Kidney function and cognitive impairment among older hospitalized patients: a comparison of four glomerular filtration rate equations.

BACKGROUND: The relationship between the estimated glomerular filtration rate (eGFR) and cognitive impairment may change as a function of the equation used. We aimed at investigating the association between four different eGFR equations and cognitive impairment among older hospitalized patients. METHODS: Our series consisted of 795 older patients consecutively admitted to 7 geriatric and internal medicine acute care wards. The eGFR was calculated by Chronic Kidney Disease Epidemiologic Collaboration (CKD-EPI), Cockcroft-Gault (CG), Berlin Initiative Study (BIS) and Full Age Spectrum (FAS) equations. Study outcomes were total Mini Mental State Examination (MMSE) < 24 and sub-scores related to orientation to time, orientation to space, registration, calculation, three words recall, language and constructional praxis. Statistical analysis was carried out by logistic or Poisson regressions when appropriate. The accuracy of eGFR equations in identifying cognitive outcomes was investigated by calculating the area (AUC) under the receiver operating characteristic (ROC) curve for each equation. RESULTS: After adjusting for potential confounders, eGFR < 30 was significantly associated with MMSE < 24 only with CKD-EPI equation (OR 2.03, 95% CI 1.04-3.96). eGFR < 30 was significantly associated with constructional apraxia with all study equations (CKD-EPI: OR 3.62, 95% CI 1.73-7.56; BIS: OR 2.86, 95% CI 1.31-6.26; FAS: OR 2.83, 95% CI 1.44-5.56; CG: OR 2.08, 95% CI 1.09-3.99). The accuracy of eGFR < 30 in identifying patients with defective constructional praxis was poor with all (BIS: AUC 0.54, 95% CI 0.52-0.55; CKD-EPI: AUC 0.55, 95% CI 0.53-0.57; CG: AUC 0.58, 95% CI 0.55-0.61; FAS: AUC 0.56, 95% CI 0.54-0.58). CONCLUSIONS: Constructional apraxia may characterize the cognitive profile of older patients with severe CKD. The accuracy in identifying patients with constructional apraxia is only fair, and studies including other biomarkers of kidney function are needed.

Relational and conjunctive binding functions dissociate in short-term memory.

Remembering complex events requires binding features within unified objects (conjunctions) and holding associations between objects (relations). Recent studies suggest that the two functions dissociate in long-term memory (LTM). Less is known about their functional organization in short-term memory (STM). The present study investigated this issue in patient AE affected by a stroke which caused damage to brain regions known to be relevant for relational functions both in LTM and in STM (i.e., the hippocampus). The assessment involved a battery of standard neuropsychological tasks and STM binding tasks. One STM binding task (Experiment 1) presented common objects and common colors forming either pairs (relations) or integrated objects (conjunctions). Free recall of relations or conjunctions was assessed. A second STM binding task used random polygons and non-primary colors instead (Experiment 2). Memory was assessed by selecting the features that made up the relations or the conjunctions from a set of single polygons and a set of single colors. The neuropsychological assessment revealed impaired delayed memory in AE. AE's pronounced relational STM binding deficits contrasted with his completely preserved conjunctive binding functions in both Experiments 1 and 2. Only 2.35% and 1.14% of the population were expected to have a discrepancy more extreme than that presented by AE in Experiments 1 and 2, respectively. Processing relations and conjunctions of very elementary nonspatial features in STM led to dissociating performances in AE. These findings may inform current theories of memory decline such as those linked to cognitive aging.

Non-verbal memory measured by Rey-Osterrieth Complex Figure B: normative data.

One of the major problems that clinical neuropsychology has had in memory clinics is to apply ecological, easily administrable and sensitive tests that can make the diagnosis of dementia both precocious and reliable. Often the choice of the best neuropsychological test is hard because of a number of variables that can influence a subject's performance. In this regard, tests originally devised to investigate cognitive functions in healthy adults are not often appropriate to analyze cognitive performance in old subjects with low education because of their intrinsically complex nature. In the present paper, we present normative values for the Rey-Osterrieth Complex Figure B Test (ROCF-B) a simple test that explores constructional praxis and visuospatial memory. We collected normative data of copy, immediate and delayed recall of the ROCF-B in a group of 346 normal Italian subjects above 40 years. A multiple regression analysis was performed to evaluate the potential effect of age, sex, and education on the three tasks administered to the subjects. Age and education had a significant effect on copying, immediate recall, and delayed recall as well as on the rate of forgetting. Correction grids and equivalent scores with cut-off values relative to each task are available. The availability of normative values can make the ROCF-B a valid instrument to assess non-verbal memory in adults and in the elderly for whom the commonly used ROCF-A is too demanding.

Short-term memory binding deficits in Alzheimer's disease.

Alzheimer's disease impairs long term memories for related events (e.g. faces with names) more than for single events (e.g. list of faces or names). Whether or not this associative or 'binding' deficit is also found in short-term memory has not yet been explored. In two experiments we investigated binding deficits in verbal short-term memory in Alzheimer's disease. Experiment 1: 23 patients with Alzheimer's disease and 23 age and education matched healthy elderly were recruited. Participants studied visual arrays of objects (six for healthy elderly and four for Alzheimer's disease patients), colours (six for healthy elderly and four for Alzheimer's disease patients), unbound objects and colours (three for healthy elderly and two for Alzheimer's disease patients in each of the two categories), or objects bound with colours (three for healthy elderly and two for Alzheimer's disease patients). They were then asked to recall the items verbally. The memory of patients with Alzheimer's disease for objects bound with colours was significantly worse than for single or unbound features whereas healthy elderly's memory for bound and unbound features did not differ. Experiment 2: 21 Alzheimer's disease patients and 20 matched healthy elderly were recruited. Memory load was increased for the healthy elderly group to eight items in the conditions assessing memory for single or unbound features and to four items in the condition assessing memory for the binding of these features. For Alzheimer's disease patients the task remained the same. This manipulation permitted the performance to be equated across groups in the conditions assessing memory for single or unbound features. The impairment in Alzheimer's disease patients in recalling bound objects reported in Experiment 1 was replicated. The binding cost was greater than that observed in the healthy elderly group, who did not differ in their performance for bound and unbound features. Alzheimer's disease grossly impairs the mechanisms responsible for holding integrated objects in verbal short-term memory.

Famous faces and voices: Differential profiles in early right and left semantic dementia and in Alzheimer's disease.

BACKGROUND: Famous face and voice recognition is reported to be impaired both in semantic dementia (SD) and in Alzheimer's Disease (AD), although more severely in the former. In AD a coexistence of perceptual impairment in face and voice processing has also been reported and this could contribute to the altered performance in complex semantic tasks. On the other hand, in SD both face and voice recognition disorders could be related to the prevalence of atrophy in the right temporal lobe (RTL). OBJECTIVE: The aim of the present study was twofold: (1) to investigate famous faces and voices recognition in SD and AD to verify if the two diseases show a differential pattern of impairment, resulting from disruption of different cognitive mechanisms; (2) to check if face and voice recognition disorders prevail in patients with atrophy mainly affecting the RTL. MATERIALS: To avoid the potential influence of primary perceptual problems in face and voice recognition, a pool of patients suffering from early SD and AD were administered a detailed set of tests exploring face and voice perception. Thirteen SD (8 with prevalence of right and 5 with prevalence of left temporal atrophy) and 25 CE patients, who did not show visual and auditory perceptual impairment, were finally selected and were administered an experimental battery exploring famous face and voice recognition and naming. Twelve SD patients underwent cerebral PET imaging and were classified in right and left SD according to the onset modality and to the prevalent decrease in FDG uptake in right or left temporal lobe respectively. Correlation of PET imaging and famous face and voice recognition was performed. RESULTS: Results showed a differential performance profile in the two diseases, because AD patients were significantly impaired in the naming tests, but showed preserved recognition, whereas SD patients were profoundly impaired both in naming and in recognition of famous faces and voices. Furthermore, face and voice recognition disorders prevailed in SD patients with RTL atrophy, who also showed a conceptual impairment on the Pyramids and Palm Trees test more important in the pictorial than in the verbal modality. Finally, in 12SD patients in whom PET was available, a strong correlation between FDG uptake and face-to-name and voice-to-name matching data was found in the right but not in the left temporal lobe. DISCUSSION: The data support the hypothesis of a different cognitive basis for impairment of face and voice recognition in the two dementias and suggest that the pattern of impairment in SD may be due to a loss of semantic representations, while a defect of semantic control, with impaired naming and preserved recognition might be hypothesized in AD. Furthermore, the correlation between face and voice recognition disorders and RTL damage are consistent with the hypothesis assuming that in the RTL person-specific knowledge may be mainly based upon non-verbal representations.

Applause sign in Alzheimer's disease: relationships to cognitive profile and severity of illness.

The present study aims to investigate the potential clinical utility of applause sign in Alzheimer's disease (AD), exploring whether it is consequent to the severity of cognitive impairment or to specific neuropsychological profiles. According to the current debate, the role of apraxia is also investigated. A total of 105 patients with AD were enrolled and classified on the basis of the severity of the disease: 37 had mild AD, 38 moderate AD, and 30 severe AD. They were compared to 42 normal subjects. The applause sign was detected using the three clap test. All patients underwent a broad neuropsychological examination and 95 AD patients were tested for the presence of apraxia with a detailed praxis battery. Applause sign was present in all AD patient groups, which showed a significant difference with respect to normal controls, but not between each other. No significant difference was reported between apraxic and non-apraxic patients. Applause sign correlated with measures of frontal lobe dysfunction. No correlations were found between the applause sign and other cognitive functions examined.

Short-term memory binding is impaired in AD but not in non-AD dementias.

Binding is a cognitive function responsible for integrating features within complex stimuli (e.g., shape-colour conjunctions) or events within complex memories (e.g., face-name associations). This function operates both in short-term memory (STM) and in long-term memory (LTM) and is severely affected by Alzheimer's disease (AD). However, forming conjunctions in STM is the only binding function which is not affected by healthy ageing or chronic depression. Whether this specificity holds true across other non-AD dementias is as yet unknown. The present study investigated STM conjunctive binding in a sample of AD patients and patients with other non-AD dementias using a task which has proved sensitive to the effects of AD. The STM task assesses the free recall of objects, colours, and the bindings of objects and colours. Patients with AD, frontotemporal dementia, vascular dementia, lewy body dementia and dementia associated with Parkinson's disease showed memory, visuo-spatial, executive and attentional deficits on standard neuropsychological assessment. However, only AD patients showed STM binding deficits. This deficit was observed even when memory for single features was at a similar level across patient groups. Regression and discriminant analyses confirmed that the STM binding task accounted for the largest proportion of variance between AD and non-AD groups and held the greatest classification power to identify patients with AD. STM conjunctive binding places little demands on executive functions and appears to be subserved by components of the memory network which are targeted by AD, but not by non-AD dementias.

Dissociation apraxia secondary to right premotor stroke.

Apraxia is usually associated with damage to the dominant parietal cortex, but several other areas, including the left dorsolateral frontal cortex and subcortical structures, have also been implicated, suggesting that the praxis system is mediated by an anatomically distributed network. The right premotor frontal cortex is commonly assumed to play a secondary role in this system. We describe a patient who developed left upper limb apraxia after a right premotor ischaemic stroke. The neuropsychological examination ruled out impairment of other cognitive functions, including those subserved by the parietal-temporal cortex. Neither pyramidal signs nor interhemispheric transfer syndrome were detected, suggesting that the right primary motor cortex and corpus callosum were intact and that apraxia arose from a right prefrontal cortical lesion. An additional feature was the patient's inability to copy a gesture or posture demonstrated by the examiner (visual input) or to execute a verbal command (auditory input), even though he could copy the position in which the examiner placed his right arm while blindfolded (proprioceptive input). The disturbance was interpreted as "dissociation apraxia". To our knowledge this type of dissociation has never been reported in a patient with focal brain damage. The case of this patient highlights the importance of the right premotor cortex in the praxis system, and lends support to the hypothesis of a modular and multimodal organization of brain functioning.