[Resilience to mental disorders in old age]. / Resilienz gegenüber psychischen Störungen im Alter.

BACKGROUND: Why does the aspect of aging justify a special survey of resilience to the development of mental disorders? Patterns of chronic stress burden change with age (e. g. disappearance of workplace-related stress, but increased risk of frequent chronic diseases). Moreover, capabilities and cognitive strategies of stress coping differ between young and older adults. MATERIAL AND METHODS: The article summarizes relevant age aspects of resilience to mental disorders and evaluates the current knowledge concerning consecutive development of prevention strategies for avoidance of affective disorders and dementia. RESULTS AND DISCUSSION: Stress-aggravating reduced cognitive functioning (especially executive problem solving) can be observed together with, probably stress-reducing, age-specific appraisal preferences (positivity effect) in older persons. Other age-specific aspects are resilience mechanisms against cognitive decline and dementia development despite cerebrovascular and neurodegenerative brain pathology-related conditions, which are referred to as cognitive reserve. Different cognitive reserve enhancing strategies can effectively contribute to dementia prevention.

[Psychotherapy with mild cognitive impairment and dementia]. / Psychotherapie bei leichter kognitiver Beeinträchtigung und Demenz.

BACKGROUND: Despite evidence for psychotherapy (PT) in elderly patients, it is not standard care in patients with mild cognitive impairment and dementia. Although neuropsychiatric symptoms are frequent in these patients, there is a lack of studies investigating the importance and efficiency of PT. OBJECTIVE: Can patients with mild cognitive impairment and dementia benefit from PT? If so, which modifications of therapeutic strategies are necessary for treating elderly patients with mild cognitive impairments? MATERIAL AND METHODS: Evaluation of empirical evidence on the efficiency of PT for patients with mild cognitive impairment and dementia. Presentation of interventions and modifications of therapeutic strategies. RESULTS: Empirical evidence points towards beneficial effects of PT on depressive symptoms and quality of life. The treatment of anxiety disorders has so far been broadly neglected. Modifications of therapeutic strategies include simplification of content, repetitions, implementation of external memory aids and inclusion of caregivers into therapeutic process. CONCLUSION: Psychotherapy can be effective in patients with mild cognitive impairment and early stages of dementia. When practicing PT, an adaptation of therapeutic strategies is necessary. Nevertheless, there is a need for further studies investigating the benefits and implementation of PT into standard care, especially as pharmacological interventions are very limited in their efficiency and tolerability in this patient population.

[Psychotherapeutic approaches for treatment of the elderly]. / Psychotherapeutische Ansätze bei der Behandlung älterer Menschen.

BACKGROUND: This article focusses on the possibilities, varieties, indications, and benefits of psychotherapy with elderly patients. OBJECTIVE: Which basic principles can be differentiated, what theoretical rationales are helpful for psychotherapy with the elderly and what kind and forms of psychotherapy are available? MATERIAL AND METHODS: Based on relevant references and research, clinically relevant and evidence-based psychotherapies are described, to understand the theoretical rationale, the goals, the procedure and main strategies. RESULTS: Cognitive behavior therapy, problem solving therapy, life review therapy, interpersonal psychotherapy, and psychodynamic psychotherapy are available to treat various psychological and somatic problems in elderly patients. In particular, cognitive behavior therapy, problem solving therapy, and life review therapy are evidence-based and empirically validated. Evidence for interpersonal psychotherapy is mixed and for psychodynamic psychotherapy is missing. CONCLUSION: Psychotherapy with old and very old patients is possible, well received, and successful. Age per se is no longer considered to be a relevant variable for indications of psychotherapy.

Association of basal forebrain volumes and cognition in normal aging.

The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative alterations during normal aging and severe atrophy in Alzheimer's disease (AD). It has been suggested that functional and structural alterations of the BFCS mediate cognitive performance in normal aging and AD. But, it is still unclear to what extend age-associated cognitive decline can be related to BFCS in normal aging. We analyzed the relationship between BFCS volume and cognition using MRI and a comprehensive neuropsychological test battery in a cohort of 43 healthy elderly subjects spanning the age range from 60 to 85 years. Most notably, we found significant associations between general intelligence and BFCS volumes, specifically within areas corresponding to posterior nuclei of the nucleus basalis of Meynert (Ch4p) and the nucleus subputaminalis (NSP). Associations between specific cognitive domains and BFCS volumes were less pronounced. Supplementary analyses demonstrated that especially the volume of NSP but also the volume of Ch4p was related to the volume of widespread temporal, frontal, and parietal gray and white matter regions. Volumes of these gray and white matter regions were also related to general intelligence. Higher volumes of Ch4p and NSP may enhance the effectiveness of acetylcholine supply in related gray and white matter regions underlying general intelligence and hence explain the observed association between the volume of Ch4p as well as NSP and general intelligence. Since general intelligence is known to attenuate the degree of age-associated cognitive decline and the risk of developing late-onset AD, the BFCS might, besides the specific contribution to the pathophysiology in AD, constitute a mechanism of brain resilience in normal aging.

[Effectivity of early psychosocial counselling for family caregivers in general practioner based dementia care]. / Hausarztbasierte Demenzversorgung: Effektivität früher psychosozialer Beratung der Angehörigen.

BACKGROUND: Psychoeducation and professional support of family caregivers are regarded as important aspects in dementia care. In the context of a general practitioner's (GP) based dementia care project we investigated if professional counselling after making a diagnosis of dementia can reduce the development of depression in family caregivers. METHODS: 42 patients with dementia and their family caregivers took part in the prospective, randomized study with a follow-up after 18 months. 29 families received psychosocial counselling, the control group was provided an information brochure about dementia including helpful contact addresses. Counselling included education about the illness. Additionally, the current individual needs were identified and assistance was administered if necessary. RESULTS: The counseling was rated as "very helpful" or "helpful" by most of the caregivers as well as by the partaking GPs. While depression rate between counseling and control group did not differ significantly at baseline, the depression rate was significantly increased in the control group after 18 month as compared to the intervention group. CONCLUSION: Despite the small study size we provide first strong evidence that early psychosocial counselling can reduce the development of depression in family caregivers. Early, professional counselling improves the quality of dementia care within a GP-based dementia care setting and it might stabilize and extend the home care duration of dementia patients.

[Dementia guidelines: what should come to general practice--an interdisciplinary consensus of physicians in private practice]. / Demenzleitlinien: was in der Praxis ankommen sollte--Ein interdisziplinärer Konsens von Praktikern.

BACKGROUND: Guidelines of Medical Societies aim at supporting the quality of medical care in general, and particularly in private practice. Usually, physicians in private practice are not part of the expert committees of medical societies that author guidelines. Guidelines represent a consensus appraising evidence from clinical studies on efficacy and side effects but also evaluating aspects of the health care system such as costs. Guidelines commonly do not account for regional specifics. Transfer of knowledge from guidelines to general practice, therefore, is incomplete. METHODS: We describe a consensus of neuropsychiatric and general physicians (n=12; 10 to 38 years of professional experience) on prioritization of diagnostic and therapeutic procedures for patients with Alzheimer's dementia as judged by relevance and practicability compared to the guideline of the Society for General Medicine (DEGAM-guideline No. 12) and the S3-guideline dementia of the German Society for Psychiatry, Psychotherapy and Neuropsychiatry (DGPPN). RESULTS: If patients and proxies do not oppose diagnosis, e. g. in cases of progressive impairment of memory with everyday relevance, the appropriate diagnostic procedures should be performed for every patient. Age or setting in which the patients live, in itself are no reason to limit antidementia therapy. Symptom fluctuations or decline of individual symptoms are compatible with treatment success. Clinical scales may only be used as supportive means to evaluate disease progression. CONCLUSION: Diagnosis and treatment of dementia are experienced as complex tasks by physicans in private practice. Practicing physicians need to adapt guidelines of medical societies on local and individual specifics.

Use of coffee, caffeinated drinks and caffeine tablets for cognitive enhancement in pupils and students in Germany.

INTRODUCTION: Substance use for cognitive enhancement (CE) is a topic of increasing importance. There are only few data about substances, prevalence rates and factors associated with CE. The aim of this study was to assess first data about the use of coffee, caffeinated drinks and caffeine tablets for CE at school and university. METHODS: A self-report questionnaire was developed to analyze 1 547 pupils and students about their use of coffee, caffeine tablets, and caffeinated drinks for CE and factors associated with this use. RESULTS: Lifetime, past-year, and past-month prevalence for the use of coffee for CE was 53.2%, 8.5%, and 6.3%, for the use of caffeinated drinks 39%, 10.7%, and 6.3%, and for the use of caffeine tablets 10.5%, 3.8%, and 0.8%. Use of caffeinated substances for CE was influenced by gender and school grades. DISCUSSION: The use of coffee and caffeinated drinks for CE was found to be widespread in the surveyed population. Although the use of caffeine tablets was found to be smaller than the above-mentioned means, it still indicates a relatively high disposition for using tablets for purposes of CE.

Non-medical use of prescription stimulants and illicit use of stimulants for cognitive enhancement in pupils and students in Germany.

INTRODUCTION: The aim of this study was to assess for the first time the prevalence and factors associated with stimulant use exclusively for cognitive enhancement among pupils and university students in Germany. METHODS: A sample of 1 035 pupils (vocational and grammar schools) in small and big cities and 512 university students of 3 Departments (Medicine, Pharmacy, Economics) completed a questionnaire regarding knowledge and use of stimulants for cognitive enhancement and factors associated with their use. RESULTS: Lifetime prevalence for use of prescription stimulants (methylphenidate, amphetamines) for cognitive enhancement in pupils was 1.55% and in students 0.78%. Last-year and last-month prevalence rates were significantly lower. 2.42% of pupils and 2.93% of students reported lifetime illicit use of stimulants (amphetamines, cocaine, ecstasy) for cognitive enhancement with lower last-year and last-month rates. Prevalence was higher in male pupils, pupils from vocational schools and pupils with bad marks. DISCUSSION: The illicit use of stimulants for cognitive enhancement is significantly higher than non-medical use of prescription stimulants among pupils and students. Stimulant use is determined by gender, school type, and school marks. The potential risks associated with stimulant use require early awareness and intervention strategies.

Neuropsychiatric symptoms and brain structural alterations in Fabry disease.

BACKGROUND: Neuropsychiatric symptoms (NPS), mainly cognitive deficits up to dementia and depressive syndromes have been described repeatedly in Fabry disease (FD). However, examinations regarding the pattern, extent, and frequency of the NPS in FD are still lacking. Moreover, the relationship between NPS and brain structural alterations in FD is unknown. The aim of this study was 1) to characterize NPS in a relatively large cohort of adult subjects with FD, and 2) to explore the association of cognitive performance and depressive syndromes with the FD-typical brain structural findings. METHODS: Twenty-five Fabry patients (age 36.5 ± 11.0) with mild to moderate disease involvement and 20 age, gender-, and education-matched healthy controls were extensively studied by neuropsychiatric assessment, structural magnetic resonance imaging, magnetic resonance angiography, and diffusion-tensor imaging. RESULTS: Patients with FD showed deficits only in the attention domain. Clinically relevant depressive syndromes were noted in 60% of the patients. The subgroup of patients with markedly elevated volumes of white matter lesions (not associated with actual stroke; n=7) showed slightly more learning and memory deficits, but no higher depression rate compared to less affected patients. CONCLUSIONS: Against the prevailing assumption, Fabry patients, even those with marked brain structural alterations, showed only mild cognitive deficits. The high frequency of depression in FD is likely to be related to the burden of this chronic multiorganic hereditary disease, but not to the FD-typical brain structural alterations. Longitudinal studies are necessary to clear, if the mild cognitive deficits in FD might precede clinically relevant cognitive decline.

[Improving general practitioners guided dementia care: the pilot project start-modem in Rheinland-Pfalz, Germany]. / Verbesserte ambulante Demenzversorgung. Das hausarztbasierte rheinland-pfälzische Modellprojekt "start-modem".

BACKGROUND: The study examined the ability of trained General Practitioners (GPs) to carry out guideline based diagnostics and therapy of dementia. The article reports the GP-related findings. METHODS: 100 GPs took part in the prospective multi-centre study. 34 GPs started self-guided medical dementia care after attending a special training. The control group of 66 GPs referred patients suspected of dementia to specialist centres. Time of recruiting was 13 months. In case of dementia diagnosis patients and caregivers received professional psychosocial counselling. RESULTS: Trained GPs reported improvements of sensitization and qualification through the project. The cross-linkage of GPs' medical dementia care and psychosocial counselling found a broad acceptance of the participants (GPs, patients, caregivers). 92 of the 156 included patients were diagnosed as dementia. Guideline conformity was violated in 65.4 % of all cases concerning structural imaging and in 30.1 % regarding laboratory tests. "Unspecified Dementia" was the most frequent ICD-10-diagnosis by GPs. CONCLUSION: Despite the broad acceptance of the project a limited guideline-conformity as well as the diagnostic uncertainty suggests that the implemented training is only a first step towards GP guided dementia care. To extend GPs guided dementia care and to improve the quality of GPs dementia diagnostics and therapy sensitization of more GPs for active dementia care as well as supervised practical training will be necessary.

Association between cingulum bundle structure and cognitive performance: an observational study in major depression.

BACKGROUND: Major depression can be regarded as a systemic neurobehavioral disorder resulting from dysfunction of the limbic-cortical networks. The cingulum bundle represents a major association fiber tract of those networks. The aim of our study was to determine the association of brain structural tissue markers of the cingulum bundle and cognitive function in patients with major depression. METHODS: Region-of-interest-based analyses of the middle-anterior and middle-posterior cingulum bundle fractional anisotropy (FA) and mean diffusivity (MD) using color-coded diffusion-tensor imaging and neuropsychological assessment in 14 patients with major depression. RESULTS: FA of the middle-anterior and middle-posterior cingulum bundle was significantly correlated to the performance in a planning and divided attention task. Furthermore, MD of the middle-posterior cingulum bundle was significantly correlated to a planning task. There was no significant correlation between FA and MD of the cingulum bundle and selective attention or memory. CONCLUSIONS: Brain structural tissue markers of the middle-anterior and middle-posterior cingulum bundle were found to be associated with executive functioning and divided attention in patients with major depression. Disconnection within the limbic-cortical networks may underlay cognitive dysfunction in major depression.

[From symptomatic to disease modifying therapy? Recent developments in the pharmacotherapy of Alzheimer's disease]. / Von der symptomatischen zur kausalen Therapie? Neue Entwicklungen in der Pharmakotherapie der Alzheimer-Demenz.

Until today the pharmacological therapy of Alzheimer's disease (AD) is still limited to symptomatic temporary improvement or stabilization of cognitive performance and activities of daily living, and the reduction of neuropsychiatric symptoms of the disease. Available symptomatic treatment options are the acetylcholinesterase inhibitors (ACh-I) donepezil, galantamine, rivastigmine, and the partial N-Methyl-D-Aspartat-(NMDA)-antagonist memantine. Further substances with symptomatic targets, especially selective acetylcholine and histamine receptors, are currently under development. Numerous of disease-modifying substances mainly targeting components of the amyloidogenic pathway of AD are presently studied in different phases of preclinical and clinical trials. Against earlier expectations which derived from promising preclinical immunization studies the breakthrough of disease-modification in AD is not in sight yet. Aim of this review is to summarize established pharmacological treatment options and the stage of development of upcoming symptomatic and disease-modifying substances of AD.

Diagnostic utility of different MRI and MR angiography measures in Fabry disease.

BACKGROUND: Neurologic hallmarks of Fabry disease (FD) include small fiber neuropathy as well as cerebral micro- and macroangiopathy with premature stroke. Cranial MRI shows progressive white matter lesions (WML) at an early age, increased signal intensity in the pulvinar, and tortuosity and dilatation of the larger vessels. To unravel the most promising imaging tool for the detection of CNS involvement in FD we compared the diagnostic utility of the different MR imaging findings. METHODS: Twenty-five clinically affected patients with FD (age 36.5 +/- 11.0) and 20 age-matched controls were investigated by structural MRI, MR angiography, and diffusion tensor imaging (DTI). Individual WML volumes, global mean diffusivity (MD), and mean cerebral artery diameters were determined. RESULTS: Using receiver operating characteristic analyses, enlarged diameters of the following cerebral arteries significantly separated patients with FD from controls: middle cerebral artery: area under curve (AUC) = 0.75, p = 0.005; posterior cerebral artery: AUC = 0.69, p = 0.041; carotid artery: 0.69, p = 0.041; basilar artery: AUC = 0.96, p < 0.0005. A total of 87% of the individuals were correctly classified by basilar artery diameters (sensitivity 95%, specificity 83%). WML volumes and global MD values did not significantly separate patients from controls. CONCLUSIONS: With an accuracy of 87%, basilar artery diameters were superior to all other MR measures for separating patients with Fabry disease (FD) from controls. Future studies should adopt basilar artery measurements for early detection and monitoring of brain involvement in FD. Moreover, further investigations should reveal if the dilated vasculopathy in FD could be a screening marker to detect FD in a cohort of other cerebrovascular diseases, especially in cryptogenic stroke.

Experimental evidence for a motivational origin of cognitive impairment in major depression.

BACKGROUND: Diagnostic criteria and empirical evidence support the existence of cognitive deficits in depression. However, depressed mood, loss of interest and low self-efficacy might influence cognitive performance. METHOD: Goal-setting instructions were used to promote motivation in depressed patients and control subjects during neuropsychological assessment. The resulting performance was compared with performance using standard instructions. Sixty in-patients with non-psychotic unipolar depression and 60 age- and education-matched healthy control subjects were assessed with standard neuropsychological tests [the Auditory Verbal Learning Test (AVLT), the Digit Symbol Test (DST), the Regensburg Word Fluency Test (RWT), and the Number Combination Test (Zahlen-Verbindungs-Test, ZVT)] using either goal-setting or standard test instructions. RESULTS: Depressed patients showed lower baseline performance and lower generalized self-efficacy (p<0.0005) than controls. However, goal-setting instructions significantly improved patients' memory performance by 10% [AVLT: F(5, 54)=3.611, p=0.007] and psychomotor performance by 13% [ZVT: F(3, 56)=3.667, p=0.017]. Consequently, patients and control subjects demonstrated similar results when goal-setting instructions were applied. Goal-setting instructions showed a statistical trend, increasing patients' performance in the DST by 12% [F(1, 58)=2.990, p=0.089], although their verbal fluency measured by the RWT did not increase. No significant correlations of increased performance with generalized self-efficacy were found. CONCLUSIONS: Cognitive deficits in depressed patients are influenced by motivational shortcomings. Because generalized self-efficacy failed to correlate to increased test performance, future research needs to disentangle the effective components of goal-setting instructions. Task-specific self-efficacy as well as enhancement of task-focused attention might underlie the significant goal-setting effect in depressed patients.

Voxel based analyses of diffusion tensor imaging in Fabry disease.

BACKGROUND: Fabry disease (FD) is a lysosomal storage disorder associated with marked cerebrovascular disease. Conventional MRI shows an extensive load of white matter lesions (WMLs) which may already be present at an early stage in the disease. OBJECTIVE: Investigator independent and sensitive quantification of structural changes in the brain in clinically affected men and women with FD. METHODS: We performed a voxel based analysis of diffusion tensor images (DTI) in 25 patients with FD and 20 age matched normal controls. RESULTS: DTI revealed significant increases in cerebral white matter mean diffusivity (MD) in patients with FD, which were pronounced in the periventricular white matter. Even the subgroup of patients without significant WMLs load (n = 18) showed increased diffusivity in the cerebral white matter. In gray matter areas, MD elevation was detected only in the posterior part of the thalamus, independent of the visible pulvinar alterations on T1 weighted images. Voxel based fractional anisotropy measurements did not differ significantly between patients and controls. CONCLUSIONS: The present study demonstrates the clinical feasibility of voxel based analysis of DTI as a sensitive tool to quantify brain tissue alterations in FD. The pattern of increased brain tissue diffusivity is probably due to microangiopathic alterations, mainly affecting the long perforating arteries.

[Pathophysiological aspects of brain structural disturbances in patients with Fabry disease: literature review]. / Pathophysiologische Aspekte hirnstruktureller Veränderungen bei Morbus Fabry: Literaturübersicht.

Fabry Disease (FD) is a rare X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A (alpha-GAL) enzyme activity. Neutral glycosphingolipides (esp. Gb3) accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. Cerebral manifestations that might be mainly due to progressive cerebrovascular dysfunction, are one major and often life-threatening burden of the disease. We reviewed the present literature concerning brain structural alterations in FD and discuss the possibly relevant underlying pathophysiological aspects of these disturbances. Cerebrovascular events (TIA, stroke) occur in FD at a rather early age. In female FD patients who were considered to be less affected "carriers" for a long time, the prevalence of cerebrovascular events seems to be at last as high as in male patients. In structural imaging white matter lesions (WML) can be found frequently even in young FD patients. In a recent study clinically equally affected men and women with FD showed a comparable severity of WML load. Different pathophysiological aspects of cerebral angiopathy and WML development are discussed against the background of current concepts (e. g. accumulation of Gb3 in vascular endothelium with consecutive cell proliferation and luminal stenosis, acceleration of focal intravasal pressure and disturbances of vascular auto-regulation). Pathological increase of pulvinar signal in T1-weighted MRI has also been described in FD. This finding was assumed to be caused by calcification as a consequence of disturbed local circulation. To enhance our knowledge about the relevant neurobiological processes the authors propose a more sensitive and early detection of brain structural changes in FD. New brain structural MRI methods such as diffusion-tensor imaging could provide a pattern of ultrastructural changes even in young patients without visible WML. This strategy could be as well useful for quantification of possible effects of the enzyme replacement therapy on brain structural alterations in FD. Based on recent data a systematic FD-screening by measuring Gb3 in urine of young patients with cryptogenic stroke should be discussed. Basically in such cases FD should be clinically considered.

Distribution characteristics, reproducibility, and precision of region of interest-based hippocampal diffusion tensor imaging measures.

BACKGROUND AND PURPOSE: For adequate interpretation of diffusion tensor imaging (DTI) parameters empirical distribution characteristics, precision, and reproducibility should be known. The present study investigated distribution and reliability parameters of hippocampal fractional anisotropy (FA) and mean diffusivity (MD). METHODS: FA and MD values were averaged in hippocampal regions of interest in 20 subjects (10 women and 10 men; age range, 25-69 years). Regions of interest were manually placed bilaterally by one investigator at 2 occasions, and by a second independent investigator. Sample distributions of FA and MD values were compared with normal distributions. Intraclass coefficients (ICCs), standard errors of measurement (SEMs), and coefficients of variation (CVs) with confidence intervals (CI95s) were computed. RESULTS: The results did not show any deviation of averaged FA (0.237 +/- 0.017) and MD (775 +/- 28 microm2/s) values from normal distribution. Intraobserver reliability (ICC > or = 0.90) and precision (CV < or = 3.5%) were high for all measures. Interobserver reliability reached values of ICC > or = 0.84 and CV < or = 4.1%. FA yielded lower precision (CV 2.2-4.1%) than MD (CV 1.3-2.5%), CI95s were around +/-0.015-0.020 and +/-25-30 microm2/s for FA and MD, respectively. FA differences of 0.020-0.030 and MD differences of 40-50 microm2/s can be assumed to reflect reliably distinct values in hippocampal regions. CONCLUSION: The results are in line with previous reports on reliability of DTI measures by using different designs and methodology. Notwithstanding the difficulties associated with region of interest-derived DTI measurements in hippocampal regions, the present approach provides estimates of distribution characteristics and precision applicable to routine assessments of DTI parameters in clinical and research context.

[Psychiatric and neuropsychological signs and symptoms in patients with fabry disease: literature review]. / Psychiatrische und neuropsychologische Auffälligkeiten bei Patienten mit Morbus Fabry: Literaturübersicht.

Fabry Disease (FD) is an X-linked lysosomal storage disorder (prevalence about 1 : 100 000) caused by a genetic defect associated with a lack of alpha-galactosidase A (alpha-GAL) enzyme activity. As a consequence, neutral glycosphingolipides can not be cleaved and metabolized, and accumulate in lysosomes of several tissues, particularly in vascular endothelium and smooth muscle cells. The most prominent symptoms comprise pain attacks and acroparesthesia, angiokeratoma, corneal opacity, renal and cardiac dysfunction, hypo- and anhidrosis, gastrointestinal symptoms, and cerebrovascular dysfunction with vertigo, headache, and cerebral ischemia. Characteristic symptoms of FD can occur in male and female patients with the same prevalence, while females with FD seem to be less severely affected. The course of untreated illness is progressive with considerable interindividual variability. Since 2001 two enzyme replacement therapies are approved which can possibly stop the disease progress and alleviate symptoms. The very few reports and clinical observations have shown that a very high proportion of FD patients develop neuropsychiatric symptoms. However, accurate data are lacking. Although the pathophysiologic mechanisms are quite unknown, it is surmised that sphingolipid deposits in the endothelium of small cerebral vessels lead to regional cerebral ischemia accompanied by neuropsychiatric symptoms and deficits. Furthermore, patients with FD are chronically distressed by pain attacks and additional somatic and psychological impairment. Frequently, pain attacks are triggered by psychosocial stress. The high interindividual variability can, thus, also be interpreted on the basis of existing stress and coping models. The present paper will review the presently available psychiatric and neuropsychological findings in FD and will discuss difficulties associated with classification and differential diagnosis of psychiatric disorders occurring in patients with FD.

White matter lesion severity in male and female patients with Fabry disease.

In male patients with Fabry disease (FD), significant age-related cerebral white matter lesions (WMLs) can be found. Although characteristic symptoms including cerebrovascular events are highly prevalent also in females with FD, cerebral structural changes have not been investigated in female FD patients yet. The authors quantified the WML load of 13 male and 14 age-matched female patients with FD and could demonstrate a comparably high frequency and severity of WMLs in both groups.