◽  
Stroke Risk Factors ◽  
Age Related ◽  
Increased Risk ◽  
The Impact ◽  
Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

scholarly journals Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies

npj Vaccines ◽  
2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Changyoun Kim ◽  
Armine Hovakimyan ◽  
Karen Zagorski ◽  
Tatevik Antonyan ◽  
Irina Petrushina ◽  
...  
Keyword(s):  
Dna Vaccines ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
The Elderly ◽  
Brain Regions ◽  
Dependent Manner ◽  
Lewy Neurites ◽  
The Brain

AbstractAccumulation of misfolded proteins such as amyloid-β (Aβ), tau, and α-synuclein (α-Syn) in the brain leads to synaptic dysfunction, neuronal damage, and the onset of relevant neurodegenerative disorder/s. Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are characterized by the aberrant accumulation of α-Syn intracytoplasmic Lewy body inclusions and dystrophic Lewy neurites resulting in neurodegeneration associated with inflammation. Cell to cell propagation of α-Syn aggregates is implicated in the progression of PD/DLB, and high concentrations of anti-α-Syn antibodies could inhibit/reduce the spreading of this pathological molecule in the brain. To ensure sufficient therapeutic concentrations of anti-α-Syn antibodies in the periphery and CNS, we developed four α-Syn DNA vaccines based on the universal MultiTEP platform technology designed especially for the elderly with immunosenescence. Here, we are reporting on the efficacy and immunogenicity of these vaccines targeting three B-cell epitopes of hα-Syn aa85–99 (PV-1947D), aa109–126 (PV-1948D), aa126–140 (PV-1949D) separately or simultaneously (PV-1950D) in a mouse model of synucleinopathies mimicking PD/DLB. All vaccines induced high titers of antibodies specific to hα-Syn that significantly reduced PD/DLB-like pathology in hα-Syn D line mice. The most significant reduction of the total and protein kinase resistant hα-Syn, as well as neurodegeneration, were observed in various brain regions of mice vaccinated with PV-1949D and PV-1950D in a sex-dependent manner. Based on these preclinical data, we selected the PV-1950D vaccine for future IND enabling preclinical studies and clinical development.

Geriatric Trauma

2019 ◽  
Author(s):  
Sigrid Burruss ◽  
Lillian Min ◽  
Areti Tillou
Keyword(s):  
Risk Factors ◽  
Care Coordination ◽  
Unintentional Injury ◽  
The Elderly ◽  
Geriatric Trauma ◽  
Trauma Patients ◽  
Age Related ◽  
Trauma Population ◽  
Downward Spiral ◽  
Risk Factors For Falls

The geriatric trauma population continues to grow as life expectancy and unintentional injury increase. Age-related physiologic changes and complex comorbidities may not only lead to injury but also may precipitate a downward spiral. The injury patterns, presentation of life-threatening injury, and response to injury are unique in the elderly trauma population, and dedicated evaluation of elderly trauma patients at a trauma center may be beneficial. Aggressive, early intervention with a focus on geriatric-specific needs and care coordination are an integral part of the management to reduce morbidity and mortality. Much of the unintentional injuries may be preventable with identification of risk factors for falls and fall prevention programs. Frailty measurements may be used to predict morbidity and functional status. Surgeons must become familiar with geriatric-specific issues and how best to treat the geriatric trauma population.  This review contains 3 figures, 2 tables, and 133 references. Key Words: care coordination, elderly, frailty, geriatric, injury, prevention, risk factors, trauma, triage

scholarly journals Risk Factors for Age-Related Maculopathy

2009 ◽  
Vol 2009 ◽  
pp. 1-39 ◽  
Author(s):  
Paul P. Connell ◽  
Pearse A. Keane ◽  
Evelyn C. O'Neill ◽  
Rasha W. Altaie ◽  
Edward Loane ◽  
...  
Keyword(s):  
Risk Factors ◽  
Epidemiologic Study ◽  
Case Series ◽  
The Elderly ◽  
Factor H ◽  
Environment Interaction ◽  
Complement Factor ◽  
Case Control Studies ◽  
Cross Sectional ◽  
Age Related

Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

scholarly journals Age and oral health: current considerations

2007 ◽  
Vol 21 (spe) ◽  
pp. 29-33 ◽  
Author(s):  
Andrew Tawse-Smith
Keyword(s):  
Risk Factors ◽  
Periodontal Disease ◽  
Dental Plaque ◽  
Alveolar Bone ◽  
Periodontal Diseases ◽  
The Elderly ◽  
Preventive Program ◽  
Age Related ◽  
The Individual ◽  
Complex Scenario

Dental plaque is still considered the main etiological factor for periodontal diseases. Our understanding of periodontal disease has advanced from the previous concepts where gingivitis slowly progressed to periodontitis to a more complex scenario that correlates several risk factors in the pathogenesis of periodontal disease. Among these factors, age has been associated with increased rates of periodontal disease as the population gets older. Although the loss of alveolar bone and periodontal attachment is common in the elderly population, and there is evident age-related changes in the periodontium, severe periodontitis is not a natural consequence of ageing. The importance of identifying the risk factors that participate in the pathogenesis of periodontal disease at an early phase, both of the individual and the disease, as well as evaluating the capacity of the individual to control dental plaque will enable the implementation of an adequate preventive program, where the needs and limitations of the individual are considered to specifically tailor the oral hygiene procedures and the mouthwashes to be used.

scholarly journals Investigation of the prevalence of Cognitive Impairment and its risk factors within the elderly population in Shanghai, China

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Longbing Ren ◽  
Yongtao Zheng ◽  
Lezhou Wu ◽  
Yijun Gu ◽  
Yusheng He ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Elderly Population ◽  
The Elderly

scholarly journals Improving Dignity of Care in Community-Dwelling Elderly Patients with Cognitive Decline and Their Caregivers. The Role of Dignity Therapy

2020 ◽  
Vol 10 (12) ◽  
pp. 178
Author(s):  
Heifa Ounalli ◽  
David Mamo ◽  
Ines Testoni ◽  
Martino Belvederi Murri ◽  
Rosangela Caruso ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Early Stage ◽  
Psychosocial Interventions ◽  
The Elderly ◽  
Community Dwelling ◽  
Anticipatory Grief ◽  
Dignity Therapy ◽  
Existential Distress ◽  
Age Related

Demographic changes have placed age-related mental health disorders at the forefront of public health challenges over the next three decades worldwide. Within the context of cognitive impairment and neurocognitive disorders among elderly people, the fragmentation of the self is associated with existential suffering, loss of meaning and dignity for the patient, as well as with a significant burden for the caregiver. Psychosocial interventions are part of a person-centered approach to cognitive impairment (including early stage dementia and dementia). Dignity therapy (DT) is a therapeutic intervention that has been shown to be effective in reducing existential distress, mood, and anxiety symptoms and improving dignity in persons with cancer and other terminal conditions in palliative care settings. The aims of this paper were: (i) To briefly summarize key issues and challenges related to care in gerontology considering specifically frail elderly/elderly with cognitive decline and their caregivers; and (ii) to provide a narrative review of the recent knowledge and evidence on DT in the elderly population with cognitive impairment. We searched the electronic data base (CINAHL, SCOPUS, PSycInfo, and PubMed studies) for studies regarding the application of DT in the elderly. Additionally, given the caregiver’s role as a custodian of diachronic unity of the cared-for and the need to help caregivers to cope with their own existential distress and anticipatory grief, we also propose a DT-dyadic approach addressing the needs of the family as a whole.

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