Alterations in tau protein metabolism during normal aging

It is unknown whether aging and Alzheimer's disease (AD) are on the same continuum, or whether they are qualitatively distinct. Tau protein has been identified as a major constituent of paired helical filaments (PHFs) and AD is characterised by a major redistribution of the normal tau protein pool into PHFs. Little is known about the changes in tau protein distribution that occur in the course of normal aging. We have examined PHF-bound and normal tau fractions in frontal, temporal, parietal and occipital neocortex, cerebellum, hippocampus and entorhinal cortex in 15 cognitively unimpaired individuals aged 19-88 years at death. Insoluble tau protein in the PHF fraction did not increase with aging in any brain region, despite the appearance of neurofibrillary pathology at low density in the more elderly cases. By contrast, normal tau protein decreased with aging (r = 0.32, p < 0.001), with an average loss of 14% of soluble tau per decade after the age of 20 years. This was unrelated either to neurofibrillary or beta-amyloid pathology. Frontal grey matter and hippocampus were most vulnerable to age-related tau loss, decreasing by as much as 90% in the older subgroup. These findings contrast with those we have previously reported in AD, where the redistribution of tau protein into the PHF-bound fraction was highly correlated with the extent of neurofibrillary pathology, and suggest that the mechanisms of tau loss in aging and AD are distinct. Age-related tau loss may underlie the neuropsychological impairments seen in the non-demented elderly.     

Changes of cerebrovascular CO2 reactivity during normal aging

BACKGROUND AND PURPOSE: During the past decade, transcranial Doppler sonography has widely been used to assess blood flow velocities in the basal intracranial arteries and cerebrovascular reactivity (CR) to various stimuli. Although numerous studies have shown a decline of cerebral blood flow velocity with age, the age dependency of CR, including cerebrovascular CO2 reactivity, however, is controversial. Recently, we have reported a significant sex-related difference in CR, stressing the need to study the relation between normal aging and CR in both sexes separately. METHODS: By means of transcranial Doppler sonography, CR was determined in 100 healthy, nonsmoking volunteers (age 20 to 70 years, 10 men and 10 women per decade). RESULTS: In men, no change of CR with increasing age could be observed (P=0.98). In contrast, CR in women declined significantly, with a step decrease from the 4th to the 5th decades (F=4.413; P<0.01) and was significantly higher in the 3rd and 4th compared with the 5th, 6th, and 7th decades (P<0.05). Information on hormone replacement therapy (HRT) in women of the 6th and 7th decades was obtained retrospectively. HRT was associated with enhanced CR (HRT, n = 7 versus non-HRT, n = 13; P<0.001), with values similar to those found in premenopausal women. CONCLUSIONS: There are no changes of CR during normal aging in men, whereas CR declines significantly from the 4th to the 5th decades in women. HRT in postmenopausal women appears to enhance CR.     

Amianthoid change: orientation of normal collagen fibrils during aging

High-angle x-ray diffraction provides direct evidence that amianthoid change, occurring during aging of costal cartilage, corresponds to a transformation from an isotropic to a marked anisotropic distribution of collagen fibrils. Low-angle x-ray diffraction and electron microscopy show that the fibrils have the customary 67-nanometer axial periodicity. Electron microscopy shows that wide amianthoid collagen fibrils consist of smaller parallel fibrils fused together. Similarities between amianthoid change and tendon morphogenesis are briefly discussed. Amianthoid change is remarkable in that aging is accompanied by increased order.     

Memory complaints and abilities among depressed older adults.

The relation between complaints of memory problems and memory test performance was examined among depressed (n?=?25) and nondepressed (n?=?25) adults over the age of 40 years. Depressed adults were diagnosed from interviews using Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria and from responses to the Beck Depression Inventory. A dissociation between memory complaints and performance was observed. Depressed adults complained of greater problems in memory than nondepressed adults. However, the memory test performances of both groups were in the average-to-above-average range. These results are discussed in light of the role of self-deprecating cognitive distortions in the tendency of depressed individuals to negatively evaluate all their abilities, including their memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Initial validation of Russell's Revised Wechsler Memory Scale: A comparison of normal aging versus dementia.

Results of a study with 29 normal aging volunteers and 29 dementia patients (ages in both groups, 55–85 yrs) indicate that E. W. Russell's (see record 1976-08657-001) Revised Wechsler Memory Scale discriminated between the 2 groups on all variables. Both groups experienced greater loss in figural than in semantic memory. Results suggest that memory loss in normal aging and dementia is a selective rather than a general disability. (1 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory and learning abilities in everyday life of the elderly

Self-evaluations by adults (varying in age from 45-92 years) of their memory and learning abilities were investigated and related to performance on laboratory and ecological memory tasks. Hardly any association was found between subjective and objective measures. Self-evaluations were strongly influenced by (systematically varied) frames of reference: optimistic in comparisons with other people, pessimistic in comparisons with their own previous level of functioning. The most frequent problems were 'learning something new' and 'remembering names'. In contrast to external memory aids, cognitive strategies were rarely used spontaneously. Strategy training led to significant improvement of performance, that remained stable at follow-up. A further opportunity for improving performance was realized by ergonomic adaptations of computerized systems (teleshopping). Problems in learning to use such systems were strongly reduced by decreasing the load on working memory and by adapting the system to existing knowledge and skills of the users. A general observation in the different projects was that age-differences could explain only a small percentage of the variance in subjective and objective memory measures.     

Memory and aging: The role of retrieval processes.

A review of the literature demonstrates that production deficiency hypotheses are unable to account fully for the fact that older adults perform more poorly on memory tasks than young adults. The possibility is explored that age-related differences are due to changes in fundamental processes involved in retrieval of information from memory, namely, (a) utilization of contextual information and (b) activation processes occurring in semantic memory. Automatic as well as intentional processes are examined. (5? p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Event-related brain potentials during semantic categorization in normal aging and senile dementia of the Alzheimer's type

To assess the effects of normal aging and senile dementia of the Alzheimer's type (SDAT) on semantic analysis of words, we examined the N400 component of the event-related potential (ERP) elicited during the processing of highly constrained (opposites) and less constrained materials (category-category exemplars) in 12 young control subjects, 12 elderly control subjects and 12 patients with SDAT. We employed a priming paradigm in which a context phrase was spoken and a target word (congruent or incongruent) was presented visually. The N400 effect was reduced in amplitude and delayed in the elderly control group relative to that of the younger subjects, and was further attenuated in amplitude, delayed in latency and somewhat flatter in its distribution across the scalp in the SDAT patients. These findings are consistent with less efficient processing and integration of lexical items with semantic context in normal aging, which is further exacerbated by SDAT. Differences in the N400 range associated with the opposite and category conditions were observed only in the young subjects, suggesting less use of controlled attentional resources or perhaps weaker associative links with age.     

Developmental and endocrine aspects of normal ovarian aging

The fluorescence plus Giemsa (FPG) and fluorescence in situ hybridization (FISH) techniques have been used to determine, respectively, the frequencies of sister chromatid exchanges (SCEs) and stable chromosome aberrations (translocations) induced by different concentrations of BrdU in the Chinese hamster ovary cell mutant EM9 and its parental line AA8. The results indicate that BrdU induced a high frequency of SCEs and translocations in EM9 as compared with AA8, and that the translocation/dicentric ratio was also higher in the mutant cell line than in the parental cell line in both untreated and BrdU-treated cultures. These observations may indicate a possible relationship between the molecular mechanisms involved in the formation of SCEs and translocations.     

Memory and aging: Selected research directions and application issues.

Everyday memory failures and long-term memory changes are among the most empirically established, socially expected, personally disconcerting, and widely misinterpreted aspects of human aging. A large, sophisticated, and still growing theoretical research base on memory aging has accumulated over the last several decades. Following a brief summary of a broad swath of selected basic memory aging phenomena, we identify a small subset of relatively recent but well-researched topics that may hold promise for optimizing memory adaptation in late life. Linking research with potential application, we sketch key objectives for three potential directions of intervention in memory and aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory function in aging and Parkinson''s disease--an event-related potential study]

PURPOSE: Though case management has been recommended to improve the outcomes of patients with costly or morbid conditions, it has seldom been studied in controlled trials. We performed a randomized, controlled clinical trial of an intensive, multidisciplinary case management program for patients with chronic renal insufficiency and followed patients for 5 years. PATIENTS AND METHODS: We enrolled 437 primary-care patients (73% of those eligible) with chronic renal insufficiency (estimated creatinine clearance consistently < 50 mL/min with the last serum creatinine level > 1.4 mg/dL) who were attending an urban academic general internal medicine practice. The intensive case management, administered during the first 2 years after enrollment, consisted of mandatory repeated consultations in a nephrology case management clinic staffed by two nephrologists, a renal nurse, a renal dietitian, and a social worker. Control patients received usual care. Primary outcome measurements included serum creatinine level, estimated creatinine clearance, health services use, and mortality in the 5 years after enrollment. Secondary measures included use of renal sparing and potentially nephrotoxic drugs. RESULTS: There were no differences in renal function, health services use, or mortality in the first, second, or third through fifth years after enrollment. There were significantly more outpatient visits among intervention patients, mainly because of the added visits to the nephrology case management clinic. There were also no significant differences in the use of renal sparing or selected potentially nephrotoxic drugs. The annual direct costs of the intervention were $89,355 ($484 per intervention patient). CONCLUSION: This intensive, multidisciplinary case-management intervention had no effect on the outcomes of care among primary-care patients with established chronic renal insufficiency. Such expensive and intrusive interventions, despite representing state-of-the-art care, should be tested prospectively before being widely introduced into practice.     

Genetic variance in processing speed drives variation in aging of spatial and memory abilities.

Previous analyses have identified a genetic contribution to the correlation between declines with age in processing speed and higher cognitive abilities. The goal of the current analysis was to apply the biometric dual change score model to consider the possibility of temporal dynamics underlying the genetic covariance between aging trajectories for processing speed and cognitive abilities. Longitudinal twin data from the Swedish Adoption/Twin Study of Aging, including up to 5 measurement occasions covering a 16-year period, were available from 806 participants ranging in age from 50 to 88 years at the 1st measurement wave. Factors were generated to tap 4 cognitive domains: verbal ability, spatial ability, memory, and processing speed. Model-fitting indicated that genetic variance for processing speed was a leading indicator of variation in age changes for spatial and memory ability, providing additional support for processing speed theories of cognitive aging. (PsycINFO Database Record (c) 2010 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)     

Effect of normal aging on rate of forgetting.

Used a verbal paired associate paradigm to examine rate of forgetting in 181 normal adults (aged 18–91 yrs). Ss were administered the Expanded Paired Associate Test (EPAT) derived from a related subscale of the Wechsler Memory Scale and which includes both acquisition and delayed-recall tasks. Older Ss performed below the levels obtained by younger Ss on both phases of the EPAT. However, analysis revealed no differences among age groups in rate of forgetting. Lower scores for older Ss on the delayed-recall task appeared to reflect differences in initial learning, not an accelerated rate of forgetting. Normative data for rate of forgetting are provided for Ss in all age groups. (PsycINFO Database Record (c) 2010 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)     

Ragged red fibers in normal aging and inflammatory myopathy

Ragged red fibers are an important marker for mitochondrial disease. To evaluate the hypothesis that mitochondrial dysfunction may play a role in the pathogenesis of aging and inclusion body myositis, we studied the frequency of ragged red fibers in muscle biopsy specimens from 15 young and 13 old normal adults, and from 27 patients with inclusion body myositis, polymyositis, or dermatomyositis. Serial transverse cryostat sections were stained with modified Gomori trichrome, modified succinic dehydrogenase, and cytochrome c oxidase. The frequency of ragged red fibers, determined by measuring the percent number of succinic dehydrogenase-positive ragged red fiber equivalents, was significantly higher in old compared to young normal subjects (0.33 vs. 0.02%, p < 0.0001). With the exception of a single polymyositis biopsy specimen showing a large number of ragged red fibers, the frequency of ragged red fibers in patients with polymyositis or dermatomyositis was similar to that of age-matched normal control subjects. The frequency of ragged red fibers was more than 1% in 7 of 8 patients with inclusion body myositis (maximum, 15%). The modified succinic dehydrogenase stain was more sensitive than the modified Gomori trichrome in detecting accumulation of mitochondria in muscle fibers. Cytochrome c oxidase activity was deficient in most ragged red fibers. We conclude that the number of ragged red fibers increases with normal aging and may reflect an age-related decline in muscle mitochondrial oxidative metabolism. The frequent occurrence of ragged red fibers in inclusion body myositis suggests that mitochondrial function may be impaired in this disease.