scholarly journals Prion protein codon 129 polymorphism in mild cognitive impairment and dementia: the Rotterdam Study

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Hata Karamujić-Čomić ◽  
Shahzad Ahmad ◽  
Thom S Lysen ◽  
Alis Heshmatollah ◽  
Gennady V Roshchupkin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Odds Ratio ◽  
Prnp Gene ◽  
Rotterdam Study ◽  
Incident Dementia ◽  
Jakob Disease ◽  
Codon 129

Abstract Creutzfeldt–Jakob disease is a rare, fatal, neurodegenerative disease caused by the accumulation of abnormally folded prion proteins. The common polymorphism at codon 129 (methionine/valine) in the prion protein (PRNP) gene is the most important determinant of genetic susceptibility. Homozygotes of either allele have a higher risk of sporadic Creutzfeldt–Jakob disease. Various studies suggest that this polymorphism is also involved in other forms of dementia. We studied the association between the codon 129 polymorphism of the PRNP gene and mild cognitive impairment in 3605 participants from the Rotterdam Study using logistic regression analyses. Subsequently, we studied the association between this polymorphism and incident dementia, including Alzheimer’s disease, in 11 070 participants using Cox proportional hazard models. Analyses were adjusted for age and sex. We found the prevalence of mild cognitive impairment to be higher for carriers of the methionine/methionine genotype (odds ratio, 1.40; 95% confidence interval, 1.11–1.78; P = 0.005) as well as for carriers of the valine/valine genotype (odds ratio, 1.37; 95% confidence interval, 0.96–1.97; P = 0.08). The codon 129 polymorphism was not associated with the risk of incident dementia or Alzheimer’s disease. In conclusion, we found a statistically significant higher prevalence of mild cognitive impairment in carriers of the methionine/methionine genotype in the codon 129 polymorphism of the PRNP gene within this population-based study. No associations were found between the codon 129 polymorphism and dementia or Alzheimer’s disease in the general population.

scholarly journals Amnestic mild cognitive impairment and incident dementia and Alzheimer's disease in geriatric depression

2014 ◽  
Vol 26 (12) ◽  
pp. 2029-2036 ◽  
Author(s):  
David C Steffens ◽  
Douglas R McQuoid ◽  
Guy G Potter
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Memory Impairment ◽  
Laboratory Data ◽  
Amnestic Mild Cognitive Impairment ◽  
Cognitive Diagnosis ◽  
Geriatric Depression ◽  
Incident Dementia

ABSTRACTBackground:Memory impairment in geriatric depression is understudied, but may identify individuals at risk for development of dementia and Alzheimer's disease (AD). Using a neuropsychologically based definition of amnestic mild cognitive impairment (aMCI) in patients with geriatric depression, we hypothesized that patients with aMCI, compared with those without it, would have increased incidence of both dementia and AD.Methods:Participants were aged 60 years and older and consisted of depressed participants and non-depressed volunteer controls. The depressed cohort met criteria for unipolar major depression. All participants were free of dementia and other neurological illness at baseline. At study entry, participants were administered a standardized clinical interview, a battery of neurocognitive tests, and provided a blood sample for determination of apolipoprotein E genotype. A cognitive diagnosis was assigned by a panel of experts who convened annually and reviewed available clinical, neuropsychological and laboratory data to achieve a consensus cognitive diagnosis to determine a consensus diagnosis. Survival analysis examined the association between aMCI and later dementia (all-cause) and AD.Results:Among 295 depressed individuals, 63 (21.36%) met criteria for aMCI. Among 161 non-depressed controls, four (2.48%) met aMCI criteria. Participants were followed for 6.28 years on average. Forty-three individuals developed dementia, including 40 (13.6%) depressed and three (1.9%) control participants. Both aMCI and age were associated with incident dementia and AD.Conclusions:The presence of aMCI is a poor prognostic sign among patients with geriatric depression. Clinicians should carefully screen elderly depressed adults for memory impairment.

Commentary on: amnestic mild cognitive impairment and incident dementia and Alzheimer's disease in geriatric depression

2014 ◽  
Vol 26 (12) ◽  
pp. 2027-2028
Author(s):  
John T. O’brien
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Geriatric Depression ◽  
Incident Dementia ◽  
Diagnostic Certainty ◽  
Risk Of Progression ◽  
The Relationship

In this month's “Paper of the Month,” Steffens and colleagues (Steffens et al., 2014) report on the relationship between depression, mild cognitive impairment (MCI) and future risk of progression to dementia. It has long been known that there is a complex relationship between depression and cognitive impairment, with depression common in those with cognitive impairment and dementia, and subsequent cognitive decline frequent in patients with depression (Wallin et al., 2013). This relationship has often been difficult to study, not least because definitions have often been mutually exclusive. For example, many studies of MCI have excluded patients with depression. This is not unreasonable to increase diagnostic certainty and obtain a more “pure” group of those with MCI who are likely to progress to Alzheimer's disease, but of course at the same time limits the ability to determine interactions between MCI and depression. On the other hand, it is known that non-cognitive symptoms, most particularly depression, frequently occur in those with MCI and have been shown to increase the risk of likely future decline.

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