Aspects of Subcortical Ischaemic Vascular Disease : Early clinical manifestations and associations with Type 2 diabetes mellitus
Year: 2006
Type: dissertation
Abstract: Summary \n \nSubcortical ischaemic vascular disease (SIVD) is an important cause of cognitive impairment in elderly patients. Screening and diagnostic tests are needed to identify these patients. The HIV dementia scale (HDS) is a reliable and quantitative scale for identifying HIV dementia1. The cognitive profile of HIV dementia has subcortical features that resemble subcortical ischaemic vascular disease (SIVD). The clinical syndrome is characterized by early impairment of attention and executive function, accompanied by a slowing of motor performance and information processing, while memory functions remain relatively intact2. \n \nChapter 2 reported the results of an attempt to validate the HDS for elderly SIVD patients. The primary hypotheses were that the HDS could be used as a screening test in SIVD patients and that it could be used as a screening test for patients who have vascular risk factors. The HDS consists of four items and is easy to administer. All items of the HDS represent characteristics of subcortical cognitive functions, (i.e. psychomotor speed, concentration, executive functions and memory skills). Because the neuropsychological profiles of patients with normal pressure hydrocephalus (NPH) are identical to those of SIVD patients, NPH patients were also included in the study population2,3. The results of the study indicated that the HDS is capable of discriminating between patients with cognitive impairments due to SIVD or a NPH and normal control subjects in an older population. Patients had HDS scores of 5.1 ± 3.5 (maximum score 16), and control subjects had scores of 13.0± 2.4 (p < 0.0001). The results further showed that the HDS is of additional value for subjects whose Mini Mental State Examination (MMSE) scores fall within the normal range. The results of this study suggest that the HDS is capable of detecting cognitive impairment in SIVD patients and may therefore be used in clinical trials in SIVD patients or those who are at risk for SIVD. \n \nThe central hypothesis of Chapter 3 was that a clinical neurophysiological test could be helpful for detecting cognitive impairment in SIVD patients. The late responses that are elicited by the auditory oddball paradigm are considered to be related to cognitive processing4. It has been shown that the latency of the N2 complex and the P3 is prolonged in patients with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Binswanger’s disease and depression5-7. Several studies have investigated the auditory oddball paradigm in patients with vascular white matter disease (i.e. leukoaraiosis or lacunar infarcts)6,8-11. These studies, however, used either a definition of cognitive decline that was based on DSM-IV criteria for Alzheimer’s dementia12 or tests of cognitive function that were not described in detail. In addition, these studies analyzed only the P3 wave. We attempted to determine whether the various deflections of the event-related potential (N1, N2 complex and P3) that are evoked by the auditory oddball paradigm could differentiate between patients who have vascular cognitive impairment (VCI) caused by SIVD in an early phase of the disease and age-matched control subjects. We demonstrated that N2 latency was significantly longer in patients with VCI (254.6 ± 25.1 milliseconds) than it was in age-matched control subjects (235 ± 28.6 milliseconds) (p = 0.001), whereas the latencies of P3 and N1 were not significantly different. The peak-to-peak amplitude of the N2 complex to the P3 wave was significantly lower in the patient group (patients 11.5 ± 7.0 microvolt vs. controls 15.4 ± 9.4 microvolt, p = 0.02). White-matter lesions revealed by MRI were not correlated with N2 latency (r = -0.255, p = 0.3). These data show that the latency of the N2 complex is longer and the peak-to-peak amplitude of the N2 to P3 wave is lower for a well-defined group of VCI patients than it is for healthy control subjects. \n \nSubcortical ischaemic vascular disease incorporates both white-matter lesions and lacunar infarcts. While hypertension is the most important and consistent risk factor for white-matter lesions and lacunar infarcts, the data on the relation between these lesions and diabetes mellitus (DM) are not consistent. Because of the frequency of both SIVD and DM among elderly subjects we investigated the relation between DM and SIVD. \n \nChapter 4 reports the result of a systematic review addressing the association between DM and structural brain-imaging abnormalities. It is known that DM increases the risk of cerebral large-vessel disease two to threefold. Whether DM is a risk factor for SIVD, including white-matter lesions and lacunar infarcts, remains unclear. Our systematic review addressed available data on brain-imaging changes in diabetic patients, as revealed by computer tomo-graphy (CT) and magnetic resonance imaging (MRI); it also analysed studies that use magnetic resonance spectroscopy (MRS), positron emission tomo-graphy (PET) and single-photon emission computer tomography (SPECT) to investigate the relationship between DM and abnormalities. We also assessed the relationship of these cerebral changes to cognition, and related disease variables, including DM subtype, age and hypertension, DM duration, medi-ation use and glycaemic control. Eligible studies were evaluated according to predefined inclusion criteria (i.e. clear imaging-outcome measures, a clear definition of DM and a sample size of at least 20 DM patients). Data on study design, DM type, treatment and associated comorbidity, imaging modality (MRI, MRS, CT, SPECT or PET) and imaging findings were extracted from the fifty-five articles that were included in the review. The methodology of these studies with regard to population selection, DM assessment, neuro-imaging rating methods and data analyses were heterogeneous. DM was associated with cerebral atrophy in eight out of ten studies that investigated this relationship. Eight of nineteen studies reported an association between DM and lacunar infarcts. We found little evidence of an association with white-matter lesions. Studies that used PET and SPECT reported regional abnormalities of cerebral blood flow and cerebral glucose metabolism. None of the studies assessed the relationship between imaging findings and cognition. Data on the relationship between imaging findings and disease variables (e.g. age, hypertension, medication use, glycaemic control) were scarce as well. We concluded that DM is associated with cerebral atrophy and lacunar infarcts, but that the association with white-matter lesions is equivocal. \n \nChapter 5 elaborated on the conclusions that were drawn in Chapter 4 by reporting results from a cross-sectional study that compared a well-defined population of independently living elderly patients with Type 2 DM to healthy control subjects in order to investigate the association between DM, white-matter lesions, lacunar infarcts and brain atrophy. We also compared DM patients who had hypertension to those who did not, in order to determine whether concomitant hypertension could be defined as a relevant disease variable in DM patients. In addition, we investigated the relationship of DM to other disease determinants. The study population consisted of forty-five patients who suffered from Type 2 DM without hypertension (mean age 73.2 ± 5.1 years, mean duration of DM 16.7 ± 11.4 years), forty-five patients with type 2 DM and hypertension (mean age 73.3 ± 5.9 years, mean duration of DM 11.3 ± 9.1 years) and forty-four control subjects (mean age 73.0 ± 5.3 years). All patients and control subjects underwent MRI brain scans. White-matter lesions (WML), cerebral atrophy and medial temporal lobe atrophy (MTA) were rated using a standardized visual rating scale. WML occurred more frequently among DM patients (both with hypertension and without hypertension) than it did among healthy control subjects. Significantly more DWML (deep white-matter lesions) were found among DM patients (with and without hypertension) than were found among control subjects, although no difference was found in the occurrence of periventricular hyperintensities (PVH). Although higher atrophy scores were seen among DM patients than among control subjects, this result was not significant. The association between Type 2 DM and DWML is supported by significant positive correlations between the severity of DWML and the value of glycolysated haemoglobin (HbA1c) and the duration of DM. Data from this cross-sectional study suggest that Type 2 DM is an independent risk factor for DWML in independently living elderly patients. \n \nChapter 6 addressed the detailed neuropsychological profiles of independently functioning patients who have Type 2 DM. It also examined correlations between cognitive impairment and brain lesions (i.e. SIVD, atrophy and lacunar infarcts) that were revealed by MRI. The chapter discusses the influence of relevant disease variables. After adjusting for hypertension neuro-psychological scores for each cognitive domain except for memory functions were worse for a group of elderly patients with Type 2 DM than they were for healthy control subjects. Periventricular hyperintensities (PVH) were an inde-pendent predictor of motor speed, while none of the other MRI measures was independently associated with cognitive impairment. No interactions between the various MRI measures were found. HbA1c and duration of DM were both significantly associated with cognitive dysfunction. Data from this cross-sectional study show that Type 2 DM is associated with diminished cognitive functioning in various cognitive domains, while memory is less affected, after adjusting for hypertension. The association of cognitive impairment with MRI measures is equivocal, although HbA1c and duration of DM were significantly associated with cognitive dysfunction. \n \n \nGen
Author: Barbera van Harten
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1534938904