Theoretical exploration of the neural bases of behavioural disinhibition, apathy and executive dysfunction in preclinical Alzheimer's disease in people with Down's syndrome: potential involvement of multiple frontal-subcortical neuronal circuits

• Published in: JIDR. Journal of intellectual disability research (Print) 2010-04, Vol.54 (4), p.320-336
• Main Authors: Ball, S. L., Holland, A. J., Watson, P. C., Huppert, F. A.
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Aged; Aging (Individuals); Alzheimer Disease - diagnosis; Alzheimer Disease - epidemiology; Alzheimer's disease; Alzheimers Disease; Apathy; Behavior Change; behavioural change; Biological and medical sciences; Brain - physiopathology; Child; Child Behavior Disorders - diagnosis; Child Behavior Disorders - physiopathology; Chromosome aberrations; Circuits; Cognition Disorders - diagnosis; Cognition Disorders - epidemiology; Cognitive Processes; Cognitive psychology; Comorbidity; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dementia; Disabilities; Diseases; Disinhibition; Down Syndrome; Down Syndrome - diagnosis; Down Syndrome - epidemiology; Down's syndrome; Drug Use; Executive Function; Female; frontal lobe; Frontal Lobe - physiopathology; Humans; Inhibition; Male; Medical genetics; Medical sciences; Memory; Mental Disorders; Mental Retardation; Middle Aged; Moderate Intellectual Disability; Multiple Regression Analysis; Nerve Net - physiopathology; Neurology; Neuropsychological Tests; Older Adults; Organic mental disorders. Neuropsychology; Personality; Psychological Patterns; Psychological Theory; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Regression analysis; Severity of Illness Index; Short Term Memory; Task performance
• ISSN: 0964-2633; 1365-2788
• DOI: 10.1111/j.1365-2788.2010.01261.x

Background  Recent research has suggested a specific impairment in frontal‐lobe functioning in the preclinical stages of Alzheimer's disease (AD) in people with Down's syndrome (DS), characterised by prominent changes in personality or behaviour. The aim of the current paper is to explore whether particular kinds of change (namely executive dysfunction (EDF), disinhibition and apathy), associated in the literature with disruption of different underlying frontal‐subcortical circuits, are a) more or less frequently reported than others and b) related to poor performance on tasks involving different cognitive processes. Method  Seventy‐eight participants (mean age 47 years, range 36–72) with DS and mild to moderate intellectual disability (based on ICD‐10 criteria), without a diagnosis of dementia of Alzheimer's type (DAT) or other psychiatric disorders, were selected from a larger sample of older adults with DS (n = 122). Dementia diagnosis was based on the CAMDEX informant interview, conducted with each participant's main carer. Informant‐reported changes in personality/behaviour and memory were recorded. Participants were scored based on symptoms falling into three behavioural domains and completed five executive function (EF) tasks, six memory tasks (two of which also had a strong executive component) and the BPVS (as a measure of general intellectual ability). Multiple regression analyses were conducted to determine the degree to which the behavioural variables of ‘EDF’, ‘disinhibition’ and ‘apathy’, along with informant‐reported memory decline and antidepressant medication use, predicted performance on the cognitive tasks (whilst controlling for the effects of age and general intellectual ability). Results  Strikingly, disinhibited behaviour was reported for 95.7% of participants with one or more behavioural change (n = 47) compared to 57.4% with reported apathy and 36.2% with reported EDF. ‘Disinhibition’ score significantly predicted performance on three EF tasks (designed to measure planning, response inhibition and working memory) and an object memory task, (also thought to place high demands on working memory), while ‘apathy’ score significantly predicted performance on two different tasks, those measuring spatial reversal and prospective memory (p