Small vessel disease and hippocampal volume in Alzheimer's disease vs. controls

Abstract

Background: This study examined the prevalence and clinical impact of white matter hyperintensities (WMH), cerebral microbleeds (CMB) and medial temporal lobe atrophy (MTLA) in patients with Alzheimer's disease (AD). Methods: We analysed the data for 69 patients with AD and 36 age-matched cognitively normal controls recruited from Memory and Geriatric Medicine Clinics, Queen Mary Hospital. Controls had no history of dementia, stroke, Parkinson’s disease, head injury, seizures, AF, cancers within 5 years, end-stage organ failure, excessive alcohol or drug use, or psychiatric disease. 3T MRI brain images were retrospectively examined for the severity and location of WMH (Fazekas Score 0-3, >1 abnormal), CMB (Microbleed Anatomical Rating Scale 0-3, >0 abnormal) and MTLA (Scheltens Score 0-4, >1 abnormal). Results were adjusted for age, vascular risks including hypertension, stroke, TIA, hyperlipidaemia, and use of anti-thrombtic agents. Results: Mean (± s.d.) ages were similar for AD patients (76.6 ± 8.6 yrs) and controls (74.8 ± 6.6 yrs). Gender and history of diabetes, hypertension, hyperlipidaemia, and ischaemic heart disease were similar. AD patients were more likely to be dependent (p=.018), and live in nursing homes (p=.05). Controls were more likely to have atrial fibrillation (p=.007) and take antiplatelets (p=.02) or anticoagulants (p=.009). In the AD group, 13% of patients had a history of stroke or TIA, and the mean MMSE was 18.9 ± 4.9. Comparing AD vs. control groups, the prevalence of: a) abnormal periventricular WMH was 26% vs. 17% (p=.02); b) abnormal subcortical WMH was 40% vs. 72% (p=.002); c) CMB was 9% vs. 6% (p=.44); and d) abnormal MTLA was 62% vs. 33% (p=.004). Severity grades of MRI abnormalities were significantly different between AD and control groups for periventricular WMH (AD worse, p<0.001), subcortical WMH (controls worse, p=.009), and MTLA (AD worse, p=.026), but not CMB (p=.58). Regression models confirmed that MMSE was independently predicted by age and vascular risk factor (model 1). Presence MTLA provided additional independent predictive power (model 2, p=.046). 3 cases in the group AD (vs. no controls) had over 15 CMBs which could be related to underlying cerebral amtloid angiopathy. Conclusion: MRI evidence of small vessel disease and medial temporal lobe atrophy are prevalent amongst AD patients and age-matched cognitively normal controls. Higher rates of AF and antithrombotic use may have accounted for more subcortical WMH lesions amongst normal controls. Occurrence of MRI abnormalities differs significantly between AD and controls, but does not independently predict cognitive function. These findings may indicate complex overlaps of neurodegenerative pathologies in AD and cerebral aging. Further studies are needed.