Alzheimer's Disease Odds Ratio Research Articles

Association between myasthenia gravis and Alzheimer's disease.

Myasthenia gravis (MG) and Alzheimer's disease (AD) are two of the most important diseases where the dysregulation of acetylcholine activity plays a crucial role. In the first, this dysregulation happens at the level of the neu-romuscular junction and in the second, in the central nervous system (CNS). To analyze the possible relationship between these two pathologies, analyzing the prevalence and the odds ratio of AD within patients previously diagnosed with MG. We will compare these data with respect to the prevalence of AD in the general population. We examined the data obtained by the electronic medical records of patients in the health care system of Castilla La Mancha using the Natural Language Process provided by a clinical platform of artificial intelligence known as the Savana Manager?. We identified 970,503 patients over the age of 60 years, of which 1,028 were diagnosed with MG. The proportion of the patients diagnosed with AD within this group (4.28%) was greater than the rest of the population (2.82%) (p = 0,0047) with an odds ratio of 1.54 (confidence interval at 95% 1.13-2.08; p = 0.0051) without finding significant differences in the bivariate analysis for the rest of the most important actual known risk factors for AD. Our results suggest that there might be an increase in the prevalence of AD in patients previously diagnosed with MG.

Stress, depression, and risk of dementia – a cohort study in the total population between 18 and 65 years old in Region Stockholm

BackgroundChronic stress and depression are potential risk factors for mild cognitive impairment and dementia, including Alzheimer disease. The aim was to investigate whether any such risk is additive.MethodsCohort study including 1 362 548 people (665 997 women, 696 551 men) with records in the Region Stockholm administrative healthcare database (VAL).Exposure was a recorded ICD-10 diagnosis of chronic stress, depression, or both, recorded in 2012 or 2013. Outcome was a diagnosis of Alzheimer disease, other dementia, or mild cognitive impairment recorded from 2014 through 2022. Odds ratios with 99% confidence intervals (CI) adjusted for age, sex, neighborhood socioeconomic status, diabetes, and cardiovascular disorders were calculated.ResultsDuring the exposure period, 4 346 patients were diagnosed with chronic stress, 40 101 with depression, and 1 898 with both. The average age at baseline was around 40 years in all groups. In the fully adjusted model, the odds ratio of Alzheimer disease was 2.45 (99% CI 1.22–4.91) in patients with chronic stress, 2.32 (99% CI 1.85–2.90) in patients with depression, and 4.00 (99% CI 1.67–9.58) in patients with chronic stress and depression. The odds ratio of mild cognitive impairment was 1.87 (99% CI 1.20–2.91) in patients with chronic stress, 2.85 (99% CI 2.53–3.22) in patients with depression, and 3.87 (99% CI 2.39–6.27) in patients with both. When other dementia was analyzed, the odds ratio was significant only in patients with depression, 2.39 (99% CI 1.92–2.96).ConclusionsDocumented chronic stress increased the risk of mild cognitive impairment and Alzheimer disease. The same was seen with depression. The novel finding is the potential additive effect of chronic stress to depression, on risk of MCI and AD.

Prevalence and Progression of Subjective Cognitive Decline Among Rural Chinese Older Adults: A Population-Based Study.

Few community-based studies have examined occurrence and progression of subjective cognitive decline (SCD). To investigate prevalence and progression of SCD among rural-dwelling Chinese elderly people. This cohort study included 2,488 cognitively unimpaired adults (age≥65 years) who were examined at baseline (2014-2015) and followed in 2018. Demographic, epidemiological, clinical, and neuropsychological data were collected via in-person interviews and clinical examinations following a structured questionnaire. At baseline, SCD was assessed using the self-rated Ascertain Dementia 8-item Questionnaire. At follow-up, Alzheimer's disease (AD) and vascular dementia (VaD) were clinically diagnosed following the international criteria. Data were analyzed using logistic regression models. The prevalence of SCD was 40.07%. SCD at baseline was associated with the multivariable-adjusted odds ratio (OR) of 1.51 (95% confidence interval 1.10-2.07) for incident cognitive impairment, no dementia (CIND) and 3.11 (1.64-5.93) for incident AD. Among people with SCD at baseline, the multivariable-adjusted OR of incident CIND was 0.55(0.32-0.96) for hyperlipidemia; the multivariable-adjusted OR of incident AD was 1.21 (1.14-1.30) for older age, 0.32 (0.12-0.88) for high education, 2.60 (1.11-6.08) for carrying APOEɛ4 allele, and 0.34 (0.13-0.86) for high social support, whereas the multivariable-adjusted OR of incident VaD was 6.30 (1.71-23.18) for obesity. SCD affects over 40% of rural-dwelling cognitively unimpaired older adults in China. SCD is associated with accelerated progression to CIND and AD. Older age, lack of school education, APOEɛ4 allele, and low social support are associated with an increased risk of progression from SCD to AD, whereas obesity is related to accelerated progression to VaD.

Circulating Chlamydia Trachomatis Antigens in Subjects With Alzheimer's Disease.

Chlamydia pneumoniae (C. pneumoniae) is implicated in the pathogenesis of Alzheimer's disease (AD). Chlamydial elementary and reticulate bodies have been identified in tissues from afflicted AD brain regions by electron and immunoelectron microscopy, whereas similar tests of non-AD brains were negative for the bacterium. Studies in mice have shown that C. pneumoniae can rapidly penetrate the central nervous system by entering glia and causing beta amyloid deposition via the nerves between the nasal cavity and the brain, which serve as invasion pathways. We used data from the UK Biobank (UKBB) to assess the relationship of chlamydia and AD. Circulating C. pneumoniae antigen measurements were not available, but UKBB data field 23037 held measurements of PorB antigen for Chlamydia trachomatis (C. trachomatis). We used C. trachomatis as a surrogate for C. pneumoniae since serum cross-reactivity to C. trachomatis and C. pneumoniae antigens occurs in patients with documented infection and in healthy children as revealed by microimmunofluorescence and immunoblotting techniques. Single nucleotide polymorphism (SNP) data for rs429358 and rs7412 were used to impute ApoE genotypes. PorB antigen levels for C. trachomatis were significantly higher in subjects with AD (p=0.007). PorB antigen levels were not related to ApoE genotype (e3e3, e3e4, e4e4) p=0.783. To control for the effects of age, sex, educational level, and apoE genotype, logistic regression analysis was performed. AD was the dependent variable. Independent variables were sqrt PorB antigen for C. trachomatis, age, sex, educational level, apoE genotype. AD odds ratio (OR) increased 1.156 for each unit increase of sqrt PorB antigen for C. trachomatis and the effect was significant (p=0.004). PorB antigens for C. trachomatis being significantly higher in subjects with AD, corroborates previous studies demonstrating that C. pneumoniae inflammation appears to play a role in AD development. AD may result from the reactivation of embryologic processes and pathways silenced at birth. A trigger for the reactivation may be bacterial or viral infections. Further studies are warranted.

Antiviral treatment associated with reduced risk of clinical Alzheimer's disease-A nested case-control study.

IntroductionIn this nested case‐control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD.MethodsFrom a large population‐based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non‐AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year.ResultsAmong those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow‐up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018).DiscussionAntiviral treatment might possibly reduce the risk for later development of HSV1‐associated AD.

Prevalence of Alzheimer's Disease and Parkinson's Disease in China: An Updated Systematical Analysis.

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are two major neurodegenerative diseases worldwide. Demographic aging is in rapid progress in China. Up-to-date estimates of AD and PD prevalence have not been provided.Methods: Studies that reported the prevalence of AD and PD in China were identified via a systematic database search from 1985 to 2018. Meta-analysis, local polynomial regression and autoregressive integrated moving average model were used for analyses.Results: A total of 99 studies were included in the study with populations of 385,312 and 227,228, respectively for AD and PD. The overall prevalence of AD and PD following age standardization was 3.20% [95% confidence interval (CI) = 3.17–3.23] and 1.06% (95% CI = 1.02–1.10), respectively in individuals over 60 years old. The rates increased drastically for every 10-years increment of age. The yearly prevalence of AD was predicted to increase from 3.81 to 6.17% in the next 5 years. Significant differences were observed between genders [male to female odds ratio (OR) for AD = 0.57, 95% CI = 0.51–0.64; OR for PD = 1.25, 95% CI = 1.06–1.46], and between education levels (Illiterate to non-illiterate OR for AD = 2.99, 95% CI = 2.38–3.75), but not between urban and rural settings.Conclusion: Our results provide an updated insight into the epidemiology of AD and PD in China and their associated rates and ratios. The findings may facilitate China policy makers and health professionals mitigate the related health issues.

Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study.

The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. This case-control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44-96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer's Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44-94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1-5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4-31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65-70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level.

Age Modifies the Association Between Apolipoprotein E Genotype and Alzheimer's Disease: A CSF Biomarker-Based Multicentric Case-Control Study

Background: We investigated the global and age-specific association between Apolipoprotein E (APOE) genotype and Alzheimer's disease (AD) in a large multicentric case-control study, using cerebrospinal fluid (CSF) biomarkers-based diagnostic criteria for AD. Methods: In this case-control design, data on 1,599 Caucasian AD cases with abnormal values of CSF biomarkers came from 9 European memory clinics and the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. AD cases were compared to 11,724 dementia-free controls, drawn from two longitudinal cohort studies (Whitehall II and 3-City). Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were reported, overall and by 5-year age categories. Findings. 63*4% of CSF biomarker-defined AD patients and 22*6% of population controls carried at least one APOE e4 allele; respective percentages for APOE e4 homozygotes were 16*7% and 1*4%. Compared to none4 carriers, heterozygous e4 carriers had a 4*6 (95% confidence interval: 4*1 - 5*2) and e4/e4 homozygotes a 25*4 (20*5 - 31*3) higher OR of AD. This association was strongly modified by age (p for interaction < 0*001). The PAF associated with carrying at least one e4 allele was greatest in the 65-70 age group (69*7%), and weaker before 55 years (14*2%) and after 85 years (22*6%). There was some evidence of a stronger effect of APOE on AD risk in women. Interpretation: Incorporating biomarkers for diagnosis of AD led to a stronger association with APOE e4 than previously reported, perhaps due to better diagnostic accuracy. This association differs according to age, with the strongest effect at 65-70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE e4 at the population level. Funding Statement: US National Institutes of Health, Fondation Plan Alzheimer. Declaration of Interests: ASM is supported by NIH/NIA R01AG056477. IZ is supported by the Robert-Koch-Institute through funds of Federal Ministry of Health (grant no. 1369-341) and DZNE (German Center for Neurodegenerative Diseases). KB reports consulting fees from Fujirebio Europe, IBL International, Roche Diagnostics. HZ is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. MB has been a consultant for Araclon, Avid, Bayer, Elan, Grifols, Janssen/Pfizer, Lilly, Neuroptix, Nutricia, Roche, Sanofi, and Servier. All other authors declare no competing interests. Ethics Approval Statement: Ethical clearance was obtained by the institutional review boards of all participating sites (European memory centers and ADNI Study sites) and all participants provided written, informed consent.

Genetically elevated gamma-glutamyltransferase and Alzheimer's disease

Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer's disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer's Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associated with GGT in a previous genome-wide association study on liver enzymes as instruments. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR.The odds ratio of AD was 1.09 (95% confidence interval, 0.98 to 1.22; p = 0.10) per one standard deviation genetically elevated GGT based on all 26 SNPs. The results were similar in both MR-Egger and weighted median MR methods. Overall, our findings cannot confirm a strong causal effect of GGT on AD risk. Further MR investigations using individual-level data are warranted to confirm or rule out causality.

Circulating insulin-like growth factors and Alzheimer disease: A mendelian randomization study.

ObjectiveTo examine whether genetically predicted variation in circulating insulin-like growth factor 1 (IGF1) or its binding protein, IGFBP3, are associated with risk of Alzheimer disease (AD), using a mendelian randomization study design.MethodsWe first examined disease risk by genotypes of 9 insulin-like growth factor (IGF)–related single nucleotide polymorphisms (SNPs) using published summary genome-wide association statistics from the International Genomics of Alzheimer's Project (IGAP; n = 17,008 cases; 37,154 controls). We then assessed whether any SNP-disease results replicated in an independent sample derived from the Swedish Twin Registry (n = 984 cases; 10,304 controls).ResultsMeta-analyses of SNP-AD results did not suggest that variation in IGF1, IGFBP3, or the molar ratio of these affect AD risk. Only one SNP appeared to affect AD risk in IGAP data. This variant is located in the gene FOXO3, implicated in human longevity. In a meta-analysis of both IGAP and secondary data, the odds ratio of AD per FOXO3 risk allele was 1.04 (95% confidence interval 1.01–1.08; p = 0.008).ConclusionsThese findings suggest that circulating IGF1 and IGFBP3 are not important determinants of AD risk. FOXO3 function may influence AD development via pathways that are independent of IGF signaling (i.e., pleiotropic actions).

Genetically-Predicted Adult Height and Alzheimer's Disease.

Observational studies have linked increased adult height with better cognitive performance and reduced risk of Alzheimer's disease (AD). It is unclear whether the associations are due to shared biological processes that influence height and AD or due to confounding by early life exposures or environmental factors. To use a genetic approach to investigate the association between adult height and AD. We selected 682 single nucleotide polymorphisms (SNPs) associated with height at genome-wide significance (p < 5×10-8) in the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Summary statistics for each of these SNPs on AD were obtained from the International Genomics of Alzheimer's Project (IGAP) of 17,008 individuals with AD and 37,154 controls. The estimate of the association between genetically predicted height and AD was calculated using the inverse-variance weighted method. The odds ratio of AD was 0.91 (95% confidence interval, 0.86-0.95; p = 9.8×10-5) per one standard deviation increase (about 6.5 cm) in genetically predicted height based on 682 SNPs, which were clustered in 419 loci. In an analysis restricted to one SNP from each height-associated locus (n = 419 SNPs), the corresponding OR was 0.92 (95% confidence interval, 0.86-0.97; p = 4.8×10-3). This finding suggests that biological processes that influence adult height may have a role in the etiology of AD.

The Plasminogen Activator Inhibitor 1 4G/5G Polymorphism and the Risk of Alzheimer's Disease.

The aim of this study was to determine whether plasminogen activator inhibitor 1 (PAI-1) is associated with the risk of Alzheimer's disease (AD) in Tunisian patients. We analyzed the genotype and allele frequency distribution of the PAI-1 polymorphism in 60 Tunisian patients with AD and 120 healthy controls. The results show a significantly increased risk of AD in carriers of the 4G/4G and 4G/5G genotypes versus the wild-type 5G/5G genotype (4G/4G: 28.33% in patients vs 10.0% in controls; P < 10-3; OR = 8.78; 4G/5G: 55.0% in patients vs 38.33% in controls; OR = 4.45; P < 10-3). The 4G allele was also more frequently found in patients compared with controls; P < 10-3; OR = 3.07. For all participants and by gender, homozygotic carriers (4G/4G) were at an increased risk of AD over heterozygotes and women were at an increased risk over their male genotype counterparts. The odds ratio for AD among 4G/4G carriers for any group was approximately twice that of heterozygotes in the same group. Women homozygotes ranked highest for AD risk (OR = 20.8) and, in fact, women heterozygotes (OR = 9.03) ranked higher for risk than male homozygotes (OR = 6.12). These preliminary exploratory results should be confirmed in a larger study.

The APOE Genotype in Idiopathic Normal Pressure Hydrocephalus.

IntroductionAmyloid plaque has been reported in brain biopsies from patients with idiopathic normal-pressure hydrocephalus (iNPH) and proposed as a significant feature of the pathophysiology. Presence of the apolipoprotein E ε4 (APOE ε4) allele is associated with increased risk of Alzheimer’s disease (AD).AimsTo compare the distribution of APOE genotype in iNPH patients with an age-matched population-based control group and with Alzheimer’s disease (AD) patients.MethodsAPOE genotype frequencies were determined in 77 iNPH patients (50 men and 27 women, mean age 71.7 years) diagnosed with iNPH, a sample of 691 AD patients and 638 age-matched population controls (299 men and 339 women) from the INTERGENE cohort.ResultsThe APOE distribution did not differ significantly between the iNPH patients and the control population. The per e4-allele odds-ratio (OR) of iNPH was given by OR = 0.90, 95% confidence interval (CI) = (0.50, 1.60) that was considerably smaller than the per-allele OR of AD, OR = 5.34 (4.10, 7.00).ConclusionThe results suggest that the APOE-related risk of AD in patients with iNPH is not higher than in the general population.

A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.

ContextThere is no rapid and cost effective tool that can be implemented as a front-line screening tool for Alzheimer's disease (AD) at the population level.ObjectiveTo generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma.Design, Setting, ParticipantsAnalysis of serum biomarker proteins were conducted on 197 Alzheimer's disease (AD) participants and 199 control participants from the Texas Alzheimer's Research Consortium (TARC) with further analysis conducted on plasma proteins from 112 AD and 52 control participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The full algorithm was derived from a biomarker risk score, clinical lab (glucose, triglycerides, total cholesterol, homocysteine), and demographic (age, gender, education, APOE*E4 status) data.Major Outcome MeasuresAlzheimer's disease.Results11 proteins met our criteria and were utilized for the biomarker risk score. The random forest (RF) biomarker risk score from the TARC serum samples (training set) yielded adequate accuracy in the ADNI plasma sample (training set) (AUC = 0.70, sensitivity (SN) = 0.54 and specificity (SP) = 0.78), which was below that obtained from ADNI cerebral spinal fluid (CSF) analyses (t-tau/Aβ ratio AUC = 0.92). However, the full algorithm yielded excellent accuracy (AUC = 0.88, SN = 0.75, and SP = 0.91). The likelihood ratio of having AD based on a positive test finding (LR+) = 7.03 (SE = 1.17; 95% CI = 4.49–14.47), the likelihood ratio of not having AD based on the algorithm (LR−) = 3.55 (SE = 1.15; 2.22–5.71), and the odds ratio of AD were calculated in the ADNI cohort (OR) = 28.70 (1.55; 95% CI = 11.86–69.47).ConclusionsIt is possible to create a blood-based screening algorithm that works across both serum and plasma that provides a comparable screening accuracy to that obtained from CSF analyses.

Higher Cathepsin B Levels in Plasma in Alzheimer's Disease Compared to Healthy Controls

Cathepsin B is suggested to be involved in amyloid-β (Aβ) processing and Alzheimer's disease (AD). Studies of cathepsin B levels in plasma and cerebrospinal fluid (CSF) have not been previously performed. We examined cathepsin B levels in plasma and CSF samples in persons with AD, mild cognitive impairment (MCI), and healthy controls in order to test the hypothesis that cathepsin B levels can discriminate persons with AD or MCI from healthy controls. Cathepsin B, Cystatin C, Aβ1-40 and Aβ1-42, total tau, phosphorylated tau, and albumin levels in plasma and CSF were analyzed by ELISA (Cathepsin B) turbidimetry (cystatin C), xMAP Luminex technology (Aβ1-40 and Aβ1-42 and tau), and Cobas C501 analyzer (albumin) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Plasma cathepsin B levels were higher in persons with AD compared to healthy controls, both in unadjusted models and in multivariable models adjusting for age, gender, APOE genotype, cystatin C, and albumin levels: Odds ratio (OR) for AD per 1 SD of plasma cathepsin B; 2.04, 95% confidence interval (CI); 1.01-4.14, p= 0.05. There was no difference between diagnostic groups in cathepsin B levels in CSF: OR for AD per 1 SD of CSF cathepsin B; 0.93, 95% CI; 0.37-2.30, p= 0.87. Plasma cathepsin B levels were higher in persons with AD compared to healthy controls whereas there was no difference between diagnostic groups in cathepsin B levels in CSF. Further investigation of cathepsin B as a predictor of AD is warranted.

Gender effect on apolipoprotein E 84 allele-associated risk for sporadic Alzheimer's disease

The role of gender in Alzheimer's disease (AD), and its possible interaction with apolipoprotein E (apoE), has been controversial. ApoE allelic frequencies and the effect of apoE epsilon4 allele dosage on risk and age at onset of AD were evaluated, separately for men and women, in 100 patients with sporadic AD and 100 age-matched controls. The distribution of apoE alleles and the odds ratio for AD, when associated with 1 or 2 epsilon4 alleles, were not statistically different between men and women. No effect of the dosage of the epsilon4 allele was found on the age at onset of dementia in the 2 sex groups. Our data suggest that the relation of the apoE genotype to AD is not dependent on sex.

Relationship between antihypertensive drug therapy and cognitive function in elderly hypertensive patients with memory complaints

To evaluate the relationship between antihypertensive treatments and cognitive function in elderly hypertensive patients with memory complaints. The association between cognitive function and antihypertensive drug therapy was studied in 1241 hypertensive elderly patients with memory complaints attending a geriatric outpatient clinic. Cognitive function was assessed using the Mini Mental State Examination (MMSE) and validated neuropsychological tests (Cognitive Efficiency Profile; CEP). Patients were classified into four categories according to their cognitive status: normal cognitive function, mild cognitive impairment (MCI), Alzheimer's disease (AD) or vascular dementia (VaD). In this population aged 78 +/- 8 years, with a mean blood pressure of 152 +/- 19/86 +/- 12 mmHg, antihypertensive treatment was prescribed for 57% of patients. After adjustment for age, sex and education, treated hypertensive patients had better cognitive function than untreated patients (MMSE score 23.9 +/- 5.6/30 versus 22.7 +/- 6.4/30, P < 0.001, CEP score 49.1 +/- 24.9/100 versus 45.4 +/- 23.7/100, P < 0.001). This association was observed independently of the cognitive status, both in normal, MCI, AD and VaD hypertensive patients. The odds ratio (OR) for AD was 0.58 [95% confidence interval (CI) 0.42-0.81] in treated compared with untreated hypertensive patients. In patients on antihypertensive therapy, higher cognitive function was observed in patients using calcium antagonists compared with those without calcium antagonists (CEP 52.9 +/- 24.6/100 versus 46.4 +/- 23.4/100, P < 0.001; OR for AD 0.67; 95% CI 0.45-0.99), independently of blood pressure level. Antihypertensive therapy was associated with a lower risk of cognitive impairment and AD. In particular, the use of calcium antagonists was associated with a decreased risk of cognitive impairment and AD independently of the blood pressure level, suggesting a specific neuroprotective effect of these antihypertensive agents.

Postmenopausal Estrogen Therapy and Alzheimer Disease: Overall Negative Findings

An inverse association between estrogen therapy (ET) and Alzheimer disease (AD) has been reported in some, but not in all studies. We investigated the association between ET and AD in postmenopausal women using a population-based case-control design. Women who developed AD from 1985 through 1989 in Rochester, MN (cases, n=264) were individually matched by age (+/-1 y) to control women free of dementia from the same population (controls, n=264). ET exposure (>/=6 mo after menopause) was ascertained by abstracting the complete medical records archived in the records-linkage system of the Rochester Epidemiology Project. The frequency of ET use was similar in cases (11.4%) and controls [10.6%; odds ratio=1.10; 95% confidence interval (CI)=0.63-1.93]. However, cases who used ET had a suggestive trend for an earlier age at start of ET compared with controls (median, 49.0 vs. 50.5 y; P=0.06). Although smoking (ever vs. never) was not associated with AD overall, we observed an interaction between smoking and ET. The odds ratio of AD in ET users was 4.55 (95% CI=1.33-15.53) among smokers, but was 0.68 (95% CI=0.35-1.32) among never-smokers (P for interaction=0.01). Our findings do not confirm a significant association between ET and AD overall; however, the possible interaction with smoking deserves further study.

Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease

The proteins cathepsin D, encoded by CTSD gene, and α 2-macroglobulin, encoded by A2M gene, are involved in the biochemical pathway leading to deposition of β-amyloid. In these proteins two amino acid polymorphisms (CTSD- Ala/Val C→ T and A2M -Ile/Val A→ G) have been associated with an increased risk for Alzheimer's disease (AD), but conflicting results have been reported. We studied the association and the mutual interactions of the CTSD- C/T and A2M -A/G polymorphisms with sporadic AD in 100 patients with late-onset AD and 136 healthy elderly subjects as controls. The CTSD- T allele and the CTSD- C/T genotype are significantly more frequent in AD than in controls. The odds ratio (OR) for CTSD- T subjects is 1.93 [95% confidence interval (CI) = 1.01–3.72], and 2.07 (95% CI = 1.01–4.21) after adjustment for age, sex and APOE ε4+ status, while no significant association was found for the A2M- A/G polymorphism. The coexistence of the CTSD- T with the A2M- G allele synergistically increased the OR for AD to 2.69 (95% CI = 1.13–6.34) [2.82 (95% CI = 1.12–7.17) after adjustment], and to 3.29 (95% CI = 1.33–8.16) if estimated for the allelic combination. Our data suggest that the CTSD- T allele of the CTSD- C/T polymorphism is associated with an increased relative risk for late-onset AD and, more interestingly, the combination of CTSD- T with the A2M- G allele seems to increase this risk.

Medial Temporal Lobe Atrophy, Apolipoprotein Genotype, and Plasma Homocysteine in Sri Lankan Patients with Alzheimer's Disease

ABSTRACT The authors studied the association of Alzheimer's disease (AD) with total plasma homocysteine (tHcy) and apolipoprotein E (apoE) genotype, and the usefulness of measuring medial temporal lobe thickness (MTL) thickness for the diagnosis of AD in Sri Lankan patients. Using criteria of the NINCDS-ADRDA, 23 AD patients and 21 controls were recruited. All underwent MTL-oriented computed tomographic (CT) scans, measurement of plasma tHcy, and apoE genotyping. Mean plasma tHcy was significantly higher in AD patients than controls (p = .001). This association was independent of age, sex, body mass index (BMI), serum folate and vitamin B12, and serum creatinine. The frequency of apoE4 allele was significantly higher (p = .003) in AD patients, and the adjusted odds ratio of AD for the presence of one or more apoE4 alleles compared with none was 10.39 (95% CI 1.77–61.10; p = .010). The mean minimum MTL thickness was significantly higher in control subjects compared to that of AD patients (p < .001). This first report of apoE4, plasma tHcy, MTL thickness, and AD from Sri Lanka shows that high plasma tHcy, the presence of apoE4 allele, and MTL atrophy are associated with AD.