Lower Plasma Klotho Concentrations Are Associated with Vascular Dementia but Not Late-Onset Alzheimer’s Disease

Background: The protein Klotho is involved in biological processes related to longevity, cardiovascular health, and cognition. Serum Klotho levels have been associated with better cognition in animal models; moreover, lower Klotho concentrations in cerebrospinal fluid from subjects with late-onset Alzheimer’s disease (LOAD) have been reported. Objective: Our study aimed to examine the possible relationship between Klotho plasma concentrations and cognitive status in the elderly. Methods: We evaluated plasma Klotho levels in a sample of 320 elderly patients admitted to a Memory Clinic. Four groups of subjects were enrolled, including cognitively intact individuals complaining about memory loss (controls) and patients affected by LOAD, mild cognitive impairment, or vascular dementia (VD). The sample was stratified by plasma Klotho tertiles. Results: Lower levels of plasma Klotho (1st tertile) were associated with older age, higher prevalence of VD, single/multiple lacunar infarcts and leukoaraiosis, coronary heart disease and stroke, and higher levels of creatinine, homocysteine, and high-sensitivity C-reactive protein. On multivariate logistic regression analysis, the risk of VD was 3- and 4-fold in subjects belonging to the 1st tertile (≤514.8 pg/mL, OR 3.54, 95% CI 1.05–11.93) and 2nd tertile (> 514.8, < 659.1 pg/mL, OR 4.28, 95% CI 1.30–14.06) compared to the 3rd tertile (≥659.1 pg/mL). A significantly increased VD risk was found for Klotho values < 680 pg/mL. Conclusion: In a sample of elderly individuals, we found a significant association between low plasma Klotho levels and VD, but not LOAD. This finding suggests that, although these 2 forms of dementia might overlap, some physiopathological mechanisms related to VD and LOAD remain distinct.

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PON-1 and ferroxidase activities in older patients with mild cognitive impairment, late onset Alzheimer’s disease or vascular dementia

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-0803 ◽

2015 ◽

Vol 53 (7) ◽

Cited By ~ 17

Author(s):

Carlo Cervellati ◽

Arianna Romani ◽

Carlo M. Bergamini ◽

Cristina Bosi ◽

Juana Maria Sanz ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Vascular Dementia ◽

Late Onset ◽

Large Body ◽

Multivariate Logistic Regression Analysis ◽

Paraoxonase 1 ◽

Prodromal Phase

AbstractA large body of evidence suggests that not only cerebral but also systemic oxidative stress (OxS) might be involved in the pathogenesis of late onset Alzheimer’s disease (LOAD) and vascular dementia (VAD), as well as of the prodromal phase of dementia, the so-called mild cognitive impairment (MCI). In the present study, we evaluated whether paraoxonase 1 (PON-1) and ferroxidase (FeOx) activities, because of their well acknowledged effectiveness as systemic antioxidants, might be associated with dementia and/or MCI.Serum arylesterase and paraoxonase of PON-1, along with FeOx I (ceruloplasmin-related) and II activities were assessed in 223 MCI, 162 LOAD, 65 VAD patients, and in 143 older normal cognitive controls.Among the enzymatic activities examined, only arylesterase significantly changed across the groups (ANOVA: p<0.001), with similar lower levels in MCI, LOAD, and VAD compared to controls. By multivariate logistic regression analysis we showed that, in respect to controls, low levels (under the median value) of serum arylesterase were independently associated with an increase in the likelihood of being affected by LOAD [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.5–5.0], VAD (OR 2.7, 95% CI 1.2–6.2), or MCI (OR 2.3, 95% CI 1.3–3.8).Overall, our results suggest that depression of PON-1, and in particular, of arylesterase activity, in serum might be an early feature of dementia-related diseases. Further longitudinal exploration of the role of this enzyme in the onset and progression of these disorders are required.

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Utility of the Neurobehavioral Cognitive Status Examination (COGNISTAT) in differentiating between depressive states in late-life depression and late-onset Alzheimer’s disease: a preliminary study

Annals of General Psychiatry ◽

10.1186/s12991-016-0091-5 ◽

2016 ◽

Vol 15 (1) ◽

Cited By ~ 6

Author(s):

Yoshiaki Tsuruoka ◽

Michio Takahashi ◽

Masatoshi Suzuki ◽

Koichi Sato ◽

Yukihiko Shirayama

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Late Onset ◽

Late Life ◽

Cognitive Status ◽

Late Life Depression ◽

Neurobehavioral Cognitive Status Examination ◽

Preliminary Study ◽

Depressive States

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Novel Blood Biomarkers for an Earlier Diagnosis of Alzheimer’s Disease: A Literature Review

International Journal of Medical Students ◽

10.5195/ijms.2020.452 ◽

2020 ◽

Author(s):

Shiavax Rao ◽

Andrew J. Boileau

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Literature Review ◽

Clinical Diagnosis ◽

Sensitivity And Specificity ◽

Memory Loss ◽

High Sensitivity ◽

Diagnostic Techniques ◽

Pubmed Database ◽

Diagnostic Approaches

Alzheimer’s disease is a neurodegenerative condition associated with neurofibrillary tangles and cortical deposition of amyloid plaques. Clinical presentation of the disease involves manifestations such as memory loss, cognitive decline and dementia with some of the earliest reported deficits being episodic memory impairment and olfactory dysfunction. Current diagnostic approaches rely on autopsy characterization of gross brain pathology, or brain imaging of biomarkers late in the disease course. The aim of this literature review is to identify and compare newly emerging and novel CSF, serum and mucosal biomarkers, with the potential of making an earlier clinical diagnosis of Alzheimer’s disease. Utilizing such techniques may allow for earlier therapeutic intervention, reduction of disability and enhancement of quality of life. Literature review and analysis was performed by screening the PubMed database for relevant studies within the past 5 years. All studies showed statistically significant (P < 0.05) differences in testing between AD patients and controls. Two categories of serum biomarkers (redox-reactive antiphospholipid antibodies and microRNAs) and an olfactory mucosal marker (microRNA-206) could discriminate between early AD patients and controls with high sensitivity and specificity. In conclusion, certain studies have shown promising results with high sensitivity and specificity, high discriminative potential for Alzheimer’s disease early in its progression, and statistically significant results in larger study samples. Utilization of such diagnostic techniques should increase the efficacy of making an earlier clinical diagnosis of Alzheimer’s disease.

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Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer’s disease and mild cognitive impairment

Scientific Reports ◽

10.1038/s41598-019-56614-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 11

Author(s):

Massimiliano Castellazzi ◽

Simone Patergnani ◽

Mariapina Donadio ◽

Carlotta Giorgi ◽

Massimo Bonora ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Late Onset ◽

Memory Loss ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Cellular Processes

AbstractDementia is a neurocognitive disorder characterized by a progressive memory loss and impairment in cognitive and functional abilities. Autophagy and mitophagy are two important cellular processes by which the damaged intracellular components are degraded by lysosomes. To investigate the contribution of autophagy and mitophagy in degenerative diseases, we investigated the serum levels of specific autophagic markers (ATG5 protein) and mitophagic markers (Parkin protein) in a population of older patients by enzyme-linked immunosorbent assay. Two hundred elderly (≥65 years) outpatients were included in the study: 40 (20 F and 20 M) with mild-moderate late onset Alzheimer’s disease (AD); 40 (20 F and 20 M) affected by vascular dementia (VAD); 40 with mild cognitive impairment (MCI); 40 (20 F and 20 M) with “mixed” dementia (MD); 40 subjects without signs of cognitive impairment were included as sex-matched controls. Our data indicated that, in serum samples, ATG5 and Parkin were both elevated in controls, and that VAD compared with AD, MCI and MD (all p < 0.01). Patients affected by AD, MD, and MCI showed significantly reduced circulating levels of both ATG5 and Parkin compared to healthy controls and VAD individuals, reflecting a significant down-regulation of autophagy and mitophagy pathways in these groups of patients. The measurement of serum levels of ATG5 and Parkin may represent an easily accessible diagnostic tool for the early monitoring of patients with cognitive decline.

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Markers of endothelial dysfunction in older subjects with late onset Alzheimer's disease or vascular dementia

Journal of the Neurological Sciences ◽

10.1016/j.jns.2008.05.020 ◽

2008 ◽

Vol 272 (1-2) ◽

pp. 164-170 ◽

Cited By ~ 76

Author(s):

G. Zuliani ◽

M. Cavalieri ◽

M. Galvani ◽

A. Passaro ◽

M.R. Munari ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Endothelial Dysfunction ◽

Vascular Dementia ◽

Late Onset ◽

Older Subjects

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Survival in Subcortical Vascular Dementia: Predictors and Comparison to Probable Alzheimer's Disease in a Tertiary Memory Clinic Population

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000434626 ◽

2015 ◽

Vol 40 (3-4) ◽

pp. 210-221 ◽

Cited By ~ 4

Author(s):

Jong Hun Kim ◽

Seok Min Go ◽

Sang Won Seo ◽

Suk Hui Kim ◽

Juhee Chin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Family History ◽

Vascular Dementia ◽

Proportional Hazards Model ◽

Late Onset ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Subcortical Vascular Dementia ◽

History Of

Background: Subcortical vascular dementia (SVaD) is one of the most common dementias, after Alzheimer's disease (AD) dementia. Few survival analyses in SVaD patients have been reported. Methods: The dates and causes of death of 146 SVaD and 725 AD patients were included. We used the Cox proportional hazards model to compare survival between SVaD and AD patients and to explore possible factors related to survival of SVaD patients. Results: The median survival time after the onset of SVaD (109 months) was shorter than that recorded for AD (152 months). The most common cause of death in SVaD was stroke (47.1%). Factors associated with shorter survival in SVaD were late onset, male sex, worse baseline cognition, absence of hypertension and a family history of stroke. Conclusions: Stroke prevention may be important in SVaD treatment because 47.1% of SVaD patients died of stroke. A family history of stroke and absence of hypertension were associated with a shorter survival in SVaD, suggesting the existence of genetic or unknown risk factors.

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