Odor identification in normal aging and early Alzheimer's disease: Effects of retrieval support.

Odor sensitivity and identification were examined in normal aging and early Alzheimer's disease (AD). The aims were to investigate AD as associated with lower odor sensitivity, odor identification as a function of retrieval support, and the relationship between global cognitive functioning (Mini-Mental State Exam [MMSE]; M. R Folstein, S. E. Folstein, & P. R. McHugh, 1975) and olfactory performance. Results indicated intact odor sensitivity but deficient odor identification in AD. Both groups benefited from cues in identification, and the size of the gains was equally large in AD patients and controls. The finding of no selective benefit from retrieval support in AD suggests that a degradation of olfactory knowledge contributes to the odor identification deficits in these patients. MMSE and identification were positively related, whereas MMSE and olfactory sensitivity were unrelated. These findings suggest that the AD-related olfactory impairment stems from lesions in cortical rather than peripheral structures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Epstein-Barr virus and Hodgkin's disease: further evidence for the three disease hypothesis

The epidemiology of Hodgkin's disease suggests that it is a heterogeneous condition comprising more than one disease entity. The Epstein-Barr virus (EBV) is present in the Reed-Sternberg cells of a proportion of cases and is likely to play a role in the pathogenesis of these cases. In this study we show that EBV association rates vary with age at diagnosis. We suggest that Hodgkin's disease can be divided into three disease entities on the basis of EBV association and age, thereby providing biological support for the multiple aetiology hypothesis proposed by MacMahon (Cancer Res 1966; 26: 1189-1290).     

The single-format assumption in arithmetic fact retrieval.

Current models of mental arithmetic disagree on whether the same mental representation is activated by numbers in different forms (single-format assumption). Two experiments examined if the response times in arithmetic fact retrieval from arabic digits, number words, or dice are independent of the graphical representation of the numbers. S. Sternberg's (1969) additive factors method was used to analyze which response time interactions are compatible with the single-format assumption. In accord with the assumption, additive effects of form and operation were found in Experiment 1. In contrast, Experiment 2 showed additive effects only when an operand was held in memory, but a strong Form?X?Operation interaction otherwise. The authors discuss how phonological interference and form-specific retrieval could produce these interactions and how the single-format assumption can be extended to handle the findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease

Oxidant stress secondary to dopamine metabolism has been proposed as a pathogenic factor in the development of Parkinson's disease. Biochemical abnormalities extending beyond the central nervous system have been identified in patients with this condition. Previous investigators have found abnormally elevated concentrations of the lipid peroxidation product, malondialdehyde, in the plasma and serum of patients with Parkinson's disease. We attempted to replicate these findings but controlled for other factors that could influence malondialdehyde levels. We detected no significant elevations in mean serum malondialdehyde concentrations in either levodopa-treated or untreated patients with Parkinson's disease, compared to normal controls; similarly, no elevation was found in a group of patients with dementia of Alzheimer's type. On the other hand, a group of subjects with diabetes mellitus but no neurodegenerative disease had significantly elevated mean serum malondialdehyde levels, consistent with previous studies of diabetic patients. Autoxidation is one of the two major routes by which dopamine and dopa metabolism may generate oxygen free radicals. We analyzed the autoxidation product of dopa, 5-S-cysteinyl-dopa, in the plasma of these same groups of patients with neurodegenerative disease and normal controls; no significant differences were identified. Serum concentrations of two other antioxidant substances, alpha-tocopherol and uric acid, were also statistically similar in these groups. In conclusion, analysis of several blood products relevant to oxidant stress, including malondialdehyde, 5-S-cysteinyl-dopa, alpha-tocopherol, and uric acid, failed to distinguish patients with Parkinson's disease or dementia of Alzheimer's type from controls.     

Combination therapy for early Alzheimer's disease: what are we waiting for?

The practical pharmacological approaches currently available to palliate the cognitive and functional losses in early Alzheimer's disease (AD) include cholinesterase inhibitors (ChEI), antioxidants (e.g., vitamin E), anti-inflammatory agents, estrogen, seligiline, vasoactive agents, and ginkgo biloba. Reviewing available data on these therapies and using models from medical illnesses such as cancer and hypertension, we highlight the urgent need for evaluating combination therapies in early AD.     

Identification of body parts in Alzheimer's disease: evidence for a body schema hypothesis

This study examined the ability of patients with Alzheimer's Disease (AD) to perform a Body Part Identification (BPI) task, and also explored the relationship between BPI, intellectual level, severity of cognitive impairment and the general insight of patients into their disorder. The results showed that although AD patients are not always impaired on BPI, the degree of impairment correlates with the level of cognitive impairment measured using the Mini-Mental State Examination. The study also showed that BPI is not, however, associated with level of insight into their illness. Taken together these results provide support for the existence of a body schema that can be disrupted by AD, but is independent of the degree of insight into the illness.     

Memory encoding and retrieval in frontotemporal dementia and Alzheimer's disease.

Memory encoding and retrieval strategies were assessed in patients with behavior-executive variant frontotemporal dementia (FTD), language variant FTD, and Alzheimer's disease (AD) using verbal and visuospatial supraspan learning tests. FTD patients obtained higher free recall, cued recall, and recognition scores than AD patients. Comparison of free recall scores with cued recall and recognition scores was similar in the 3 dementia groups. Groups did not differ in semantic clustering strategies during learning, but serial-order recall was more common in FTD patients. These data do not support the idea that FTD patients' poor memory is due to a selective retrieval disorder, though FTD patients may fail to implement sophisticated organizational strategies during learning. FTD patients' retained capacity for encoding new information into long-term declarative memory is likely due to relatively spared medial temporal lobe involvement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Category knowledge in Alzheimer's disease: Normal organization and a general retrieval deficit.

Three hypotheses that could account for deficits in the retrieval of category information in Alzheimer's disease (AD) were evaluated: abnormal organization, class- or category-specific vulnerability, and limitation by general factors, such as decreased processing speed. Relative to 18 elderly control Ss, 18 patients with AD produced fewer items in a category fluency task and had longer reaction times in a category decision task. The pattern of performance across categories on both tasks was normal in the AD group: The same categories elicited the most (or fastest) responses in both the control group and the AD group. AD patients showed normal performance in ranking of category exemplars by typicality. There was no evidence for differential accessibility by category or by class of information (animate vs inanimate). The authors conclude that a general factor or factors limit(s) retrievability equally across all categories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relearning face-name associations in early Alzheimer's disease.

Preliminary evidence for the effectiveness of cognitive rehabilitation interventions based on errorless learning principles in early-stage Alzheimer's disease (AD) was provided by Clare et al. (1999, 2000, 2001). The present study extends these findings in a controlled trial. Twelve participants meeting criteria for probable AD, with Mini-Mental State Examination scores of 18 or above, were trained in face-name associations using an effortless learning paradigm. Training produced a significant group improvement in recall of trained, but not control, items. Gains were largely maintained 6 months later, in the absence of practice. There were differences in individual response to intervention. Results did not differ according to medication status, and the intervention had no adverse effects on self-reported well-being, but participants who were more aware of their memory difficulties achieved better outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ideomotor apraxia in early Alzheimer's disease: time and accuracy measures

Twenty-six Alzheimer's disease (AD) and 42 healthy control (NC) subjects were evaluated with neuropsychological and apraxia batteries. ADs produced a greater range of error types, but did not differ from NCs in their most frequent error types. Hand sequencing ability contributed significantly to AD praxis with no predictors for NCs. Although groups did not differ in gesture time, the AD group had significantly longer response latencies for periods prior to gesture execution and the effect was prominent for transitive tasks and nondominant hand use. Results illustrate the sensitivity of timing measures in identifying abnormal praxis in early stages of AD.     

Signal transduction abnormalities in Alzheimer's disease: evidence of a pathogenic stimuli

Hippocampal and select cortical neuronal populations in Alzheimer's disease exhibit phenotypic changes characteristic of cells re-entering the cell division cycle. Therefore, in this study, we investigated whether components, known to trigger cellular proliferation and differentiation, upstream of the ras/mitogen-activated kinase pathway, could contribute to the activation of a signal transduction cascade in Alzheimer's disease. We found that proteins implicated in signal transduction from cell surface receptors via the ras pathway, namely Grb2 and SOS-1, were altered in cases of Alzheimer's disease in comparison to age-matched controls. SOS is increased in susceptible pyramidal neurons, while Grb2 shows more subtle alterations in subcellular distribution. Importantly, both SOS-1 and Grb2 show considerable overlap with early cytoskeletal abnormalities suggesting that the alteration in signal transduction molecules is a concurrent, if not preceding, event in the pathogenesis of Alzheimer's disease. Taken together with the cell cycle abnormalities previously reported, these findings suggest that a signal derived from the cell surface contributes to a stimulus for neurons in Alzheimer's disease to re-enter the cell cycle.     

Working memory in mild Alzheimer's disease and early Parkinson's disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) impair working memory (WM). It is unclear, however, whether the deficits seen early in the course of these diseases are similar. To address this issue, the authors compared the performance of 22 patients with mild AD, 20 patients with early PD and without dementia, and 112 control participants on tests of inhibition, short-term memory, and 2 commonly administered tests of WM. The results suggest that although mild AD and early PD both impair WM, the deficits may be related to the interruption of different processes that contribute to WM performance. Early PD disrupted inhibitory processes, whereas mild AD did not. The WM deficits seen in patients with AD may be secondary to deficits in other cognitive capacities, including semantic memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory enhancement for emotional stimuli is impaired in early Alzheimer's disease.

Emotional arousal is associated with enhanced memory in neurologically intact individuals, but it is unknown whether this effect is obtained in Alzheimer's disease (AD). The current study compared emotional memory and emotional reactions in patients with early AD and in older controls. Participants viewed emotionally arousing (both pleasant and unpleasant) and neutral photographs while cognitive and electrophysiological reactions were assessed. Memory was tested by free recall and recognition. Emotional reactions were normal in the AD group, but the emotional memory effect (enhanced memory for emotional vs. neutral stimuli) was impaired. Recall results indicated that this effect was normal for pleasant stimuli but abnormal for unpleasant stimuli. These results suggest that the neural basis for the emotional memory effect may be disrupted in AD. Findings are discussed in terms of the role of the amygdala in mediating emotional memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

No evidence for a higher resting metabolic rate in noninstitutionalized Alzheimer's disease patients

OBJECTIVE: It has previously been suggested that Alzheimer's disease patients have higher resting energy requirements than healthy individuals, which may contribute to their unexplained weight loss. We examined whether resting metabolic rate, the largest component of daily energy expenditure, is elevated in Alzheimer's patients compared with healthy older controls. DESIGN: Cross-sectional. SETTING: General Clinical Research Center and Baltimore VA Medical Center. PATIENTS: Twenty-five noninstitutionalized demented patients (74 +/- 8 years; mean +/- SD) with a wide range of Mini-Mental Examination scores (1 to 20) and 73 healthy older individuals (69 +/- 7 years). MEASUREMENTS: Resting metabolic rate was measured by indirect calorimetry, fat-free mass and fat mass by dual energy X-ray absorptiometry, and daily energy intake by food diaries. RESULTS: No differences in fat-free mass and fat mass were noted between Alzheimer's disease patients and healthy older controls. Resting metabolic rate was similar in Alzheimer's disease patients (5446 +/- 962 kJ/day) and healthy older individuals (5647 +/- 887 kJ/day). These results persisted when resting metabolic rate was statistically adjusted for differences in body composition and age. CONCLUSION: These results provide no evidence for an elevation in resting energy requirements in noninstitutionalized demented patients.     

Reading lexically without semantics: evidence from patients with probable Alzheimer's disease

Recent modifications of the lexical model of oral reading make the prediction that under conditions where sublexical reading processes alone cannot achieve the target pronunciation (i.e., when words have exceptional spellings or when sublexical processes are impaired), patients with severe semantic impairment should have more difficulty reading aloud semantically impaired words than semantically retained words. In a battery of lexical-semantic and reading tasks, two neurologically normal control subjects and two subjects with probable Alzheimer's disease (AD) and only moderate semantic impairment read aloud all words accurately. One AD subject with severe semantic impairment was impaired in word reading but demonstrated no difference in reading words with regular and exceptional spellings. Another AD subject with severe semantic impairment read aloud without error virtually all regular and exception words. Neither severely impaired AD subject demonstrated any relationship between oral reading accuracy and semantic knowledge of exception words. These findings support a model of word reading incorporating lexical, nonsemantic processes by which lexical orthographic input representations directly activate lexical phonological output representations without the necessity of semantic mediation.     

Learning and retention in preclinical and early Alzheimer's disease.

Accelerated forgetting has been proposed as the first sign in preclinical and early Alzheimer's disease (AD). The authors investigated learning and retention in participants who later developed AD with free and cued selective reminding (FCSR; H. Buschke, 1984; E. Grober & H. Buschke, 1987), a test that maximizes learning by inducing deep semantic processing and by controlling study and test conditions. AD patients in the preclinical stage recalled significantly fewer words than did matched control participants, indicating an impairment of learning; nonetheless, patients' retention was identical to that of control participants. A retention deficit was documented 3 years later for AD patients but not for control participants, whose retention was still perfect. Thus, a retention deficit is not present in preclinical AD when hallmark learning deficits can be documented. Detection of preclinical and very early AD may be best accomplished by using robust learning tests that control cognitive processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Does expanded retrieval produce benefits over equal-interval spacing? Explorations of spacing effects in healthy aging and early stage Alzheimer's disease.

Three experiments explored different schedules of retrieval practice in young adults, older adults, and individuals with dementia of the Alzheimer type. In each experiment, an initial acquisition phase was presented in which participants studied or attempted to retrieve response words to cues, followed by a later cued-recall test. Experiment 1 produced a benefit of expanded retrieval over equal-interval retrieval during acquisition, but this benefit was lost in final cued recall. In Experiments 2 and 3, participants received corrective feedback during acquisition and modified spacing schedules. There was again no evidence of a difference between expanded and equal-interval conditions in final cued recall. Discussion focuses on the potential benefits and costs of expanded retrieval on a theoretical and applied level. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional decline in the early stages of Alzheimer's disease.

Reports a 2-yr follow-up of 15 Alzheimer's disease (AD) patients (mean age 67.8 yrs) characterized by mild functional impairment and 22 age-, sex-, and education-matched controls. In a previous cross-sectional study by P. Prinz et al (see record 1983-30633-001) of these 37 Ss and 16 AD patients (mean age 70.2 yrs) with moderate functional impairment, measures of memory and attention deficits accounted for much of the impairment observed in functional competence. The current longitudinal study found that these same initial assessments could be used to predict functional decline in the 15 mildly impaired Ss, who were observed to decline to levels similar to those of the 16 moderate patients. In contrast, the controls exhibited little decline during the same period. Results affirm that it is possible to diagnose AD in its mild form and demonstrate the validity of the initial diagnosis. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Event-related brain potential evidence of spared knowledge in Alzheimer's disease.

The authors recorded event-related brain potentials (ERPs) to picture primes and word targets (picture-name verification task) in patients with Alzheimer's disease (AD) and in elderly and young participants. N400 was more negative to words that did not match pictures than to words that did match pictures in all groups: In the young, this effect was significant at all scalp sites; in the elderly, it was only at central-parietal sites; and in AD patients, it was limited to right central-parietal sites. Among AD patients pretested with a confrontation-naming task to identify pictures they could not name, neither the N400 priming effect nor its scalp distribution was affected by ability to name pictures correctly. This ERP evidence of spared knowledge of these items was complemented by 80% performance accuracy. Thus, although the name of an item may be inaccessible in confrontation naming, N400 shows that knowledge is intact enough to prime cortical responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)