Semantic memory and depressive symptoms in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

BACKGROUND: Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment. METHODS: 323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated. RESULTS: Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS. CONCLUSIONS: We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.

The impact of depressive symptoms on health-related quality of life in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

BACKGROUND: Health-related quality of life (HRQOL) is an important issue in the context of dementia care. The purpose of this study was to investigate the association between HRQOL and depressive symptoms in patients with subjective cognitive decline (SCD) and subtypes of mild cognitive impairment (MCI) and Alzheimer´s disease (AD). METHODS: In this cross-sectional, observational study, a control group and four experimental groups (SCD, non-amnestic MCI, amnesticMCI, AD) were compared. Neuropsychological measurers (NTBV) and psychological questionnaires were used for data collection. RESULTS: The control group scored higher than patients with SCD, naMCI, aMCI, or AD for the Mental Health Component Score (MHCS) of the Short Form of the Health Survey (SF-36). The Physical Health Component Score (PHCS) of the SF-36 differed only between some groups. Furthermore, cognitive variables were more strongly associated with the physical aspects of HRQOL, whereas depressive symptoms were more strongly related with the mental aspects of HRQOL. CONCLUSIONS: HRQOL and depressive symptoms are closely related in patients with cognitive impairments. Therefore, it is of great importance to assess patients with subjective impairment carefully in terms of depressive symptoms.

Facial emotion recognition in patients with subjective cognitive decline and mild cognitive impairment.

BACKGROUND: Deficits in facial emotion recognition (FER) have been shown to substantially impair several aspects in everyday life of affected individuals (e.g. social functioning). Presently, we aim at assessing differences in emotion recognition performance in three patient groups suffering from mild forms of cognitive impairment compared to healthy controls. METHODS: Performance on a concise emotion recognition test battery (VERT-K) of 68 patients with subjective cognitive decline (SCD), 44 non-amnestic (non-aMCI), and 25 amnestic patients (aMCI) with mild cognitive impairment (MCI) was compared with an age-equivalent sample of 138 healthy controls all of which were recruited within the framework of the Vienna Conversion to Dementia Study. Additionally, patients and controls underwent individual assessment using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (NTBV), the Beck Depression Inventory (BDI), and a measure of premorbid IQ (WST). RESULTS: Type of diagnosis showed a significant effect on emotion recognition performance, indicating progressively deteriorating results as severity of diagnosis increased. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from -0.30 to -0.83) except for SCD versus controls. Moreover, emotion recognition performance was higher in women and positively associated with premorbid IQ. CONCLUSIONS: Our findings indicate substantial effects of progressive neurological damage on emotion recognition in patients. Importantly, emotion recognition deficits were observable in non-amnestic patients as well, thus conceivably suggesting associations between decreased recognition performance and global cognitive decline. Premorbid IQ appears to act as protective factor yielding lesser deficits in patients showing higher IQs.

Subjective memory complaints, depressive symptoms and cognition in patients attending a memory outpatient clinic.

BACKGROUND: The goals of this study were to establish prevalence of subjective memory complaints (SMC) and depressive symptoms (DS) and their relation to cognitive functioning and cognitive status in an outpatient memory clinic cohort. METHODS: Two hundred forty-eight cognitively healthy controls and 581 consecutive patients with cognitive complaints who fulfilled the inclusion criteria were included in the study. RESULTS: A statistically significant difference (p < 0.001) between control group and patient group regarding mean SMC was detected. 7.7% of controls reported a considerable degree of SMC, whereas 35.8% of patients reported considerable SMC. Additionally, a statistically significant difference (p < 0.001) between controls and patient group regarding Beck depression score was detected. 16.6% of controls showed a clinical relevant degree of DS, whereas 48.5% of patients showed DS. An analysis of variance revealed a statistically significant difference across all four groups (control group, SCI group, naMCI group, aMCI group) (p < 0.001). Whereas 8% of controls reported a considerable degree of SMC, 34% of the SCI group, 31% of the naMCI group, and 54% of the aMCI group reported considerable SMC. A two-factor analysis of variance with the factors cognitive status (controls, SCI group, naMCI group, aMCI group) and depressive status (depressed vs. not depressed) and SMC as dependent variable revealed that both factors were significant (p < 0.001), whereas the interaction was not (p = 0.820). CONCLUSIONS: A large proportion of patients seeking help in a memory outpatient clinic report considerable SMC, with an increasing degree from cognitively healthy elderly to aMCI. Depressive status increases SMC consistently across groups with different cognitive status.

Using static and dynamic canonical correlation coefficients as quantitative EEG markers for Alzheimer's disease severity.

We analyzed the relation between Alzheimer's disease (AD) severity as measured by Mini-Mental State Examination (MMSE) scores and quantitative electroencephalographic (qEEG) markers that were derived from canonical correlation analysis. This allowed an investigation of EEG synchrony between groups of EEG channels. In this study, we applied the data from 79 participants in the multi-centric cohort study PRODEM-Austria with probable AD. Following a homogeneous protocol, the EEG was recorded both in resting state and during a cognitive task. A quadratic regression model was used to describe the relation between MMSE and the qEEG synchrony markers. This relation was most significant in the δ and θ frequency bands in resting state, and between left-hemispheric central, temporal and parietal channel groups during the cognitive task. Here, the MMSE explained up to 40% of the qEEG marker's variation. QEEG markers showed an ambiguous trend, i.e. an increase of EEG synchrony in the initial stage of AD (MMSE>20) and a decrease in later stages. This effect could be caused by compensatory brain mechanisms. We conclude that the proposed qEEG markers are closely related to AD severity. Despite the ambiguous trend and the resulting diagnostic ambiguity, the qEEG markers could provide aid in the diagnostics of early-stage AD.

Depth of word processing in Alzheimer patients and normal controls: a magnetoencephalographic (MEG) study.

Effects related to depth of verbal information processing were investigated in probable Alzheimer's disease patients (AD) and age matched controls. During word encoding sessions 10 patients and 10 controls had either to decide whether the letter "s" appeared in visually presented words (alphabetical decision, shallow encoding), or whether the meaning of each presented word was animate or inanimate (lexical decision, deep encoding). These encoding sessions were followed by test sessions during which all previously encoded words were presented again together with the same number of new words. The task was then to discriminate between repeated and new words. Magnetic field changes related to brain activity were recorded with a whole cortex MEG.5 probable AD patients showed recognition performances above chance level related to both depths of information processing. Those patients and 5 age matched controls were then further analysed. Recognition performance was poorer in probable AD patients compared to controls for both levels of processing. However, in both groups deep encoding led to a higher recognition performance than shallow encoding. We therefore conclude that the performance reduction in the patient group was independent of depth of processing. Reaction times related to false alarms differed between patients and controls after deep encoding which perhaps could already be used for supporting an early diagnosis. The analysis of the physiological data revealed significant differences between correctly recognised repetitions and correctly classified new words (old/new-effect) in the control group which were missing in the patient group after deep encoding. The lack of such an effect in the patient group is interpreted as being due to the respective neuropathology related to probable AD. The present results demonstrate that magnetic field recordings represent a useful tool to physiologically distinguish between probable AD and age matched controls.

Magnetoencephalographic--features related to mild cognitive impairment.

We recorded changes of brain activity from 10 MCI patients and 10 controls related to shallow (nonsemantic) and deep (semantic) word encoding using a whole-head MEG. During the following recognition tasks, all participants had to recognize the previously encoded words, which were presented again together with new words. In both groups recognition performance significantly varied as a function of depth of processing. No significant differences were found between the groups. Reaction times related to correctly classified new words (correct rejections) and incorrectly classified repetitions (misses) of MCI patients showed a strong tendency toward prolongation compared to controls, although no statistically significant differences occurred. Strikingly, in patients the neurophysiological data associated with nonsemantic and semantic word encoding differed significantly between 250 and 450 ms after stimulus onset mainly over left frontal and left temporal sensors. They showed higher electrophysiological activation during shallow encoding as compared to deep encoding. No such significant differences were found in controls. The present results might reflect a dysfunction with respect to shallow encoding of visually presented verbal information. It is interpreted that additional neural activation is needed to compensate for neurodegeneration. This finding is suggested to be an additional tool for MCI diagnosis.

[Differential diagnosis of dementia]. / Differentialdiagnose der Demenzen.

Owing to the progress of individual life expectancy, the number of demented people will clearly increase in the next decades. Cognitive impairment refers not only to dementia, but also to mild cognitive impairment (MCI), associated with reduced complex daily activity and decreased quality of live. It may, in many cases (10-15% per year) progress to permanent dementia. The most frequent aetiologies of dementia syndromes are the Alzheimer's Disease (AD), vascular Dementia (VD), the combination of both and Lewy-Body-Disease. Primarily neuro-psychiatric and internal medical reasons for cognitive decline have also to be taken into account for rational treatment.

[Psychosocial risk factors for Alzheimer's disease]. / Psychosoziale Risikofaktoren für die Alzheimer Krankheit.

Psychosocial stress has been shown to contribute to neurodegenerative changes and has been discussed as a pathogenic element in Alzheimer's disease (AD). However, studies investigating this aspect are rare. We performed a case-control study on 50 clinically diagnosed probable AD patients and 90 controls consisting of surgical patients. Interviews were performed by trained personnel, using a questionnaire, a semi-structured interview, and a psychosocial risk list protocol. Findings are presented as marginal and partial odds ratio from linear logistic regressions. Adapting to an active but unproductive working style as well as living with a dominant spouse is associated with significant risk for AD. Protective factors are high self-esteem and working in one's desired job. Our results indicate psychosocial factors as a possible agent in the latent development of AD and may shift the focus from more traditional risk factors to hitherto almost neglected psychosocial factors in a disease of still unknown etiology.

Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial.

OBJECTIVES: To assess the effects of rivastigmine on the core domains of Alzheimer's disease. DESIGN: Prospective, randomised, multicentre, double blind, placebo controlled, parallel group trial. Patients received either placebo, 1-4 mg/day (lower dose) rivastigmine, or 6-12 mg/day (higher dose) rivastigmine. Doses were increased in one of two fixed dose ranges (1-4 mg/day or 6-12 mg/day) over the first 12 weeks with a subsequent assessment period of 14 weeks. SETTING: 45 centres in Europe and North America. PARTICIPANTS: 725 patients with mild to moderately severe probable Alzheimer's disease diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. OUTCOME MEASURES: Cognitive subscale of the Alzheimer's disease assessment scale, rating on the clinician interview based impression of change incorporating caregiver information scale, and the progressive deterioration scale. RESULTS: At the end of the study cognitive function had deteriorated among those in the placebo group. Scores on the Alzheimer's disease assessment scale improved in patients in the higher dose group when compared with patients taking placebo (P<0.05). Significantly more patients in the higher dose group had improved by 4 points or more than had improved in the placebo group (24% (57/242) v 16% (39/238)). Global function as rated by the clinician interview scale had significantly improved among those in the higher dose group compared with those taking placebo (P<0.001), and significantly more patients in the higher dose group showed improvement than did in the placebo group (37% (80/219) v 20% (46/230)). Mean scores on the progressive deterioration scale improved from baseline in patients in the higher dose group but fell in the placebo group. Adverse events were predominantly gastrointestinal, of mild to moderate severity, transient, and occurred mainly during escalation of the dose. 23% (55/242) of those in the higher dose group, 7% (18/242) of those in the lower dose group, and 7% (16/239) of those in the placebo group discontinued treatment because of adverse events. CONCLUSIONS: Rivastigmine is well tolerated and effective. It improves cognition, participation in activities of daily living, and global evaluation ratings in patients with mild to moderately severe Alzheimer's disease. This is the first treatment to show compelling evidence of efficacy in a predominantly European population.

Olfactory functions in Parkinson's disease and Alzheimer's disease.

The aim of this investigation was to compare olfactory functions of patients suffering from Parkinson's disease (PD) and Alzheimer's disease (AD). Olfactory threshold, odor identification ability and odor memory performance were assessed in 21 non-demented PD patients and in 22 AD patients. Both patient groups were impaired in relation to an age-matched control group for the measure of odor identification. AD patients showed a higher olfactory threshold and poorer odor memory performance.

The mydriatic effect of tropicamide and its diagnostic use in Alzheimer's disease.

The mydriatic effect of topically administered tropicamide was investigated as a possible diagnostic indicator for Alzheimer's disease. Although an initial series seemed to show a correlation between hypersensitivity to tropicamide and intellectual impairment, subsequent testing showed a greater inter- and intra-individual variation than that between the normal group and the group of patients with intellectual impairment. This procedure seems, therefore, to lack sufficient specificity to be useful for such a diagnostic purpose.

[Etiology of Alzheimer's disease]. / Zur Atiologie der Alzheimer-Krankheit.

The major factor that causes problems in studies on the aetiology of Alzheimer's disease (AD) is the clinical heterogeneity of the condition. Familial early-onset AD and familial late-onset AD are differentiated from sporadic AD. Aetiologically a genetic defect on chromosome 21 is the most important factor, at least in some cases of AD. In familial AD and autosomal dominant inheritance with complete penetrance in old age is thought to be possible. In sporadic AD the role of genetic and exogenous factors (infectious agents, aluminium) is unknown. The current status of knowledge about the aetiology of Alzheimer's disease is reviewed with reference to the literature.

Subarachnoid hemorrhage of unknown etiology: early prognostic factors for long-term functional capacity.

Forty-one patients suffering subarachnoid hemorrhage (SAH) of unknown etiology were re-investigated at an average of 91 months after the bleed to determine functional capacity. Nineteen patients were performing at their previous level of work, five were employed part-time, and four could not work due to the SAH. Five patients showed a moderate disability in activities of daily living but were not dependent on help, one patient was severely disabled, and two had died. There was one rebleed. Early prognosis of an unfavorable outcome was possible on the basis of three clinical variables on admission: a history of hypertension, a Hunt and Hess grade of greater than II, and the presence of focal neurological deficits. In addition, the presence of an organic mental syndrome at discharge was identified as a predictive factor for reduced functional capacity later on. Other clinical variables in the acute stage, including sex, age, history of headache, interval between SAH and admission, impaired consciousness, and cognitive deficits, were not related to a limited functional level. Residual neurological deficits and the Glasgow Outcome Scale score on discharge were also not predictive of restrictions in global functions evaluated by means of the Karnofsky Performance Scale status at follow-up review.

Clinical comparison of dementia in Parkinson's and Alzheimer's disease.

Neuropsychological, neuropathological and neurochemical findings show different types of dementias. Few of them have been able to confirm a division into "subcortical" and "cortical" dementia, so this concept has to be questioned. The present clinical study compared type and severity of dementia in 12 Parkinson-patients (PD) and 12 Alzheimer-patients (AD). The age-adjusted normal value differed a significantly from both patient groups. No significant difference in pattern of neuropsychological deficits between PD- and AD-patients was apparent. However, after similar duration of illness, dementia was more severe in AD- than in PD-patients.

Early diagnosis of Alzheimer dementia?

The main problems in early diagnosis of Alzheimer dementia (AD) are: 1. The differentiation between normal aging and AD i.e. difficulties in the assessment of cognitive disturbances in the healthy elderly and in early demented subjects. 2. Interference with other dementia syndromes. 3. Lack of information in the population and among physicians about the different causes and courses of dementia syndromes. The first two aspects are discussed in this paper.

Galanthamine treatment in Alzheimer's disease.

18 patients who had fulfilled the NINCDS-ADRDA criteria for "possible AD" took part in a clinical study to evaluate the effect of the cholinesterase inhibitor Galanthamine, 30 mg/day. Neuropsychological und social parameters were rated. This open clinical pilot-study showed no statistic significant change in neuropsychological test-results. However after 1 year treatment 6 patients are still taking the drug. According to their care-persons there was a positive changes in competence of everyday-routine and/or in the emotional situation.

Pattern electroretinogram and luminance electroretinogram in Alzheimer's disease.

Visual symptoms are often among the first complaints of patients suffering from Alzheimer's disease and several studies showed a delay in flash visual evoked potentials. Hinton et al. (1986) described optic nerve degenerations in patients with Alzheimer's disease and Sadun published a dropout of retinal ganglion cells that range from 30% to 60%. The reduction of neurotransmitters, especially of acetylcholine, found in the brain might also occur in the retina. Therefore we examined the retinal functions of patients suffering from Alzheimer's disease. In eight patients the pattern-electroretinograms and the scotopic and photopic luminance-electroretinograms were recorded and compared to an age-matched control group. We could not find any abnormalities in the pattern- and the luminance electroretinograms of patients with Alzheimer's disease. Although cholinergic cells have been found in the retina, our results did not reveal an involvement of retinal functions in Morbus Alzheimer.

Spontaneous subarachnoid hemorrhage. Prognostic factors for social readjustment.

Sixty-seven patients surviving spontaneous subarachnoid haemorrhage (SAH) have been followed up for 2-12 years (mean: 7 years) in order to determine prognostic factors concerning the long-term disability in familial and social functioning. A correlation was found between the severity of the neurological deficit at the time of admission and the degree of familial and social disability at the end of the observation period. In addition, the Barthel-Index on discharge was shown to be of prognostic value for readjustment for social--but not for familial--functioning. Other clinical variables in the acute stage, however, including source of bleeding, sex, age, interval between SAH and admission, level of consciousness, cognitive functions, as well as initial Hunt and Hess grading and Glasgow Coma Scale scoring, did not influence the long-term social prognosis. Furthermore, residual neurological signs, cognitive dysfunctions, and the Glasgow Outcome score on discharge were not related to the extent of social handicap in the long-term outcome. At the end of the observation period, significant correlations were found between the presence of persisting neurological and cognitive deficits but also disability in ADL functions and occupational capacity and the decline in familial and social functioning.