Vitamin D in relation to cognitive impairment, cerebrospinal fluid biomarkers, and brain volumes.

BACKGROUND: Low vitamin D status is associated with poorer cognitive function in older adults, but little is known about the potential impact on cerebrospinal fluid (CSF) biomarkers and brain volumes. The objective of this study was to examine the relations between plasma 25-hydroxyvitamin D (25(OH)D) and cognitive impairment, CSF biomarkers of Alzheimer's disease (AD), and structural brain tissue volumes. METHODS: A total of 75 patients (29 with subjective cognitive impairment, 28 with mild cognitive impairment, 18 with AD) referred to the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden were recruited. Plasma 25(OH)D, CSF levels of amyloid ß (Aß(1-42)), total-tau, and phosphorylated tau, and brain tissue volumes have been measured. RESULTS: After adjustment for several potential confounders, the odds ratios (95% confidence interval) for cognitive impairment were as follows: 0.969 (0.948-0.990) per increase of 1 nmol/L of 25(OH)D and 4.19 (1.30-13.52) for 24(OH)D values less than 50 nmol/L compared with values greater than or equal to 50 nmol/L. Adjusting for CSF Aß(1-42) attenuated the 25(OH)D-cognition link. In a multiple linear regression analysis, higher 25(OH)D levels were related to higher concentrations of CSF Aß(1-42) and greater brain volumes (eg, white matter, structures belonging to medial temporal lobe). The associations between 25(OH)D and tau variables were not significant. CONCLUSIONS: This study suggests that vitamin D may be associated with cognitive status, CSF Aß(1-42) levels, and brain tissue volumes.

A clinical review of the association of thyroid stimulating hormone and cognitive impairment.

Clinical and subclinical hypothyroidism as well as overt hyperthyroidism in middle-aged and elderly adults are both associated with decreased cognitive functioning as memory, reaction time, and visuospatial organization. Subclinical hyperthyroidism (SH) or low serum concentrations of TSH concentrations have been associated with dementia in previous epidemiological studies, but the association in the elderly has not been established. There is little or no consensus regarding how thyroid function is associated with cognitive performance in the elderly. In this focused review, we have performed an examination between eleven studies from the last five years examining the association between thyroid function and cognitive performance in elderly people, a group who is overrepresented among individuals with minor abnormalities in serum TSH and thyroid hormone concentration. Six of the studies showed a consistent finding of an association between SH with cognitive impairment or dementia. In general, taking into account the largest and most powerfully designed studies, there is a strong body of evidence supporting the association between SH and cognitive impairment. The scarce number of publications on these topics indicates the need of more research especially regarding longitudinal and interventional studies thus hopefully enabling confirmation or rejection of causality between TSH abnormalities and dementia.

A prospective study on the development of Alzheimer's disease with regard to thyroid-stimulating hormone and homocysteine.

BACKGROUND/AIM: The combination of elevated total homocysteine (tHcy) levels and low levels of thyroid-stimulating hormone (TSH) are linked to Alzheimer's disease (AD) in some studies, although the evidence is mixed. Our objective was to prospectively investigate the association between tHcy and TSH and the subsequent development of AD. METHODS: A subsample of 200 nondemented subjects was taken from the Kungsholmen Project, a population-based study among people > or =75 years. Information about tHcy and TSH levels were taken from the baseline investigation of the Kungsholmen Project study. RESULTS: Increased tHcy levels were related to an elevated risk of AD (n = 61) after a mean follow-up time of 6.7 years. People with high tHcy (the 3rd tertile) had more than twice as high a risk of developing AD than those with low tHcy, even after adjusting for age, sex, education, ApoE status, MMSE score and laboratory parameters. tHcy was negatively correlated with TSH (p = 0.02). There was neither an influence of TSH nor an interaction between tHcy and TSH in the development of AD. CONCLUSIONS: These results suggest that homocysteine, but not TSH, is involved in the development of AD. The connection between elevated tHcy and low TSH levels needs to be studied further.

The significance of thyroid-stimulating hormone and homocysteine in the development of Alzheimer's disease in mild cognitive impairment: a 6-year follow-up study.

Mild cognitive impairment (MCI) represents a transition between normal aging and Alzheimer's disease (AD). The aim of this study was to investigate the predictive value of vitamin B12/folate, homocysteine, standard laboratory parameters, and concomitant diseases for development of AD in persons with an MCI diagnosis. Development of dementia was followed for 6 years in 93 consecutively recruited MCI persons. Information concerning the above factors was obtained from medical journals. Thirty-four percent of participants converted to AD within 6 years. A forward stepwise logistic regression was performed. The odds ratio (OR) for the Mini-Mental State Examination (MMSE) was 0.777; for age, 1.084; and for thyroid stimulating hormone (TSH), 0.287. The OR for homocysteine was 1.287 at 60 years of age and 1.087 at 65 years of age. Lower TSH levels together with the more established factors lower MMSE, higher homocysteine levels, and age were found to be predictive factors of AD. This may have clinical implications with regard to monitoring TSH levels and thyroxin substitution in MCI patients.

The relation between homocysteine levels and development of Alzheimer's disease in mild cognitive impairment patients.

The aim of this study was to investigate over a 3-year period the connection between homocysteine (Hcy) levels and development of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). Hcy was analyzed in 68 men, mean age 65 years, and 68 women, mean age 64 years. Age, sex, cobalamin, folate, creatinine, and thyroid profiles as well as results of Mini-Mental State Examination at the first visit to the memory investigation unit of a geriatric department were recorded from patient journals collected between 1992 and 1999. The total numbers of persons who converted to AD within a period of 3 years from initial investigation with baseline Hcy sampling was 12 of 46 (26%) males, and 18 of 50 women (36%). The total percentage of men and women converting to AD was 31%. Thirty-three percent of men with Hcy levels >20 micromol/l converted to AD. The corresponding figure for men with Hcy levels 20-17 micromol/l was 50%, whereas none of the 18 men with Hcy levels <17 micromol/l converted to AD. These differences were statistically significant. There was also a statistically significant difference between the percentage of women with Hcy levels >16 micromol/l who converted to AD (45%) as compared to those with Hcy levels <16 micromol/l who converted (21%). These findings are inconsistent with the results of other studies showing a positive correlation with hyperhomocysteinemia and occurrence of AD. However, our findings tentatively suggest a possible protective effect of low/normal Hcy levels on dementia conversion in MCI patients.