Network "Rodent-borne pathogens" in Germany: longitudinal studies on the geographical distribution and prevalence of hantavirus infections.

Hantavirus infections are known in Germany since the 1980s. While the overall antibody prevalence against hantaviruses in the general human population was estimated to be about 1-2%, an average of 100-200 clinical cases are recorded annually. In the years 2005 and 2007 in particular, a large increase of the number of human hantavirus infections in Germany was observed. The most affected regions were located in the federal states of Baden-Wuerttemberg, Bavaria, North Rhine Westphalia, and Lower Saxony. In contrast to the well-documented situation in humans, the knowledge of the geographical distribution and frequency of hantavirus infections in their rodent reservoirs as well as any changes thereof was very limited. Hence, the network "Rodent-borne pathogens" was established in Germany allowing synergistic investigations of the rodent population dynamics, the prevalence and evolution of hantaviruses and other rodent-associated pathogens as well as their underlying mechanisms in order to understand their impact on the frequency of human infections. A monitoring of hantaviruses in rodents from endemic regions (Baden-Wuerttemberg, Bavaria, North Rhine Westphalia, Lower Saxony) and regions with a low number of human cases (Mecklenburg Western-Pomerania, Brandenburg, Saxony, Saxony-Anhalt) was initiated. Within outbreak regions, a high prevalence of Puumala virus (PUUV) was detected in bank voles. Initial longitudinal studies in North Rhine Westphalia (city of Cologne), Bavaria (Lower Bavaria), and Lower Saxony (rural region close to Osnabrück) demonstrated a continuing presence of PUUV in the bank vole populations. These longitudinal studies will allow conclusions about the evolution of hantaviruses and other rodent-borne pathogens and changes in their distribution, which can be used for a risk assessment of human infections. This may become very important in order to evaluate changes in the epidemiology of rodent-borne pathogens in the light of expected global climate changes in the future.

Worsening of quality of life after epilepsy surgery: effect of seizures and memory decline.

BACKGROUND: Surgery for intractable temporal lobe epilepsy usually controls seizures and improves health-related quality of life (HRQOL), but some patients experience continued seizures, memory decline, or both. The relative impact of these unfavorable outcomes on HRQOL has not been described. METHODS: We studied seizure control, memory change, and HRQOL among 138 patients in the Multicenter Study of Epilepsy Surgery (MSES), an ongoing, prospective study of epilepsy surgery outcomes. Seizure remission at 2 years and 5 years was prospectively determined based upon regularly scheduled follow-up calls to study patients throughout the follow-up period. HRQOL was assessed annually using the Quality of Life in Epilepsy Inventory (QOLIE-89). Memory decline was determined by change in verbal delayed recall from baseline to the 2- or 5-year follow-up. RESULTS: HRQOL improved in patients who were in remission at the 2-year or 5-year follow-up, regardless of memory outcome. Among those not in remission at both 2 and 5 years (25/138, 18%), HRQOL remained stable when memory did not decline (14/138, 10%), but HRQOL declined when memory did decline (11/138, 8%). These 11 patients had baseline characteristics predictive of poor seizure or memory outcome. Declines were most apparent on HRQOL subscales assessing memory, role limitations, and limitations in work, driving, and social activities. CONCLUSIONS: After temporal resection, health-related quality of life (HRQOL) improves or remains stable in seizure-free patients despite memory decline, but HRQOL declines when persistent seizures are accompanied by memory decline. These results may be useful in presurgical counseling and identifying patients at risk for poor psychosocial outcome following surgery.

The relative frequency of "dementia of unknown etiology" increases with age and is nearly 50% in nonagenarians.

CONTEXT: With the recent change in pathological criteria for Alzheimer disease (AD), a group of patients has emerged who do not meet pathological criteria for any well-characterized degenerative dementias. Whether these unclassified patients have vascular dementia or some other form of dementia is not known. OBJECTIVE: To determine the clinical characteristics, pathological substrate, and relative frequency of dementia not caused by well-characterized degenerative dementias. DESIGN/SETTING: Clinicopathological study of a prospectively observed sample of elderly nondemented and demented subjects recruited from our urban community. METHODS: In our series of 128 subjects with prospective neuropsychological evaluations as well as neuropathology, we identified 35 clinically nondemented subjects and 20 demented patients who did not meet pathological criteria for well-characterized degenerative dementias such as AD or dementia with Lewy bodies. The 20 demented patients were grouped together under the term dementia of unknown etiology (DUE). We compared clinical, genetic, neuropsychological, pathological, and neurochemical characteristics of the nondemented group, patients with DUE, and 28 patients with AD and no other pathological abnormality. RESULTS: Mean age at death for patients with DUE was 89.1 +/- 5.8 years compared with 79.9 +/- 11.4 years for AD (P<.001). Patients with AD and DUE did not differ in sex, risk factors, apolipoprotein E genotype, neuropsychological features, or neurological features. Hippocampal sclerosis (in 11 patients with dementia and no controls) and leukoencephalopathy (in 7 patients with dementia and 1 control) were associated with cognitive impairment; other vascular markers were not. Dementia of unknown etiology accounted for 5% of all cases of dementia among patients dying in their 70s, 21% for patients dying in their 80s, and 48% for patients dying in their 90s. CONCLUSIONS: A significant percentage of demented patients older than 80 years do not meet pathological criteria for AD or dementia with Lewy bodies. Hippocampal sclerosis and leukoencephalopathy are common in these patients but rare in clinically nondemented subjects.

Psychiatric disorders in patients with fibromyalgia. A multicenter investigation.

The authors conducted an investigation in four tertiary-care centers to determine if psychiatric comorbidity and psychological variables were predictive of functional impairment in patients with fibromyalgia syndrome (FMS). Seventy-three individuals were administered the Structured Clinical Interview for DSM-III-R, the Rand 36-item Health Survey (SF-36), and multiple self-report measures. The patients with FMS were found to have a high lifetime and current prevalence of major depression and panic disorder. The most common disorders were major depression (lifetime [L] = 68%, current [C] = 22%); dysthymia (10% [C only]); panic disorder (L = 16%, C = 7%); and simple phobia (L = 16%, C = 12%). The self-report scales revealed significant elevations in depression, anxiety, neuroticism, and hypochondriasis. Functional impairment on all measures of the SF-36 was severe (e.g., physical functioning = 45.5 and role limitations due to physical problems = 20.0). Stepwise multiple-regression analysis revealed that current anxiety was the only variable that predicted a significant proportion of the variance (29%) in SF-36 physical functioning. Thus, in this multicenter study, the persons with FMS exhibited marked functional impairment, high levels of some lifetime and current psychiatric disorders, and significant current psychological distress. Current anxiety level appears to be an important correlate of functional impairment in individuals with FMS.

Pain, fatigue, and sleep in eosinophilia-myalgia syndrome: relationship to neuropsychological performance.

Cognitive problems are frequently reported in patients with eosinophilia-myalgia syndrome (EMS). This is the first study to explore, in EMS, the relationship between specific neuropsychological deficits and fatigue and pain. Relationships among depression, sleep disturbance, and neuropsychological deficits in EMS were also examined. Neither fatigue nor pain was correlated with memory impairment. Sleep disturbance was significantly correlated with verbal memory impairment, but not with deficits in visuospatial memory. These results suggest that cognitive loss in EMS cannot be attributed to pain or fatigue. Although some aspects of memory impairment may be associated with disturbed sleep, visual memory deficits are clearly independent of sleep deficits and may result from direct effects of the disease on the central nervous system.

The effect of dementia risk factors on comparative and diagnostic selective reminding norms.

Robust comparative and diagnostic norms for the elderly are provided for the Selective Reminding Test (Buschke, 1973). Correcting for factors such as age and education level are appropriate for comparative norms, which are intended for ranking individuals with respect to their age and education matched peers. However, because age and education are both risk factors for dementia, correcting for these factors decreases test sensitivity for detecting dementia. Age- and education-corrected Selective Reminding scores have a sensitivity for detecting dementia that is 28% lower than uncorrected scores. Using information about age in combination with memory scores provided optimal discrimination of dementia. It is concluded that statistically removing the contribution of dementia risk factors from memory test scores can severely decrease discriminative validity for detecting dementia in the elderly.

The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis.

BACKGROUND: Amantadine hydrochloride and pemoline, both frequently used to treat the fatigue of multiple sclerosis (MS), may also improve attention and other cognitive functions in MS. To our knowledge, these agents have never been compared in a placebo-controlled trial of patients with MS. OBJECTIVE: To evaluate the effects of amantadine and pemoline on cognitive functioning in MS. METHODS: A total of 45 ambulatory patients with MS and severe fatigue were treated for 6 weeks with amantadine, pemoline, or placebo using a parallel group design. They underwent comprehensive neuropsychological testing to determine treatment effects on cognitive functioning. Primary outcome measures were tests of attention (Digit Span, Trail Making Test, and Symbol Digit Modalities Test), verbal memory (Selective Reminding Test), nonverbal memory (Benton Visual Retention Test), and motor speed (Finger Tapping Test). RESULTS: Fatigue did not significantly correlate with any of the neuropsychological outcome measures at baseline or after treatment. All three treatment groups improved on tests of attention (P < .003), verbal memory (P < .001), and motor speed (P < .002). There were no significant differences between amantadine, pemoline, and placebo. CONCLUSIONS: Cognitive functioning in MS is independent of fatigue. Neither amantadine nor pemoline enhances cognitive performance in MS compared with placebo.

Associations of status and change measures of neuropsychological function with pathologic changes in elderly, originally nondemented subjects.

OBJECTIVE: To describe the association between status and change of neuropsychological function and postmortem neuropathologic findings in subjects with Alzheimer's disease, vascular dementia, normal aging, and pathologic aging. DESIGN: Volunteer cohort study. SETTING: Volunteers were interviewed and tested in outpatient-clinical research offices. PARTICIPANTS: Nondemented, healthy, community-residing subjects, initially between 75 and 85 years of age, who participated in the Bronx Aging Study and had at least 2 years of neuropsychological data and quantitative neuropathologic examinations. MAIN OUTCOME MEASURES: Initial summary neuropsychological score, rate of change score. RESULTS: Summary neuropsychological scores at baseline in subjects who subsequently developed pathologically confirmed Alzheimer's disease or vascular dementia were 0.8 z units lower than those of subjects classified in the normal or pathologic aging subgroups (P < .05). Subjects with Alzheimer's disease showed more neuropsychological change over time than subjects in the normal or pathologic aging groups (P < .001). Normal subjects and subjects with pathologic aging did not differ in baseline scores or rate of change. Level of education was strongly associated with initial neuropsychological scores (P < .004), but not with change scores. CONCLUSIONS: Among elderly, initially nondemented subjects who were followed up until death, subjects with pathologically confirmed Alzheimer's disease or vascular dementia had lower neuropsychological scores at initial evaluation than normal subjects or subjects with pathologic aging. Subjects with Alzheimer's disease had a more rapid rate of decline than normal subjects or subjects with pathologic aging.

Neuropsychological prediction of dementia and the absence of dementia in healthy elderly persons.

Identification of elderly individuals with low and high risk for future dementia has emerged as an important clinical and public health issue. To address this issue, we assessed neuropsychological performance in 317 initially nondemented elderly persons between 75 and 85 years of age and followed them for at least 4 years as part of the Bronx Aging Study. Four measures of cognitive function from the baseline assessment (delayed recall from the Buschke Selective Reminding Test, recall from the Fuld Object Memory Evaluation, the Digit Symbol subtest from the Wechsler Adult Intelligence Scale, and a verbal fluency score) can identify one subgroup with an 85% probability of developing dementia over 4 years and another with a 95% probability of remaining free of dementia. The model achieved an overall positive predictive value of 68%, or three times the base rate, for prediction of the development of dementia in our sample. The overall negative predictive value for prediction of absence of dementia was 88%. Baseline measures of cognitive function, often performed many years before the actual diagnosis of dementia, can provide important information about dementia risk. The group likely to develop dementia becomes a target for preventive or early therapeutic interventions, and the group unlikely to develop dementia can be reassured.

Cognitive functioning and depression in patients with chronic fatigue syndrome and multiple sclerosis.

OBJECTIVE: To assess cognitive function in patients with chronic fatigue syndrome (CFS) and multiple sclerosis (MS) and to evaluate the role of depressive symptoms in cognitive performance. DESIGN: Case-control. All subjects were given a neuropsychological battery, self-report measures of depression and fatigue, and a global cognitive impairment rating by a neuropsychologist "blinded" to clinical diagnosis. Patients with MS and CFS were additionally evaluated with a Structured Clinical Interview for DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition) disorders. SETTING: Institutional and private neurological practices and the community at large. PATIENTS: Twenty patients with CFS diagnosed in accord with the Centers for Disease Control and Prevention-revised criteria who had cognitive complaints; 20 patients with clinically definite MS who were ambulatory and were matched for fatigue severity, age, and education to CFS subjects; and 20 age- and education-matched healthy controls. RESULTS: Patients with CFS had significantly elevated depression symptoms compared with patients with MS and healthy controls (P < .001) and had a greater lifetime prevalence of depression and dysthymia compared with MS subjects. Patients with CFS, relative to controls, performed more poorly on the Digit Symbol subtest (P = .023) and showed a trend for poorer performance on logical memory (P = .087). Patients with MS compared with controls had more widespread differences of greater magnitude on the Digit Span (P < .004) and Digit Symbol (P < .001), Trail Making parts A (P = .022) and B (P = .037), and Controlled Oral Word Association (P = .043) tests. Patients with MS also showed a trend of poorer performance on the Booklet Category Test (P = .089). When patients with CFS and MS were directly compared, MS subjects had lower scores on all measures, but the differences reached significance only for the Digit Span measure of attention (P = .035). CONCLUSIONS: Patients with CFS compared with MS have more depressive symptoms but less cognitive impairment. Relative to controls, a subset of CFS subjects did poorly on tests of visuomotor search and on the logical memory measure of the Wechsler Memory Scale-revised. Poor performance of logical memory in CFS appears to be related to depression, while visuomotor deficits in CFS are unrelated. Cognitive deficits in patients with MS are more widespread compared with those in patients with CFS and are independent of depressive symptoms.

Neurocognitive dysfunction in the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome (EMS), a multisystem disorder associated with ingestion of L-tryptophan-containing products, causes sclerodermatous skin changes, cardiopulmonary disease, and a range of peripheral neurologic complications. Many EMS patients also report cognitive difficulty in association with the disease. To determine the frequency of objective neurocognitive impairment in EMS patients with subjective complaints of cognitive difficulty and to assess the relationship of neurocognitive loss with demographic features, degree of peripheral eosinophilia, and psychiatric diagnosis, we compared 24 EMS patients with 32 age- and education-matched healthy controls, using a comprehensive neuropsychological test battery. EMS patients additionally underwent a psychiatric interview and rheumatologic evaluation. Sixty-two percent (15 of 24) of the EMS patients demonstrated neurocognitive deficits. Compared with healthy controls, EMS patients demonstrated significant impairment on tests of verbal memory, visual memory, conceptual reasoning, and motor speed. Cognitively impaired EMS patients did not differ from those without cognitive impairment on demographic markers, degree of peripheral eosinophilia, presence of peripheral neuropathy, or frequency of concurrent psychiatric disorder, including major depression. These data support the hypothesis that EMS is associated with an encephalopathy in addition to its previously recognized peripheral neuropathy and other rheumatologic manifestations.

Fluent aphasia in children: definition and natural history.

We compared the course of a preschool child we followed for 4 years with published reports of 24 children with fluent aphasia. Our patient spoke fluently within 3 weeks of the injury. She was severely anomic and made many semantic paraphasic errors. Unlike other children with fluent aphasia, her prosody of speech was impaired initially, and her spontaneous language was dominated by stock phrases. Residual deficits include chronic impairment of auditory comprehension, repetition, and word retrieval. She has more disfluencies in spontaneous speech 4 years after her head injury than acutely. School achievement in reading and mathematics remains below age level. Attention to the timing of recovery of fluent speech and to the characteristics of receptive and expressive language over time will permit more accurate description of fluent aphasia in childhood.

Identification of normal and pathological aging in prospectively studied nondemented elderly humans.

Results of a standardized histochemical and immunocytochemical analysis of the brains of 14 nondemented elderly humans for whom prospective neurological and neuropsychological data had been collected for 3 to 8 years before death suggested that nondemented elderly humans fall into two pathological subgroups that are not clinically distinguishable. One was associated with moderate to marked cerebral amyloid deposition ("pathological aging"), while the other had either minimal or no amyloid deposition ("normal aging"). Neocortical and hippocampal neurofibrillary degeneration was either completely absent or of very limited degree in both subgroups. Both subgroups had ubiquitin-immunoreactive dystrophic neurites in the cerebral cortex and granular degeneration of myelin in white matter. These ubiquitin-immunoreactive structures seem to be a universal and invariant manifestation of brain aging, but the same cannot be said for amyloid deposition and neurofibrillary degeneration. Pathological aging might be preclinical Alzheimer's disease, but it currently cannot be distinguished from normal aging by even sensitive neuropsychological measures. These findings provide strong support for the hypothesis that cerebral amyloid deposition is not necessarily associated with clinically apparent cognitive dysfunction and that additional factors, such as neuronal or synaptic loss or widespread cytoskeletal aberrations, are necessary for dementia in AD.

Cognitive functioning in late Lyme borreliosis.

Lyme borreliosis, a tick-borne multisystem disease, may cause a variety of neurologic complications, including meningoencephalitis and encephalopathy. To evaluate neurobehavioral function following treated Lyme borreliosis, 15 patients with Lyme disease and complaints of persistent cognitive difficulty a mean of 6.7 months following antibiotic treatment underwent neuropsychological evaluation and were compared with 10 healthy controls, matched in aggregate for age and education, who underwent the identical neuropsychological assessment. Compared with controls, patients with Lyme disease exhibited marked impairment on memory tests and particularly on selective reminding measures of memory retrieval. The memory impairment did not correlate with serum or cerebrospinal fluid anti-Borrelia burgdorferi antibody titers and was not explained by magnetic resonance imaging findings or depression. The cause of this encephalopathy is currently unknown; however, indirect effects of systemic infection or other toxic-metabolic factors may be partly responsible.

Dementia. Age-dependent incidence, prevalence, and mortality in the old old.

Age has been reported as a strong risk factor for dementia. Supporting data have been derived mainly from prevalence studies, which had varied criteria and sample compositions that precluded direct comparisons, especially among those aged 85 years and older. Data regarding rates of dementia are presented based on 85 incident cases in the Bronx (NY) Aging Study, a prospective study of 488 initially nondemented, old old persons (mean age on entry, 79 years). Overall, the incidence rate over 8 years of follow-up for all-cause dementia was 3.4 per 100 per year (43% Alzheimer's disease, 30% mixed Alzheimer's and vascular, and 27% other). Incidence rose significantly, irrespective of gender, as subjects were followed up through three age intervals--ages 75 to 79 years (1.3/100 per year), 80 to 84 years (3.5), and 85 years and older (6.0). The comparable age-associated prevalence rates of dementia were 3.7%, 12.2%, and 23.9%, respectively, with an overall period prevalence of 22.8%. Additionally, there was a threefold greater mortality associated with dementia. In conclusion, despite the shortened life expectancy of demented persons, dementia is a highly prevalent condition among those aged 85 years and older. Public policy attention is warranted, since this group is the fastest growing population subgroup.

Object-memory evaluation for prospective detection of dementia in normal functioning elderly: predictive and normative data.

In a prospective study of dementia in initially normal functioning elderly, a brief form of the Fuld Object-Memory Evaluation (OM) was administered to 474 cognitively normal community-residing volunteers aged 75-85 at baseline and annually thereafter. Seventy-two subjects later became demented. Memory test data from the last annual evaluation before cognitive change was noted were available for 56. Although the entire population recalled 7.28 (SD = 1.33) of the 10 objects on Trial 1 of the test at baseline, these 56 subjects recalled only 5.96 (SD = 1.85). When recall of 6 or fewer objects was used as a predictor, the OM test identified 32 of the 56 who subsequently became demented. Compared to an estimated base rate of 15% for dementia, the predictive value of a positive test (PV+) was 39%, and that of a negative test (PV-) was 89%. With a cutoff of 5 or fewer items recalled, the PV+ rose to 59% and the PV- was 94%. Although the OM test was only moderately sensitive to incipient dementia (.57), it was fairly specific (.84), and lowering the cutoff to 5 increased the specificity to .96. Memory testing would therefore seem to hold promise as a predictor of dementia in cognitively normal elderly.

Predicting development of dementia in the elderly with the Selective Reminding Test.

The ability to predict the development of dementia through the detection of memory impairment in nondemented individuals was assessed with the Selective Reminding Test (SR), a popular test of verbal memory functioning in the elderly. The SR was administered to 385 nondemented volunteer subjects (mean age = 80.4 years) enrolled in a longitudinal study of risk factors in the development of dementia. Of these, 36 subjects ultimately became demented. SR scores obtained from 1 to 2 years prior to the diagnosis of dementia were compared with a set of previously established cutoff scores derived from a cognitively normal elderly sample. The results demonstrated that sum of recall and delayed recall were the SR measures best able to predict dementia with sensitivities of 47% and 44%, respectively. The predictive values were 37% and 40%, respectively, or better than two-and-one-half times the base rate. The contributions of both the SR Test and the Fuld Object-Memory Test (OM) were discussed in terms of the further understanding of the characteristics of the preclinical phase of dementia.

Women, myocardial infarction, and dementia in the very old.

Dementia is a major public health problem among the very old. Available information on incidence and prevalence is sparse and variable; however, there appears to be a higher prevalence among very old women. We present data from a prospective study of initially nondemented community-residing elderly. There were 75 incident dementia cases (up to 7 years of follow-up) of which at least 47% were probable Alzheimer's disease. Based on a proportional hazards analysis, women were over 3 times more likely to develop dementia than men despite controlling for baseline demographic, psychosocial, and medical history variables. Poor word fluency and a high normal Blessed test score at baseline were also strong predictors of dementia. We did not find age, head trauma, thyroid disease, or family history of dementia to be risk factors. A new finding is that history of myocardial infarction (MI) is associated with dementia, such that women with a history of MI were 5 times more prone to dementia than those without a history. This observation was not true for men.

Preservation of musical memory in Alzheimer's disease.

An 82 year old musician with Alzheimer's disease (AD) showed a preserved ability to play previously learned piano compositions from memory while being unable to identify the composer or titles of each work. He also showed a preserved ability to learn the new skill of mirror reading while being unable to recall or recognise new information. Both anterograde and retrograde procedural memory may be relatively spared in AD.