Biomedical subjects

Jason Brandt

Publications and source records attributed to Jason Brandt.

At least 37 records · Page 2Linked to original sources

PubMed2004

Functional brain changes in presymptomatic Huntington's disease.

Evidence suggests early structural brain changes in individuals with the Huntington's disease (HD) genetic mutation who are presymptomatic for the movement symptoms of the illness. The aim of this study was to investigate the presence of functional brain changes in this same population using functional magnetic resonance imaging. Subjects and matched controls underwent an functional magnetic resonance imaging "interference" protocol, a task known to be mediated in part by corticostriatal circuitry. In the setting of normal cognitive performance, presymptomatic HD subjects had significantly and specifically less activation in the left anterior cingulate cortex (BA 24, 32) compared with matched controls.

Adult↗

PubMed2004

Patient predictors of response to treatment of depression in Alzheimer's disease: the DIADS study.

OBJECTIVE: To investigate patient predictors of response to treatment of Major Depressive Episode (MDE) in Alzheimer's disease (AD). METHODS: Forty-four outpatients with AD and MDE were randomized to receive either sertraline or placebo in a 12-week placebo-controlled, flexible-dose clinical trial after a one week single-blind placebo phase. All participants were evaluated for depression at entry using the 21-item Hamilton Depression Rating Scale (HDRS) and the Cornell Scale for Depression in Dementia (CSDD). All subjects completed baseline neuropsychological testing. Caregiver burden and depression were also measured. The forty-two subjects who completed at least one post-enrollment follow-up visit were included in the analysis. RESULTS: No baseline demographic, mood, neuropsychiatric, neuropsychological, or caregiver variable was a statistically significant predictor of response to treatment. There were trends for African-American patients (p=0.07) and those with milder baseline agitation/aggression (p=0.08) to respond better. CONCLUSION: No baseline characteristic assessed clearly predicts response to treatment of MDE in AD. A diverse population of depressed AD patients may thus respond similarly to the same treatment.

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PubMed2004

Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease.

OBJECTIVE: To evaluate the efficacy and safety of donepezil, an acetylcholinesterase inhibitor, as a treatment for cognitive impairment and dementia in patients with Parkinson' s disease (PD). METHODS: Using a randomized, double-blind, placebo-controlled design, nine patients received placebo and seven patients received donepezil (2.5-10 mg/day) for a mean (SD) duration of 15.2 (3.4) weeks. The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory, attention, psychomotor speed, and visuospatial and executive functions. Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings. Primary safety measures were motor signs and assessments of adverse effects. RESULTS: Patients on donepezil showed selective and significant (p<0.05) improvement on the memory subscale of the Dementia Rating Scale. There was also a trend toward improvement on a measure of psychomotor speed and attention. There were no group differences in psychiatric status, motor function, or activities of daily living as measured at baseline or end-point. Adverse effects resulted in premature withdrawal of four patients on donepezil, two for peripheral cholinergic effects and one for increased parkinsonism. Side effects were associated with dosage increases. CONCLUSION: Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment. However, variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD, especially with dosage increases.

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PubMed2004

A controlled trial of aromatherapy for agitation in nursing home patients with dementia.

OBJECTIVES: Two controlled trials of aromatherapy to decrease agitation in persons with dementia have recently produced promising results. However, both studies combined the use of essential oils with massage. Thus, it is unclear if the effect of the aromatherapy intervention was the result of smelling or the cutaneous absorption of the oils. The purpose of this study was to determine whether smelling lavender oil decreases the frequency of agitated behaviors in patients with dementia. DESIGN: The study design was within-subjects ABCBA (A = lavender oil, B = thyme oil, C = unscented grapeseed oil): 4 weeks of baseline measurement, 2 weeks for each of the five treatment conditions (10-week total intervention time), and 2 weeks of postintervention measurement. Oil was placed every 3 hours on an absorbent fabric sachet pinned near the collarbone of each participant's shirt. SETTING: A long-term care facility specifically for persons with dementia. PARTICIPANTS: Seven agitated nursing home residents with advanced dementia. MEASUREMENTS: Agitation was assessed every 2 days using a modified Cohen-Mansfield Agitation Inventory. Olfactory functioning was assessed with structured olfactory identification and discrimination tasks, and with qualitative behavioral observation during those tasks. RESULTS: Split-middle analyses conducted separately for each patient revealed no treatment effects specific to lavender, no treatment effects nonspecific to pleasant smelling substances, and no treatment effects dependent on order of treatment administration. There were no differences between participants with more and less intact olfactory abilities. CONCLUSION: There is significant evidence in the neurologic and neuropsychologic literature that persons with dementia have impaired olfactory abilities. Concordant with this literature, this study found no support for the use of a purely olfactory form of aromatherapy to decrease agitation in severely demented patients. Cutaneous application of the essential oil may be necessary to achieve the effects reported in previous controlled studies.

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PubMed2004

Prevalence of major depression one year after predictive testing for Huntington's disease.

Psychiatric hospitalizations, completed suicides, and suicide attempts are rare after predictive testing for Huntington's disease (HD). Case studies have shown that major depression can be a consequence of being tested, although no studies have shown how common this is. The present study evaluated the prevalence of major depression during the first year after disclosure. We conducted retrospective data and chart reviews of 153 persons (50 testing positive, 103 testing negative) evaluated every 3 months for depression. There was no significant baseline difference in the percentage of "positives" and "negatives" who had pre-testing major depressive episodes (14% vs. 12%, respectively). A senior psychiatrist reviewed data from the Schedule for Affective Disorders and Schizophrenia-Change Version, from the Beck Depression Inventory, and from clinical notes for every follow-up contact completed. The 1-year prevalence of major depression among positives was 6.0%, compared to 3.0% among negatives (p = 0.30), and an estimated 3% population prevalence. One-year prevalence of clinically significant depressive symptoms, whether or not major depression was diagnosed, was 20.0% in positives and 12.6% in negatives (p = 0.17). Although not statistically significant, depressive symptoms and major depression occurred more frequently among those who tested positive. Despite some evidence to the contrary, including our own studies, a positive predictive test for HD is not psychologically benign. Clinical testing programs should assess patients for depressive symptoms after testing, and patients with clinically significant complaints should be referred to a mental health professional.

Adult↗

PubMed2004

The cognitive outcome of hemispherectomy in 71 children.

PURPOSE: Long-term neuropsychological outcome was studied in 71 patients who underwent hemispherectomy for severe and intractable seizures at The Johns Hopkins Hospital between 1968 and 1997 and who agreed to participate. Seizures were due to cortical dysplasias (n = 27), Rasmussen syndrome (n = 37), or vascular malformations or strokes (n = 7). Both presurgical and follow-up results are available and reported for 53 patients. METHODS: Patients and caretakers were interviewed, and patients were administered standard measures of intelligence, receptive and expressive language, visual-motor skills, adaptive/developmental functioning, and behavior. RESULTS: Mean age at surgery was 7.2 years. At follow-up, on average 5.4 years after surgery, 65% are seizure free, 49% are medication free, and, of those responding, none rated quality of life as worse than before surgery. Mean IQ was in the 70s for Rasmussen and vascular patients and in the 30s for cortical dysplasia patients. Language and visual-motor skills were consistent with IQ. For Rasmussen patients only, language was significantly more impaired for left than for right hemispherectomy, both before surgery and at follow-up. Adaptive skills were mildly impaired, with greatest impairment in the physical domain. Cognitive measures typically changed little between surgery and follow-up, with IQ change <15 points for 34 of 53 patients; of the remainder, 11 declined and eight improved. Behavior was free of major problems, but social interactions and activities were limited. CONCLUSIONS: The most significant predictor of cognitive skills at follow-up was etiology, with dysplasia patients scoring lowest in intelligence and language but not in visual-motor skills. Regardless of etiology, most patients showed only moderate change in cognitive performance at follow-up.

Child↗

PubMed2004

The Maryland Assisted Living Study: prevalence, recognition, and treatment of dementia and other psychiatric disorders in the assisted living population of central Maryland.

OBJECTIVES: To obtain a direct estimate of the prevalence of dementia and other psychiatric disorders in residents of assisted living (AL) in Central Maryland, and their rates of recognition and treatment. DESIGN: Comprehensive review of history and cognitive and neuropsychiatric evaluations using widely accepted instruments in a randomized cohort of AL residents, stratified by facility size. An expert multidisciplinary consensus panel determined diagnoses and appropriateness of treatment. SETTING: Twenty-two (10 large and 12 small) randomly selected AL facilities in the city of Baltimore and seven Maryland counties. PARTICIPANTS: One hundred ninety-eight volunteers who were residents of AL, 75% were aged 80 and older, and 78% were female. Potential participants were randomly chosen by room number. There was a 67% participation rate. MEASUREMENTS: Overall rate of dementia, noncognitive active psychiatric disorders, and recognition and adequate treatment of dementia and psychiatric disorders, as determined by consensus panel. RESULTS: Two-thirds (67.7%) of participants had dementia diagnosable according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (81% small facilities and 63% large). Family or caregivers recognized 78% to 80% of dementias. Seventy-three percent of dementias were adequately evaluated, and 52% were adequately treated. Of the 26.3% of participants who had an active noncognitive psychiatric disorder, 58% to 61% were recognized and 52% adequately treated. CONCLUSION: Dementia and psychiatric disorders are common in AL and have suboptimal rates of recognition and treatment. This may contribute to morbidity and interfere with the ability of residents to age in place.

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PubMed2004

Cognitive impairments in cerebellar degeneration: a comparison with Huntington's disease.

To determine the specificity of cognitive impairments in patients with cerebellar degeneration (CD), the neuropsychological test performance of 31 CD patients was compared to that of 21 patients with Huntington's disease (HD) and 29 normal adults. The CD and HD groups did not differ in age, education, or duration of illness, and their overall severity on a quantified neurological examination was similar. Fifteen neuropsychological test variables were reduced to five underlying domains: motor, verbal, spatial, memory, and executive functioning. The CD patients had their greatest impairment in the executive domain and their least in the memory domain. In contrast, the HD patients had very substantial spatial deficits and significant memory impairment, in addition to executive dysfunction. The findings indicate that 1) the cognitive impairment in CD is not as severe as in HD, and 2) the pattern of deficits in CD, while consistent with a subcortical dementia, differs in important ways from that in HD. These differences may reflect the involvement of the cerebellar dentate nucleus and the striatal nuclei in separate "loops" or closed circuits, linking them with specific areas of cerebral neocortex.

Adult↗

PubMed2003

The rate of cognitive decline and risk of reaching clinical milestones in Alzheimer disease.

BACKGROUND: Previous studies revealed that cognitive test scores were related to functional outcome in Alzheimer disease (AD). However, the relationship between the rate of cognitive decline at the initial disease phase and the risk of reaching clinical milestones in subsequent years has not yet been examined. OBJECTIVE: To examine whether the rate of cognitive decline predicts the risk of reaching functional milestones in patients with probable AD. DESIGN: A 5-year prospective study was conducted at 3 sites. SETTING: Outpatient research and treatment centers. PARTICIPANTS: Patients diagnosed with probable AD (N = 236; mean age, 73 years; 59% women; mean years of education, 13). MAIN OUTCOME MEASURES: Modified Mini-Mental State Examination (mMMSE) scores were used to assess the rate of cognitive decline over time. Total dependence score and 2 clinical milestones: (1) the need to be dressed, groomed, and washed and (2) receiving a level of care equivalent to a placement in a health-related facility, were derived from the Dependence Scale. RESULTS: General estimating equation analyses revealed that the rate of cognitive decline during the entire follow-up period was positively related to an increase in total dependence scores. Cox analyses showed that a fast rate of decline during the first year was related to an increase in the risk of reaching clinical milestones in subsequent years. Analyses controlled for age, sex, education, and baseline mMMSE scores. CONCLUSION: A fast rate of cognitive decline was associated with increasing risk of reaching clinical milestones in AD.

Activities of Daily Living↗

PubMed2003

Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS.

CONTEXT: Major depression affects about 25% of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers. Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction. OBJECTIVES: To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and to evaluate the effect of depression reduction on activities of daily living, cognition, and nonmood behavioral disturbance. DESIGN: Randomized, placebo-controlled, parallel, 12-week, flexible-dose clinical trial with a 1-week, single-blind placebo phase. The study was conducted between January 1, 1998, and July 19, 2001. SETTING: University outpatient clinic. PARTICIPANTS: Forty-four outpatients who have probable Alzheimer disease and major depressive episodes. INTERVENTION: Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned. MAIN OUTCOME MEASURES: Response rate, Cornell Scale for Depression in Dementia, Hamilton Depression Rating Scale, Mini-Mental State Examination, Psychogeriatric Depression Rating Scale-activities of daily living subscale, and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress. RESULTS: In the sertraline-treated group 9 patients (38%) were full responders and 11 (46%) were partial responders compared with 3 (20%) and 4 (15%), respectively, in the placebo-treated group (P =.007). The sertraline-treated group had greater improvements in the scores for the Cornell Scale for Depression in Dementia (P =.002) and Hamilton Depression Rating Scale (P =.01), and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale (P =.07). There was no difference between the treatment groups in Mini-Mental State Examination (P =.22) or Neuropsychiatric Inventory (P =.32) ratings over time. When full responders, partial responders, and nonresponders were compared, full responders only, or full and partial responders had significantly better ratings on activities of daily living (P =.04), behavioral disturbance (P =.01), and caregiver distress (P =.006), but not on the Mini-Mental State Examination (P =.76). Safety monitoring indicated few differences in adverse effects between the 2 treatment groups. CONCLUSIONS: Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.

Activities of Daily Living↗

PubMed2003

Predictors of neuropathological severity in 100 patients with Huntington's disease.

Subjects were followed in the Longitudinal Core Study of the Baltimore Huntington's Disease Center and given annual neurological, cognitive, and psychiatric examinations. Postmortem neuropathological grade was assigned using the system of Vonsattel and colleagues. We examined the correlations between the neuropathological grade and scores on the Quantified Neurological Examination (QNE) and its chorea and motor impairment subscales, the Mini-Mental State Examination (MMSE), the HD Activities of Daily Living (ADL) Scale, and a number of demographic variables (CAG number, age of onset, age at death, disease duration) in 100 subjects who had been examined within 1,000 days of death. All measures showed significant correlation with Vonsattel score except for chorea. The strongest effect was that of motor impairment score (r(2) = 0.351, p < 0.0001). In a stepwise correlation of clinical variables, motor impairment remained significant. The largest effect for a demographic variable was for age of onset (r(2) = 0.226, p < 0.0001) A partial correlation was significant between CAG number and Vonsattel grade, controlling for age at death or disease duration. Motor impairment appears to be a good clinical measure of neuronal cell loss, at least late in the course of HD and therefore may prove useful in observational and treatment studies.

Activities of Daily Living↗

PubMed2003

Psychopathological features in Alzheimer's disease: course and relationship with cognitive status.

OBJECTIVES: To examine the course, clinical correlates, and relationship between cognitive status and psychopathological features in patients with probable Alzheimer's disease (AD) followed over a 5-year period. DESIGN: Cohort study with follow-up of 5 years. SETTING: Patients were recruited at three sites: 91 patients at Columbia Medical Center, 84 at Johns Hopkins School of Medicine, and 61 at Massachusetts General Hospital. PARTICIPANTS: Patients diagnosed with probable AD (n = 236) enrolled in a longitudinal study (Predictors study). MEASUREMENTS: Wandering/agitation, physical aggression, hallucinations, and delusions were evaluated at 6-month intervals using the Columbia Scale for Psychopathology in Alzheimer's Disease. Descriptive analyses were used to provide estimates of prevalence and course of psychopathological features. General estimating equations determined the odds of having any of the four psychopathological behaviors as a function of cognitive status. Markov analyses provided 6-month transition probabilities for psychopathological behaviors given patients' cognitive status and the presence or absence of such behaviors in the previous evaluation. RESULTS: For wandering/agitation, prevalence (39-57%) and persistence increased as a function of time and decrement in cognitive status. Physical aggression was less prevalent (6-22%) and increased as a function of cognitive decline but tended to persist only in the more severely impaired patients. Delusions (34-49%) reached a peak at the second year and then declined. The odds of delusions were maximal with intermediate decline but remained persistent regardless of cognitive status. Hallucinations, despite some fluctuations, were relatively stable during the follow-up period (8-17%) and moderately persistent. CONCLUSION: Psychopathological features, particularly wandering/agitation and delusions, in AD were common throughout the disease course. The natural history and persistence of the four psychopathological features varied. These findings provide important information to clinicians and caregivers regarding the course, predictability, and possible treatment of psychopathological behaviors in patients with probable AD.

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PubMed2002

Longitudinal assessment of patient dependence in Alzheimer disease.

BACKGROUND: The Dependence Scale measures the amount of assistance patients with dementia require in performing daily activities. Validity and reliability of this scale have been demonstrated, but the progression throughout long periods in patients with Alzheimer disease (AD) has not previously been examined. OBJECTIVE: To determine the longitudinal course of patient dependence in a cohort of prospectively followed AD patients. METHODS: Two hundred thirty AD patients enrolled in the Predictors Study were followed up prospectively at 6-month intervals for an average of 6.5 visits. The Dependence Scale was administered to a caregiver, and patients were assessed with the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale. Dependence level and the additive sum of the Dependence Scale items were considered for analysis. RESULTS: Generalized estimating equations to regression analyses were used to determine that both Dependence Scale scores and dependence level significantly decline with time. By covarying mMMSE scores and self-care deficits factor scores of the Blessed Dementia Rating Scale, generalized estimating equations analysis also demonstrated that change in patient dependence was independent of global cognitive decline and other measures of activities of daily living, respectively. CONCLUSIONS: This study shows the validity of the Dependence Scale and demonstrated that dependency in AD significantly declines with time independent of global cognition and other self-care deficits. The scale is a valuable instrument for outcomes research, efficacy trials, and behavioral research in AD.

Activities of Daily Living↗

PubMed2002

Incidence, prevalence, and outcomes of depression in residents of a long-term care facility with dementia.

BACKGROUND: The course of depression in residents of long-term care with dementia is not well studied. OBJECTIVES: To estimate the incidence, prevalence, and outcomes of depression in long-term care residents with dementia. METHOD: 201 residents of Copper Ridge, a long-term care facility for the memory impaired, were followed every six months during the first year after their admission. RESULTS: On admission 19.9% of the residents had depression, the majority (75%) occurring in persons with a prior history of depression. At six months, only 15% of the original 40 depressed patients were still depressed, while at twelve months only 7.5% were depressed. The incidence of depression at six and twelve months was 1.8% and 6.4% respectively. Most persons with new depression at six months were no longer depressed at one year. The annual attack rate (cumulative likelihood of depression over one year) for the total population was 26.4%. The rates for the subgroup of Alzheimer's were similar to the rates of the total population, except for an annual attack rate of 17.5%, reflecting a lower rate of depression on admission. The decline in depression over the year after admission is noteworthy and likely reflects appropriate diagnosis and treatment of depression. CONCLUSIONS: These results indicate that, over the course of one year, depression afflicts a considerable proportion of long-term care residents with dementia. Admission to a long-term care facility may actually result in a reduction of depression within the year after admission in part due to rapid recognition, appropriate diagnosis and treatment.

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PubMed2002

Neuropsychological manifestations of the genetic mutation for Huntington's disease in presymptomatic individuals.

A triplet repeat (CAG) expansion mutation in the huntingtin gene on chromosome 4 is responsible for Huntington's disease (HD). Presymptomatic genetic testing for this mutation has identified clinically normal persons who are virtually certain to develop this dementing illness if they live a normal lifespan. The present study sought to determine whether these "mutation-positive" persons have impairments in cognitive functioning. Seventy-five mutation-positive persons did not differ from 128 mutation-negative persons on tests selected for their sensitivity to early-stage HD. Interestingly, however, those with the mutation viewed themselves as more likely to develop HD than did those without the mutation. Among mutation-positive subjects, having a longer CAG repeat mutation was likewise not associated with cognitive impairment. However, being closer to estimated disease onset (a product of repeat length and parent's age at onset) was associated with selected cognitive impairments. When viewed in light of previous studies showing atrophy of the caudate nucleus and putamen in mutation-carriers who are close to onset but not those far from onset, these results suggest that subtle changes in brain and behavior may be detected shortly before subjects with the HD mutation develop sufficient signs and symptoms for diagnosis. Conceptual and methodological problems associated with the search for presymptomatic cognitive and behavioral indicators of dementing illness are discussed.

Adult↗

PubMed2002

Testing prospective memory: does the value of a borrowed item help people remember to get it back?

The relationship between the value of an item borrowed from a patient for a prospective memory task and the number of cues required by the patient for requesting its return was analyzed in 63 consecutive patients referred for clinical neuropsychological evaluation. The correlation was negligible (rho = -.001). Number of cues needed was better predicted by score on the Mini-Mental State Exam (r = -.541, p <.001) than by subject's age, sex, or education, or the value of the item taken.

Adult↗

PubMed2002

Neuropsychological functioning and its relationship to antiphospholipid antibodies in patients with systemic lupus erythematosus.

While it is clear that central nervous system (CNS) lesions in systemic lupus erythematosus (SLE) adversely affect cognitive functioning, it is also evident that patients without visible lesions (non-CNS SLE) may also exhibit subtle cognitive impairment. The presence of antiphospholipid antibodies (aPLs) has been proposed as a marker of disease severity and hence should be correlated with neuropsychological dysfunction in this population. The current study compared groups of non-CNS lupus patients who were positive (LA+) or negative (LA-) for aPLs on selected measures of neuropsychological functioning. In addition, we attempted to characterize the pattern of cognitive impairment that is associated with LA status in these patients. No coherent neuropsychological pattern emerged, but LA+ patients performed worse than LA- patients on measures assessing attention, concentration, and visual search, as well as spatial learning and memory.

Adult↗

PubMed2002

Psychopathology in patients with degenerative cerebellar diseases: a comparison to Huntington's disease.

OBJECTIVE: This study estimated the psychiatric morbidity of patients with degenerative cerebellar diseases. METHOD: The study included a series of 31 patients with degenerative cerebellar diseases, compared with 21 patients with Huntington's disease and 29 neurologically healthy comparison subjects. Comprehensive psychiatric evaluations, including the Structured Clinical Interview for DSM-IV and psychopathology rating scales, were administered. RESULTS: The overall rate of noncognitive psychiatric disorders was 77% in the patients with degenerative cerebellar diseases, nearly identical to that in the patients with Huntington's disease (81%) and about double that seen in the neurologically healthy subjects (41%). There were high rates of all mood disorders in both the degenerative cerebellar diseases group (68%) and the Huntington's disease group (43%); the rate in the degenerative cerebellar diseases group was significantly higher than that in the neurologically healthy subjects (31%). The frequency of personality change in the three groups was striking: change was present in 26% of the degenerative cerebellar diseases patients, 48% of the Huntington's disease patients, and none of the neurologically healthy comparison subjects. A total of 19% of the degenerative cerebellar diseases subjects and 71% of the Huntington's disease subjects met DSM-IV criteria for either cognitive disorder or dementia. CONCLUSIONS: The high rate of psychiatric and cognitive disorders in the patients with degenerative cerebellar diseases suggests that many, if not most, patients with degenerative cerebellar diseases may benefit from psychiatric interventions. These results also support previous findings that the cerebellum may have a role in modulating emotion and cognition.

Cerebellar Diseases↗