Robert Haussmann

Treatment of lithium intoxication: facing the need for evidence

Lithium has been used as the gold standard in the treatment of major depressive and bipolar disorders for decades. Due to its narrow therapeutic index, lithium toxicity is a common clinical problem. Although risk factors for lithium intoxication seem to be well-described, lacking patient education and inexperience of treatment are assumed to contribute to the probability of lithium intoxication. A review of literature shows that the treatment of lithium intoxication has not been adequately studied or standardized. The aim of this literature review is to compile and present current evidence on the treatment of lithium intoxication and contribute to a standardization regarding general treatment recommendations as well as evidence on indication for extracorporeal methods. Against the background of this common and potentially life-threatening condition, the standardization of the treatment of lithium intoxication is definitely a task for the future.

Education and Genetic Risk Modulate Hippocampal Structure in Alzheimer’s Disease

Genetic and environmental protective factors and risks modulate brain structure and function in neurodegenerative diseases and their preclinical stages. We wanted to investigate whether the years of formal education, a proxy measure for cognitive reserve, would influence hippocampal structure in Alzheimer’s disease patients, and whether apolipoprotein Eε4 (APOE4) carrier status and a first-degree family history of the disease would change a possible association. Fifty-eight Alzheimer’s disease patients underwent 3T magnetic resonance imaging. We applied a cortical unfolding approach to investigate individual subregions of the medial temporal lobe. Among patients homozygous for the APOE4 genotype or carrying both APOE4 and family history risks, lower education was associated with a thinner cortex in multiple medial temporal regions, including the hippocampus. Our data suggest that the years of formal education and genetic risks interact in their influence on hippocampal structure in Alzheimer’s disease patients.

Risk factors for dementia are not associated with cognitive dysfunction in young people with major depressive disorder

BACKGROUND Hippocampal thinning and carrying the ε4 allele of the apolipoprotein E (APOE) are associated with reduced cognitive performance in older people. Although cognitive impairment is also frequent during and after depressive episodes, it may occur irrespective of age, which makes it difficult to determine, whether this symptom indicates a risk for or shared mechanisms with neurodegeneration. We therefore investigated the influence of genetic and brain imaging risk factors for dementia on cognitive impairment in young people with major depressive disorder. METHODS We used magnetic resonance imaging, APOE genotyping and neurocognitive assessments to examine young adults (mean age: 29.1 ± 6.3 years) with major depressive disorder and a current depressive episode, presenting with or without cognitive deficits. RESULTS Neither hippocampal thickness nor APOE genotype predicted cognitive impairment. Patients with objective cognitive deficits reported a greater number of previous depressive episodes. LIMITATIONS Our results have to be interpreted with caution. The small sample size could have prevented the detection of effects. Complementing research methods and investigations across the life span would be necessary to reveal possible interactions between risk factors for dementia, neurodegeneration, depression, and age. CONCLUSIONS In young adults, recurrent depressive episodes may increase the likelihood for cognitive deficits, while common risk factors for dementia do not.

Cognitive impairment and medial temporal lobe structure in young adults with a depressive episode

BACKGROUND Cognitive deficits are common in patients with a depressive episode although the predictors for their development and severity remain elusive. We investigated whether subjective and objective cognitive impairment in young depressed adults would be associated with cortical thinning in medial temporal subregions. METHODS High-resolution magnetic resonance imaging, cortical unfolding data analysis, and comprehensive assessments of subjective and objective cognitive abilities were performed on 27 young patients with a depressive episode (mean age: 29.0 ± 5.8 years) and 23 older participants without a history of a depressive disorder but amnestic mild cognitive impairment (68.5 ± 6.6 years) or normal cognition (65.2 ± 8.7 years). RESULTS Thickness reductions in parahippocampal, perirhinal and fusiform cortices were associated with subjective memory deficits only among young patients with a depressive episode and a measurable cognitive impairment. LIMITATIONS Long-term longitudinal data would be desirable to determine the trajectories of cognitive impairment associated with depression in patients with or without cortical structure changes. CONCLUSIONS The presence of clinically significant cognitive deficits in young people with a depressive episode may identify a patient population with extrahippocampal cortical thinning.

Family History of Alzheimer’s Disease and Subjective Memory Performance

People with a first-degree family history of Alzheimer’s disease are at an increased risk of developing dementia. Subjective memory impairment among individuals with no measurable cognitive deficits may also indicate elevated dementia risk. It remains unclear whether nondemented people with a positive family history of Alzheimer’s disease are more likely to experience cognitive deficits and whether such an association reflects underlying neuropathology. We therefore investigated subjective memory impairment and hippocampal cortical thickness in 40 healthy older adults and 35 patients with amnestic mild cognitive impairment. We found greater subjective memory impairment and left hemispheric hippocampal cortical thinning associated with a first-degree family history of Alzheimer’s disease in healthy older adults. This suggests that subjective memory impairment could reflect preclinical stage neurodegeneration among individuals with the family history risk factor.

Extrinsic and Intrinsic Help-Seeking Motivation in the Assessment of Cognitive Decline:

Diagnostic assessments for dementia include the evaluation of subjective memory impairment, dementia worries, or depressive symptoms. Data on the predictive value of these factors remain unclear, and varying help-seeking behavior may contribute to this finding. We investigate whether differentiating help-seeking motivation from other psychological factors associated with cognitive impairment would enhance the prediction of diagnostic outcomes in a memory clinic. We obtained information on help-seeking motivation from 171 patients who underwent routine diagnostic assessments. Utilizing a discriminant correspondence analysis, our results indicate that extrinsic motivation increases the likelihood of receiving a dementia diagnosis, whereas depression or the duration of deficits carries discriminatory information to further guide the differentiation of prodromal dementia. Recognizing motivational aspects of help-seeking behavior can complement the clinical evaluation of cognitive performance.

MAPT mutation associated with frontotemporal dementia and parkinsonism (FTDP-17)

We present a 56-year-old patient suffering from frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). The history included a three-generation pedigree and the patient was found to be a mutation carrier. The diagnosis was hindered by late appearance of the hypokinetic movement disorder. For clinicians, it is important to consider rare neurodegenerative disease variants in early-onset familial dementia syndromes with behavioral, cognitive, and motor symptoms.

Precuneus Structure Changes in Amnestic Mild Cognitive Impairment

Patients with amnestic mild cognitive impairment (aMCI) are at risk for developing Alzheimer’s disease. Due to their prominent memory impairment, structural magnetic resonance imaging (MRI) often focuses on the hippocampal region. However, recent positron-emission tomography data suggest that within a network of frontal and temporal changes, patients with aMCI show metabolic alterations in the precuneus, a key region for higher cognitive functions. Using high-resolution MRI and whole-brain cortical thickness analyses in 28 patients with aMCI and 25 healthy individuals, we wanted to investigate whether structural changes in the precuneus would be associated with cortical thickness reductions in frontal and temporal brain regions in patients with aMCI. In contrast to healthy people, patients with aMCI showed an association of cortical thinning in the precuneus with predominantly left-hemispheric thickness reductions in medial temporal and frontal cortices. Our data highlight structural neuronal network characteristics among patients with aMCI.

Family History of Alzheimer's Disease and Cortical Thickness in Patients With Dementia.

A first-degree family history of Alzheimer’s disease reflects genetic risks for the neurodegenerative disorder. Recent imaging data suggest localized effects of genetic risks on brain structure in healthy people. It is unknown whether this association can also be found in patients who already have dementia. Our aim was to investigate whether family history risk modulates regional medial temporal lobe cortical thickness in patients with Alzheimer’s disease. We performed high-resolution magnetic resonance imaging and cortical unfolding data analysis on 54 patients and 53 nondemented individuals. A first-degree family history of Alzheimer’s disease was associated with left hemispheric cortical thinning in the subiculum among patients and controls. The contribution of Alzheimer’s disease family history to regional brain anatomy changes independent of cognitive impairment may reflect genetic risks that modulate onset and clinical course of the disease.