OBJECTIVE COGNITIVE IMPAIRMENT AND PROGRESSION TO DEMENTIA IN WOMEN: THE PROSPECTIVE EPIDEMIOLOGICAL RISK FACTOR STUDY

Author(s):  
J. Skov Neergaard ◽  
K. Dragsbæk ◽  
C. Christiansen ◽  
M. Asser Karsdal ◽  
S. Brix ◽  
...  

Background: Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer’s disease have failed. Objectives: The objective of this study was to identify subgroups of individuals with objective cognitive impairment (OCI), who were most likely to progress to dementia and to identify the risk factors associated with progression. Design: Prospective cohort study. Setting: Population-based. Participants: 5,380 elderly women from Denmark. Measurements: The Short Blessed Test and a category fluency test with animal naming, was used to assess cognitive function, and to classify them into different groups of OCI. Results: OCI was identified in 852 subjects at baseline. The risk of dementia was elevated for OCI subjects as compared to subjects with normal cognition (HR 1.46[1.19-1.79]). The courses of OCI were studied in a sub-cohort who completed the cognitive assessment at both the baseline and the follow-up visit (n = 1,933). Of these subjects 203 had OCI at baseline. The multi-domain subtypes of OCI were associated with progressive OCI. Subjects most likely to progress were older, physically inactive, had a higher level of total cholesterol (>6.5 mmol/L) and had a history of depression as compared to subjects with a non-progressive course of OCI. Conclusions: In this cohort we identified a risk profile associated with progression from OCI in older women. The degree of impairment at baseline was an important predictor of conversion to dementia, additionally several modifiable risk factors were associated with progression.

2020 ◽  
Vol 10 (2) ◽  
pp. 45 ◽  
Author(s):  
Valentina Bessi ◽  
Juri Balestrini ◽  
Silvia Bagnoli ◽  
Salvatore Mazzeo ◽  
Giulia Giacomucci ◽  
...  

Background: Some genes could interact with cardiovascular risk factors in the development of Alzheimer’s disease. We aimed to evaluate the interaction between ApoE ε4 status, Clock T3111C and Per2 C111G polymorphisms with cardiovascular profile in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). Methods: We included 68 patients who underwent clinical evaluation; neuropsychological assessment; ApoE, Clock and Per2 genotyping at baseline; and neuropsychological follow-up every 12–24 months for a mean of 13 years. We considered subjects who developed AD and non-converters. Results: Clock T3111C was detected in 47% of cases, Per2 C111G in 19% of cases. ApoE ε4 carriers presented higher risk of heart disease; Clock C-carriers were more frequently smokers than non C-carriers. During the follow-up, 17 patients progressed to AD. Age at baseline, ApoE ε 4 and dyslipidemia increased the risk of conversion to AD. ApoE ε4 carriers with history of dyslipidemia showed higher risk to convert to AD compared to ApoE ε4− groups and ApoE ε4+ without dyslipidemia patients. Clock C-carriers with history of blood hypertension had a higher risk of conversion to AD. Conclusions: ApoE and Clock T3111C seem to interact with cardiovascular risk factors in SCD and MCI patients influencing the progression to AD.


2010 ◽  
Vol 87 (1) ◽  
pp. 44-51 ◽  
Author(s):  
Heikki Jokinen ◽  
Pasi Pulkkinen ◽  
Juha Korpelainen ◽  
Jorma Heikkinen ◽  
Sirkka Keinänen-Kiukaanniemi ◽  
...  

2016 ◽  
Vol 46 (3) ◽  
pp. 182-190 ◽  
Author(s):  
Xianghua Fang ◽  
Zhengwu Wang ◽  
Chunxiu Wang ◽  
Jian Wu ◽  
Ya Yang ◽  
...  

The Cardiovascular and Cognitive Health Study (CCHS-Beijing) is a population-based study of cardiovascular disease (CVD) and cognitive impairment in adults aged 55 and older in Beijing. The main aims of the study are to investigate the prevalence rates of CVD, asymptomatic atherosclerosis, and cognitive impairment, as well as validate the risk factors related to the onset and development of CVD, Alzheimer's disease (AD) and mild cognitive impairment (MCI). The study was designed to detect the traditional and new risk factors in this age group. Participants were recruited randomly from residential regions in the greater Beijing municipality area based on the average levels of development in Beijing, China in 2012 (based on socioeconomic, demographic, and geographical characteristics). Thorough physical and laboratory examination were performed at baseline (also the cross-sectional survey) to identify the risk factors such as hypertension, dyslipidemia, diabetes, as well as newly defined risk factors like elevated homocysteine, high sensitivity C-reactive protein, and urine micro-albumin. Subclinical disease of the cerebral vasculature included atherosclerosis of carotid arteries, intracranial arteries, and retinal vessels. Subclinical cardiac diseases included left ventricular enlargement, arrhythmias, chamber hypertrophy and myocardial ischemia. Blood pressure was documented using the ankle-arm method. In addition, neuropsychological assessments were performed for all subjects aged 65 and above. Baseline evaluation began during the period August 2013 to December 2014. Follow-up examination will occur in 5 years. The initial and recurrent CVD, AD and MCI events will be verified and validated during the follow-up period.


2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Christina Bergqvist ◽  
François Hemery ◽  
Arnaud Jannic ◽  
Salah Ferkal ◽  
Pierre Wolkenstein

AbstractNeurofibromatosis 1 (NF1) is an inherited, autosomal-dominant, tumor predisposition syndrome with a birth incidence as high as 1:2000. A patient with NF1 is four to five times more likely to develop a malignancy as compared to the general population. The number of epidemiologic studies on lymphoproliferative malignancies in patients with NF1 is limited. The aim of this study was to determine the incidence rate of lymphoproliferative malignancies (lymphoma and leukemia) in NF1 patients followed in our referral center for neurofibromatoses. We used the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital’s electronic health records. We performed a keyword search on clinical notes generated between Jan/01/2014 and May/11/2020 for patients aged 18 years or older. A total of 1507 patients with confirmed NF1 patients aged 18 years and above were identified (mean age 39.2 years; 57% women). The total number of person-years in follow-up was 57,736 (men, 24,327 years; women, 33,409 years). Mean length of follow-up was 38.3 years (median, 36 years). A total of 13 patients had a medical history of either lymphoma or leukemia, yielding an overall incidence rate of 22.5 per 100,000 (0.000225, 95% confidence interval (CI) 0.000223–0.000227). This incidence is similar to that of the general population in France (standardized incidence ratio 1.07, 95% CI 0.60–1.79). Four patients had a medical history leukemia and 9 patients had a medical history of lymphoma of which 7 had non-Hodgkin lymphoma, and 2 had Hodgkin lymphoma. Our results show that adults with NF1 do not have an increased tendency to develop lymphoproliferative malignancies, in contrast to the general increased risk of malignancy. While our results are consistent with the recent population-based study in Finland, they are in contrast with the larger population-based study in England whereby NF1 individuals were found to be 3 times more likely to develop both non-Hodgkin lymphoma and lymphocytic leukemia. Large-scale epidemiological studies based on nationwide data sets are thus needed to confirm our findings.


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