[Show abstract][Hide abstract] ABSTRACT: Cognitive impairment precedes the diagnosis of Alzheimer's disease. It is unclear which psychometric measures predict dementia, and what cut-off points should be used. Replicable cognitive measures to provide information about differential diagnosis and prognosis would be clinically useful.
In a prospective cohort study we investigated which measures distinguish between individuals with amnestic mild cognitive impairment (aMCI) that converts to dementia and those whose impairment does not, and which combination of measures best predicts the fate of people with aMCI.
Forty-four participants with aMCI underwent extensive neuropsychological assessment at baseline and annually thereafter for an average of 4 years. Differences in baseline cognitive performance of participants who were converters and non-converters to clinically diagnosed dementia were analysed. Classification accuracy was estimated by sensitivity, specificity, positive and negative predictive values and using logistic regression.
Forty-one percent of participants had progressed to dementia by the end of study, with a mean annual conversion rate of 11%. Most (63%) showed persisting or progressive cognitive impairment, irrespective of diagnosis. The Addenbrooke's Cognitive Examination together with the discrimination index of the Hopkins Verbal Learning Test - Revised (but none of the demographic indices) differentiated the participants who were converters from the non-converters at baseline with 74% accuracy.
Targeted neuropsychological assessment, beyond simple cognitive screening, could be used in clinical practice to provide individuals with aMCI with prognostic information and aid selective early initiation of monitoring and treatment among those who progress towards a clinically diagnosable dementia.
The British journal of psychiatry: the journal of mental science 08/2010; 197(2):135-40. DOI:10.1192/bjp.bp.110.077958 · 7.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Episodic memory is compromised in amnestic mild cognitive impairment (aMCI), but lesser deficits in other cognitive domains are also commonly observed and may be helpful in identifying this group. The relative difference in performance on lexical and semantic fluency tasks may be a sensitive and specific measure in aMCI and early Alzheimer's disease (AD). We compared four groups of participants, 35 early AD, 47 aMCI, 24 healthy controls, and 18 depressive out-patient controls, on semantic and lexical fluency as well as other neuropsychological tests. Early AD and aMCI patients showed a distinct pattern of semantic impairment in the two fluency measures compared with the healthy and depressive controls. The findings implicate early failure of the semantic memory system in aMCI and AD and suggest that consideration of the discrepancy in performance on semantic and lexical fluency measures may help in the early identification of AD.
[Show abstract][Hide abstract] ABSTRACT: Five patients with Alzheimer's disease and five healthy volunteers were examined by SPECT with the nicotinic receptor ligand 123I-5-IA-85380. Patients were scanned before and after 6 weeks of treatment with donepezil. Quantification by regions of interest was reliable and the optimal normalisation procedure used cerebellar ratios. We found relative reductions in 5-IA binding capacity in patients in thalamus, frontal and central regions of interest of approximately one standard deviation unit (Cohen's d = 1). Reductions in binding after treatment with the acetylcholinesterase inhibitor donepezil of the same magnitude occurred in the brain stem. The study was clearly too small to confirm group differences, but it suggests that 5-IA can be used to examine both group differences and treatment effects in patients with Alzheimer's disease.
Neurochemical Research 05/2008; 33(4):643-51. DOI:10.1007/s11064-007-9517-4 · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The dual task paradigm (Baddeley et al. 1986; Della Sala et al. 1995) has been proposed as a sensitive measure of Alzheimer's dementia, early in the disease process.
We investigated this claim by administering the modified dual task paradigm (utilising a pencil-and-paper version of a tracking task) to 33 patients with amnestic mild cognitive impairment (aMCI) and 10 with very early Alzheimer's disease, as well as 21 healthy elderly subjects and 17 controls with depressive symptoms. All groups were closely matched for age and pre-morbid intellectual ability.
There were no group differences in dual task performance, despite poor performance in episodic memory tests of the aMCI and early Alzheimer's disease groups. In contrast, the Alzheimer patients were specifically impaired in the trail-making test B, another commonly used test of divided attention.
The dual task paradigm lacks sensitivity for use in the early differential diagnosis of Alzheimer's disease.
Psychological Medicine 05/2008; 39(1):23-31. DOI:10.1017/S0033291708003346 · 5.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Suicide is one of the leading causes of death in adolescents and young people. This study aims to identify factors associated with suicidal thinking in young people. Levels of suicidal thinking in a large student population (n = 1039) were assessed using the GHQ-28; regression analysis identified personality (trait) and mood (state) correlates of suicidal thoughts. All volunteers were recruited from Universities in Edinburgh.Over 10% of students stated that they had suicidal thoughts within the last few weeks. Men scored slightly higher than women on suicidal thoughts. Variables relating to emotionality were the largest predictors of suicidal thoughts.Gender differences have also been reported in the relationship between self-rated mental health and suicide rates: males who had scored highly on the GHQ-28 had a higher suicide risk than females. Longitudinal studies in both men and women that assess personality predictors of self-harm and suicides are needed to control for confounders in non-randomised studies of suicide risk.
Personality and Individual Differences 03/2008; DOI:10.1016/j.paid.2007.10.018 · 1.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is current interest in exploring the different subtypes of mild cognitive impairment (MCI), in terms of both their epidemiology and their cognitive profile.
To examine the frequency of MCI subtypes presenting to a memory clinic and to document detailed neuropsychological profiles of patients with the amnestic subtype.
Consecutive tertiary referrals (n=187) were psychiatrically evaluated; 45 patients met criteria for amnestic mild cognitive impairment (aMCI). A subgroup of 33 patients with aMCI as well as 21 healthy controls took part in a thorough neuropsychological examination.
Of the patients who were examined in greater neuropsychological detail, ten had pure aMCI (none with visual memory impairment only). Fifteen met criteria for non-amnestic MCI. Fifteen had normal neuropsychological profiles. Using more than one test increased sensitivity to detect episodic memory impairment.
Amnestic MCI is an important diagnosis in secondary and tertiary memory clinics. There is scope to improve the efficacy and sensitivity of the clinical assessment of this impairment.
The British Journal of Psychiatry 02/2008; 192(1):59-64. DOI:10.1192/bjp.bp.107.035642 · 7.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this review of the last 5 years' developments in research into depression we focus on recent advances and current controversies. We cover epidemiology and basic science as well as the treatment of depression in adults in all its forms. Depression in , as well as in has been covered in recent Seminars in The Lancet. Depression in adulthood remains a very common and under-treated condition, resulting in a high degree of disability. Increasingly detailed knowledge about impairment of information processing in depression is being supplemented by quantitative studies of the brain processes underlying these impairments. Most patients improve with present treatments. The mechanisms of action of antidepressants are not fully understood; the hypothesis that reversing hippocampal cell loss in depression may be their active principle is a fascinating new development. Moral panic about the claim that antidepressant serotonin reuptake inhibitors cause patients to commit suicide and become addicted to their medication may have disconcerted the public and members of the medical profession. We will try to describe the considerable effort that has gone into collecting evidence to enlighten this debate.
The Lancet 02/2006; 367(9505):153-67. DOI:10.1016/S0140-6736(06)67964-6 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dementia is the global and acquired impairment of mental function and is a major health problem, particularly in the elderly. Its most common forms with substantial imaging data are dementia of the Alzheimer's type (AD), frontotemporal dementia, vascular dementia, and Lewy body dementia. The most commonly used imaging modalities are magnetic resonance imaging and emission tomography in their various forms. Imaging can be used for diagnostic purposes. Single-photon emission tomography patterns of temporal-parietal lobe hypoperfusion, for example, differentiate AD from non-AD dementia, with sensitivity between 63% and 86% and specificity between 73% and 93%. Similar data for positron emission tomography are sensitivity of 94% and specificity of 73%. There seem to be typical patterns of brain appearance in each type of dementia, which change over the natural course of the disease, thus giving systematic and potentially complete information that is only available on an accidental basis for pathological data. Neuropsychological function is specifically correlated with particularly functional imaging data, such as brain perfusion and metabolism measures. Combining functional imaging with neuropsychological techniques can help researchers and clinicians to identify regions associated with particular cognitive functions essential for performing a given cognitive task. Imaging of brain receptors has been importantly used to explore the distribution of amyloid, cholinergic, and dopaminergic receptors in patients, thus contributing to the in vivo pharmacology and potentially to the treatment of the dementias.
International Review of Neurobiology - Neuroimaging, Edited by Glabus MF, 01/2005: pages 43-72; Academic Press., ISBN: 9780123668684