N Prins

Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe

Background: Blood pressure level is associated with the risk of clinical Alzheimer disease (AD), yet the underlying mechanisms are unclear. High blood pressure levels may cause cerebral small-vessel pathology, which contributes to cognitive decline in patients with AD. Alternatively, in persons with high blood pressure, increased numbers of neurofibrillary tangles and amyloid plaques at autopsy have also been observed, suggesting direct links between blood pressure and AD. Objective: To investigate the association of blood pressure and markers of small-vessel disease (white matter lesions [WMLs] on MRI) with hippocampal and amygdalar atrophy on MRI—potential in vivo indicators of Alzheimer pathology. Methods: In 1995 to 1996, 511 nondemented elderly subjects (age 60 to 90) underwent MRI. The extent of WMLs was assessed, and volumes of the hippocampus and amygdala were measured. Blood pressure levels were assessed at the time of MRI and 5 years before the MRI. Results: Higher diastolic blood pressure 5 years before MRI predicted more hippocampal atrophy in persons untreated for hypertension (per SD increase −0.10 mL [95% CI −0.19 to −0.02, p = 0.02]). Conversely, in persons treated for hypertension, a low diastolic blood pressure was associated with more severe atrophy. Persons with more WMLs on MRI more often had severe atrophy of the hippocampus and amygdala. Conclusion: Blood pressure and indicators of small-vessel disease in the brain may be associated with atrophy of structures affected by Alzheimer pathology.

Measuring progression of cerebral white matter lesions on MRI: Visual rating and volumetrics

Objective: To evaluate the concordance of a volumetric method for measuring white matter lesion (WML) change with visual rating scales. Methods: The authors selected a stratified sample of 20 elderly people (mean age 72 years, range 61 to 88 years) with an MRI examination at baseline and at 3-year follow-up from the community-based Rotterdam Scan Study (RSS). Four raters assessed WML change with four different visual rating scales: the Fazekas scale, the Scheltens scale, the RSS scale, and a new visual rating scale that was designed to measure change in WML. The authors assessed concordance with a volumetric method with scatter plots and correlations, and interobserver agreement with intraclass correlation coefficients. Results: For assessment of change in WML, the Fazekas, Scheltens, and periventricular part of the RSS scale showed little correlation with volumetrics, and low interobserver agreement. The authors’ new WML change scale and the subcortical part of the RSS scale showed good correlation with volumetrics. After additional training, the new WML change scale showed good interobserver agreement for measuring WML change. Conclusions: Commonly used visual rating scales are not well suited for measuring change in white matter lesion severity. The authors’ new white matter lesion change scale is more accurate and precise, and may be of use in studies focusing on progression of white matter lesions.

Arterial oxygen saturation, COPD, and cerebral small vessel disease

Objective: To study whether lower arterial oxygen saturation (SaO2) and chronic obstructive pulmonary disease (COPD) are associated with cerebral white matter lesions and lacunar infarcts. Methods: We measured SaO2 twice with a pulse oximeter, assessed the presence of COPD, and performed MRI in 1077 non-demented people from a general population (aged 60–90 years). We rated periventricular white matter lesions (on a scale of 0–9) and approximated a total subcortical white matter lesion volume (range 0–29.5 ml). All analyses were adjusted for age and sex and additionally for hypertension, diabetes, body mass index, pack years smoked, cholesterol, haemoglobin, myocardial infarction, and left ventricular hypertrophy. Results: Lower SaO2 was independent of potential confounders associated with more severe periventricular white matter lesions (score increased by 0.12 per 1% decrease in SaO2 (95% confidence interval 0.01 to 0.23)). Participants with COPD had more severe periventricular white matter lesions than those without (adjusted mean difference in score 0.70 (95% confidence interval 0.23 to 1.16)). Lower SaO2 and COPD were not associated with subcortical white matter lesions or lacunar infarcts. Conclusion: Lower SaO2 and COPD are associated with more severe periventricular white matter lesions.

MR spectroscopy of brain white matter in the prediction of dementia

Background: Previous 1H-MR spectroscopy (MRS) studies compared biochemical spectra of persons with dementia with those of healthy control subjects. Given the long prodromal period of Alzheimer disease (AD), the authors sought to investigate whether biochemical changes can be observed also in the preclinical period. Methods: The authors prospectively followed 509 elderly persons (ages 60 to 90), who were free of clinical dementia at baseline, for on average 5.9 years. At baseline, 1H-MRS of the brain (1.5 T) was performed in a plane above the lateral ventricles that comprised mainly white matter voxels. Standard ratios of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were calculated. Structural MRI was administered to assess white matter lesions and hippocampal atrophy. All persons were followed for incident dementia through repeated neuropsychological testing and linkage with medical records. Results: During follow-up, 37 persons developed dementia, of whom 27 fulfilled criteria for AD. Overall, biochemical ratios on 1H-MRS at baseline were not associated with the risk of incident dementia. However, people with higher Cho/Cr ratios had a higher risk to develop dementia or AD within 4 years (hazard ratio for dementia per SD increase 1.55 [95% CI 1.05 to 2.28]). This association attenuated and became nonsignificant after adjustment for white matter lesions on MRI. Conclusion: These data suggest that there are biochemical changes on 1H-MR spectroscopy of brains of persons with presymptomatic dementia.

Plasma β amyloid and impaired CO2-induced cerebral vasomotor reactivity

Abstract Amyloid β (Aβ) may disturb cerebral autoregulation by damaging the wall of small cerebral blood vessels and by direct negative vasoactive properties. We assessed whether previous and concurrent plasma Aβ 1–40 and Aβ 1–42 levels were associated with an impaired CO 2 -induced cerebral vasomotor response. In the longitudinal population-based Rotterdam Study we measured plasma Aβ levels and cerebral vasomotor reactivity to hypercapnia with transcranial Doppler ultrasonography (TCD) in 441 people, aged 60–90 years. We performed age and sex adjusted logistic regression analysis. Plasma Aβ levels assessed on average 6.5-year before TCD were linearly associated with an impaired CO 2 -induced cerebral vasomotor response (odds ratio 1.48 (95%CI 1.19;1.84) per standard deviation increase in Aβ 1–40 , and 1.36 (95%CI 1.09;1.70) per standard deviation increase in Aβ 1–42 ). Such an association was not present for Aβ assessed concurrently with the TCD measurement. Persons whose plasma Aβ 1–40 levels had decreased in the 6.5-year period preceding TCD measurements were more likely to have an impaired CO 2 -induced vasomotor reactivity. Overall our observations are most compatible with plasma Aβ levels representing vascular Aβ deposits years later resulting in impaired CO 2 -induced vasomotor reactivity.