Cerebellar Grey Matter Volume in Older Persons Is Associated with Worse Cognitive Functioning.

The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e. symptoms of depression and apathy) and general daily functioning in a population of community-dwelling older persons with mild cognitive deficits, but without dementia. In 194 participants of the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden, the association between cerebellar GMV, WMHs, LIs and MBs and measures of cognitive, psychological and general daily functioning was analysed with linear regression analysis, adjusted for age, sex, education and cerebral volume. Cerebellar GMV was associated with the overall cognition score (standardised beta 0.20 [95% CI, 0.06-0.33]). Specifically, posterior cerebellar GMV was associated with executive function (standardised beta 0.18 [95% CI, 0.03-0.16]). No relation was found between vascular pathology and cognition. Also, no consistent associations were found on the cerebellar GMV and vascular pathology measures and psychological and general daily functioning. In this population of community-dwelling elderly, less posterior cerebellar GMV but not vascular pathology was associated with worse cognitive function, specifically with poorer executive function. No relation was found between cerebellar pathology and psychological and general daily functioning.

Self-reported cognitive functioning in postmenopausal breast cancer patients before and during endocrine treatment: findings from the neuropsychological TEAM side-study.

OBJECTIVE: This study aimed to evaluate self-reported cognitive functioning of postmenopausal breast cancer patients before and during endocrine treatment compared with healthy female controls, and to investigate associations between self-reported cognitive functioning, cognitive test performance and anxiety/depression, fatigue, and menopausal complaints. METHODS: Self-reported cognitive functioning, anxiety/depression, fatigue, menopausal complaints, and cognitive tests performance were assessed before (T1) and after 1 year (T2) of adjuvant endocrine treatment in postmenopausal chemotherapy-naïve breast cancer patients. Self-reported cognitive functioning was assessed by the cognitive failures questionnaire and interview questions concerning cognitive complaints. Patients participated in the TEAM-trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive breast cancer. Identical information was obtained from healthy postmenopausal volunteers. RESULTS: Two measures for self-reported cognitive functioning provided the distinctive results. At T1 and T2, healthy controls reported a higher frequency of cognitive failures than patients; change over time did not differ between groups. The prevalence of cognitive complaints did not differ between the groups at T1, but change over time regarding attention/concentration complaints differed between groups, due to an increased prevalence in tamoxifen users. Self-reported cognitive functioning showed moderate associations with anxiety/depression, fatigue, and menopausal complaints. Cognitive test performance was not associated with self-reported cognitive functioning, but weakly with anxiety/depression and fatigue. CONCLUSION: Adjuvant therapy with tamoxifen and exemestane did not influence the self-reported frequency of cognitive failures. Increased attention/concentration complaints were observed in tamoxifen users, but not in exemestane users. This latter finding should be confirmed with better validated instruments.

Cognitive functioning of postmenopausal breast cancer patients before adjuvant systemic therapy, and its association with medical and psychological factors.

PURPOSE: This study aimed to identify medical and psychological predictors for cognitive performance of breast cancer (BC) patients before the start of adjuvant systemic treatment and to compare cognitive performance between BC patients and healthy controls adjusting for medical and psychological variables. MATERIAL: 205 postmenopausal BC patients underwent pre-treatment neuropsychological tests and provided medical and psychological data. 124 healthy controls underwent the same assessment. RESULTS: 'Treatment for diabetes mellitus' and/or 'hypertension', 'less hours spent on cognitively stimulating activities', 'fewer days since surgery' and 'more reproductive years' were associated with worse cognitive performance in the BC patients, independent of age and IQ. Cognitive differences between BC patients and healthy controls could partly be explained by the evaluated variables. CONCLUSION: The results stress the need for adjustment for pre-treatment cognitive differences between study groups, and also indicate that further research into pre-treatment cognitive dysfunction is warranted.

[The effect of hormone therapy on cognitive function in patients with breast cancer]. / De invloed van hormonale therapie op het cognitieffunctioneren van patiënten met het mammacarcinoom.

Preclinical and clinical studies suggest that oestrogens have an important role in brain functioning and cognitive ability. Given that hormone therapies for breast cancer reduce oestrogen levels or block oestrogen receptors, it is conceivable that these agents also influence cognitive function. Several small studies have been conducted to address this issue, but many of them are methodologically insufficient. The negative effects of oophorectomy and luteinising hormone-releasing hormone (LHRH) analogues on verbal memory and working memory have been demonstrated the most consistently, albeit only in small studies. Anastrozole and tamoxifen also appear to exert some negative effect on cognition, but well-designed studies are lacking. No data are available on the influence of the aromatase inhibitors exemestane and letrozole on cognitive function. Raloxifene, a drug that has no obvious advantages over tamoxifen and will likely not be developed further for breast cancer treatment, has no negative influence on cognitive functioning. It remains unclear whether the observed effects are transient or permanent, and to what extent age, menopausal status and duration of therapy influence the severity of cognitive effects.

Effects of hormonal therapy on cognitive functioning in breast cancer patients: a review of the literature.

(Pre)clinical research suggests that estrogens play a role in brain- and cognitive functioning. It is, among others, hypothesized that estrogens have a beneficial effect on neurotransmitters that are involved in cognitive processes, protect the brain by exerting anti-inflammatory actions after ischemic injury, promote survival of brain cells, and increase cerebral blood flow and glucose transport into the brain. Neuropsychological studies suggest that natural changes in estrogen levels are associated with (small) changes in cognitive functioning, for example during the menstrual cycle. In estrogen substitution studies, however, contradicting results are found, suggesting that substitution can have both beneficial and detrimental effects on cognitive functioning. Hormonal therapy for breast carcinoma lowers estrogen levels or blocks the growth-promoting effects of estrogens. The neuropsychological studies conducted so far give, though they vary highly in design, measures and participants, some indications for effects on cognition: ovariectomy, treatment with LHRH analogues, anastrozole and tamoxifen seem to be associated with (small) negative effects on some tests. It is unclear whether those effects are reversible, and whether time on therapy is associated with the seriousness of the effects. Raloxifene, currently under study for breast cancer prevention, does not seem to have detrimental effects on cognitive functioning. For the aromatase inhibitors letrozole and exemestane no data are available yet. Because the role of hormonal therapy in breast cancer treatment is increasing, the medical grounds for prescribing are expanding and physicians can make a choice from a broad spectrum of hormonal treatments, potential effects on cognitive functioning should be part of long-term drug safety evaluations.

[Interferon-alpha treatment of the Churg-Strauss syndrome]. / Behandlung des Churg-Strauss-Syndromes mit Interferon-alpha.

HISTORY: Two patients, 60 (pat. 1; female) and 30 years of age (pat. 2; male), respectively, suffering from a histologically confirmed Churg-Strauss-syndrome and receiving immunosuppressive therapy were treated with Interferon-alpha. INVESTIGATIONS: Clinical complaints, disease activity, blood eosinophil counts, and lung function were monitored. In patient 1 the differential cell counts and immunocytology of bronchoalveolar lavage cells were assessed using flow cytometry. TREATMENT AND COURSE: Both patients were treated with interferon-alpha in dosages of 3 million units of IFN-alpha 2b or an equivalent dosage of interferon-acon thrice weekly subcutaneously. The patients were observed for a period of up to 24 months. Interferon-alpha induced remission of disease and allowed discontinuation of oral glucocorticoid therapy in both patients. Treatment also improved the peripheral polyneuropathia in patient 1 as well as the hemorrhagic cystitis and reduction of the Cushing syndrome (weight reduction of 19 kg) in patient 2. In addition, blood eosinophil counts normalised. After 12 months of treatment, the number of bronchoalveolar eosinophils decreased from 61,5% (5.7 x 106 cells/ml) to 7% (1.1 x 106 cells/ml). In addition, the proportion of CD4+ T-lymphocytes and B-cells increased, while CD8+ T-cells and NK cells decreased (pat. 1). CONCLUSION: Interferon-alpha may represent an effective alternative to the current treatment of Churg-Strauss syndrome consisting of corticosteroids and immunosuppressives.