Monika Milian

Impairment of episodic and semantic autobiographical memory in patients with mild cognitive impairment and early Alzheimer's disease

Autobiographical memory includes the retrieval of personal semantic data and the remembrance of incident or episodic memories. In retrograde amnesias, it has been observed that recall of autobiographical memories of recent events is poorer than recall of remote memories. Alzheimers disease (AD) may also be associated with a temporal gradient (TG) in memory decline, though studies have yielded inconsistent results on this point. They have also yielded inconsistent results on whether AD might differentially affect semantic and episodic remembrance. Here, we compared autobiographical memory of childhood, early adulthood, and recent life among healthy control (HC) subjects, patients with early AD, and patients with amnesic mild cognitive impairment (aMCI). Both the aMCI and AD patients exhibited declines in recall of autobiographical incidents and semantic information. In AD patients, both components of autobiographical memory had a clear TG, with better preservation of memories of childhood than those of early adulthood and recent life. The TG of autobiographical memory decline in AD patients is more compatible with the Cortical Reallocation Theory than with the Multiple Trace Theory of memory consolidation. In contrast to AD patients, aMCI patients exhibited impaired recall of personal facts and autobiographical incidents relating only to recent life. The significant decline in autobiographical memory for recent life that occurred in aMCI patients suggests that deterioration of consolidation of personal facts and events begins with commencement of functional impairment in the hippocampus.

Diagnosis of Primary Hypophysitis in Germany.

CONTEXT Representative data on diagnostic findings in primary hypophysitis (PrHy) are scarce. OBJECTIVE The objective of the study was to collate consistent data on clinical features in a large series of patients with PrHy. Another objective was to gain information on current practice in a diagnostic work-up. DESIGN The Pituitary Working Group of the German Society of Endocrinology conducted a nationwide retrospective cross-sectional cohort study in Germany. PATIENTS Seventy-six patients with PrHy were identified. MAIN OUTCOME MEASURES Clinical and endocrinological features were assessed. RESULTS Headache (50%) and increase in body mass (18%) were the most frequent nonendocrine symptoms. Hypophysitis was associated with pregnancy in only 11% of the female patients. Diabetes insipidus was found in 54% of the patients at presentation. Hypogonadotropic hypogonadism was the most frequent endocrine failure (62%), whereas GH deficiency was the least frequent (37%). With 86%, thickening of the pituitary stalk was the prevailing neuroradiological sign. Compared with surgical cases, the cases without histological confirmation presented more often with suprasellar lesions and had less severe nonendocrine symptoms. Granulomatous hypophysitis was associated with more severe clinical symptoms than lymphocytic hypophysitis. Examination of cerebrospinal fluid was predominantly performed in participating neurosurgical centers, whereas thyroid antibodies were almost exclusively assessed in endocrinological centers. CONCLUSION In contrast to the literature, hypogonadism was found to be the most frequent endocrine failure in PrHy. Weight gain was identified as a clinical sign of PrHy. In the majority of patients, PrHy can be reliably identified by characteristic clinical signs and symptoms, obviating histological confirmation. The diagnostic approach should be standardized in PrHy.

Imagine your neighbor mows the lawn: a pilot study of psychological sequelae due to awake craniotomy Clinical article

OBJECT Although it has been reported that awake neurosurgical procedures are well tolerated, the long-term occurrence of general psychological sequelae has not yet been investigated. This study assessed the frequency and effects of psychological symptoms after an awake craniotomy on health-related quality of life (HRQOL). METHODS Sixteen patients undergoing an awake surgery were surveyed with a self-developed questionnaire, the Posttraumatic Stress Disorder Inventory For Awake Surgery Patients, which adopts the core components of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) posttraumatic stress disorder (PTSD) criteria. The mean time between surgery and data collection was 97.3 ± 93.2 weeks. Health-related quality of life was assessed with the 36-Item Short Form Health Survey. RESULTS Forty-four percent of the patients stated that they had experienced either repetitive distressing recollections or dreams related to the awake surgery, 18.8% stated persistent avoidance of stimuli associated with the awake surgery, and symptoms of increased arousal occurred in 62.5%. Two patients presented with postoperative psychological sequelae resembling PTSD symptoms. Younger age at surgery and female sex were risk factors for symptoms of increased arousal. The experience of intense anxiety during awake surgery appears to favor the development of postsurgical PTSD symptoms, while recurrent distressing recollections particularly affect HRQOL negatively. CONCLUSIONS In many cases awake craniotomy is necessary to preserve language and motor function. However, in some cases awake craniotomy can lead to postoperative psychological sequelae resembling PTSD symptoms. Therefore, possible long-term effects of an awake surgery should be considered and discussed with the patient when planning this type of surgery.

Treatment of Primary Hypophysitis in Germany.

CONTEXT The best treatment of primary hypophysitis (PrHy) is a matter of debate. OBJECTIVE Our main objective was to analyze the treatment practice for PrHy in Germany and to compare the outcome of the main treatment options. DESIGN The Pituitary Working Group of the German Society of Endocrinology conducted a nationwide retrospective cross-sectional cohort study. PATIENTS Seventy-six patients with PrHy were eligible for the study. MAIN OUTCOME MEASURES Clinical and endocrinological outcomes, side effects and complications of therapy, initial response, and recurrence rates were assessed. Outcome depending on the treatment modality was evaluated. RESULTS For mere observation, regression of space-occupying lesions was observed in 46%, unchanged size in 27%, and progression reported in 27%. Pituitary function improved in 27% of patients during observation. Deterioration of pituitary function was only found in patients with progressive lesions. The initial response to glucocorticoid pulse therapy was most favorable, with early failure in only 3%. However, the overall failure and recurrence rate was 41%. Recurrence rate was not related to duration of steroid administration. Side effects of steroids occurred in 63%. The surgical approach was transsphenoidal in 94%. The histological subtype was lymphocytic hypophysitis in 70% and granulomatous hypophysitis in 30%. Progression or recurrence was observed in 25% after surgical treatment. CONCLUSION Glucocorticoid pulse therapy is associated with a high recurrence rate. Evidence suggests that surgery is not able to prevent recurrence. Considering the favorable results of observation, conservative management is recommended in PrHy unless symptoms are severe or progressive.

The development of the Tuebingen Cushing’s disease quality of life inventory (Tuebingen CD-25). Part I: construction and psychometric properties

Objective  To develop a disease‐specific questionnaire for Cushing’s disease (CD), the Tuebingen Cushing’s disease quality of life inventory (Tuebingen CD‐25).

The minute hand phenomenon in the Clock Test of patients with early Alzheimer disease.

Common scoring systems for the Clock Test do not sufficiently emphasize the correct time representation by the clock hands. We compared Clock Drawing, Clock Setting, and Clock Reading in healthy control persons, patients with mild cognitive impairment, early Alzheimer disease and progressed Alzheimer disease particularly analyzing clock time representation. We found that healthy control persons and participants with mild cognitive impairment did not show any impairment in Clock Test performance. Patients with early Alzheimer disease could be discriminated from healthy control persons and participants with mild cognitive impairment solely by misplacement of the minute hand in Clock Drawing and Clock Setting. The progressed Alzheimer disease group showed significantly more impairments in all Clock Test variants. It is assumed that early stage Alzheimer disease patient deficits in Clock Tests are mainly determined by a reduced access to semantic memory about the appearance and functionality of a clock.

Clock Test Deficits Are Associated With Semantic Memory Impairment in Alzheimer Disease

Based on previous findings, we hypothesized that Clock Test deficits in patients with Alzheimer disease (AD) are associated primarily with the impairment of semantic memory regarding the appearance and functionality of a clock. To scrutinize this hypothesis, we developed a Clock Questionnaire that examined the semantic knowledge of the concept of a ‘‘Clock’’ and correlated scores from the questionnaire with performance in Clock Drawing, Clock Setting, and Clock Reading by healthy control participants and patients with mild cognitive impairment, early AD, and progressed AD. The Rey-Osterrieth-Complex-Figure is known to measure both visuospatial abilities and executive functions, and was chosen as a control variable. We found that deteriorated semantic memory best predicted Clock Test performance. In progressed AD, degraded knowledge regarding the appearance of a clock can explain the reduced ability to draw a clock face, while in early AD, impaired access to semantic knowledge about the minute hand might explain observed difficulties in drawing, setting, and reading the minute hand.

The development of the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25). Part II: normative data from 1784 healthy people

Objective  In part I of the study, a health‐related quality of life (HRQoL) inventory for Cushing’s disease (CD), the Tuebingen Cushing‐25 quality of life inventory (Tuebingen CD‐25) was developed. In this second part, we aimed to assess normative data from healthy controls (HC) with which the individual patients’ scores can be compared.

Predictive factors for neurocognitive function and Quality of Life after surgical treatment for Cushing’s disease and acromegaly

Background: Cushing’s disease (CD) and acromegaly (AC) are associated with impairment in quality of life (QoL) and neurocognition that can persist after successful treatment. Aim: To investigate the influence of current disease status (remission vs no remission) on neurocognitive function and QoL in treated CD and AC patients and to determine predictive factors (e.g. demographic, clinical, neurosurgical, endocrinological) for post-operative neurocognition and QoL. Subjects and methods: Twenty-four CD and 37 AC patients underwent neuropsychological testing 1 to 10 yr following surgical therapy. Additionally, QoL was assessed. An overnight 2-mg dexamethasone suppression test in CD and IGF-I and GH levels in AC patients were assessed to determine current disease status. The results were compared with 28 sex-, education- and age-matched healthy controls (HC). Results: Impaired QoL was more pronounced than neurocognitive decrease in both pathologies compared to HC. This finding was independent of the current status of disease. In AC, persistent comorbidities were associated with impaired QoL (p<0.05). Older age at operation in AC patients was a significant predictor for adverse effects on psychomotor speed and attentional functions (p<0.05). In CD persistent hypocortisolism, not hypercortisolism, had adverse effects on neurocognition (p<0.01). Conclusions: The current status of disease plays a subordinate role in postoperative outcome concerning QoL and neurocognition in either pathology. A possible explanation might be the considerably improved endocrinopathy after treatment compared to untreated patients, even if no cure is achieved. The lasting impairments might be explained by irreversible changes that have occurred during the active phase of the disease.

Changes in Cortical Activation during Retrieval of Clock Time Representations in Patients with Mild Cognitive Impairment and Early Alzheimer's Disease

Objective: We investigated healthy controls (HCs), and patients with mild cognitive impairment (MCI) and early Alzheimer’s disease (AD) to identify neuronal correlates of clock time representation and changes resulting from neurodegenerative processes using functional magnetic resonance imaging. Methods: Two clock-specific tasks demanding conceptual knowledge of clock hands, i.e. a minute hand and an hour hand task, were compared with a semantic control task. Results: We observed that the minute hand task provoked a stronger activation of areas in the parietal lobes known to be involved in spatial mental imagery, while the semantic task primarily activated regions of the superior temporal lobes associated with verbal conceptual knowledge. The performance of the MCI group did not differ from that of the HC group, but additional activation was found in several brain regions. Decreased activation was detected during the minute hand task in the right middle temporal gyrus. Patients with early AD showed deteriorated performance in both clock tasks along with reduced activation in the occipital lobes and the left fusiform gyrus. Additional activation was detected in the precuneus. Conclusions: The fusiform gyrus might be crucial for the visual-semantic retrieval of clock time representation. In patients with early AD, access to this visual-semantic knowledge appears to be reduced.