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The Lancet. Neurology Dec 2016Autosomal dominant familial Alzheimer's disease (ADAD) is a rare disorder with non-amnestic neurological symptoms in some clinical presentations. We aimed to compile and... (Comparative Study)
Comparative Study Meta-Analysis Review
Neurological manifestations of autosomal dominant familial Alzheimer's disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS).
BACKGROUND
Autosomal dominant familial Alzheimer's disease (ADAD) is a rare disorder with non-amnestic neurological symptoms in some clinical presentations. We aimed to compile and compare data from symptomatic participants in the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS) with those reported in the literature to estimate the prevalences of non-amnestic neurological symptoms in participants with ADAD.
METHODS
We prospectively collected data from the DIAN-OBS database, which recruited participants from study centres in the USA, Europe, and Australia, between Feb 29, 2008, and July 1, 2014. We also did a systematic review of publications to extract individual-level clinical data for symptomatic participants with ADAD. We used data for age of onset (from first report of cognitive decline), disease course from onset to death, and the presence of 13 neurological findings that have been reported in association with ADAD. Using multivariable linear regression, we investigated the prevalences of various non-amnestic neurological symptoms and the contributions of age of onset and specific mutation type on symptoms.
FINDINGS
The DIAN-OBS dataset included 107 individuals with detailed clinical data (forming the DIAN-OBS cohort). Our systematic review yielded 188 publications reporting on 1228 symptomatic individuals, with detailed neurological examination descriptions available for 753 individuals (forming the published data cohort). The most prevalent non-amnestic cognitive manifestations in participants in the DIAN-OBS cohort were those typical of mild to moderate Alzheimer's disease, including visual agnosia (55·1%, 95% CI 45·7-64·6), aphasia (57·9%, 48·6-67·3), and behavioural changes (61·7%, 51·5-70·0). Non-amnestic cognitive manifestations were less prevalent in the published data cohort (eg, visual agnosia [5·6%, 3·9-7·2], aphasia [23·0%, 20·0-26·0], and behavioural changes [31·7%, 28·4-35·1]). Prevalence of non-cognitive neurological manifestations in the DIAN-OBS cohort was low, including myoclonus and spasticity (9·3%, 95% CI 3·8-15·0), and seizures (2·8%, 0·5-5·9) and moderate for parkinsonism (11·2%, 5·3-17·1). By constrast, prevalence was higher in the published data cohort for myoclonus and spasticity (19·4%, 16·6-22·2 and 15·0%, 12·5-17·6, respectively), parkinsonism (12·5%, 10·1-15·0), and seizures (20·3%, 17·4-23·2). In an analysis of the published data cohort, ischaemic stroke was more prevalent at older ages of onset of symptoms of ADAD (odds ratio 1·09 per 1 year increase in age of onset, 95% CI 1·04-1·14, p=0·0003); and motor symptoms were more common at younger age of onset (myoclonus 0·93, 0·90-0·97, p=0·0007; seizures 0·95, 0·92-0·98, p=0·0018; corticobulbar deficits 0·91, 0·86-0·96, p=0·0012; and cerebellar ataxia 0·82, 0·74-0·91, p=0·0002). In the DIAN-OBS cohort, non-cognitive symptoms were more common at more severe stages of disease.
INTERPRETATION
The non-cognitive clinical manifestations of Alzheimer's disease seem to affect a small proportion of participants with mild to moderate ADAD, and are probably influenced by disease severity, environmental, and genetic factors. When evaluating patients with potential ADAD, clinicians should note that cognitive symptoms typical of sporadic Alzheimer's disease are the most consistent finding, with some patients manifesting non-cognitive neurological symptoms. Future work is needed to determine the environmental and genetic factors that cause these neurological symptoms.
FUNDING
National Institutes of Health and German Center for Neurodegenerative Diseases.
Topics: Alzheimer Disease; Humans
PubMed: 27777020
DOI: 10.1016/S1474-4422(16)30229-0 -
American Journal of Alzheimer's Disease... Aug 2016Clinicians often have difficulty distinguishing between various forms of dementia to achieve a correct diagnosis. Little research has been done to examine whether... (Review)
Review
Clinicians often have difficulty distinguishing between various forms of dementia to achieve a correct diagnosis. Little research has been done to examine whether awareness of one's cognitive deficits, or metacognitive monitoring, might differ between dementia diagnoses, thereby providing an additional means of differentiating between dementia subtypes. We review articles examining metacognitive comparisons between two of the most common dementia subtypes: Alzheimer's disease and frontotemporal dementia. Greater monitoring deficits were apparent in frontotemporal dementia than in Alzheimer's disease, and participants with frontotemporal dementia were less likely to utilize task experience to update and improve the accuracy of subsequent monitoring judgments. Results provide evidence for the utility of metacognitive measures as a means of distinguishing between Alzheimer's disease and frontotemporal dementia.
Topics: Agnosia; Alzheimer Disease; Awareness; Cognition Disorders; Frontotemporal Dementia; Humans
PubMed: 26705377
DOI: 10.1177/1533317515618899 -
Cortex; a Journal Devoted To the Study... Dec 2014This review provides an overview of research into anosognosia after stroke over the past 35 years. We are specifically interested in the assessment of anosognosia in... (Review)
Review
This review provides an overview of research into anosognosia after stroke over the past 35 years. We are specifically interested in the assessment of anosognosia in group studies and in how any changes in assessment procedures have impacted the study of anognosia. Our work is based on a systematic review of reports drawn from electronic databases covering the period from 1978 to 2013 (CINAHL, PubMedMEDLINE, PsycINFO, Web of Knowledge). Sixty-four articles met the selection criteria. The results of our review show that a deeper understanding has evolved of the multifaceted syndrome of anosognosia during the past decade. The most recent studies made more extensive use of research, observational and performance-based procedures as well as traditional interview methods. Modality specificities and patients with language impairment also receive closer consideration than earlier. Furthermore, the results are more often obtained from homogeneous patient groups. The limitations of recent anosognosia research include the diversity of assessment methods used and the variation in the assessment times between and within patient groups, and the tendency to rely on only 1 method to assess and diagnose anosognosia. In order to improve the comparability of anosognosia studies it would be useful to have guidelines for the number and type of assessment methods used in studying different subtypes of anosognosia, and to focus on homogeneous patient samples. Furthermore, it is recommended that more research be done to explore chronic anosognosia and its impact on daily living.
Topics: Agnosia; Awareness; Diagnosis, Differential; Functional Laterality; Hemiplegia; Humans; Stroke
PubMed: 24912851
DOI: 10.1016/j.cortex.2014.04.008 -
Brain Imaging and Behavior Sep 2013This paper presents the first systematic review and meta-analysis of neuropsychological and brain morphometry studies comparing posterior cortical atrophy (PCA) to... (Comparative Study)
Comparative Study Meta-Analysis Review
This paper presents the first systematic review and meta-analysis of neuropsychological and brain morphometry studies comparing posterior cortical atrophy (PCA) to typical Alzheimer's disease (tAD). Literature searches were conducted for brain morphometry and neuropsychological studies including a PCA and a tAD group. Compared to healthy controls (HC), PCA patients exhibited significant decreases in temporal, occipital and parietal gray matter (GM) volumes, whereas tAD patients showed extensive left temporal atrophy. Compared to tAD patients, participants with PCA showed greater GM volume reduction in the right occipital gyrus extending to the posterior lobule. In addition, PCA patients showed less GM volume loss in the left parahippocampal gyrus and left hippocampus than tAD patients. PCA patients exhibit significantly greater impairment in Immediate Visuospatial Memory as well as Visuoperceptual and Visuospatial Abilities than patients with tAD. However, tAD patients showed greater impairment in Delayed Auditory/Verbal Memory than patients with PCA. PCA is characterized by significant atrophy of the occipital and parietal regions and severe impairments in visuospatial functioning.
Topics: Agnosia; Alzheimer Disease; Atrophy; Cerebral Cortex; Comorbidity; Humans; Neuropsychological Tests; Prevalence
PubMed: 23690254
DOI: 10.1007/s11682-013-9236-1 -
International Archives of Medicine Apr 2013Amusia, a music-specific agnosia, is a disorder of pitch interval analysis and pitch direction change recognition which results in a deficit in musical ability. The full...
BACKGROUND
Amusia, a music-specific agnosia, is a disorder of pitch interval analysis and pitch direction change recognition which results in a deficit in musical ability. The full range of aetiological factors which cause this condition is unknown, as is each cause's frequency. The objective of this study was to identify all causes of amusia, and to measure each of their frequencies.
DESIGN
systematic review was conducted by search of multiple databases for articles related to the aetiology of amusic auditory dysfunction. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting of systematic reviews were followed, utilizing the PRISMA checklist and PRISMA flowchart methodology.
SETTING
Retrospective medical database review.
MAIN OUTCOME MEASURES
evidence yielded from the systematic review process.
RESULTS
The initial search protocol identified 5723 articles. Application of a classification review filter and exclusion of irrelevant or duplicates led to the initial identification of 56 relevant studies which detailed 301 patients. However, these studies were of poor quality. Because of this, synthesis and statistical analysis were not appropriate.
CONCLUSION
Although initially a large number of relevant studies were identified, and might point in future to potential diagnostic categories, it was not appropriate to synthesise and analyse them due to poor quality, considerable heterogeneity and small numbers. This suggests that large, high quality studies focussed directly on understanding the aetiology of amusia are required.
PubMed: 23618339
DOI: 10.1186/1755-7682-6-16 -
Brain : a Journal of Neurology Dec 2007Anosognosia is the lack of awareness or the underestimation of a specific deficit in sensory, perceptual, motor, affective or cognitive functioning due to a brain... (Review)
Review
Anosognosia is the lack of awareness or the underestimation of a specific deficit in sensory, perceptual, motor, affective or cognitive functioning due to a brain lesion. This self-awareness deficit has been studied mainly in stroke hemiplegic patients, who may report no deficit, overestimate their abilities or deny that they are unable to move a paretic limb. In this review, a detailed search of the literature was conducted to illustrate clinical manifestations, pathogenetic models, diagnostic procedures and unresolved issues in anosognosia for motor impairment after stroke. English and French language papers spanning the period January 1990-January 2007 were selected using PubMed Services and utilizing research words stroke, anosognosia, awareness, denial, unawareness, hemiplegia. Papers reporting sign-based definitions, neurological and neuropsychological data and the results of clinical trials or historical trends in diagnosis were chosen. As a result, a very complex and multifaceted phenomenon emerges, whose variable behavioural manifestations often produce uncertainties in conceptual definitions and diagnostic procedures. Although a number of questionnaires and diagnostic methods have been developed to assess anosognosia following stroke in the last 30 years, they are often limited by insufficient discriminative power or a narrow focus on specific deficits. As a consequence, epidemiological estimates are variable and incidence rates have ranged from 7 to 77% in stroke. In addition, the pathogenesis of anosognosia is widely debated. The most recent neuropsychological models have suggested a defect in the feedforward system, while neuro-anatomical studies have consistently reported on the involvement of the right cerebral hemisphere, particularly the prefrontal and parieto-temporal cortex, as well as insula and thalamus. We highlight the need for a multidimensional assessment procedure and suggest some potentially productive directions for future research about unawareness of illness.
Topics: Agnosia; Awareness; Brain; Brain Mapping; Denial, Psychological; Hemiplegia; Humans; Stroke
PubMed: 17533170
DOI: 10.1093/brain/awm106 -
Acta Neurologica Scandinavica Nov 2006This review provides an update on recent research findings concerning the methods used in the assessment of anosognosia, the occurrence and subtypes of anosognosia, the... (Review)
Review
PURPOSE
This review provides an update on recent research findings concerning the methods used in the assessment of anosognosia, the occurrence and subtypes of anosognosia, the association between anosognosia and neglect, and the impact of anosognosias on functional outcome.
METHODS
A systematic review covering the period from 1995 to 2005 was carried out on reports drawn from electronic databases (MEDLINE, PSYCHLIT) and identified from the references in these reports. Twenty-seven articles met the selection criteria.
RESULTS
The results of this review are in line with previous findings in the following respects: anosognosia was more often associated with right hemisphere damage, neglect and anosognosia co-occurred, and anosognosia had predictive value on poor functional outcome. The variation in the methods used in the assessment of anosognosia, patient samples and assessment times influence the occurrence rates and the predictive value of anosognosia, which might undermine the generalizability of the results.
CONCLUSIONS
More homogeneous patient samples and consistency in the assessment methods and evaluation times would facilitate comparisons of the occurrence and the impact of anosognosia on functional outcome. New methods need to be developed for the assessment of anosognosia. These new methods should take account of the subtypes of anosognosia both at verbal and at non-verbal levels.
Topics: Agnosia; Cerebral Cortex; Disability Evaluation; Functional Laterality; Humans; Neurologic Examination; Neuropsychological Tests; Perceptual Disorders; Predictive Value of Tests; Prognosis; Stroke
PubMed: 17022776
DOI: 10.1111/j.1600-0404.2006.00723.x