bluuebunny/crossref_metadata_2025 huggingface dataset:
Hashimoto's Encephalopathy in the Elderly: Relationship to Cognitive Impairment
Authors: Galluzzi Samantha , Geroldi Cristina , Zanetti Orazio , Frisoni Giovanni B.
Published: March 2014

Hashimoto's encephalopathy (HE) is a steroid-responsive encephalopathy associated with high titers of antithyroid antibodies. To date, 57 pediatric-, adult-, and elderly-onset cases have been described in the literature. The clinical picture is pleomorphic, and cognitive impairment is a frequently reported symptom. We report the case of a patient with slowly progressive cognitive impairment possibly caused by HE. The issue of the differential diagnosis with primary dementia is discussed. A review of cases of HE showing cognitive deterioration is also presented, and factors possibly related to characteristics of cognitive impairment and outcome after therapy are considered.
Familial Lewy Body Diseases
Authors: Gwinn-Hardy Katrina , Singleton Amanda Adam
Published: March 2014

Lewy body disease includes clinically and pathologically defined disorders in which Lewy bodies occur in the nervous system. In recent years, the molecular features of these disorders have been emerging. Several genetic loci have been identified in association with familial Lewy body disease; however, the genetic risks underlying most cases of familial Lewy body disease remain to be discovered. The fact that Lewy bodies stain strongly with antibodies to α-synuclein and that mutations in the α-synuclein gene lead to syndromes in which parkinsonism and dementia occur gives us important clues regarding the biologic processes leading to disease. Pursuit of additional mendelian causes of familial Lewy body disease and study of the factors contributing to the complex phenotypes associated with Lewy body disorders will elucidate underlying disease pathways and, thus, possible targets for therapeutic intervention. (J Geriatr Psychiatry Neurol 2002; 15:000–000).
A Two-Year Longitudinal Study of Cognitive Function in Normal Aging and Alzheimer's Disease
Authors: Flicker Charles , Ferris Steven H. , Reisberg Barry
Published: March 2014

A group of 136 elderly subjects were administered a comprehensive neuropsychological test battery, which was readministered 2 years later. Among the 136 elderly subjects, 86 were assigned a diagnosis of probable Alzheimer's disease. An additional 33 young subjects were administered the assessment battery at baseline only. The normal elderly group exhibited no decline in cognitive test performance over the 2-year follow-up interval. Subjects with mild cognitive impairment, however, were as likely to deteriorate between baseline and follow-up as the more severely impaired subjects. The tests that exhibited longitudinal decline in the Alzheimer's disease patients constituted a subset of the tests that revealed cross-sectional deficits relative to the normal elderly. Differences in baseline cognitive test performance and in rate of cognitive deterioration were examined in relatively young versus relatively old Alzheimer's disease patients. Potential psychometric predictors of cognitive decline in the normal elderly were identified.
Evaluation of Multiple Doses of Milacemide in the Treatment of Senile Dementia of the Alzheimer's Type
Authors: Cutler Neal R. , Fakouhi T. Daniel , Smith Ward T. , Hendrie Hugh C. , Matsuo Fumisuke , Sramek John J. , Herting Robert L.
Published: March 2014

A multicenter, double-blind, placebo-controlled, parallel group study was conducted to assess the safety and efficacy of three doses of milacemide in the treatment of patients with senile dementia of the Alzheimer type of mild to moderate severity. Patients were randomly assigned to receive one of three dosages of milacemide (400, 800, or 1200 mg/day) or placebo for 4 weeks followed by a single-blind 4-week placebo period. One hundred forty-eight men and women older than 50 years of age were enrolled, and 129 patients completed the study. The differences among treatment groups were not statistically different with respect to total scores on the Alzheimer's Disease Assessment Scale or any items and subscales that were examined, nor were significant differences on the Clinical Global Impression Scale found. Clinically significant increases in liver function tests, specifically aspartate aminotransferase and alanine aminotransferase (AST and ALT), were reported for five of the patients receiving milacemide, requiring their withdrawal from the study.
Motoric Sensitization and Levodopa Accumulation After Chronic Levodopa Treatment in an Animal Model of Parkinson's Disease
Authors: Carey Robert J.
Published: March 2014

One month after rats were subjected to unilateral injections of either 6-hydroxydopamine (6-OHDA) or vehicle into the midbrain tegmentum, they were given daily injections of either saline or levodopa (10 mg/kg and 1 mg/kg carbidopa) for 30 days. On the first and last day of treatment the spontaneous behavior of the rats was evaluated with a video image analysis system that detected directional movement asymmetries. Although vehicle-injected rats exhibited very little movement asymmetry, the 6-OHDA rats were strongly asymmetric. On day 1, both saline and levodopa-treated 6-OHDA rats exhibited rotational movement directed toward the dopamine-deficient hemisphere. On day 30 of treatment, however, the chronic levodopa group displayed a complete reversal and exaggeration of the rotational bias, and all asymmetric movement was directed toward the dopamine-intact hemisphere. Thus chronic levodopa treatment shifted behavioral dominance from the intact to the dopamine-denervated hemisphere. Subsequent biochemical measurement of dopamine and levodopa in striatal and limbic tissue samples indicated that chronic levodopa treatment did not alter dopamine tissue concentrations but did substantially increase levodopa concentrations, both in the dopamine-denervated striatum and in limbic tissue. This increased levodopa loading in brain with chronic levodopa treatment occurring in 6-OHDA rats but not in vehicle-injected rats that were given the same levodopa regimen. This selectivity in the effect of chronic levodopa treatment to the 6-OHDA rats appeared to rule out the possibility of peripheral metabolic factors for the levodopa accumulation. It is suggested that chronic levodopa stimulation of dopamine-denervated tissue can produce significant metabolic changes in brain uric acid and that these effects affect brain metabolism of levodopa.
Aluminum Induces Neurite Elongation and Sprouting in Cultured Hippocampal Neurons
Authors: Uemura Etsuro , Lartius Raj K. , Martens Catherine
Published: March 2014

It has been reported that the aluminum content in the human brain increases with age, and it is particularly high in those with Alzheimer's disease. In this study, we found that a low aluminum concentration (100 μmol/L) in the culture media of opossum hippocampal neurons can induce extensive neurite outgrowth (ie, elongation and branching of neurites) and sprouting (ie, outgrowth of filiform processes from neurite varicosities) within 48 hours. Such changes in neurite morphology were remarkably similar to those described in the aged or Alzheimer's disease brain. Neurites that responded to aluminum varied greatly in length, thickness, and branching pattern. Many neurites appeared to have no clear directional growth pattern because they frequently changed their course and formed a meshwork of neurites with others originating from the same cell body. Sprouting neurites varied in length, thickness, and branching pattern, but they always originated from a globular enlargement of neurites along the neurite shaft or at the terminal end. Such growth pattern and extensive sprouting of neurites did not fit the growth pattern displayed by the control neurons. Our findings suggest that aluminum may be involved in the neuronal remodeling characteristic of aging and Alzheimer's disease.
Factor Structure and Reliability of the Alzheimer's Disease Assessment Scale in a Multicenter Trial With Linopirdine
Authors: Kim Yong S. , Nibbelink Donald W. , Overall John E.
Published: March 2014

The Alzheimer's Disease Assessment Scale (ADAS) has assumed a primary role in assessment of treatment responses in large-scale multicenter trials of drugs being evaluated for treatment of dementia in elderly patients. Data from 280 patients with Alzheimer's disease were analyzed to evaluate factor structure and reliability. Results confirm the presence of three primary factors interpreted as mental status, verbal fluency, and praxis. The presence of a large general factor underlying those more specific dimensions also supports the utility of the composite ADAS cognitive score that has been used as a primary outcome measure in previous drug trials. Test-retest reliability of the factor scores were calculated to be 0.83, 0.78, and 0.87. Test-retest reliability of the composite ADAS cognitive score was 0.90. Statistics useful for estimation of sample sizes for future multicenter trials are provided.
Neurologic Diseases Presenting With Gait Impairment in the Elderly
Authors: Fuh Jong-Ling , Lin Ker-Neng , Wang Shuu-Jiun , Ju Tsyi-Huey , Chang Ray , Liu Hsiu-Chih
Published: March 2014

We conducted a prospective study to evaluate the underlying diseases and their frequencies in 50 consecutive patients older than 50 years of age admitted to our neurologic service because of walking difficulty. The diseases identified in our study were as follows: multiple cerebral infarcts, 24%; myelopathy, 22%; parkinsonism, 12%; cerebellar degeneration, 8%; other diseases, 24%; and unknown etiology, 10%. Potentially treatable causes of gait impairment were found in nearly one third of patients.
Hyper-and Hyponatremia among Geropsychiatric Inpatients
Authors: Vieweg Victor , Lombana Al , Lewis Robert
Published: March 2014

We report our experience treating 14 elderly psychiatric patients with altered sodium states. Hypernatremia occurs more commonly among elderly psychiatric patients than among their younger counterparts, and elderly hypernatremic psychiatric patients suffer most commonly from dementia. Dilutional hyponatremia is less common and less severe among elderly schizophrenic patients compared with younger patients with schizophrenia. Central nervous system changes induced by altered sodium states among elderly psychiatric patients are sufficiently similar whether hyper- or hyponatremia is present; therefore, the clinician must not wait for specific features to develop, but must quickly measure serum sodium concentration in elderly psychiatric patients with altered mental states. Treatment of hypernatremia involves rehydration with normal saline or hypotonic solutions, and treatment of dilutional hyponatremia largely involves fluid restriction.
Seizures in Alzheimer's Disease: Clinicopathologic Study
Authors: Mendez Mario F. , Catanzaro Peter , Doss Robert C. , Arguello Raul , Frey William H.
Published: March 2014

New-onset epileptic seizures occur in patients with Alzheimer's disease (AD), but the nature and underlying reasons for these seizures are unclear. We identified new-onset, nonsymptomatic seizures in 77 (17%) of 446 patients with uncomplicated, definite AD on autopsy. Among these seizure patients, 69 had generalized tonic-clonic seizures, and 55 had less than three total seizures. The seizure patients had a younger age of dementia onset than did the remaining AD patients; however, at seizure onset, they averaged 6.8 years into their AD and had advanced dementia. When further compared to 77 AD controls, matched for age of onset and duration, the seizure patients did not differ on medical illnesses, amount of medications, and degree of focal neuropathology. We conclude that a few unprovoked generalized seizures frequently occur late in the course of AD, and that AD patients with a younger age of dementia onset are particularly susceptible to seizures.
Anticholinergic Effects in a Depressed Parkinsonian Patient
Authors: Huszonek John J.
Published: March 2014

Depression is commonly associated with idiopathic Parkinson's disease. Various antidepressants can be helpful in the treatment of this type of depression. Anticholinergic medications are at times used for treating the motor symptoms of parkinsonism. While some authors have reported euphorigenic effects from anticholinergics in other groups of patients, generally, they have not been used in the treatment of depression, with or without parkinsonism. In the case presented, a depressed patient with Parkinson's disease on levodopa/carbidopa and fluoxetine was given benztropine for his motor symptoms. The result was some improvement in his motor symptoms and a wide, dose-related spectrum of other central nervous system changes ranging from delirium to mania, hypomania, and euthymia from a “baseline” of residual depression. At a very low dose (0.25 mg per day), benztropine appeared to have an augmenting antidepressant effect that rendered the patient euthymic.
Disruptive Nocturnal Behavior in Parkinson's Disease and Alzheimer's Disease
Authors: Bliwise Donald L. , Watts Ray L. , Watts Nancy , Rye David B. , Irbe Dainis , Hughes Morgen
Published: March 2014

Disruptive nocturnal behavior, often referred to as sundowning, is a commonly encountered clinical problem in most forms of dementia. This study compared disruptive nocturnal behavior in patients with Alzheimer's disease (AD) and Parkinson's disease (PD). Questionnaire data were collected from 60 AD and 48 PD caregivers. Respondents were asked to record the typical time of day when any of seven disruptive behaviors were evidenced in their patients, if at all. Two scores were computed: (1) a sundowning score (number of nocturnal disruptive behaviors, range 0–7), and (2) a total score (number of disruptive behaviors without regard to time, range 0–7). Results indicated PD patients were more likely than AD patients to exhibit disruptive nocturnal behavior. The dose, timing, or number of years on antiparkinsonian medication were not related to nocturnal disruptive behavior within the PD patient group. These findings raise the possibility that sundowning in PD patients may be a manifestation of dopaminergic depletion within the basal ganglia or other abnormalities involving the cholinergic, serotoninergic and/or noradrenergic systems in the brainstem.
Study of Alzheimer's Dementia Patients with Parkinsonian Features
Authors: Snowden Mark B. , Bowen James D. , Hughes James , Larson Eric B.
Published: March 2014

This paper presents a study to test the hypothesis that a parkinsonian subtype of Alzheimer's disease exists. Twenty-one patients with dementia of the Alzheimer's type (DAT) and coexistent parkinsonian features were matched to 21 DAT control patients without parkinsonian signs. All subjects were drawn from 136 patients with DAT evaluated between 1980 and 1982. Items from a standardized clinical evaluation at the time of diagnosis, from continuous yearly follow-ups, and neuropathologic examination were compared to determine if qualitative differences exist between the two groups. Those with parkinsonian features had significantly shorter duration of symptoms prior to presentation, a trend toward more reports of decreased self-care, and more primitive reflexes on physical examination. While the total Folstein Mini-Mental State Exam (MMSE) scores at presentation were not significantly different, the cases showed greater impairment in language and registration subitems. During follow-up, no differences were observed in performance on MMSE and Dementia Rating Scale scores. Survival curves showed a trend toward poorer survival in the cases. Neuropathologic data were obtained on seven patients with both DAT and parkinsonian features and showed three cases with Alzheimer's disease (AD) alone and four with AD and Parkinson's disease. Four of the DAT control patients were examined neuropathologically, and all had AD without evidence of Parkinson's disease. The results provide preliminary evidence that Alzheimer's patients with parkinsonian signs are a subtype characterized by distinct neurologic signs and a more rapid course.
Safety and Efficacy of Caffeine-Augmented ECT in Elderly Depressives: A Retrospective Study
Authors: Kelsey Mark C. , Grossberg George T.
Published: March 2014

Prior studies have shown that in younger depressives undergoing ECT whose seizure durations declined despite maximum settings on three different ECT devices, pretreatment with caffeine lengthened seizures and resulted in clinical improvement. Caffeine (half life, 140-270 minutes) was well tolerated even in patients with pre-existing cardiovascular disease. The purpose of this retrospective study was to determine the safety and efficacy of caffeine augmented ECT in elderly depressed patients. The charts of 14 elderly depressives (average age 75.6, range 59-83; 2 males, 12 females) who received caffeine-augmented ECT were reviewed. Patients pre- and post-ECT medications, blood pressure, pulse, and seizure times (cuff and EEG) for each ECT performed were noted. The following conclusions were drawn from our study: (1) Caffeine definitely increases the seizure length and was useful in our setting when the energy settings could not be increased anymore. (2) Caffeine augmentation inconsistently causes an increase in pulse rate, on average, in the elderly. (3) Caffeine inconsistently produces an increase in mean arterial pressure. (4) Caffeine did not consistently produce an increase in the maximum rate-pressure product. We conclude from this study that caffeine-augmented ECT is safe and effective in increasing seizure duration in the elderly. However, more research needs to be done to determine optimal dosing and tolerability.
Comparison of TCAs and SSRIs in the Treatment of Major Depression in Hospitalized Geriatric Patients
Authors: Miller Frank T. , Freilicher Judith
Published: March 2014

This study compares a cohort of hospitalized geriatric patients with major depression, treated with tricyclic antidepressants (TCAs), with a cohort of patients treated with selective serotonin reuptake inhibitors (SSRIs). The groups were compared on demographic, treatment, and outcome variables. Demographically, the groups were similar and did not differ on measures of outcome or risk for side effects. We conclude that SSRIs are equal to TCAs in the treatment of major depression in hospitalized geriatric patients.
ERP Indices and Neuropsychological Performance as Predictors of Functional Outcome in Dementia
Authors: Cohen Ronald A. , O'Donnell Brian R , Meadows Mary-Ellen , Moonis Majaz , Stone William F. , Drachman David A.
Published: March 2014

We compared the relative value of neuropsychological and event-related potentials (ERPs) obtained during both passive and active auditory oddball paradigm measures for determining functional outcome in dementia 4 years following initial assessment. Functional outcome was assessed by structured interview of family members of 29 patients with dementia, and patients' functional status was rated in seven areas: mortality, incontinence, institutionalization, ADL dependence, verbal responsiveness, recognition of family members, and capacity for social interaction. A total functional outcome score (ADLTOTAL) was obtained by summing across these individual outcome measures. Many of the neuropsychological measures correlated strongly with overall functional outcome, whereas P3 amplitude and latency on the active ERP condition were the only ERP indices to predict functional outcome. When ERP and neuropsychological measures were considered simultaneously using stepwise multiple regression analyses, the neuropsychological measures were better predictors of most functional outcomes, although P3 latency was the best predictor of mortality. However, neuropsychological performance and ERPs appear to be sensitive to different functional outcomes. Therefore, evaluation of both ERPs and neuropsychological performance may ultimately have prognostic utility in the assessment of patients with dementia.
Tolerability of Divalproex Sodium in Elderly Psychiatric Patients with Mixed Diagnoses
Authors: Puryear Lucy J. , Kunik Mark E. , Workman Richard
Published: March 2014

This study addresses the tolerability of divalproex sodium in elderly psychiatric inpatients with various Axis I diagnoses, using structured assessments. A chart review for a 7-month period on a geropsychiatry inpatient unit identified 13 patients who had been treated with divalproex sodium. All 13 patients received standardized ratings on the Cohen-Mansfield Agitation Inventory (CMAI), Brief Psychiatric Rating Scale (BPRS), Rating Scale for Side Effects (RSSE), and Mini-Mental State Examination (MMSE) on admission and discharge, which were compared using paired f-tests for 12 of the 13 patients. The thirteenth patient was withdrawn from valproate prior to discharge after developing a delirium thought to be secondary to a divalproex-phenytoin interaction. All of the remaining 12 patients tolerated divalproex sodium well with no significant change in MMSE scores ( P = .486), CMAI scores ( P = .0546), or RSSE scores ( P = .124). The change in BPRS score was found to be significant ( P = .004). Based on the present study and previously reported case series, divalproex sodium appears to be well tolerated in an elderly psychiatric population.
Rate of Progression in Familial Alzheimer's Disease
Authors: Swearer Joan M. , O'Donnell Brian F. , Ingram Susan M. , Drachman David A.
Published: March 2014

The clinical course of early-onset, dominantly inherited, familial Alzheimer's disease (FAD) was contrasted with late-onset, sporadic Alzheimer's disease (AD). Eight FAD and 23 sporadic AD patients were followed over a mean of 63 months from estimated disease onset. The two groups did not differ notably in duration of symptoms from onset, global disease severity, or degree of cognitive deficits on initial evaluation. The Kaplan-Meier lifetable method was used to assess time from estimated disease onset to dependence in self-care, institutionalization, and death. A greater percentage of FAD patients became dependent in self-care and died earlier than did sporadic AD patients. The lifetable results suggest that FAD may have a more rapid course than does late-onset sporadic AD.
Late-Onset Huntington's Disease: A Geriatric Psychiatry Perspective
Authors: Shulman Kenneth I. , Lennox Anne , Karlinsky Harry
Published: March 2014

Late-onset Huntington's disease is more common than has been generally appreciated and is associated with a wide range of psychiatric symptoms and syndromes. Geriatric psychiatrists have an important role to play in establishing the diagnosis and providing guidance to elderly patients and their families as they struggle with difficult management decisions. An illustrative case report and selective literature review are presented that highlight the genetic and clinical aspects of the condition.
Psychiatric Illnesses in the Elderly: A Review
Authors: Jenike Michall A.
Published: March 2014

Neuropsychiatric disorders in the elderly, such as dementia, depression, anxiety, and psychosis, may occur alone or in combination with neurologic or medical illness. Geriatricians must be familiar not only with diagnostic issues but also with treatment options and medication-induced alterations in mental status.
Management of the Prescription-Drug-Dependent Adult: Case of Meprobamate Abuse and Its Treatment
Authors: Gonzales Junius J. , Emmerich Anne D. , Rauch Scott L. , Stern Theodore A.
Published: March 2014

Misuse of prescription drugs in the elderly can be a serious problem that is difficult to manage. Prescriptions for non-narcotic central nervous system (CNS) depressants (e.g., anxiolytics and sedative-hypnotics) are commonly written, and their use is associated with severe intoxication and withdrawal effects. The presence of comorbid psychiatric conditions (e.g., depression or panic disorder), for which these agents are prescribed frequently, complicates the clinical picture. This paper, using case examples of meprobamate abuse, describes how physicians can recognize, manage, and treat a patient who is abusing a non-narcotic CNS depressant.
Failure to Record Delirium as a Complication of Intra-aortic Balloon Pump Treatment: A Retrospective Study
Authors: Glick Rachel E. Lipson , Sanders Kathy M. , Stern Theodore A.
Published: March 2014

This study was conducted to determine whether or not diagnosis and treatment of delirium among patients treated with the intra-aortic balloon pump (IABP) correlates with the recording of this complication on discharge records. Since prior episodes of delirium are one of the few clear risk factors for future episodes of delirium, accurate recording of delirium on the discharge summary and list of discharge diagnoses is useful to clinicians. A retrospective review of the charts of all patients (N = 198) who underwent placement of an IABP during 1988; assessment of the type and frequency of medical and neuropsychiatric complications during IABP treatment; and comparison of chart review findings with the Massachusetts General Hospital's computer-generated lists of discharge diagnoses for the same IABP-treated patients was completed. Only 12% of patients diagnosed and treated for delirium had delirium recorded as a discharge diagnosis. In contrast, 44% and 52% of patients who had been diagnosed and treated for cerebrovascular accident and pneumonia, respectively, had these diagnoses recorded among the discharge diagnoses. Receiving a discharge diagnosis of organic brain syndrome increased the likelihood that delirium was recorded as a discharge diagnosis. Delirium is underdiagnosed as a complication associated with IABP-treatment and is under-reported on the list of discharge diagnoses, even when it is diagnosed. Further study is warranted to determine if making the diagnosis of delirium during a patient's hospital course and recording it's a complication at the time of discharge is translated into a higher level of preparedness by physicians during subsequent hospitalizations.
The Cognitive Assessment Screening Test (CAST) for Dementia
Authors: Drachman David A. , Swearer Joan M. , Kane Kevin , Osgood Diane , O'Toole Colleen , Moonis Majaz
Published: March 2014

The purpose of this study was to assess the usefulness, the sensitivity, and the specificity of the Cognitive Assessment Screening Test (CAST), a paper-and-pencil self-administered cognitive test designed to screen elderly people for possible dementia, for use in general physicians' offices, requiring little expertise or staff time. CAST consists of three parts: part A (relatively easy), part B (more demanding), and part C (self-report of concerns). CAST was administered in two studies to: (1) 19 patients known to be mildly to moderately demented versus 24 age-matched normal controls (to establish cutoff standards); and (2) a “real world” sample of 26 elderly patients not known to be demented, attending a general medicine clinic. The sensitivity and specificity of CAST were compared with the Mini-Mental State Examination (MMSE) and the Blessed Dementia Scale cognitive portion (BDS-cog). In study 1, controls were given a detailed neuropsychological battery; in study 2, all patients were given the neuropsychological battery, which served as the “gold standard” to identify individuals with cognitive impairment. In study 1, the cutoff scores for dementia using CAST (Parts A and B) were established. CAST discriminated demented patients from controls with a sensitivity of 95% and a specificity of 88%; the MMSE had a sensitivity of 74% and a specificity of 100%; and the BDS-cog had a sensitivity of 100% and a specificity of 96%. In study 2, CAST discriminated cognitive impairment with a sensitivity of 88% and a specificity of 100%, the MMSE had a sensitivity of 38% and a specificity of 100%; and the BDS-cog had a sensitivity of 50% and a specificity of 94%. Part C was not used to discriminate demented from normal elderly individuals, but to screen for those concerned about their cognitive functioning. CAST is highly useful as a dementia screening test, with sensitivity and specificity equal to or better than the MMSE and BDS-cog, yet requiring minimal examiner time and little training or experience to administer.
Interfamilial and Intrafamilial Phenotypic Heterogeneity in Familial Alzheimer's Disease
Authors: Lopez-Alberola Robert F. , Barker Warren W. , Harwood Dylan G. , Loewenstein David A. , George-Hyslop Peter H. St. , Tsuda Takehide , Rogaeva Evgeny A. , Duara Ranjan
Published: March 2014

The features of Alzheimer's disease (AD) are very heterogenous, and some component of the variability of AD is likely to be related to genetic factors. To investigate this question, we evaluated 19 clinical neuropsychiatric and brain imaging features in 32 familial Alzheimer's disease (FAD) kindred, primarily of late onset. Within families, patients displayed a high degree of phenotypic heterogeneity (PH), which occurred irrespective of gender, ethnicity, or apolipoprotein E genotype. Overall, an equivalent amount of PH was observed in both the between- (37%) and within-family (31%) groups. However, for onset age and rate of decline between families, there was greater PH than within families ( P = .002 and P = .01, respectively). A similar trend was found for severity of cortical atrophy ( P = .05). These observations suggest a weak genetic influence, and possibly strong nongenetic influences, on the degree of phenotypic heterogeneity in late-onset FAD. In early-onset AD kindred, a much smaller degree of phenotypic heterogeneity may be expected within families, because genetic influences in phenotypic expression tend to be more prominent in early-onset cases.
Neurodegeneration, Sleep, and Cerebral Energy Metabolism: A Testable Hypothesis
Authors: Mamelak Mortimer
Published: March 2014

Varying degrees of metabolic arrest are used by many living species to survive in a harsh environment. For example, in hibernating mammals, neuronal activity and cerebral metabolism are profoundly depressed in most regions of the brain and limited energy resources are deployed to maintain vital cell functions. Gathering evidence suggests that energy resources are also limited in both Alzheimer's and Parkinson's diseases, and that this promotes metabolic stress and the degenerative process. Key steps in this process are energy requiring, and this further compromises cell energy reserves. It may be possible to slow the progress of these diseases by inducing slow-wave sleep (SWS) at night with gammahydroxybutyrate. Patients with these diseases sleep poorly and generate little SWS. SWS and hibernation are thought to be on a continuum of energy conservation. Thus, the induction of SWS may retard the degenerative process by depressing cell metabolism and by directing energy utilization to vital cell functions. In this way, GHB-induced SWS may duplicate the effects of hibernation and extend biologic time.
Use of Clozapine to Treat Levodopa-Induced Psychosis in Parkinson's Disease: Retrospective Review
Authors: Widman Lawrence P. , Burke William J. , Pfeiffer Ronald F. , McArthur-Campbell Delores
Published: March 2014

Levodopa-induced psychosis can complicate the treatment of Parkinson's disease (PD). In this retrospective, uncontrolled report, we describe our experience treating PD-related psychosis with clozapine, emphasizing those patients treated for longer than 1 year. Twenty-seven patients were treated, 14 for longer than 1 year. Most patients showed a rapid improvement from baseline within 1 month using the Clinical Global Impression and Global Psychosis Rating Scores. Five patients discontinued the drug due to side effects, but only two patients reported side effects after 6 months of treatment. Clozapine appears to be effective in treating PD related psychotic symptoms while not interfering with motor function.
Behavioral Phenomenology in Alzheimer's Disease, Frontotemporal Dementia, and Late-Life Depression: A Retrospective Analysis
Authors: Swartz J. Randolph , Miller Bruce L. , Lesser Ira M. , Booth Ruth , Darby Amy , Wohl Marcy , Benson D. Frank
Published: March 2014

Often patients in the early stages of Alzheimer's disease (AD), frontotemporal dementia (FTD), and late-life depression can be difficult to differentiate clinically. Although subtle cognitive distinctions exist between these disorders, noncognitive behavioral phenomenology may provide additional discriminating power. In 19 subjects with AD, 19 with FTD, 16 with late-life psychotic depression (LLPD), and 19 with late-life nonpsychotic depression (LLNPD), noncognitive behavioral symptoms were quantified retrospectively using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and compared using both a one-way ANOVA and a multivariate stepwise discriminant analysis, which utilized a jackknife procedure. The FTD group showed the highest mean total SCAN score, while the AD group showed the lowest. ANOVA showed significant differences in the mean total SCAN scores between the four diagnostic groups ( P < .0001). With the discriminant analysis, the four disorders demonstrated different clusters of behavioral abnormalities and were differentiated by these symptoms ( P < .0001). A subset of 14 SCAN item group symptoms was identified that collectively classified correctly the following percentages of subjects in each diagnostic category: AD 94.7%, FTD 100%, LLPD 87.5%, and LLNPD 100%. These results indicate that AD, FTD, LLPD, and LLNPD were distinguished retrospectively by the SCAN without using cognitive data. Better definition of the longitudinal course of noncognitive behavioral symptoms in different dementias and psychiatric disorders will be valuable both for diagnosis and to help define behavioral syndromes that are associated with selective neuroanatomic and neurochemical brain pathology.
Alois Alzheimer (1864–1915)—Student Days and First Scientific Activities
Authors: Kircher Tilo , Wormstall Henning
Published: March 2014

This article gives an overview of Alois Alzheimer's years as a medical student, his most influential teachers, and the origin of his interest in (neuro)histopathology. The neuron theory discussions of that time are reviewed briefly.
Huntington Disease: Clinical, Genetic, and Social Aspects
Authors: Nance Martha A.
Published: March 2014

Huntington disease (HD) is a fascinating neurodegenerative disorder whose features straddle the boundaries of psychiatry, neurology, and genetics. The clinical symptoms of HD consist of a triad of motor, cognitive, and psychiatric/behavioral disturbances. In 1993, the HD Collaborative Research Group identified the gene and the mutation responsible for HD. HD was one of the first neurodegenerative disorders discovered to be caused by a novel mutational mechanism known as trinucleotide repeat expansion. Since then, HD has been the model for autosomal dominant neurogenetic disorders. The clinical, pathological, and genetic aspects of the disease are reviewed and some of the questions that remain to be answered by researchers of the 21st century are outlined.
Clinical and Genetic Aspects of Progressive Supranuclear Palsy
Authors: Litvan Irene , Hutton Michael
Published: March 2014

Progressive supranuclear palsy (PSP) is, after Parkinson's disease, the most common form of degenerative parkinsonism. Several clinical features are used in the recognition of this disorder as well as in the differentiation from related disorders. Clinical criteria that could increase diagnostic accuracy in research studies are also emphasized. Due to a better understanding of the genetic aspects of PSP, recent studies have suggested that it is a recessive disorder in linkage disequilibrium with the tau (τ) gene, rather than a sporadic disorder. In addition, the recent identification of mutations in the τ gene associated with a similar neurodegenerative condition (frontotemporal dementia and parkinsonism linked to chromosome 17) has further strengthened the argument that τ dysfunction is somehow involved in the pathogenesis of PSP. Nongenetic factors that could trigger or perpetuate the cascade of events leading to neuronal degeneration in PSP are also reviewed.
Pathophysiology of Delirium
Authors: van der Mast Rose C.
Published: March 2014

Hypotheses about the pathophysiology of delirium are speculative and largely based on animal research. According to the neurotransmitter hypothesis, decreased oxidative metabolism in the brain causes cerebral dysfunction due to abnormalities of various neurotransmitter systems. Reduced cholinergic function, excess release of dopamine, norepinephrine, and glutamate, and both decreased and increased serotonergic and γ-aminobutyric acid activity may underlie the different symptoms and clinical presentations of delirium. According to the inflammatory hypothesis, increased cerebral secretion of cytokines due to a wide range of physically stressful events plays an important role in the occurrence of delirium. Since cytokines can influence the activity of various neurotransmitter systems, these mechanisms may interact. Also, more fundamental processes like intraneuronal signal transduction, second messenger systems that at the same time use neurotransmitters as first messengers and play an important role in their synthesis and release, may be disturbed. Furthermore, severe illness and physiologic stress may give rise to modification of blood-brain barrier permeability, the sick euthyroid syndrome with abnormalities of thyroid hormone concentrations, and increased activity of the hypothalamic-pituitary-adrenal axis. These circumstances possibly also contribute to changes in neurotransmitter synthesis and release of cytokines in the brain, and consequently to the occurrence of delirium. Elderly patients are more at risk for developing delirium, very likely due to age-related cerebral changes in stress-regulating neurotransmitter and intracellular signal transduction systems. This paper will expand upon these current theories and discuss their applicability to research and clinical work with elderly patients suffering from delirium.
Complementary and Alternative Medicines for Alzheimer's Disease
Authors: Ott Brian R. , Owens Norma J.
Published: March 2014

The recent successes of large, multicenter clinical trials of acetylcholinesterase inhibitors for symptomatic treatment of Alzheimer's disease have spawned enthusiasm that this common and fatal neurologic disease is “treatable.” A parallel explosion has occurred in the consumption of alternative medicines by the public seeking more effective, natural, or safer methods for treatment of dementia. Some of these medicines may, in fact, be biologically active in modulating the disease as well as producing side effects and interactions with accepted pharmaceuticals. This review brings to focus the scientific evidence presently available regarding such agents.
Depression and Dementia: Comorbidities, Identification, and Treatment
Authors: Meyers Barnett S.
Published: March 2014

Depression is a highly prevalent concomitant of dementia. Concurrent depression (DD) can meet full criteria for a disorder or take the form of a depressive syndrome. Although phenomenologic overlap can confound diagnosis, careful assessment demonstrates that a true depressive component is present in a substantial percentage of dementia cases. DD has been associated with excess disability, increased caregiver burden, and greater mortality. Efficacy studies have demonstrated high placebo response rates, indicating transience of many depressive symptoms, and adverse cognitive effects of older antidepressants. Studies demonstrating that new antidepressants can be efficacious and improve cognitive functioning are reviewed.
Asymmetric ground effects of a tailless unmanned aerial vehicle model
Authors: Yang Muqing , Ma Dongli
Published: March 2014

Ground effect is asymmetric when an unmanned aerial vehicle takes off by using the catapult nearest to the edge of the deck from a carrier, because a large part of the wing is out of the deck. Asymmetric ground effect would induce rolling and yawing moments, which are critical factors affecting the safety of takeoff operations. In this research, focus was on asymmetric ground effect, especially on the lateral and directional aerodynamic characteristics. Effects of height, velocity, and wind over deck were studied. Computational fluid dynamics method was used and validated by comparing it with the experimental data presented in early reports. Height is the most important factor that influences lift, rolling moment, and yawing moment. Lateral and directional stabilities are weakened by reducing height. Lateral stability decreased 2.8% and 5.6% as the height was reduced from 1.5 m to 1.2 m and to 1.0 m, respectively. By increasing velocity, lift is increased significantly, while yawing moment is little influenced. Magnitudes of both lift and rolling moment are amplified slightly with the increase of wind over deck. When wind over deck varied from 0 m/s to 15 m/s, lift and rolling moment varied only within 1% and 3.4%, respectively, and thus the effect of wind over deck is secondary.
Restoring Walking after Spinal Cord Injury
Authors: Thompson Aiko K. , Wolpaw Jonathan R.
Published: March 2014

People with incomplete spinal cord injury (SCI) frequently suffer motor disabilities due to spasticity and poor muscle control, even after conventional therapy. Abnormal spinal reflex activity often contributes to these problems. Operant conditioning of spinal reflexes, which can target plasticity to specific reflex pathways, can enhance recovery. In rats in which a right lateral column lesion had weakened right stance and produced an asymmetrical gait, up-conditioning of the right soleus H-reflex, which increased muscle spindle afferent excitation of soleus, strengthened right stance and eliminated the asymmetry. In people with hyperreflexia due to incomplete SCI, down-conditioning of the soleus H-reflex improved walking speed and symmetry. Furthermore, modulation of electromyographic activity during walking improved bilaterally, indicating that a protocol that targets plasticity to a specific pathway can trigger widespread plasticity that improves recovery far beyond that attributable to the change in the targeted pathway. These improvements were apparent to people in their daily lives. They reported walking faster and farther, and noted less spasticity and better balance. Operant conditioning protocols could be developed to modify other spinal reflexes or corticospinal connections; and could be combined with other therapies to enhance recovery in people with SCI or other neuromuscular disorders.
Diagnostic Utility of the Pediatric Attention Disorders Diagnostic Screener
Authors: Newman Erik , Reddy Linda A.
Published: March 2014

Objective: The Pediatric Attention Disorders Diagnostic Screener (PADDS) is an evidence-based screener of attention and executive functioning that combines computer-based Target Tests of Executive Function (TTEFs; Target Recognition, Target Sequencing, and Target Tracking) with parent and teacher behavioral reports to efficiently screen children ages 6 to 12 for ADHD. The present study is the first to examine the utility of the TTEFs in predicting ADHD status. Method: The PADDS TTEFs were administered to 76 children (age = 6-12) with ADHD and 76 matched controls. Logistic regression and diagnostic efficiency statistics were used to evaluate the ability of the three TTEFs to predicted ADHD status. Results: All three TTEFs significantly discriminated ADHD participants from controls, but each had a different diagnostic efficiency profile. Classification accuracy was improved when results of all three TTEFs were combined. Conclusion: The PADDS is a promising tool for quickly and reliably screening for ADHD in clinic and school settings.
Male sexual function and pelvic floor surgery of their female partner: A one-year follow-up study
Authors: Lonnée-Hoffmann Risa AM , Salvesen Øyvind , Mørkved Siv , Schei Berit
Published: March 2014

Objective

The aim of this study was to examine if sexual function of male partners changed after surgery for pelvic floor disorders and to explore associated factors.

Study design

This was an observational follow-up study at the Gynecological Department at the St Olavs University Hospital, Trondheim. The sample consisted of 35 male partners of women scheduled for pelvic organ prolapse or stress urinary incontinence surgery. Self-administered questionnaires, containing validated instruments as well as exploratory questions, were sent to women and their partners before and one year after pelvic floor surgery. Vaginal dimensions were measured in all women according to the Pelvic Organ Prolapse Quantification System, both before and after the surgery.

Main outcome measures

The Brief Sexual Function Instrument and the presence of erectile dysfunction.

Results

One year after pelvic floor surgery, scores for sexual drive, erection and overall satisfaction from the Brief Sexual Function Instrument were unchanged; the ejaculation score (range 0–4) had mildly improved from a range of 4 (median 4) to a range of 3.5 (median 4), ( p = 0.014). The proportion of men with erectile dysfunction was unchanged, while the proportion of men reporting vaginal wind had significantly decreased ( p = 0.016). None of the baseline factors, subjective experiences or vaginal dimensions at baseline or follow-up were associated with the improved ejaculation score; only a reduction in the proportion of men reporting their partners with dyspareunia (ns) was significantly correlated (Spearman’s rho 0.42, p = 0.019).

Conclusion

Sexual function of male partners was unchanged or mildly improved after pelvic floor surgery.
On the oscillation of solutions for a class of second-order nonlinear stochastic difference equations
Authors: Yu Zheng , Zhu Enwen , Zeng Junshan
Published: March 2014

In this paper, we investigate the asymptotical behavior for a partial sum sequence of independent random variables, and we derive a law of the iterated logarithm type. It is worth to point out that the partial sum sequence needs not to be an independent increment process. As an application of the theory established, we also give a sufficient criterion on the almost sure oscillation of solutions for a class of second-order stochastic difference equation of neutral type.
A comparative study on the physicochemical and biological stability of IgG1 and monoclonal antibodies during spray drying process
Authors: Ramezani Vahid , Vatanara Alireza , Najafabadi Abdolhossein Rouholamini , Shokrgozar Mohammad Ali , Khabiri Alireza , Seyedabadi Mohammad
Published: March 2014

Background

The main concern in formulation of antibodies is the intrinsic instability of these labile compounds. To evaluate the physicochemical stability of antibody in dry powder formulations, physical stability of IgG1 and a monoclonal antibody (trastuzumab) during the spray drying process was studied in a parallel study and the efficacy of some sugar based excipients in protection of antibodies was studied.

Results

The SDS-PAGE analysis showed no fragmentation of antibodies after spray drying in all formulations. The secondary structure of antibodies contained 40.13 to 70.19% of β structure in dry state. Also, CD spectroscopy showed the similar secondary structure for trastuzumab after reconstitution in water. ELISA analysis and cell culture studies were conducted in order to evaluate bioactivity of monoclonal antibody. Formulations containing combination of excipients provided maximum tendency of trastuzumab to attach to the ELISA antigen (86.46% ± 2.3) and maximum bioactivity when incubated with SKBr3 cell line (the cell viability was decreased to 65.99% ± 4.6). Incubation of formulations with L929 cell line proved the biocompatibility of the excipients and non-toxic composition of formulations.

Conclusion

The IgG1 and trastuzumab demonstrated similar behavior in spray drying process. The combination of excipients containing trahalose, hydroxypropyl beta cyclodextrin and beta cyclodextrin with proper ratio improved the physical and chemical stability of both IgG1 and monoclonal antibody.