Cognitive profile in CADASIL

Abstract

Background: The spectrum of cognitive alterations associated with CADASIL, a model of pure vascular dementia, has not been thoroughly evaluated. Objectives: The aims of this study were: (i) to describe the cognitive profile in CADASIL patients according to age; (ii) to compare the profile of patients with dementia with that of patients without dementia; and (iii) to determine the association between alterations in performance in different cognitive domains. Methods: Forty two consecutive individuals with CADASIL (35-73 years old) were investigated. Cognitive skills were analysed in five domains (executive functions, reasoning, attention, memory, visuospatial abilities) according to age and compared between patients with and without dementia. Associations between cognitive performance and stroke were tested. Results: The youngest patients presented with attention (69%), memory (70%), and executive disturbances (100%). Visuospatial abilities and reasoning deteriorated with age, mainly after the age of 60. About one quarter of patients had dementia, and 75% of these were .60 years of age. Age .60 years was associated with a Rankin score .3 and a significant deficit in all cognitive domains. No association was found between dementia and the number of ischaemic attacks. Episodic memory disorder was characterised by difficulties in retrieval rather than impairment of the encoding process. Conclusion: Cognitive decline in CADASIL is dominated by early impairment of executive functions. Skills in other cognitive domains deteriorate with age and are found to be diffusely impaired in patients with dementia. The relative preservation of the encoding process in episodic memory impairment, even in individuals with dementia, is noteworthy.

CADASIL: pathogenesis, clinical and radiological findings and treatment

“…This same pattern of mnestic change may still be present in advanced disease stages in up to two thirds of patients 86 . In many cases, however, as age advances and the burden of white matter lesions and subcortical infarcts increases, a general decline in cognitive function tends to manifest with progressive involvement of new cognitive domains, such as instrumental activities, reasoning, language, and visuospatial functions 86,87,93 . This general decline indicates increasing cortical dysfunction combined with the initial subcortical aggression, and is associated with the development of more or less diffuse brain atrophy and extensive spread of white matter aggression.…”

“…The error profile on memory tests is characteristic and represents preservation of the mesiotemporal cortex circuits responsible for the processes of encoding information (usually damaged in Alzheimer's disease and related conditions). In trials evaluating various aspects of memory, such as the Grober and Buschke test (16 words of different semantic categories) 91 and other similar tests, patients with CADASIL have relative preservation of the stages of encoding information and recognition of the saved information but in contrast exhibit marked disturbance on free recall -early and late -of this information (often with intrusions), although its performance improve partially with the presentation of hints and tips 86,92 . This same pattern of mnestic change may still be present in advanced disease stages in up to two thirds of patients 86 .…”

“…In trials evaluating various aspects of memory, such as the Grober and Buschke test (16 words of different semantic categories) 91 and other similar tests, patients with CADASIL have relative preservation of the stages of encoding information and recognition of the saved information but in contrast exhibit marked disturbance on free recall -early and late -of this information (often with intrusions), although its performance improve partially with the presentation of hints and tips 86,92 . This same pattern of mnestic change may still be present in advanced disease stages in up to two thirds of patients 86 . In many cases, however, as age advances and the burden of white matter lesions and subcortical infarcts increases, a general decline in cognitive function tends to manifest with progressive involvement of new cognitive domains, such as instrumental activities, reasoning, language, and visuospatial functions 86,87,93 .…”

“…Worried family members not infrequently bring patients to assessment, with the vague impression of innatention, behavioural changes or indifference. The initial signs denote essentially underlying dysfunction of frontal-subcortical circuits 86,88 . In this initial stage, verbal episodic memory and visuospatial functions -which tend to predominate in standard screening tests commonly performed in clinical practice -are usually preserved, which can lead to the false impression of depression and normal cognitition.…”

“…De-mentia is an ominous prognostic finding, present in about 80% of patients at the time of death 49 . In young people, manifestations of executive dysfunction (almost 100% between 35 and 50 years of age) and attentional deficits (69%) are among the earliest cognitive changes 86 . Working memory is also hampered 87 .…”