ABSTRACT: Mild cognitive impairment (MCI) may affect several cognitive domains, including attention and reasoning, but is often first characterized by memory deficits. The purpose of this study was to ask these 2 questions: 1) Can levels of CSF tau proteins and amyloid beta 42 peptide explain thinning of the cerebral cortex in patients with MCI? 2) How are brain morphometry, CSF biomarkers, and apolipoprotein E (APOE) allelic variation related to episodic memory function in MCI?
Hippocampal volume and cortical thickness were estimated by MR imaging and compared for patients with MCI (n = 18) and healthy controls (n = 18). In addition, regions of interest (ROIs) were selected in areas where the MCI group had atrophy and which overlapped with the episodic memory network (temporal, entorhinal, inferior parietal, precuneus/posterior cingulate, and frontal). Relationships among morphometry, CSF biomarkers, APOE, and memory were tested. The analyses were repeated with an independent sample of patients with MCI (n = 19).
Patients with MCI and pathologic CSF values had hippocampal atrophy. However, both patients with pathologic and patients with nonpathologic CSF had a thinner cortex outside the hippocampal area. CSF pathology was related to hippocampal volume, whereas relationships with cortical thickness were found mainly in one of the samples. Morphometry correlated robustly with memory performance across MCI samples, whereas less stable results were found for tau protein.
The differences in hippocampal volume between the MCI and the healthy control groups were only found in patients with pathologic CSF biomarkers, whereas differences in cortical thickness were also found for patients without such pathologic features. Morphometry in areas in the episodic memory network was robustly correlated with memory performance. It is speculated that atrophy in these areas may be associated with the memory problems seen in MCI.
American Journal of Neuroradiology 07/2008; 29(6):1183-9. · 2.93 Impact Factor
ABSTRACT: To identify possible associations between white matter lesions (WML) and cognition in patients with memory complaints, stratified in groups with normal and low cerebrospinal fluid (CSF) Abeta42 values.
215 consecutive patients with subjective memory complaints were retrospectively included. Patients were stratified into two groups with normal (n = 127) or low (n = 88) CSF Abeta42 levels (cut-off is 450 ng/l). Cognitive scores from the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat) were used as continuous dependent variables in linear regression. WML load was used as a continuous independent variable and was scored with a visual rating scale. The regression model was corrected for possible confounding factors.
WML were significantly associated with MMSE and all Cognistat subscores except language (repetition and naming) and attention in patients with normal CSF Abeta42 levels. No significant associations were observed in patients with low CSF Abeta42.
WML were associated with affection of multiple cognitive domains, including delayed recall and executive functions, in patients with normal CSF Abeta42 levels. The lack of such associations for patients with low CSF Abeta42 (i.e. with evidence for amyloid deposition), suggests that amyloid pathology may obscure cognitive effects of WML.
Acta Neurologica Scandinavica 06/2008; 118(6):373-8. · 2.47 Impact Factor
ABSTRACT: To analyze a putative relationship between white matter lesions (WMLs), risk factors for WMLs, and Alzheimer disease (AD) as measured with the surrogate marker CSF Abeta42.
The authors analyzed effects of acquired risk factors for cerebrovascular disease and WMLs on AD as measured with an intermediate marker, CSF Abeta42. A total of 127 consecutive patients with subjective memory impairment (mean age 66 years; 57 women) investigated at a university-based memory clinic had brain MRI scans. WMLs were rated on a 12-point scale with a semiquantitative procedure. They used path analysis with established and possible risk factors for WMLs and for reduced CSF Abeta42 (age, hypertension, hyperhomocysteinemia, hypercholesterolemia, APOE-epsilon4) as variables.
The WML score was 1.5 points higher (p < 0.05) in hypertensive than in nonhypertensive patients and 1.9 points higher (p < 0.05) in patients with hyperhomocysteinemia than in those with normal homocysteine levels. Hypercholesterolemia increased the probability of low CSF Abeta42 levels by 0.2 (p < 0.05). For each point increase in WML score, the probability of low CSF Abeta42 levels increased by 0.03 (p < 0.05). APOE-epsilon4 was associated with reduced CSF Abeta42 (p < 0.01).
Both hypercholesterolemia and white matter lesions may contribute to low CSF Abeta42 by independent mechanisms.
Neurology 09/2006; 67(5):830-3. · 8.31 Impact Factor
ABSTRACT: To compare serum ferritin concentration and transferrin saturation in patients with alcoholic and non-alcoholic chronic liver diseases.
Consecutive patients with liver diseases.
The department of internal medicine in a teaching hospital.
Three hundred and twelve patients with different liver diseases consecutively admitted between 1987 and 1992.
Fasting serum iron, transferrin and ferritin.
Serum ferritin was increased above 200 micrograms L-1 in all 18 patients with haemochromatosis (range 310-6500 micrograms L-1), in 64 of 111 alcoholics (58%) and in 30 of 137 (22%) with chronic non-alcoholic liver diseases (P < 0.01). Twelve of 111 alcoholics (11%) had serum ferritin above 1000 micrograms L-1 compared with one of 137 (0.7%) with chronic non-alcoholic liver diseases. In 13 alcoholics who abstained after admission, serum ferritin decreased from 1483 micrograms L1 +/- 1134 to 388 micrograms L-1 +/- 237 (P < 0.001) after 1 1/2 to 6 weeks. The transferrin saturation was increased above 62% in 13 of 18 patients (72%) with haemochromatosis, in 16 of 105 alcoholics (15.2%) and in three of 132 (2.3%) with chronic non-alcoholic liver disease (P < 0.01).
Serum ferritin is more frequently elevated in abusing patients with alcoholic liver disease than in patients with other chronic liver diseases such as autoimmune liver diseases and hepatitis C. Because serum ferritin decreases rapidly during abstinence, the measurement of ferritin for the detection of haemochromatosis in patients abusing alcohol should be postponed until the patients are abstaining. Most of the patients with increased serum ferritin have normal transferrin saturation values which can be used to separate them from haemochromatosis.
Journal of Internal Medicine 10/1994; 236(3):315-22. · 5.48 Impact Factor