Renal function is a determinant of subjective well-being in active seniors but not in patients with subjective memory complaints.

BACKGROUND: During our whole life span, factors influencing health and functioning are accumulated. In chronic kidney disease, quality of life is adversely affected. We hypothesized that biomarkers of renal function could also be determinants of subjective well-being (SWB) in Swedish elderly subjects. SWB was assessed by the Psychological General Well-Being index (PGWB index) in two study groups: Active seniors (AS) consisted of community-dwelling elderly Swedes leading an active life (n = 389), and the DGM cohort (n = 300) consisted of subjects referred to the Memory Unit at the Department of Geriatrics for memory problems, Serum creatinine, cystatin C, and eGFR (CKD-EPI) were used as biomarkers of renal function. RESULTS: There were no significant differences in cystatin C and eGFR values between the two cohorts: cystatin C medians 0.88 vs 0.86 mg/L and eGFR 73 vs 80 mL/min/1.73 m2 (AS vs DGM). In the AS cohort cystatin C was negatively related to PGWB index in women (P < 0.001, R2 ≈ 5%), and the covariates age and BMI did not improve the models. The renal biomarkers were unrelated to the PGWB index in the DGM cohort. Cystatin C in the AS cohort was adversely related to the PGWB subdimensions anxiety, depressed mood, positive well-being, and vitality in women, but in men only to depressed mood (P < 0.006; R2 ≈ 6%). In the DGM cohort, depressed mood in men was also significantly related to cystatin C (P = 0.050), but not in women. CONCLUSIONS: Renal function even within the normal range, measured by serum cystatin C concentration, has significant and sex specific associations with subjective well-being and its subdimensions in healthy elderly subjects. Maintenance of good renal function in aging may be of importance in maintaining a high subjective well-being.

Subjective well-being in Swedish active seniors or seniors with cognitive complaints and its relation to commonly available biomarkers.

Well-being (WB) is a complex variable in its relation to physical health and other personal and social characteristics. The aim was to study subjective well-being (SWB) and its possible associations with traditional biomarkers of cardiovascular risk or dementia, in Swedish seniors. SWB was estimated by the Psychological General Well-Being (PGWB) index in two study groups. The active seniors (AS) group consisted of community-dwelling elderly Swedes leading an active life (n=389). The DGM cohort (n=300) consisted of subjects referred to the Memory Unit at the Department of Geriatrics, the cognitive problems had to be subjective, mild or moderate (MMSE≥10). There were differences in all six subdimensions of SWB or distress, and in the sum of PGWB scores, between the two study groups (p<0.001 for all), and adjustment for differences in biomarkers of somatic health (age, sex, blood pressure, BMI, HDL cholesterol, ApoB/ApoA1 ratio, creatinine, and homocysteine) did not attenuate these differences. In addition, cognition as assessed by the Clock-Drawing Test (CDT) showed independent associations with four of the PGWB subdimensions and with the PGWB sum. Among the subjects in the DGM cohort, SWB was equally low among subjects with an MCI (minor cognitive impairment) diagnosis or without a dementia diagnosis as among subjects diagnosed with dementia disorder. We conclude that the nosological grouping variable (AS vs. DGM cohort) and a cognitive factor were the main independent predictors of SWB in this sample of elderly Swedes, whereas biomarkers of somatic health played a subordinated role.

Blood Concentrations of Homocysteine and Methylmalonic Acid among Demented and Non-Demented Swedish Elderly with and without Home Care Services and Vitamin B(12) Prescriptions.

BACKGROUND AND AIMS: Total plasma homocysteine (tHcy) has been suggested as a risk factor of dementia. Our aim was to investigate potential differences in tHcy status in relation to the prescription of vitamin B(12) and dementia diagnosis. We examined whether vitamin B(12) prescriptions, a family history of dementia, or the need for home care service might be associated with tHcy values. METHODS: A cross-sectional monocenter study comprising 926 consecutive subjects attending our Memory Care Unit was conducted. RESULTS: Demented subjects being prescribed vitamin B(12) had higher serum vitamin B(12) (p = 0.025) but also higher tHcy (p < 0.001) and serum methylmalonate (p = 0.032), and lower serum folate (p < 0.001) than those who did not receive vitamin B(12) prescriptions. tHcy levels were significantly higher in non-demented subjects receiving home care service (p = 0.007). This group also had lower serum albumin (dementia: p < 0.001; non-dementia: p = 0.004). There was no difference in renal function (estimated glomerular filtration rate) in demented or non-demented subjects with or without vitamin B(12) prescriptions (dementia with/without vitamin B(12) prescription: p = 0.561; non-dementia with/without vitamin B(12) prescription: p = 0.710). CONCLUSION: Despite vitamin B(12) prescriptions, demented subjects had higher tHcy and methylmalonate values. The elevated metabolite values could not be explained by differences in renal function. Thus, elderly subjects on vitamin B(12) prescription appear to have unmet nutritional needs.

Relative telomere length in patients with late-onset Alzheimer's dementia or vascular dementia.

Telomeres generally shorten with age. An accelerated shortening of the telomeres has been linked to several age-related disorders. We hypothesized that the relative length of telomeres could discriminate between patients with late-onset Alzheimer's disease (AD) and vascular dementia (VaD). A quantitative real-time PCR method was used to calculate the relative telomere length in 76 age-matched and sex-matched, newly diagnosed late-onset AD or VaD patients recruited from our Memory Unit. No significant difference was found in the relative telomere length between AD and VaD cases neither in men (P=0.315) nor women (P=0.12). Thus, we could not confirm that the length of telomeres would predict which form of dementia, late-onset AD or VaD that develops.

CSF/serum folate gradient: physiology and determinants with special reference to dementia.

BACKGROUND: Folate depletion has been implicated as a risk factor for neurodegenerative disorders. We hypothesized that transport of folate to the cerebrospinal fluid (CSF) compartment could be involved in the pathophysiology of these disorders. METHODS: The CSF/serum folate gradient (R(CSF/S)) was studied in 205 subjects with suspected cognitive disorder. Its relation to clinical and biochemical indices, including the integrity of the blood-CSF barrier, were characterized. RESULTS: In subjects who were diagnosed as nondemented (ND) the mean R(CSF/S )+/- SD was 2.46 +/- 0.62 versus 2.09 +/- 0.67 (p = 0.008) in the dementia subgroup with a vascular component (VaD + mixed). The ND subgroup had higher CSF folate (p = 0.001) and lower serum homocysteine values (p = 0.001) than the VaD + mixed subgroup. The folate gradient R(CSF/S) was negatively correlated with serum folate (p < 0.001, R(2) = 0.518) and to the albumin ratio, a blood-CSF barrier biomarker (beta = -0.235). The Alzheimer patients had R(CSF/S) and albumin ratios similar to the ND subjects. CONCLUSION: The R(CSF/S) was significantly lower in the VaD + mixed dementia subgroup, suggestive of a defect in the transport of folate over the choroid plexus that seems to be characteristic of, and limited to, the VaD + mixed dementia subgroup.

Mutations in exons 2 and 3 of the FOLR1 gene in demented and non-demented elderly subjects.

We have previously reported six novel mutations in the 5'-UTR of the gene for folate receptor-alpha (FOLR1). In our search for additional mutations we screened patients, referred for investigation of suspected dementia (DGM subgroup) by SSCP and DNA sequencing from the end of exon 1 to the first bases of intron 3. We found 4 sequence variations, FOLR1 g.1314G>A, g.1816delC, g.1841G>A, and g.1928C>T. Pyrosequencing genotyping assays were developed for all of them, and 389 active seniors (AS subgroup) and the 202 DGM patients were genotyped for these mutations. The frequency q of the mutated allele was, among the AS subjects, 0.068, 0.0026, 0.0026, and 0.024 respectively, and among the DGM subjects, 0.067, 0.0076, 0.0078, and 0.023. The g.1816delC and g.1841G>A mutations thus were more frequent in the DGM than in the AS subgroup, but the difference did not reach statistical significance. The mutated alleles, FOLR1 1816(-) and 1841A, always occurred together in the same subjects, suggestive of a rare double-mutant haplotype. The two common polymorphisms, FOLR1 g. 1314G>A and g.1928C>T seemed not to raise tHcy plasma levels, whereas the double-mutated g.1816(-)-g.1841A haplotype may possibly have a slight tHcy-raising effect. Thus, so far 8 novel rare FOLR1 mutations with a combined prevalence of approximately 1.3% in Whites as well as two common polymorphisms with 5% and 13%, respectively, have been demonstrated. Only a few of the rare mutations may potentially be associated with raised plasma tHcy concentrations. No association with dementia was found.