Understanding verbal fluency in healthy aging, Alzheimer's disease, and Parkinson's disease.

Objective: Verbal fluency measures are frequently part of batteries designed to assess executive function (EF), but are also used to assess semantic processing ability or word knowledge. The goal of the present study was to identify the cognitive components underlying fluency performance. Method: Healthy young and older adults, adults with Parkinson's disease, and adults with Alzheimer's disease performed letter, category, and action fluency tests. Performance was assessed in terms of number of items generated, clustering, and the time course of output. A series of neuropsychological assessments were also administered to index verbal ability, working memory, EF, and processing speed as correlates of fluency performance. Results: Findings indicated that regardless of the particular performance measure, young adults performed the best and adults with Alzheimer's disease performed most poorly, with healthy older adults and adults with Parkinson's disease performing at intermediate levels. The exception was the action fluency task, where adults with Parkinson's disease performed most poorly. The time course of fluency performance was characterized in terms of slope and intercept parameters and related to neuropsychological constructs. Speed of processing was found to be the best predictor of performance, rather than the efficiency of EF or semantic knowledge. Conclusions: Together, these findings demonstrate that the pattern of fluency performance looks generally the same regardless of how performance is measured. In addition, the primary role of processing speed in performance suggests that the use of fluency tasks as measures of EF or verbal ability warrants reexamination. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Attentional control in normal aging and Alzheimer's disease.

Objective: Attentional control, the ability to maintain goal-directedness in the face of distraction, has been shown to decline in normal aging (NA) and Alzheimer's disease (AD), yet the nature and extent of deficits is under debate. This study investigated attentional control in NA and AD compared to healthy young adults in several tasks such as setting, suppressing, switching, and preparing attention. Method: Fifty-two participants (17 AD, 17 NA, and 18 young participants) underwent the Tower of London, the Zoo map test, the Stroop test, letter verbal fluency, a computerized version of the Rule shift cards tests, the Trail making test, the Plus-minus test, and a reaction time task with variable preparatory intervals. Results: Analyses of variance showed that NA as compared to young participants were impaired in the Tower of London, the Stroop test, and the Rule shift cards tests. AD as compared to NA participants were impaired in all tests except the Stroop test. Principal component analysis in young adults confirmed the modularity of attentional tasks, which was reduced in NA and AD participants. Principal component analysis in all populations showed a decline of attentional control with NA and AD regardless of the tasks, with an increase in between-participants variability only between young and NA participants. Conclusions: Attentional control dysfunction is different in NA and AD: NA affects suppressing attention, switching attention for unpredictable but not predictable events, and preparing attention for unpredictable events, whereas AD affects setting, suppressing, switching, and preparing attention with less specificity. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Quantitative brain SPECT in Alzheimer's disease and normal aging

To improve the diagnostic utility of brain single-photon emission computed tomography (SPECT) in Alzheimer's disease (AD), we have developed and evaluated an objective method of differentiating patients and healthy elderly controls using a quantitative image analysis protocol. HMPAO-SPECT image datasets from 29 patients with probable AD and 78 age-matched controls were registered to a common anatomic frame of reference. Activity levels within 120 standardized cortical volumes were determined by an automated procedure. Subjects were classified into normal and AD groups by quadratic discriminant analysis using two features: global average activity level and average normalized activity levels within the two clusters of standardized volumes identified as most significantly different in AD by analysis of covariance. The classification used split-half replication to ensure valid results. Classification performance quantified by the area under a binormal ROC curve fitted to the data was 0.923 +/- 0.036; at a threshold likelihood ratio of 1, the sample sensitivity was 91% and specificity was 86%. We conclude that quantitative SPECT accurately distinguishes AD patients from elderly controls.     

Attentional networks in normal aging and Alzheimer's disease.

By combining a flanker task and a cuing task into a single paradigm, the authors assessed the effects of orienting and alerting on conflict resolution and explored how normal aging and Alzheimer's disease (AD) modulate these attentional functions. Orienting failed to enhance conflict resolution; alerting was most beneficial for trials without conflict, as if acting on response criterion rather than on information processing. Alerting cues were most effective in the older groups--healthy aging and AD. Conflict resolution was impaired only in AD. Orienting remained unchanged across groups. These findings provide evidence of different life span developmental and clinical trajectories for each attentional network. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cortical variability and asymmetry in normal aging and Alzheimer's disease

The onset of Alzheimer's disease (AD) is accompanied by a complex and distributed pattern of neuroanatomic change, difficult to distinguish clinically from dynamic alterations in normal aging. Extreme variations in the sulcal patterns of the human cortex have made it difficult to identify diffuse and focal variations in cortical structure in neurodegenerative disease. We report the first comprehensive 3D statistical analysis of deep sulcal structure in vivo, in both normal aging and dementia. High-resolution 3D T1-weighted fast SPGR (spoiled GRASS) MRI volumes were acquired from 10 patients diagnosed with AD (NINCDS-ARDRA criteria; age: 71.9 +/- 10.7 years) and 10 normal subjects matched for age (72.9 +/- 5.6 years), gender, educational level and handedness. Scans were digitally transformed into Talairach stereotaxic space. To determine specific patterns of cortical variation in dementia patients, 3D average and probabilistic maps of primary deep sulci were developed for both normal and AD groups. Major sulci (including supracallosal, cingulate, marginal, parieto-occipital, anterior and posterior calcarine sulci, and Sylvian fissures) were modeled as complex systems of 3D surfaces using a multi-resolution parametric mesh approach. Variations and asymmetries in their extents, curvature, area and surface complexity were evaluated. Three-dimensional maps of anatomic variability, structural asymmetry and local atrophy indicated severe regionally selective fiber loss in AD. A midsagittal area loss of 24.5% at the corpus callosum's posterior midbody (P < 0.025) matched increases in structural variability in corresponding temporo-parietal projection areas. Confidence limits on 3D cortical variation, visualized in 3D, exhibited severe increases in AD from 2 to 4 mm at the callosum to a peak SD of 19.6 mm at the posterior left Sylvian fissure. Normal Sylvian fissure asymmetries (right higher than left; P < 0.0005), mapped for the first time in three dimensions, were accentuated in AD (P < 0.0002), and were greater in AD than in controls (P < 0.05). Severe AD-related increases in 3D variability and asymmetry may reflect disease-related disruption of the commissural system connecting bilateral temporal and parietal cortical zones, regions known to be at risk of early metabolic dysfunction, perfusion deficits and selective neuronal loss in AD.     

Effects of normal aging and Alzheimer's disease on emotional memory.

Recall is typically better for emotional than for neutral stimuli. This enhancement is believed to rely on limbic regions. Memory is also better for neutral stimuli embedded in an emotional context. The neural substrate supporting this effect has not been thoroughly investigated but may include frontal lobe, as well as limbic circuits. Alzheimer's disease (AD) results in atrophy of limbic structures, whereas normal aging relatively spares limbic regions but affects prefrontal areas. The authors hypothesized that AD would reduce all enhancement effects, whereas aging would disproportionately affect enhancement based on emotional context. The results confirmed the authors' hypotheses: Young and older adults, but not AD patients, showed better memory for emotional versus neutral pictures and words. Older adults and AD patients showed no benefit from emotional context, whereas young adults remembered more items embedded in an emotional versus neutral context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cholinergic system in Alzheimer's disease

The past decade has witnessed an enormous increase in our knowledge of the variety and complexity of neuropathological and neurochemical changes in Alzheimer's disease. Although the disease is characterized by multiple deficits of neurotransmitters in the brain, this overview emphasizes the structural and neurochemical localization of the elements of the acetylcholine system (choline acetyltransferase, acetylcholinesterase, and muscarinic and nicotinic acetylcholine receptors) in the non-demented brain and in Alzheimer's disease brain samples. The results demonstrate a great variation in the distribution of acetylcholinesterase, choline acetyltransferase, and the nicotinic and muscarinic acetylcholine receptors in the different brain areas, nuclei and subnuclei. When stratification is present in certain brain regions (olfactory bulb, cortex, hippocampus, etc.), differences can be detected as regards the laminar distribution of the elements of the acetylcholine system. Alzheimer's disease involves a substantial loss of the elements of the cholinergic system. There is evidence that the most affected areas include the cortex, the entorhinal area, the hippocampus, the ventral striatum and the basal part of the forebrain. Other brain areas are less affected. The fact that the acetylcholine system, which plays a significant role in the memory function, is seriously impaired in Alzheimer's disease has accelerated work on the development of new drugs for treatment of the disease of the 20th century.     

Different patterns of cognitive slowing produced by Alzheimer's disease and normal aging.

Aging has previously been shown to produce a generalized proportional slowing of all cognitive operations. In contrast, the present results suggested that Alzheimer's disease produces a disproportionate reduction in the speed with which patients carry out one or more mental operations. The tasks that demented patients found particularly difficult involved either a self-directed search of their lexicon or the use of familiarity information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use of the Rey Auditory Verbal Learning Test in differentiating normal aging from Alzheimer's and Parkinson's dementia.

38 elderly control Ss performed better than did 18 patients with moderate Alzheimer's disease (AD), 33 with severe AD, or 12 with Parkinson's dementia (PD) on all measures of the Rey Auditory Verbal Learning Test (RAVLT). The moderate-AD group performed better than did the severe-AD group on the 5 learning trials of List A. Unlike the controls and PD patients, both AD groups showed a greater recency than primacy effect, and both performed equally poorly on recall of List A after List B had been presented. The PD group showed poorer recall on List B than did the moderate-AD group but had better recognition scores than did both AD groups. These findings indicate that the RAVLT is useful in distinguishing between PD and AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Repetition priming in normal aging and Alzheimer's disease: A review of findings and theories.

On repetition priming tasks, memory is measured indirectly as a change in performance due to recent experience. It is often functionally and neurally dissociated from performance on explicit memory tasks, which directly measure conscious recall or recognition of recent events. Repetition priming has therefore been extensively studied in normal aging and Alzheimer's disease, which feature mild to severe changes in explicit memory. Initial studies indicated that repetition priming was immune to the effects of aging and greatly reduced in Alzheimer's disease (AD). As more studies have been performed, however, these initial conclusions appear less clear than before and, in the case of AD, actually misleading. The purpose of this article is to provide a comprehensive review of this rapidly expanding literature, articulate the issues that are critical to interpreting the empirical results, and discuss what new conclusions are suggested by the overall pattern of findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease.

Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Predictors of perceived memory impairment: do they differ in Alzheimer's disease versus normal aging?

Predictors of perceived memory impairment were investigated in 40 elderly normal adults and 28 individuals with Alzheimer's disease. Measures of perceived memory impairment, global cognitive functioning, memory, use of memory strategies, memory strategy efficacy, and depressive symptomatology were obtained for all participants. The elderly normal and Alzheimer's disease groups did not differ in the extent to which they reported perceived memory impairment. For both participant groups, more frequent use of memory strategies and lower perceived memory strategy efficacy were significant predictors of perceived memory impairment. Depressive symptomatology was an additional, significant determinant of perceived memory impairment for the elderly normal group.     

Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia

OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimer's disease; patients with Alzheimer's disease showed more severe anosognosia and disinhibition than patients with Parkinson's disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinson's disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimer's disease. CONCLUSION: There were significant psychiatric differences between patients with Alzheimer's disease and demented patients with Parkinson's disease, but neuropsychological differences were restricted to a single cognitive domain.     

Alterations of visual search strategy in Alzheimer's disease and aging.

Visual search, characterized by eye fixation patterns, was examined in 8 patients with Alzheimer's disease (AD), 8 cognitively intact, age-matched individuals, and 8 young control participants as they searched for a number among a nonlinear array of letters on a large computer screen. Among the 3 groups, target detection accuracy differed and detection time increased linearly. There were more fixations, and fixation duration was significantly longer in the AD patients than in the other 2 groups. These factors contributed to the lengthening of target detection time. This qualitative difference in the architecture of visual search between AD and aging may reflect a specific deficit in the disengagement of visual spatial attention, a prolongation of saccade initiation, or inefficiency in planning a search strategy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ornithine decarboxylase in human brain: influence of aging, regional distribution, and Alzheimer's disease

Although experimental animal data have implicated ornithine decarboxylase, a key regulatory enzyme of polyamine biosynthesis, in brain development and function, little information is available on this enzyme in normal or abnormal human brain. We examined the influence, in autopsied human brain, of postnatal development and aging, regional distribution, and Alzheimer's disease on the activity of ornithine decarboxylase. Consistent with animal data, human brain ornithine decarboxylase activity was highest in the perinatal period, declining sharply (by approximately 60%) during the first year of life to values that remained generally unchanged up to senescence. In adult brain, a moderately heterogeneous regional distribution of enzyme activity was observed, with high levels in the thalamus and occipital cortex and low levels in cerebellar cortex and putamen. In the Alzheimer's disease group, mean ornithine decarboxylase activity was significantly increased in the temporal cortex (+76%), reduced in occipital cortex (-70%), and unchanged in hippocampus and putamen. In contrast, brain enzyme activity was normal in patients with the neurodegenerative disorder spinocerebellar ataxia type I. Our demonstration of ornithine decarboxylase activity in neonatal and adult human brain suggests roles for ornithine decarboxylase in both developing and mature brain function, and we provide further evidence for the involvement of abnormal polyamine system activity in Alzheimer's disease.     

Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease

The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT.