Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for ...severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.
Age-related dysfunction of frontal systems can result in deficits in planning, organization, self-control, and awareness of problems, which are likely to affect the ability to care for one's self. ...The purpose of this study was to determine the relationship between age-related frontal/executive deficits and impairment in instrumental activities of daily living (IADLs) in elderly individuals. Twenty-seven community-dwelling individuals were administered a comprehensive battery of neuropsychological tests and a performance-based evaluation of IADLs. Multiple regression analyses indicated that executive function and depression severity accounted for a significant proportion of variance in IADLs, with executive function making the greatest contribution. Tests measuring other cognitive functions, such as memory, language, and spatial skills, did not contribute significantly to the prediction of functional status. Furthermore, executive measures accounted for more variance than other demographic characteristics such as general health status, age, and educational level. The results of this study indicate that executive dysfunction in normal aging may be the best predictor of functional decline. A better understanding of the mechanisms that underlie IADL skills will ultimately aid in the development of compensatory and intervention strategies designed to delay the onset of assisted living and nursing home placement.
Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73-90% (ref. 1). Inheritance patterns are complex, and ...the number and type of genetic variants involved are not understood. Copy number variants (CNVs) have been identified in individual patients with schizophrenia and also in neurodevelopmental disorders, but large-scale genome-wide surveys have not been performed. Here we report a genome-wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high-density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15-fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single-occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo-cardio-facial syndrome, which includes psychotic symptoms in 30% of patients. Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome-wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome-wide and at specific loci.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Reliability and construct validity are reported for the Frontal Lobe Personality Scale (FLOPS), a brief neurobehavior rating scale. The FLOPS Family form was completed by family members of 24 frontal ...lobe brain-damaged patients, 15 non-frontal lobe braindamaged patients, and 48 healthy controls. Intrascale reliability was demonstrated (internal consistency .96; split half .93). Validity studies of frontal lobe patients post-lesion compared to their pre-lesion status, to healthy controls, and of frontal lobe patients preand post-lesion compared to non-frontal lobe patients preand post-lesion, indicated that frontal lobe patients post-lesion showed significantly more "frontal" behavior than (a) pre-lesion frontal lobe patients, (b) healthy controls, and (c) post-lesion non-frontal lobe patients. The FLOPS appears to be useful for quantifying frontal lobe behavior in clinical and research settings.
The authors examined whether scores on two recently developed measures of behavioral disturbance, the Frontal Lobe Personality Scale (FLOPS) and the Neuropsychiatric Inventory (NPI), are associated ...with functional impairments in patients with dementia. Caregivers of 30 dementia patients were administered the FLOPS Family Form, the NPI, and an Activities of Daily Living (ADL) scale. Findings indicated a relationship between behavioral changes and functional limitations in patients with dementia. Moreover, the FLOPS, an instrument designed to specifically measure behaviors subserved by frontal lobe systems, was more strongly related to failures in instrumental ADLs than was the NPI. The authors conclude that behavioral measures add information over and above that available from cognitive tests in determining ADL functioning.
Treating Apathy in Alzheimer’s Disease Boyle, Patricia A.; Malloy, Paul F.
Dementia and geriatric cognitive disorders,
01/2004, Letnik:
17, Številka:
1-2
Journal Article
Recenzirano
Apathy, a syndrome of decreased initiation and motivation, affects over 70% of individuals with Alzheimer’s disease (AD) and is the most common neuropsychiatric symptom reported in AD patients. The ...syndrome of apathy is associated with functional impairment among patients and elevated stress among their caregivers. Apathy is one of the primary neuropsychiatric manifestations of frontal system dysfunction, and AD-related apathy is thought to reflect the interaction between cholinergic deficiency and neuropathological changes in frontal brain regions. This article reviews the assessment and treatment of apathy in AD, with emphasis on the utility of acetylcholinesterase inhibitors for reducing apathy in AD. The potential benefits of other pharmacologic agents and combined pharmacologic-behavioral interventions are also discussed, and recommendations for future research are provided.
A 1994 survey by the Research Committee of the American Neuropsychiatric
Association revealed that 58% of respondents employed formal assessment of
cognitive status; the Mini-Mental State Examination ...(MMSE) and
neuropsychological testing were the commonest techniques. Literature review
on common cognitive screening instruments found that the MMSE has
widespread popularity, ease of use, and a large body of research
demonstrating its sensitivity to common neuropsychiatric disorders. The
Committee recommends that clinicians who employ the MMSE 1) use it as a
minimum screening for cognitive dysfunction; 2) employ age- and
education-normative corrections; and 3) supplement it with specific
measures of spatial functions, delayed memory, and executive abilities. The
Modified MMSE and the Neurobehavioral Cognitive Status Examination also
show promise as screening tools.
The Frontal Systems Behavior Scale (FrSBe), formerly called the Frontal Lobe Personality Scale (FLOPS), is a brief behavior rating scale with demonstrated validity for the assessment of behavior ...disturbances associated with damage to the frontal-subcortical brain circuits. The authors report an exploratory principal factor analysis of the FrSBe–Family Version in a sample including 324 neurological patients and research participants, of which about 63% were diagnosed with neurodegenerative diseases (Huntington's, Parkinson's, and Alzheimer's diseases). The three-factor solution accounted for a modest level of variance (41%) and confirmed a factor structure consistent with the three subscales proposed on the theoretical basis of the frontal systems. Most items (83%) from the FrSBe subscales of Apathy, Disinhibition, and Executive Dysfunction loaded saliently on three corresponding factors. The FrSBe factor structure supports its utility for assessing both the severity of the three frontal syndromes in aggregate and separately.
Apathy refers to a reduction in self-initiated behavior, and it is commonly reported by patients infected with human immunodeficiency virus (HIV). It remains unclear whether apathy among HIV patients ...reflects a direct effect of the virus on subcortical brain circuits or a secondary neuropsychiatric symptom. In the present study we examined the relationship between ratings of apathy and quantitative analysis of the nucleus accumbens (NA), a subcortical brain structure that regulates initiation of behavioral activation. Twelve HIV-positive individuals without dementia were administered the Marin Apathy Scale and underwent neuroimaging. Voxel-based quantification of the nucleus accumbens was completed using a segmentation protocol. Results of our study revealed that increased ratings of apathy were significantly correlated with lower volume of the nucleus accumbens. By contrast, ratings of depression were unrelated to either apathy or nucleus accumbens volume. These findings provide preliminary evidence that apathy reflects direct involvement of the central nervous system in patients with HIV.
Contemporary research has shown that delusions are often the product of identifiable neurologic disease, particularly when the delusions have a specific theme or are confined to one ...topic--monosymptomatic or content-specific delusions. Although these delusions are considered rare, some of them can be found at high rates in certain populations and settings. The literature on several classes of content-specific delusions (misidentification, sexual, and somatic) is critically reviewed. The review demonstrates that when adequate diagnostic workups are conducted, a high proportion of such delusions are found to have a neurologic basis. Lesions of the frontal lobes and the right hemisphere are shown to be critical to the development and persistence of many content-specific delusions.
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