Effects of Medial Temporal Atrophy and White Matter Hyperintensities on the Cognitive Functions in Patients with Alzheimer’s Disease

Abstract

Aims: We conducted this study to investigate the independent association of medial temporal atrophy (MTA) and white matter hyperintensities (WMH) with cognitive impairments of Alzheimer’s disease (AD) patients and the interaction between MTA and WMH. Methods: From 13 centers, a total of 216 AD patients were consecutively recruited and their MTA and WMH were visually rated. We evaluated the association of MTA and WMH with the various cognitive domains, and the interaction between MTA and WMH. Results: MTA independently correlated with scores of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale (CDR), delayed recalls of the Seoul Verbal Learning Test (SVLT), the Boston Naming Test (BNT), and Word Fluency. WMH independently correlated with MMSE, CDR, Digit Span, and Stroop word reading, but not with delayed recall. There were interactions of WMH and MTA on CDR (p = 0.004), SVLT (p = 0.023), BNT (p = 0.002) and the semantic Word Fluency (p = 0.007). Conclusion: MTA and WMH independently affected cognitive deficits in AD patients, with somewhat different patterns where MTA was associated mostly with memory and language, while WMH were associated with attention and frontal executive functions. This study also showed interactions between MTA and WMH on some cognitive deficits and dementia severity, suggesting that they synergistically contribute to cognitive impairment in AD.

Effect of White Matter Hyperintensity on Medial Temporal Lobe Atrophy in Alzheimer’s Disease

“…The severity of WMH was evaluated semiquantitatively on FLAIR images using a scale developed by the Clinical Research Center for Dementia of South Korea Study (CREDOS) [2,10,15,23] with modifications based on Fazeka’s [24] and Schelten’s criteria [25]. The longest diameter of white matter changes around the lateral ventricles (capping or banding on the periventricular areas) and deep white matter area (particularly the centrum semiovale area) were evaluated separately.…”

“…This brain atrophy is easily observed with structural magnetic resonance imaging (MRI). Cumulative evidence indicates that medial temporal atrophy (MTA) is a sensitive marker for the diagnosis of AD [1,2]. In particular, the hippocampus is thought to be an important structure in early diagnosis and in differentiating AD from normal aging.…”

“…Some reports suggest that WMH are associated with an increased risk of dementia [8] and rapid declines in global cognitive performance and executive function [2,9,10], but others have not found an association between WMH and AD [11] or memory functioning [12]. WMH is thought to be caused by ischemia, amplifying the effect of AD pathology and cognitive decline in various ways.…”

Ankle-Brachial Pressure Index and Pulse Wave Velocity as Markers of White Matter Hyperintensities and Cognitive Impairment

“…The imaging protocol for MRA was the three-dimensional time-of-flight method. The periventricular WMHs (PVHs) and the deep WMHs (DWHs) were separately evaluated, as proposed by the Clinical Research for Dementia Of South Korea (CREDOS) [35]. The severity of DWHs was rated according to their largest diameter, with the categories D1 (<10 mm), D2 (≥ 10 and <25 mm), and D3 (≥ 25 mm).…”

“…With modification from prior criteria [36], we added Grade 0 (absence; D0 or P0) in the individual ratings of PVHs and DWHs, and the severity of total WMHs was reclassified into none (Grade 0), minimal (Grade 1), moderate (Grade 2), and severe (Grade 3) [35]. Table 1 presents modified CREDOS ratings of WMHs for all subjects.…”