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Background: high TSH concentrations and cognitive decline are both very common among older people and could be linked., Objective: to assess cognition in our cohort of 335 home-dwelling older people (75 years and older) and to cross-sectionally relate the results to thyroid-stimulating hormone (TSH) concentrations. Our special focus was on the upper normal TSH range and subclinical hypothyroidism., Methods: cognitive performance was evaluated using the Consortium to Establish a Registry for Alzheimer's disease neuropsychological battery (CERAD-nb). The Clinical Dementia Rating (CDR) scale was used to evaluate severity of cognitive disorder. The APOEε4 genotype was also defined. Subjects were divided into quartiles based on the TSH concentrations, and results were compared between these groups., Results: expected relations were observed between CERAD domains and both educational level and APOEε4 genotype. Female sex significantly associated with better performance in Boston naming (OR = 0.48; 95% CI = 0.27-0.85). In the whole cohort, higher TSH concentrations tended to associate with better scores in most parts of the CERAD-nb tests, but differences were not statistically significant. However, subjects with the highest TSH concentration (90th TSH percentile, range 4.14-14.4 mU/l) had better CDR scores compared with subjects with the lowest TSH concentration (10th percentile, range 0.001-0.63 mIU/l; OR 0.10; 95% CI 0.014-0.76)., Conclusions: our results do not support the notion that higher TSH concentrations, not even in the range of subclinical hypothyroidism, would adversely affect cognition among older people., (© The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Many potentially inappropriate drugs prescribed to older people have anticholinergic properties and may therefore be harmful. Drugs with anticholinergic properties (DAPs) are associated with cognitive decline., Objective: Our aim was to study the profile of various cognitive functions related to current use of DAPs., Methods: A cross-sectional study was conducted in Helsinki, Finland, and included 400 home-dwelling individuals aged 75-90 years without major clinical dementia but with a history of stable atherosclerotic disease who were participants of the DEBATE (Drugs and Evidence-Based Medicine in the Elderly) study. The cognition of the users (n = 295) and non-users (n = 105) of DAPs was measured with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery., Results: Use of DAPs was statistically significantly associated with a low score in verbal fluency, in naming, and on the Mini-Mental State Examination (MMSE). In the logistic regression analysis, the difference remained for low verbal fluency (odds ratio [OR] 1.84, 95 % CI 1.02-3.32; p = 0.044) and naming (OR 1.81, 95 % CI 1.09-3.00; p = 0.021) but not for MMSE score after adjusting for age, sex and education., Conclusions: Performances for verbal fluency and naming were poorer in DAP users than in non-users, suggesting a possible impairment of executive functioning and semantic memory. The dimensions of the CERAD test assessing episodic memory-the subtests that are the most sensitive in terms of detecting early Alzheimer's disease-did not show differences between users and non-users of DAPs.

Overexposure to glucocorticoids may link prenatal adversity with detrimental outcomes in later life. Glycyrrhiza, a natural constituent of licorice, inhibits placental 11-beta-hydroxysteroid dehydrogenase type 2, the feto-placental "barrier" to higher maternal levels of cortisol. The authors studied whether prenatal exposure to glycyrrhiza in licorice exerts detrimental effects on cognitive performance (subtests of the Wechsler Intelligence Scale for Children III as well as the Children's Developmental Neuropsychological Assessment and the Beery Developmental Test of Visual-Motor Integration) and psychiatric symptoms (Child Behavior Checklist) in 321 Finnish children 8.1 years of age born in 1998 as healthy singletons at 35-42 weeks of gestation. In comparison to the group with zero-low glycyrrhiza exposure (0-249 mg/week), those with high exposure (>or=500 mg/week) had significant decrements in verbal and visuospatial abilities and in narrative memory (range of mean differences in standard deviation units, -0.31 to -0.41; P < 0.05) and significant increases in externalizing symptoms and in attention, rule-breaking, and aggression problems (range of odds ratios, 2.15 to 3.43; P < 0.05). The effects on cognitive performance appeared dose related. Data are compatible with adverse fetal "programming" by overexposure to glucocorticoids and caution against excessive intake of licorice-containing foodstuffs during pregnancy.

Objectives: To clarify the association between anticholinergic drugs and apolipoprotein E epsilon4 allele carrier status (APOE4) and cognitive dysfunction., Design: Cross-sectional analyses of current drug use and cognitive functioning according to the baseline assessments of the Drugs and Evidence-Based Medicine in the Elderly Study., Setting: Helsinki, Finland., Participants: Four hundred community-dwelling people aged 75 to 90 without clinical dementia but with a history of stable atherosclerotic disease., Measurements: Cognitive function according to the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Scale (CDR). Participants' use of anticholinergic drugs was estimated using definitions from previous scientific literature. APOE alleles determined from peripheral blood leukocyte deoxyribonucleic acid using standard polymerase chain reaction-based methods., Results: There was an association between anticholinergic drugs and lower MMSE scores (P for trend <.001). The higher the number of anticholinergic drugs, the lower the MMSE score. Subjects with the APOE4 allele and using drugs with anticholinergic properties had the lowest median MMSE score (26), whereas those without the APOE4 allele and not using drugs with anticholinergic properties had the highest median MMSE score (28). When adjusted for age, sex, and education, the difference between the groups remained significant. The finding was similar for CDR scores., Conclusion: Use of drugs with anticholinergic properties was associated with lower cognitive function irrespective of APOE4 carrier status. Having lower cognitive function as a group, APOE4 carriers may be more vulnerable to this undesirable effect, but a follow-up study is needed to demonstrate this.

Objectives: To compare the predictive value of biomarkers commonly measured in older patients with cardiovascular disease (CVD) with an indicator of cognitive function., Design: Prospective cohort study., Setting: Helsinki, Finland., Participants: Three hundred ninety-eight home-dwelling older persons (261 women, mean age 80) with stable CVD and without a diagnosis of clinical dementia., Measurements: Simple laboratory and clinical measurements (including the Mini Mental State Examination (MMSE, maximum score 30 points) and New York Heart Association (NYHA) classification) were used to predict mortality. A MMSE score between 18 and 24 points was considered to indicate cognitive impairment., Results: At baseline, median MMSE score was 27 (interquartile range 25-28), with 59 individuals having a score below 24 points. During a mean follow-up of 6.0 years, 129 participants died. In the fully adjusted Cox proportional hazards model, low MMSE score was the strongest predictor of mortality, with a relative hazard of 2.38 (95% confidence interval=1.52-3.74; P<.001). Of the various clinical and laboratory variables, only creatinine, C-reactive protein, and history of congestive heart failure were significant independent predictors, whereas conventional risk factors were not., Conclusion: Only a few clinical variables independently predicted 6-year mortality in older home-living patients with CVD. The strongest predictor was impaired cognitive function assessed using MMSE.

While high age, low level of education and APOE epsilon4 allele are known to predict dementia, there is recent data suggesting that certain viruses and subtypes of APOE epsilon3 could be involved, too. We investigated these relationships in a home-dwelling cohort of 357 elderly people with various cardiovascular diseases (DEBATE study). MMSE score below 24 was used to define cognitive impairment (n = 58). When adjusted for age and the presence of diabetes, multivariate analysis demonstrated maximally increased risk of cognitive impairment in association with a combination of three factors: seropositivity for herpesviridae, presence of APOE epsilon4, and low education (risk ratio 6.1, 95% CI 2.4-15.2). In the subcohort of APOE3/3 individuals (n = 216) homozygosity for the -219G epsilon3 haplotype showed a similar association (risk ratio 8.8, 95% CI 2.6-29.8). These results demonstrate an interaction of specific genetic (APOE) and environmental (education and herpesviridae) risk factors in the development of cognitive impairment and indicate that not only the epsilon4 allele of APOE but also the epsilon3 haplotype is a risk factor for dementia.

Background: The search for preventable and remediable risk conditions of cognitive decline is ongoing, but results have thus far been inconsistent. According to the hypothesis of our 10-year prospective study, the predictive values of different risk indicators change over time in a general 75+ population., Methods: A population-based sample of 75-, 80-, and 85-year-old individuals (n=650) underwent comprehensive clinical examinations in 1990 in Helsinki, Finland. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) and/or Clinical Dementia Rating (CDR) at baseline and after 1, 5, and 10 years., Results: At baseline, a low MMSE score was associated with age, history of stroke, apolipoprotein E allele epsilon4 (APOE4), and intermittent claudication. After 1 year, cognitive decline was typical of participants suffering from vascular diseases, e.g., heart failure and intermittent claudication. Five-year decline was predicted by the presence of atrial fibrillation (RR [relative risk] 2.8), APOE4 (RR 2.4), elevated C-reactive protein (CRP) (RR 2.3), diabetes mellitus (RR 2.2), and heart failure (RR 1.8). They also tended to increase 5-year all-cause mortality. At 10 years, the decline associated with APOE4 (RR 3.3), slightly elevated serum ionized calcium (RR 3.3), and feelings of loneliness (RR 3.0)., Conclusions: Long follow-up of a general aged population explains several inconsistencies of earlier reports. In 75+ individuals, general ill health is a strong associate of cognitive deficits. The strongest predictors of both cognitive decline and mortality are age, APOE4, manifest vascular diseases, and diabetes. The role of new potential predictors, feelings of loneliness and hypercalcemia, needs clinical testing.

Infectious agents have been suspected as contributing factors to dementia, especially in Alzheimer disease. We intended to test whether viral or bacterial seropositivity is associated with cognitive impairment among home-dwelling elderly. Viral burden (seropositivity for herpes simplex type 1 (HSVI), type 2 (HSV2), or cytomegalovirus (CMV), and bacterial burden (Chlamydia pneumoniae and Mycoplasma pneumoniae) were tested among 383 home-dwelling individuals with vascular disease (mainly coronary heart disease) in the ongoing DEBATE study (mean age 80 years). Mini-mental state examination (MMSE) and its changes were used to define cognitive impairment. At baseline, 0-1, 2, and 3 positive titers toward viruses were found in 48 (12.5 %), 229 (59.8 %), and 106 (27.7 %) individuals,respectively. MMSE points decreased with increasing viral burden (p = 0.03). At baseline,58 individuals (15.1 %) had cognitive impairment (MMSE < 24 points) which after adjustments was significantly associated with seropositivity for 3 viruses (risk ratio 2.5, 95%confidence interval 1.3 to 4.7). MMSE score decreased in 150 cases (43%) during 12-month follow-up. After adjustment for MMSE score at baseline and with 0-1 seropositivities as reference (1.0), the risk ratios were 1.8 (95 % confidence interval 0.9 to 3.6) and 2.3 (95% confidence interval 1.1 to 5.0) for 2 and 3 seropositivities, respectively. No significant associations were observed between bacterial burden and cognition. Viral burden of herpes virus and cytomegalovirus was associated with cognitive impairment in home-dwelling elderly. The association may offer a preventable cause of cognitive decline.

Background and Purpose: Inflammation and infectious etiology have been implicated in the pathogenesis of dementia. We sought to investigate whether the seropositivity of common infections was associated with cognitive function., Methods: Viral burden (seropositivity for herpes simplex virus type 1 [HSV-1], herpes simplex virus type 2 [HSV-2], or cytomegalovirus [CMV]) and bacterial burden (Chlamydia pneumoniae and Mycoplasma pneumoniae) were related to cognitive status and its impairment among 383 home-dwelling elderly with cardiovascular diseases (mean age, 80 years). The Mini-Mental State Examination (MMSE) and its changes and the Clinical Dementia Rating (CDR) were used to define cognitive impairment., Results: At baseline, 0 to 1, 2, and 3 positive titers toward viruses were found in 48 (12.5%), 229 (59.8%), and 106 individuals (27.7%), respectively. MMSE points decreased with increasing viral burden (P=0.03). At baseline, 58 individuals (15.1%) had cognitive impairment, which after adjustments was significantly associated with seropositivity for 3 viruses (hazard ratio, 2.5; 95% CI, 1.3 to 4.7). MMSE score decreased in 150 (43% of 348) during 12-month follow-up. After adjustment for MMSE score at baseline and with 0 to 1 seropositivities as reference (1.0), the hazard ratios were 1.8 (95% CI, 0.9 to 3.6) and 2.3 (95% CI, 1.1 to 5.0) for 2 and 3 seropositivities, respectively. The prevalence of possible or definite dementia according to CDR also increased with viral burden. No significant associations were observed between bacterial burden and cognition., Conclusions: Viral pathogen burden of HSV and CMV was associated with cognitive impairment in home-dwelling elderly persons with cardiovascular diseases. The results need to be tested in larger databases, but they may offer a preventable cause of cognitive decline.