Anhedonia as a Potential Risk Factor of Alzheimer’s Disease in a Community-Dwelling Elderly Sample: Results from the ZARADEMP Project

(1) Introduction: Dementia is a major public health problem, and Alzheimer’s disease (AD) is the most frequent subtype. Clarifying the potential risk factors is necessary in order to improve dementia-prevention strategies and quality of life. Here, our purpose was to investigate the role of the absence of hedonic tone; anhedonia, understood as the reduction on previous enjoyable daily activities, which occasionally is underdetected and underdiagnosed; and the risk of developing AD in a cognitively unimpaired and non-depressed population sample. (2) Method: We used data from the Zaragoza Dementia and Depression (ZARADEMP) project, a longitudinal epidemiological study on dementia and depression. After excluding subjects with dementia, a sample of 2830 dwellers aged ≥65 years was followed for 4.5 years. The geriatric mental state examination was used to identify cases of anhedonia. AD was diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. A multivariate survival analysis and Cox proportional hazards regression model were performed, and the analysis was controlled by an analysis for the presence of clinically significant depression. (3) Results: We found a significant association between anhedonia cases and AD risk in the univariate analysis (hazard ratio (HR): 2.37; 95% CI: 1.04–5.40). This association persisted more strongly in the fully adjusted model. (4) Conclusions: Identifying cognitively intact individuals with anhedonia is a priority to implement preventive strategies that could delay the progression of cognitive and functional impairment in subjects at risk of AD.

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Treatment of Sleep Disturbance May Reduce the Risk of Future Probable Alzheimer’s Disease

Journal of Aging and Health ◽

10.1177/0898264318795567 ◽

2018 ◽

Vol 31 (2) ◽

pp. 322-342 ◽

Cited By ~ 3

Author(s):

Shanna L. Burke ◽

Tianyan Hu ◽

Christine E. Spadola ◽

Aaron Burgess ◽

Tan Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sleep Disturbance ◽

Proportional Hazards ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Data Set ◽

Proportional Hazards Regression ◽

Increased Risk ◽

Research Questions

Objective: This study explored two research questions: (a) Does sleep medication neutralize or provide a protective effect against the hazard of Alzheimer’s disease (AD)? (b) Do apolipoprotein (APOE) e4 carriers reporting a sleep disturbance experience an increased risk of AD? Method: This study is a secondary analysis of the National Alzheimer’s Coordinating Center’s Uniform Data Set ( n = 6,782) using Cox proportional hazards regression. Results: Sleep disturbance was significantly associated with eventual AD development. Among the subset of participants taking general sleep medications, no relationship between sleep disturbance and eventual AD was observed. Among individuals not taking sleep medications, the increased hazard between the two variables remained. Among APOE e4 carriers, sleep disturbance and AD were significant, except among those taking zolpidem. Discussion: Our findings support the emerging link between sleep disturbance and AD. Our findings also suggest a continued need to elucidate the mechanisms that offer protective factors against AD development.

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Suicide risk within one year of cognitive impairment diagnosis in older adults: a nationwide retrospective cohort study

10.21203/rs.2.19129/v1 ◽

2019 ◽

Author(s):

Jae Woo Choi ◽

Kang Soo Lee ◽

Euna Han

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mental Disorders ◽

Suicide Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

One Year

Abstract Background This study aims to investigate suicide risk within one year of receiving a diagnosis of cognitive impairment in older adults without mental disorders. Methods This study used National Health Insurance Service-Senior Cohort data on older adults with newly diagnosed cognitive impairment including Alzheimer’s disease, vascular dementia, other/unspecified dementia, and mild cognitive impairment from 2004 to 2012. We selected 41,195 older adults without cognitive impairment through 1:1 propensity score matching using age, gender, Charlson Comorbidity Index, and index year, with follow-up throughout 2013. We eliminated subjects with mental disorders and estimated adjusted hazard ratios (AHR) of suicide deaths within one year after diagnosis using the Cox proportional hazards models. Results We identified 49 suicide deaths during the first year after cognitive impairment diagnosis. The proportion of observed suicide deaths was the highest within one year after cognitive impairment diagnosis (48.5% of total); older adults with cognitive impairment were at a higher suicide risk than those without cognitive impairment (AHR, 1.89; 95% confidence interval [CI], 1.18–3.04). Subjects with Alzheimer’s disease and other/unspecified dementia were at greater suicide risk than those without cognitive impairment (AHR, 1.94, 1.94; 95% CI, 1.12–3.38, 1.05–3.58). Suicide risk in female and young-old adults (60–74 years) with cognitive impairment was higher than in the comparison group (AHR, 2.61, 5.13; 95% CI, 1.29–5.28, 1.48–17.82). Conclusions Older patients with cognitive impairment were at increased suicide risk within one year of diagnosis. Early intervention for suicide prevention should be provided to older adults with cognitive impairment.

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Changes in Metabolic Syndrome Status and Risk of Dementia

Journal of Clinical Medicine ◽

10.3390/jcm9010122 ◽

2020 ◽

Vol 9 (1) ◽

pp. 122 ◽

Cited By ~ 2

Author(s):

Ji Eun Lee ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Dahye Kim ◽

Jung Eun Yoo ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Blood Pressure ◽

Alzheimer's Disease ◽

Metabolic Syndrome ◽

Vascular Dementia ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model

This study investigated the effects of changes in metabolic syndrome (MS) status and each component on subsequent dementia occurrence. The study population was participants of a biennial National Health Screening Program in 2009–2010 and 2011–2012 in Korea. Participants were divided into four groups according to change in MS status during the two-year interval screening: sustained normal, worsened (normal to MS), improved (MS to normal), and sustained MS group. Risk of dementia among the groups was estimated from the second screening date to 31 December 2016 using a Cox proportional hazards model. A total of 4,106,590 participants were included. The mean follow-up was 4.9 years. Compared to the sustained normal group, adjusted hazard ratios (aHR) (95% confidence interval) were 1.11 (1.08–1.13) for total dementia, 1.08 (1.05–1.11) for Alzheimer’s disease, and 1.20 (1.13–1.28) for vascular dementia in the worsened group; 1.12 (1.10–1.15), 1.10 (1.07–1.13), and 1.19 (1.12–1.27) for the improved group; and 1.18 (1.16–1.20), 1.13 (1.11–1.15), and 1.38 (1.32–1.44) for the sustained MS group. Normalization of MS lowered the risk of all dementia types; total dementia (aHR 1.18 versus 1.12), Alzheimer’s disease (1.13 versus 1.10), and vascular dementia (1.38 versus 1.19). Among MS components, fasting glucose and blood pressure showed more impact. In conclusion, changes in MS status were associated with the risk of dementia. Strategies to improve MS, especially hyperglycemia and blood pressure, may help to prevent dementia.

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THE TRIAL-READY COHORT FOR PRECLINICAL/PRODROMAL ALZHEIMER’S DISEASE (TRC-PAD) – A FUNDAMENTAL ALLY IN AD PREVENTION RESEARCH

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2020.41 ◽

2020 ◽

pp. 1-2

Author(s):

A.P. Porsteinsson ◽

E.D. Clark

Keyword(s):

Public Health ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Financial Burden ◽

Public Health Problem ◽

Symptomatic Treatment ◽

Health Impact ◽

Major Public Health Problem ◽

Medical Needs ◽

Clinical Benefits

Alzheimer’s disease (AD) remains one of our greatest unmet medical needs, without any approved disease-modifying therapies. The emotional and financial burden of AD is enormous and predicted to grow exponentially with increasing median population age, posing a major public health problem. The potential to prevent or improve cognitive decline due to AD has important implications. There are medications currently approved for symptomatic treatment of AD, but they have limited clinical benefits and do not change the ultimate trajectory of the disease. The need to find effective treatments for AD that can prevent, slow, arrest, or even reverse the disease is ever more urgent and interventions that delay the symptomatic onset of AD would have a major public health impact (1).

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Mid- and Late-Life Migraine Is Associated with an Increased Risk of All-Cause Dementia and Alzheimer’s Disease, but Not Vascular Dementia: A Nationwide Retrospective Cohort Study

Journal of Personalized Medicine ◽

10.3390/jpm11100990 ◽

2021 ◽

Vol 11 (10) ◽

pp. 990

Author(s):

Hyun-Joo Lee ◽

Hyunjae Yu ◽

Son Gil Myeong ◽

Kijoon Park ◽

Dong-Kyu Kim

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Vascular Dementia ◽

Proportional Hazards ◽

Comparison Group ◽

Late Life ◽

Cox Proportional Hazards ◽

Increased Risk ◽

Migraine Group ◽

Prospective Association

We used a nationwide cohort sample of data from 2002 to 2013, representing approximately 1 million patients to investigate the prospective association between migraine and dementia. The migraine group (n = 1472) included patients diagnosed between 2002 and 2004, aged over 55 years; the comparison group was selected using propensity score matching (n = 5888). Cox proportional hazards regression analyses was used to calculate the hazard ratios (HRs). The incidence of dementia was 13.5 per 1000 person-years in the migraine group. Following adjustment for sociodemographic and comorbidities variables, patients with migraine developed dementia more frequently than those in the comparison group (adjusted HR = 1.37, 95% confidence interval [CI], 1.16–1.61). In the subgroup analysis, we found a higher HR of dementia events in male, the presence of comorbidities, and older age (≥65) patients with migraine, compared to those without migraine. Moreover, patients with migraine had a significantly higher incidence of Alzheimer’s disease (adjusted HR = 1.31, 95% CI, 1.08–1.58), but not vascular dementia, than those without migraine. Therefore, our findings suggest that mid- and late-life migraines may be associated with an increased incidence of all-cause dementia and Alzheimer’s disease, but not vascular dementia.

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Neighborhood Deprivation and Incident Alzheimer's Disease: A Regional Cohort Study of Electronic Medical Records

Innovation in Aging ◽

10.1093/geroni/igab046.230 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 60-60

Author(s):

Jarrod Dalton ◽

Elizabeth Pfoh ◽

Kristen Berg ◽

Douglas Gunzler ◽

Lyla Mourany ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Electronic Medical Records ◽

Medical Records ◽

Proportional Hazards ◽

Outcome Data ◽

Cox Proportional Hazards ◽

Area Deprivation ◽

Composite Outcome ◽

Neighborhood Deprivation

Abstract The prevalence of Alzheimer’s disease (AD) is anticipated to increase drastically. Neighborhood socioeconomic position (SEP) has been related to multiple processes of health. Understanding whether SEP is related to AD can inform who is at greatest risk of developing this disease. We analyzed electronic medical records of 394892 patients from the two largest health systems in Northeast Ohio to evaluate the relationship between Ohio Area Deprivation Index quintiles (defined at the census tract level) and hazard for a composite outcome of AD diagnosis or primary AD death. We included residents of Cuyahoga and neighboring counties, and used the first outpatient visit beyond age 60 occurring between 2005 and 2015 as study baseline. Outcome data were censored at the earlier of a) the beginning of any 3-year time period without visits or b) non-AD death. We estimated a Cox proportional hazards regression model, adjusting ADI quintile effects for the interaction between age at baseline, sex and race as well as birth year. We used quadratic terms for continuous predictors. After adjusting for these factors, ADI quintile was significantly related (χ2 = 83.0 on 4 d.f.; p < 0.0001) to the composite time-to-event outcome. Compared to the lowest-deprivation quintile, ADI quintiles 4 (adjusted hazard ratio [95% confidence interval]: 1.18 [1.10, 1.26]) and 5 (1.37 [1.28, 1.47]) had significantly higher hazard for the composite outcome. In conclusion, neighborhood deprivation may be a risk factor for AD independent of demographic factors. Preventive efforts should target individuals living in neighborhoods with high levels of deprivation.

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Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer’s disease

Brain Science Advances ◽

10.1177/2096595820902582 ◽

2019 ◽

Vol 5 (2) ◽

pp. 94-105 ◽

Cited By ~ 1

Author(s):

Ya-Nan Ou ◽

Hao Hu ◽

Zuo-Teng Wang ◽

Wei Xu ◽

Lan Tan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Rate Of Change ◽

Neurofilament Light ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Β Amyloid ◽

Longitudinal Biomarker

Objective: To examine whether plasma neurofilament light (NFL) might be a potential longitudinal biomarker for Alzheimer’s disease (AD). Methods: A total of 835 individuals from the Alzheimer’s Disease Neuroimaging Initiative were involved. Correlations of the rate of change in plasma NFL with cerebrospinal fluid biomarkers, cognition, and brain structure were investigated. Cox proportional hazards models were used to assess the associations between quartiles of plasma NFL and the risk of AD conversion. Results: Participants were further divided into β amyloid-positive (Aβ+) versus β amyloid-negative (Aβ−), resulting in five biomarker group combinations, which are CN Aβ−, CN Aβ+, MCI Aβ−, MCI Aβ+ and AD Aβ+. Plasma NFL concentration markedly increased in the five groups longitudinally ( p < 0.001) with the greatest rate of change in AD Aβ+ group. The rate of change in plasma NFL was associated with cognitive deficits and neuroimaging hallmarks of AD over time ( p < 0.005). Compared with the bottom quartile, the top quartile of change rate was associated with a 5.41-fold increased risk of AD (95% CI = 1.83−16.01) in the multivariate model. Conclusion: Our finding implies the potential of plasma NFL as a longitudinal noninvasive biomarker in AD.

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Confrontation naming does not add incremental diagnostic utility in MCI and Alzheimer's disease

Journal of the International Neuropsychological Society ◽

10.1017/s1355617704104177 ◽

2004 ◽

Vol 10 (4) ◽

pp. 504-512 ◽

Cited By ~ 37

Author(s):

JULIE A. TESTA ◽

ROBERT J. IVNIK ◽

BRADLEY BOEVE ◽

RONALD C. PETERSEN ◽

V. SHANE PANKRATZ ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Regression Analysis ◽

Proportional Hazards ◽

Normal Subjects ◽

Cox Proportional Hazards ◽

Diagnostic Utility ◽

Delayed Recall ◽

Increased Risk ◽

Cognitively Normal Subjects

As the incidence of dementia increases, there is a growing need to determine the diagnostic utility of specific neuropsychological tests in the early diagnosis of Alzheimer's disease (AD). In this study, the relative utility of Boston Naming Test (BNT) in the diagnosis of AD was examined and compared to the diagnostic utility of other neuropsychological measures commonly used in the evaluation of AD. Individuals with AD (n = 306), Mild Cognitive Impairment (MCI; n = 67), and cognitively normal subjects (n = 409) with at least 2 annual evaluations were included. Logistic regression analysis suggested that initial BNT impairment is associated with increased risk of subsequent AD diagnosis. However, this risk is significantly less than that imparted by measures of delayed recall impairments. A multivariate Cox proportional hazards regression analysis suggested that BNT impairment imparted no additional risk for subsequent AD diagnosis after delayed recall impairments were included in the model. Although BNT impairment occurred in all severity groups, it was ubiquitous only in moderate to severe dementia. Collectively these results suggest that although BNT impairments become more common as AD progresses, they are neither necessary for the diagnosis of AD nor particularly useful in identifying early AD. (JINS, 2004, 10, 504–512.)

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Plasma Brain-Derived Neurotropic Factor Levels Are Associated with Aging and Smoking But Not with Future Dementia in the Rotterdam Study

Journal of Alzheimer s Disease ◽

10.3233/jad-200371 ◽

2021 ◽

Vol 80 (3) ◽

pp. 1139-1149

Author(s):

Sara Galle ◽

Silvan Licher ◽

Maarten Milders ◽

Jan Berend Deijen ◽

Erik Scherder ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Proportional Hazards ◽

Long Term Potentiation ◽

Cox Proportional Hazards ◽

Activity Level ◽

Rotterdam Study ◽

Increased Risk ◽

Neurotropic Factor

Background: Brain-derived neurotropic factor (BDNF) plays a vital role in neuronal survival and plasticity and facilitates long-term potentiation, essential for memory. Alterations in BDNF signaling have been associated with cognitive impairment, dementia, and Alzheimer’s disease. Although peripheral BDNF levels are reduced in dementia patients, it is unclear whether changes in BDNF levels precede or follow dementia onset. Objective: In the present study, we examined the association between BDNF plasma levels and dementia risk over a follow-up period of up to 16 years. Methods: Plasma BDNF levels were assessed in 758 participants of the Rotterdam Study. Dementia was assessed from baseline (1997–1999) to follow-up until January 2016. Associations of plasma BDNF and incident dementia were assessed with Cox proportional hazards models, adjusted for age and sex. Associations between plasma BDNF and lifestyle and metabolic factors are investigated using linear regression. Results: During a follow up of 3,286 person-years, 131 participants developed dementia, of whom 104 had Alzheimer’s disease. We did not find an association between plasma BDNF and risk of dementia (adjusted hazard ratio 0.99; 95%CI 0.84–1.16). BDNF levels were positively associated with age (B = 0.003, SD = 0.001, p = 0.002), smoking (B = 0.08, SE = 0.01, p = < 0.001), and female sex (B = 0.03, SE = 0.01, p = 0.03), but not with physical activity level (B = –0.01, SE = 0.01, p = 0.06). Conclusion: The findings suggest that peripheral BDNF levels are not associated with an increased risk of dementia.

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Factors Affecting Rapid Cognitive Decline in Patients with Alzheimer’s Disease: A Longitudinal Follow-Up Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18168576 ◽

2021 ◽

Vol 18 (16) ◽

pp. 8576

Author(s):

Chih-Chuan Pan ◽

Che-Sheng Chu ◽

Chien-Liang Chen ◽

Yao-Chung Chuang ◽

Nai-Ching Chen

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Protective Factor ◽

Proportional Hazards ◽

Acetylcholinesterase Inhibitors ◽

Cox Proportional Hazards ◽

Research Database ◽

Clinical Dementia Rating ◽

Rapid Cognitive Decline

We investigated the preventive and risk factors of rapid cognitive decline in patients with Alzheimer’s disease (AD). Using the Chang Gung Research Database (CGRD), we enrolled patients with AD aged over 65 years between 1 January 2001 and 30 May 2019, and followed up for at least two years. Rapid cognitive decline was defined by a Mini-Mental State Examination (MMSE) score decline of ≥4 in 2 years. A longer prescription of acetylcholinesterase inhibitors (AChEIs) was defined as 22 months based on the median treatment duration of the cohorts. The Cox proportional hazards regression model adjusted for age, sex, medication, and physical comorbidities was used to examine the candidate risk and protective factors. We analyzed data from 3846 patients with AD (1503 men, 2343 women) with a mean age and percentage of females of 77.8 ± 6.2 years and 60.9%, respectively. The mean duration of patients with AD receiving AChEIs was 658.7 ± 21.9 days. In general, 310 patients with AD showed a rapid cognitive decline, accounting for 8.1%. Treatment of a consecutive AChEI prescription for >22 months in patients with AD was a protective factor against rapid cognitive decline (adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.33–0.52, p < 0.001). Patients with AD aged >85 years (aHR = 0.53, 95% CI = 0.36–0.79, p < 0.01) and aged 75–85 years (aHR = 0.73, 95% CI = 0.57–0.93, p < 0.05) had a significantly lower risk of rapid cognitive decline than those aged 65–75 years. Additionally, patients with mild and moderate AD (clinical dementia rating (CDR = 1, aHR = 1.61, 95% CI = 1.26–2.07, p < 0.001; CDR = 2, aHR = 2.64, 95% CI = 1.90–3.65, p < 0.001) were more likely to have rapid cognitive decline than those with early AD (CDR = 0.5). Sex, medication with different types of AChEIs, and physical comorbidities were not associated with rapid cognitive decline. These findings indicate that it is important to maintain longer consecutive AChEI prescriptions in patients with AD to prevent cognitive decline.

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