Minna Löppönen

Characteristics of two telephone screens for cognitive impairment

We studied 56 subjects, 30 patients with a clinical diagnosis of Alzheimer’s disease (AD) and 26 healthy controls, using two telephone screens for cognitive impairment, a self-report interview referred to as the TELE and the Telephone Interview for Cognitive Status (TICS). The sensitivity and specificity of the TELE to differentiate AD patients from healthy controls was 90.0 and 88.5% and those of the TICS were 86.7 and 88.5%, respectively. When receiver operator characteristic curves were constructed, the area under the curve for the TELE was 96.0% (SE 2.4%) and for the TICS 90.3% (SE 4.2%). Pearson’s correlation between the TELE and the Mini-Mental State Examination (MMSE) was 0.87 (p < 0.0001) and between the TICS and the MMSE 0.86 (p < 0.0001). The correlation between the TELE and the sum of the boxes of the Clinical Dementia Rating scale (CDR-SB) was –0.71 (p < 0.0001) and –0.75 between the TICS and the CDR-SB (p < 0.0001). These results indicate that both screens are sensitive and specific instruments for differentiating AD patients from healthy controls and have a strong correlation with face-to-face measures of cognitive function.

Fractures as predictors of excess mortality in the aged—A population-based study with a 12-year follow-up

Introduction and objective The association between fractures and excess mortality in old age is ambiguous. The objective of this study was to analyze the long-term gender-specific association between fractures and mortality among older persons by controlling several survival related confounders. Methods A population-based prospective cohort study in the municipality of Lieto, south-western Finland. Data on health, health behaviour, fractures, and mortality in 482 men and 695 women aged 65 or older was collected from 1991 until 2002. The Cox Proportional Hazards regression model with fractures as time-dependent variables was used in the analyses. Results During the 12-year follow-up, 295 (25%) persons sustained at least one fracture. Sustaining any kind of fracture was related to excess mortality both in men (age-adjusted Hazards Ratio, HR 2.2, 95% confidence intervals, CI 1.6–3.1) and in women (HR 1.6, 95% CI 1.3–2.1). In the multivariate analyses, hip fractures in men (HR 8.1, 95% CI 4.4–14.9) and in women (HR 3.0, 95% CI 1.9–4.9), and proximal humerus fractures in men (HR 5.4, 95% CI 1.6–17.7) were related to increased mortality. Conclusion A hip fracture was a powerful independent predictor of long-term excess mortality in both genders but the risk in men was more than 2-fold compared to women. Proximal humerus fractures were associated with increased mortality in men. Actions to improve prevention, acute care and rehabilitation of fractures are needed in order to reduce excess mortality in older people.

Overweight and Obesity in Old Age Are Not Associated with Greater Dementia Risk

OBJECTIVES: To describe the association between body mass index (BMI) and dementia risk in older persons.

RIA for Serum Holo-Transcobalamin: Method Evaluation in the Clinical Laboratory and Reference Interval

BACKGROUND Decreased serum holo-transcobalamin (holoTC) could be the earliest marker of cobalamin (Cbl) deficiency, but there has been no method suitable for routine use. We evaluated a new commercial holoTC RIA, determined reference values, and assessed holoTC concentrations in relation to other biochemical markers of Cbl deficiency. METHODS The reference population consisted of 303 individuals 22-88 years of age, without disease or medication affecting Cbl or homocysteine metabolism. In elderly individuals (>or=65 years), normal Cbl status was further confirmed by total homocysteine (tHcy; <19 micro mol/L) and methylmalonic acid (MMA; <0.28 micro mol/L) concentrations within established reference intervals. HoloTC in Cbl deficiency was studied in a population of 107 elderly individuals with normal renal function. The Cbl deficiency was graded as potential (total Cbl <or=150 pmol/L or tHcy >or=19 micro mol/L), possible (total Cbl <or=150 pmol/L and either tHcy >or=19 micro mol/L or MMA >or=0.45 micro mol/L), and probable (tHcy >or=19 micro mol/L and MMA >or=0.45 micro mol/L). RESULTS The intra- and between-assay imprecision (CV) for the holoTC RIA were 4-7% and 6-8%, respectively. A 95% central reference interval for serum holoTC was 37-171 pmol/L. All participants (n = 16) with probable Cbl deficiency, 86% of those with possible, and 30% of those with potential Cbl deficiency had holoTC below the reference limit (<37 pmol/L). The holoTC correlated with total Cbl (r(s) = 0.80; P <0.0001) and inversely with MMA (r(s) = -0.52; P <0.0001). HoloTC concentrations were significantly (P = 0.01) higher in women than in men. CONCLUSIONS The new holoTC RIA is precise and simple to perform. Low holoTC is found in individuals with biochemical signs of Cbl deficiency, but the sensitivity and specificity of low holoTC in diagnosis of Cbl deficiency need to be further evaluated.

Undiagnosed Diseases in Patients with Dementia – A Potential Target Group for Intervention

Objective: To study undiagnosed diseases in older people with and without dementia. Design: Cross-sectional population-based study in Lieto, southwestern Finland. Participants: All the inhabitants aged 64 and more in Lieto. Participation rate was 82% (n = 1,260). Measurements: Dementia and its subtypes were diagnosed according to prevailing criteria. Medical conditions were assessed in clinical examinations and from medical records. Results: 112 patients with dementia were found; 66% of them had at least 1 undiagnosed disease compared to 48% of the non-demented group (p = 0.041). The demented subjects had more undiagnosed hypercholesterolaemia (p = 0.039) and undiagnosed hypothyroidism (p = 0.032) than the controls. Conclusion: Undiagnosing is more common among patients with dementia. Screening strategies should be developed further to find these patients.

Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study

BackgroundPrevious studies have found associations between the use of central nervous system medication and the risk of cognitive decline in the aged. Our aim was to assess whether the use of a single central nervous system (CNS) medication and, on the other hand, the combined use of multiple CNS medications over time are related to the risk of cognitive decline in an older (≥ 65 yrs) population that is cognitively intact at baseline.MethodsWe conducted a longitudinal population-based study of cognitively intact older adults. The participants were 65 years old or older and had Mini-Mental State Examination (MMSE) sum scores of 24 points or higher. The study included a 7.6-year follow-up. The use of benzodiazepines and related drugs (BZDs), antipsychotics (APs), antidepressants (ADs), opioids (Ops), anticholinergics (AChs) and antiepileptics (AEs) was determined at baseline and after a 7.6-years of the follow-up period. Cognitive functioning was used as an outcome variable measured with MMSE at baseline and at the mean follow-up of 7.6 years. Control variables were adjusted with analyses of covariance.ResultsAfter adjusting for control variables, the use of Ops and the concomitant use of Ops and BZDs as well as the use of Ops and any CNS medication were associated with cognitive decline. The use of AChs was associated with decline in cognitive functioning only in men.ConclusionsOf all the CNS medications analyzed in this study, the use of Ops may have the greatest effect on cognitive functioning in the ageing population. Due to small sample sizes these findings cannot be generalized to the unselected ageing population. More studies are needed concerning the long-term use of CNS medications, especially their concomitant use, and their potential cognitive effects.

The effect of thyroid antibody positivity on reference intervals for thyroid stimulating hormone (TSH) and free thyroxine (FT4) in an aged population

Abstract Our aims were: 1) to analyze the effect of the methodology used to derive clinically feasible cut-off values for thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), which exhibit highly skewed distributions; and 2) to describe the influence of thyroid antibodies on thyroid stimulating hormone (TSH) and free thyroxine (FT4) reference intervals among thyroid disease-free aged subjects. The reference population consisted of 1086 individuals with a mean age of 73years. The impacts of TPOAb and/or TgAb positivity on the reference intervals of TSH and FT4 were evaluated by both including and excluding subjects with elevated thyroid antibodies. The exclusion of subjects with elevated thyroid antibodies had no effect on the FT4 reference interval in either gender or on the TSH reference interval in men. Among women, the exclusion of 196 (34%) thyroid antibody-positive subjects resulted in lowering of the upper reference limit of TSH from 7.2 to 5.8mIU/L. When the more stringent “mode-method” by summing mode+(mode–2.5th percentile) was used, 334 women (58%) were excluded and the upper reference limit of TSH remained essentially identical. Regardless of the statistical methodology used to derive cut-off values, the effect of antibody positivity was found to be less than expected.

Renal impairment compromises the use of total homocysteine and methylmalonic acid but not total vitamin B12 and holotranscobalamin in screening for vitamin B12 deficiency in the aged.

Abstract Background: Vitamin B12 deficiency and renal impairment are common in the aged, and therefore the screening test for vitamin B12 deficiency should not be affected by renal function. Renal impairment has been associated with increased concentrations of plasma total homocysteine and methylmalonic acid, as well as increased total vitamin B12 and holotranscobalamin concentrations. Methods: The effect of renal impairment on vitamin B12-related biochemical variables was assessed in 1011 aged subjects. Results: Renal function as indicated by serum cystatin C correlated strongly with plasma total homocysteine (rs=0.53, p<0.001) and serum methylmalonic acid (rs=0.27, p<0.001), but not with serum total vitamin B12 (rs=−0.04, p=0.227) or holotranscobalamin (rs=−0.01, p=0.817). Conclusions: Either total vitamin B12 or holotranscobalamin rather than homocysteine or methylmalonic acid should be used when screening an aged population prone to renal impairment. Clin Chem Lab Med 2007;45:197–201.

Circulating oxidised LDL lipids, when proportioned to HDL-c, emerged as a risk factor of all-cause mortality in a population-based survival study

BACKGROUND AND OBJECTIVE the data concerning the predictive role of oxidised LDL (ox-LDL) in all-cause mortality are scarce. We investigated whether circulating ox-LDL would stand out as a risk factor of total mortality in the elderly. Study subjects, design and methods: a total of 1,260 elderly inhabitants (533 men, 727 women) aged 64 years or more from Lieto, South-Western Finland participated the study in 1998-99. Medical records were re-examined approximately a decade later in January 2009. Circulating ox-LDL lipids were used as the main outcome measure. The comparisons were obtained by the Cox hazard ratio model. RESULTS during the 10-year follow-up, 467 participants had died (37%), of whom 36% had died of atherosclerotic cardiovascular diseases. Ox-LDL was a significant predictor of all-cause mortality, when proportioned to low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) or apolipoprotein A1 (apoA1). These findings were independent of age, sex, body mass index, smoking, blood pressure and diabetes (P < 0.05 for all). CONCLUSION circulating ox-LDL lipids, when proportioned to LDL-c, HDL-c or apoaA1, stand out as a risk factor for all-cause mortality independent of major confounding attributes. In the prospective survival and increasing disease burden caused by accumulating age, oxidative stress may have a considerable role.

Dementia Associates with Undermedication of Cardiovascular Diseases in the Elderly

Objective: To compare medication use in patients suffering from cardiovascular disease with and without dementia. Subjects: All inhabitants aged 75 and older in Lieto, Finland (n = 462, participation rate 82%). Measurements: Direct standardised assessments of dementia and cardiovascular diseases. Quantification of drug use by self-report and by prescription and drug container checks. Results: In multivariate analyses, the odds ratio for demented cardiovascular patients receiving any cardiovascular medication (use vs. non-use) was 0.31 (95% confidence interval 0.12–0.82). Compared to the non-demented, demented stroke patients were treated less often with antithrombotic agents (p = 0.041) and demented hypertensive patients less often with β-blockers (p = 0.045). Conclusion: Demented cardiovascular patients, even mildly to moderately demented, were prescribed fewer evidence-based cardiovascular medications than non-demented patients.