Apathy: a major symptom in CADASIL

Objective: The frequency and impact of apathy in subcortical ischemic vascular dementia (SIVD) remain undetermined. The frequency, clinical, neuropsychological, and imaging correlates of apathy were assessed in a large cohort of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a genetic model of SIVD. Methods: Apathy was diagnosed based on Neuropsychiatric Inventory assessment. Degree of disability was assessed by modified Rankin scale, cognitive impairment by Mattis Dementia Rating Scale (MDRS) and Mini-Mental State Examination (MMSE), autonomy by the Instrumental Activities of Daily Living (IADL) scale, and quality of life by SEP-59 self-questionnaire. Validated imaging methods were used to determine the total burden of cerebral lesions. Results: Among 132 patients, 54 (41%) were apathetic. Apathetic patients were older than nonapathetic subjects, had a lower MMSE and MDRS score, had more global disability, and were more limited in IADL. Apathetic patients were more frequently depressed compared to nonapathetic patients and more frequently presented additional neuropsychiatric symptoms. Multiple regression modeling showed a significant and independent association between apathy and a lower score of overall quality of life and between apathy and a higher load of white matter and lacunar lesions. Conclusions: The results suggest that apathy is common in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), appears in association with cognitive impairment, global functional disability, and severe neuropsychiatric symptoms during the course of the disease, and can occur separately from depression. Apathy has an independent impact on the overall quality of life in CADASIL. CADASIL = cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; IADL = Instrumental Activities of Daily Living; ICC = intracranial cavity; LL = lacunar lesions; MDRS = Mattis Dementia Rating Scale; MMSE = Mini-Mental State Examination; mRS = modified Rankin scale; NA = not applicable because of insufficient observations; nCM = number of cerebral microhemorrhages; nLL = normalized volume of lacunar lesions; NPI = Neuropsychiatric Inventory; nWMH = normalized volume of white matter hyperintensities; QOL = quality of life; SIVD = subcortical ischemic vascular dementia; TIA = transient ischemic attack; WMH = white matter hyperintensities.