Difference In Rate Of Decline Research Articles

Cohort Profile: The European Male Ageing Study

The European Male Ageing Study (EMAS) was designed to examine the hypothesis that inter-individual and regional variability in symptomatic dysfunctions, alterations in body composition and health outcomes in ageing men can be explained by different rates of decline in anabolic hormones, the most important of which being testosterone. Between 2003 and 2005, 3369 community-dwelling men, aged between 40 and 79 years, were recruited from population-based registers in eight European centres to participate in the baseline survey, with follow-up investigations performed a median of 4.3 years later. Largely, identical questionnaire instruments and clinical investigations were used in both phases to capture contemporaneous data on general health (including cardiovascular diseases and chronic conditions), physical and cognitive functioning, mental health, sexual function, quality of life, bone health, chronic pain, disease biomarkers, hormones (sex hormones and metabolic hormones) and genetic polymorphisms. EMAS actively encourages new collaborations, data sharing for validation studies and participation in genetic study consortia. Potential collaborators should contact the principal investigator (F.C.W.W.) in the first instance.

Factors Affecting the Outcome of Artificial Insemination Using Cryopreserved Spermatozoa in the Giant Panda (Ailuropoda melanoleuca)

Artificial insemination (AI) is an important component of captive breeding programs for endangered species, such as the giant panda. The panda has been the subject of increasingly successful captive breeding programs involving a compilation of assisted breeding techniques, including AI using cryopreserved spermatozoa. AI implementation is currently hampered by a lack of understanding of the factors that may cause failure. We investigated factors influencing the probability of success of AI for 14 giant panda females housed at the China Center for Research and Conservation of the Giant Panda (CCRCGP) inseminated in a total of 20 instances using cryopreserved spermatozoa from 11 males currently residing in 6 different captive breeding institutions. One of the pandas was the oldest giant panda female to ever successfully conceive from AI (20.5 years old). The success of AI was significantly affected by the timing of AI in relationship to both timing of peak urinary estrogen of the female and percent decline in urinary estrogen between the peak level and the first AI attempt. Our results suggest that the window for successful AI in giant pandas may be narrower than previously suspected, although individual differences in rates of decline in urinary estrogen may reflect some degree of variation in this crucial window across females. Our results are consistent with recent research on pandas and other species that demonstrates the efficacy of cryopreserved spermatozoa for AI and highlights the need for more in-depth analysis of factors related to female physiology that may influence its success.

Terminal Pathologies Affect Rates of Decline to Different Extents and Age Accelerates the Effects of Terminal Pathology on Cognitive Decline

To test whether different terminal pathologies are associated with different rates of age-related decline in fluid and crystallized mental abilities and whether pathology-associated declines are accelerated by age. During a 20-year longitudinal study, 6203 participants were quadrennially assessed on the Heim's (Heim, A 1970) The AH4 series of intelligence tests Slough, U.K.: NEP) AH4-1 and AH4-2 tests of fluid intelligence and on the Raven's (Raven, J. C. 1965) The Mill Hill Vocabulary Scale London: H.K. Lewis) Mill Hill A and B tests of recognition and production vocabulary. Dates and proximate causes of death were logged for 2499 participants. Multilevel modelling compared rates of decline after effects of sex, demographics, and practice were taken into consideration. Rates of cognitive decline markedly differed across pathologies, being most rapid for dementias and infections, slower for malignancies, and most prolonged for cardiovascular conditions. Pathologies were associated with faster declines in older individuals. After sex, age, and demographics have also been considered, different terminal pathologies are associated with markedly different rates of decline. Age accelerates pathology-related decline. This raises the further question as to whether any, or how much of, age-related cognitive decline is brought about by other causes than an increasing burden of pathologies.

Rate of 6‐[18F]fluorodopa uptake decline in striatal subregions in Parkinson's disease

Rate of decline in 6-L-[(18)F]fluorodopa (FDOPA) uptake within the striatum has been reported as showing regional differences in Parkinson's disease (PD). We acquired longitudinal brain FDOPA positron emission tomography (PET) studies in 26 PD subjects and 11 controls over 4.5 years. We analyzed both spatially normalized voxel-wise maps of radiotracer influx (Kocc) and average Kocc values for six non-overlapping volumes of interest (VOIs) encompassing the striatum. The voxel-wise analysis showed that in PD, FDOPA Kocc decline spanned the striatum but was greatest in the posterior putamen ipsilateral and anterior putamen contralateral to initial symptoms. The VOI approached showed that absolute rates of Kocc decline were significantly greater in PD than control subjects, but that the slope of decline did not differ between subregions. In PD, ratios of uptake between subregions did not change during the study with the exception of the ipsilateral putamen/caudate ratio. Decline rates were marginally greater during earlier time segments. Both male gender and advancing age were associated with lower baseline FDOPA uptake, but no difference in decline rates. VOI Kocc values were significantly correlated with disease duration, but only moderately correlated with clinical measures. We conclude that FDOPA uptake in subregions of the striatum is strongly correlated with disease duration and age, and declines approximately equally from symptom onset in PD. This implies that in idiopathic PD, relative preservation of uptake in the anterior striatum reflects a delay in pathologic involvement of nigrostriatal projections to this region.

Vaccine-induced T cells Provide Partial Protection Against High-dose Rectal SIVmac239 Challenge of Rhesus Macaques

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4(+) T cells. In addition, the two vaccinated Mamu-A*01(+) macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1.

Pulmonary exacerbations are associated with subsequent FEV1 decline in both adults and children with cystic fibrosis

Patients with cystic fibrosis (CF) frequently experience pulmonary exacerbations that may lead to a faster subsequent decline in pulmonary function; however, this relationship has not been clearly established. The purpose of this study was to determine the association between the frequency of pulmonary exacerbations and subsequent forced expiratory volume in 1 sec (FEV(1) ) decline in adults and children with CF. Cohort study of subjects followed in the Cystic Fibrosis Foundation Patient Registry from 2003 through 2006. Mixed effects modeling was used to estimate differences in rates of decline in FEV(1) in 2004-2006 for patients with 0, 1, 2, or 3+ pulmonary exacerbation(s) in 2003. Of 8,490 subjects who met inclusion criteria, 60% had 0 exacerbations, 23% had 1, 10% had 2, and 7% had 3+ exacerbations in 2003. Compared to children with no pulmonary exacerbations in 2003, children with one or more exacerbations experienced a significantly (P < 0.001) greater rate of FEV(1) decline in 2004-2006. In contrast, among adults, only those with 3+ exacerbations in 2003 had a significantly (P = 0.01) greater rate of FEV(1) decline in 2004-2006 than those with no exacerbations in 2003. There is a strong association between the frequency of pulmonary exacerbations and subsequent decline in pulmonary function. In adults, having 3+ exacerbations, and among children, having any exacerbations is associated with a greater rate of decline in the ensuing 3 years. Improved prevention, identification, and treatment of pulmonary exacerbations are likely to have long-term benefits for patients with CF, especially children.

Vitamin D status and longitudinal lung function decline in the Lung Health Study

Low blood vitamin D levels have been postulated to be a risk factor for worse lung function, based largely on cross-sectional data. We sought to use longitudinal data to test the hypothesis that baseline plasma 25-hydroxyvitamin D (25(OH)D) is lower in subjects with more rapid lung function decline, compared to those with slow lung function decline. We conducted a nested, matched case-control study in the Lung Health Study 3 cohort. Cases and controls were continuous smokers with rapid and slow lung function decline, respectively, over ~6 yrs of follow-up. We compared baseline 25(OH)D levels between cases and controls, matching date of phlebotomy and clinical centre. Among 196 subjects, despite rapid and slow decliners experiencing strikingly and significantly different rates of decline of forced expiratory volume in 1 s (-152 versus -0.3 mL·yr⁻¹; p < 0.001), there was no significant difference in baseline 25(OH)D levels (25.0 versus 25.9 ng·mL⁻¹; p = 0.54). There was a high prevalence of vitamin D insufficiency (35%) and deficiency (31%); only 4% had a normal 25(OH)D level in the winter. Although vitamin D insufficiency and deficiency are common among continuous smokers with established mild-to-moderate chronic obstructive pulmonary disease, baseline 25(OH)D levels are not predictive of subsequent lung function decline.

Clinical Trial of Lutein in Patients With Retinitis Pigmentosa Receiving Vitamin A

To determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A. Randomized, controlled, double-masked trial of 225 nonsmoking patients, aged 18 to 60 years, evaluated over a 4-year interval. Patients received 12 mg of lutein or a control tablet daily. All were given 15,000 IU/d of vitamin A palmitate. Randomization took into account genetic type and baseline serum lutein level. The primary outcome was the total point score for the Humphrey Field Analyzer (HFA) 30-2 program; prespecified secondary outcomes were the total point scores for the 60-4 program and for the 30-2 and 60-4 programs combined, 30-Hz electroretinogram amplitude, and Early Treatment Diabetic Retinopathy Study acuity. No significant difference in rate of decline was found between the lutein plus vitamin A and control plus vitamin A groups over a 4-year interval for the HFA 30-2 program. For the HFA 60-4 program, a decrease in mean rate of sensitivity loss was observed in the lutein plus vitamin A group (P = .05). Mean decline with the 60-4 program was slower among those with the highest serum lutein level or with the highest increase in macular pigment optical density at follow-up (P = .01 and P = .006, respectively). Those with the highest increase in macular pigment optical density also had the slowest decline in HFA 30-2 and 60-4 combined field sensitivity (P = .005). No significant toxic effects of lutein supplementation were observed. Lutein supplementation of 12 mg/d slowed loss of midperipheral visual field on average among nonsmoking adults with retinitis pigmentosa taking vitamin A. Application to Clinical Practice Data are presented that support use of 12 mg/d of lutein to slow visual field loss among nonsmoking adults with retinitis pigmentosa taking vitamin A. ClinicalTrials.gov Identifier: NCT00346333.

Do changes in the subjective experience of recognition over time suggest independent processes?

Two experiments examined the nature of recognition memory by asking how subjective reports of remembering change over time. In Experiment 1, participants were asked to report their experience of remembering using the well-known remember-know-guess procedure. Estimates of recollection declined over a 14-day period, but estimates of familiarity remained constant, suggesting that the processes are independent. In Experiment 2, participants were asked to report their confidence in their recognition decisions. Subjective reports of confidence were analysed via receiver operating characteristics and also indicated different rates of decline for recollection and familiarity. Superficially, the data appear to support a dual-process account of recognition, but close inspection shows the data to be consistent with a simple signal detection model. The conclusion is that although the phenomenal experience of remembering changes over time this is most likely to be predicated on a single process.

Ethnic Differences in Cognitive Function Over Time

Minority group membership in old age has been implicated as a risk factor for lower scores on cognitive function tests, independent of education level. In addition, differential rates of cognitive decline by ethnic group have been identified in several epidemiologic studies. However, others have not been able to detect differences. In order to determine if health disparities in cognitive function scores extend to rates of decline, the current research examined rates of change in memory and mental status over the course of 9 years (1996-2004) in a nationally representative sample of late middle-aged and older white, black, and Hispanic adults who were part of the nationally representative Health and Retirement Study. Change in cognitive function was measured by separate indices of memory and mental status items and analyzed with multivariable mixed modeling. Results indicated that, after controlling for demographic, social, and health-related variables, ethnicity was associated with cognitive function scores across waves (P<0.01), but did not greatly impact rates of decline. Furthermore, although education was associated with cognitive function scores across waves (P<0.01), education level did not impact decline rates. Some health disparities in cognitive function exist even in late middle age, but ethnic differences in rates of decline are mixed.

Trajectories of Cognitive Function in Late Life in the United States: Demographic and Socioeconomic Predictors

This study used mixed-effects modeling of data from a national sample of 6,476 US adults born before 1924, who were tested 5 times between 1993 and 2002 on word recall, serial 7's, and other mental status items to determine demographic and socioeconomic predictors of trajectories of cognitive function in older Americans. Mean decline with aging in total cognition score (range, 0-35; standard deviation, 6.00) was 4.1 (0.68 standard deviations) per decade (95% confidence interval: 3.8, 4.4) and in recall score (range, 0-20; standard deviation, 3.84) was 2.3 (0.60 standard deviations) per decade (95% confidence interval: 2.1, 2.5). Older cohorts (compared with younger cohorts), women (compared with men), widows/widowers, and those never married (both compared with married individuals) declined faster, and non-Hispanic blacks (compared with non-Hispanic whites) and those in the bottom income quintile (compared with the top quintile) declined slower. Race and income differences in rates of decline were not sufficient to offset larger differences in baseline cognition scores. Educational level was not associated with rate of decline in cognition scores. The authors concluded that ethnic and socioeconomic disparities in cognitive function in older Americans arise primarily from differences in peak cognitive performance achieved earlier in the life course and less from declines in later life.

Does educational level influence lung function decline (Doetinchem Cohort Study)?

Low socioeconomic status is associated with reduced lung function in adults. In addition, there are indications that lung function decline with age is accelerated in low socioeconomic groups, but, to date, findings have been inconclusive. In order to investigate the relation between educational level, forced expiratory volume in 1 s (FEV1) and decline in FEV1 over time, linear mixed-effects models were fitted to baseline and 10-yr-follow-up data from the Doetinchem Cohort Study. The study population (26-66 yrs at baseline) consisted of 2,679 males and 3,026 females with an FEV1 measurement in at least one of the three rounds of follow-up and information on relevant covariables. High educational level was used as the reference class. Low educational level was associated with a higher prevalence of smoking and with a lower smoking-adjusted FEV1 at baseline (-148 mL in males and -47 mL in females). In females, low educational level was associated with a faster FEV1 decline (3.4 mL x yr(-1), age- and height-adjusted), which was not explained by smoking. In males, no differences in rates of decline between educational levels were observed. FEV1 decline was faster in less-educated females, independent of smoking. In males, FEV1 decline did not differ between educational levels.

Exclusive Breast Feeding and Child Survival in Pakistan and Other South Asian Countries

Exclusive Breast-feeding culture is an important child survival strategy. Breast-feeding is the most effective intervention for saving new born and infant lives and preventing early malnutrition. Nearly, all studies mention that during first 6 months exclusive breast feeding produces higher survival rates than partial breast feeding. The extent and severity of infection among preterm and low birth weight infants are generally greater in infants endangered by infant formula inadequacies (Giashuddin and Kabir, 2004). Hence, Breast feeding puts favorable influence on infections diseases prevention, child development and survival as compared to bottle feeding (Brinton et al., 1995). The earlier breast-feeding expression is commenced the better the lactation outcome (Hill et al., 2001; Hartmann et al., 2003; Riordan, 2005). A World Health Organization study of less developed countries found a doubled risk of death in the second year of life for those weaned prematurely or never receiving breast milk (Morisky et al., 2002). Breast feeding also plays a major role in birth spacing (Sayers et al., 1995). The longer the duration of breast feeding; the longer is the interval between the last birth and next pregnancy (Economic Survey of Pakistan, 20042005). Of the 9.7 million under-five deaths globally 2.1 million are India alone. 27 millions births occur every year in India and Pakistan out of which 1.7 million children die before one year of age and 1.08 million new born die within one month of age. Most of these deaths during first few months are related to optimal breast-feeding. Early breast-feeding within one hour can reduce newborn infections by 6 times: exclusive breast-feeding for the first 6 months can reduce diarrhea and pneumonia by 3 and 2.5 times, respectively. Breastfeeding is thus and important issue for child survival: we can certainly reduce infant mortality breast-feeding rates are enhanced (Infant Health at Risk in India, 2008). World development report 2005 indicates that child survival statistics present a much bleaker picture for Pakistan as compared to other South Asian countries. Historical data shows that for Pakistan IMR was much below that of Bangladesh and only slightly higher than India but due to differences in rate of decline in 2005 IMR is the highest in Pakistan (Fig. 1). Table 1: United nations population divisio wn.orld population prospects: The 1998 revision. (United Nations publication, forthcoming) Country IMR U5MR PGR EBF Pakistan 67 95 1.9 16 India 55 78 1.5 51 Bangladesh 52 69 1.7 52 IMR: Infant Mortality Rate per 1000 Year 2003, U5MR: Mortality Rate under 5 per 1000 Year 2003, PGR: Population Avg. Annual (%) Growth Year 2003, EBF: Exclusively Breast Fed (0-3 Months), Source: World development report 2005

Cognitive and sensory declines in old age: Gauging the evidence for a common cause.

Resource accounts of behavioral aging postulate that age-associated impairments within and across intellectual and sensory domains reflect, in part, a common set of senescent alterations in the neurochemistry and neuroanatomy of the aging brain. Hence, these accounts predict sizeable correlations of between-person differences in rates of decline, both within and across intellectual and sensory domains. The authors examined reliability-adjusted variances and covariances in longitudinal change for 8 cognitive measures and for close visual acuity, distant visual acuity, and hearing in 516 participants in the Berlin Aging Study (ages 70 to 103 years at 1st measurement). Up to 6 longitudinal measurements were distributed over up to 13 years. Individual differences in rates of cognitive decline were highly correlated, with a single factor accounting for 60% of the variance in cognitive change. This amount increased to 65% when controlling for age at first measurement, distance to death, and risk of dementia. Contrary to expectations, the correlations between cognitive and sensory declines were only moderate in size, underscoring the need to delineate both domain-general and function-specific mechanisms of behavioral senescence.

Physician Use of Brand Versus Generic Drug Names in 1993–1994 and 2003-2004

Physicians often refer to drugs by their brand names, which can result in brand name drugs being dispensed even when bioequivalent generic alternatives are available. As a result, use of brand-name terminology may result in increased drug costs. To evaluate how often physicians use brand and generic names of drugs, how the use of terminology changes over time, and factors associated with this change. This was a serial cross-sectional study using data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey in 1993/1994 and 2003/2004. Over the 4 study years, data were collected on 376,383 subjects. Using forms completed by physicians that described medication regimens, we determined the proportion of drug names that were recorded using brand vs nonproprietary (ie, generic) terminology. In 1993/1994, the 25 most commonly mentioned drugs were referred to by their brand names a median of 89% of the time. Over the ensuing decade, use of brand-name terminology decreased by a median of 11%. Drugs that first faced generic competition within 10 years of the baseline study year had large declines in brand-name use (43-58% decline), whereas drugs that first faced generic competition more than 10 years before or after the baseline study year had minimal change in brand-name use (2-3% decline; p = 0.02 for difference in rate of decline among drug groups). Year of drug introduction, baseline rate of brand-name use, clinical setting, and national region were not associated with reductions in brand-name use. Brand-name terminology is commonly used and decreases over time with the introduction of generic competition. Interventions that standardize medication-naming practices may hasten this decline and increase use of nonproprietary terminology in medicine.

A longitudinal study of cognition in nursing home residents with multiple sclerosis

Purpose. Examine cognitive change in nursing home residents with multiple sclerosis (MS) over the first 4 years of their nursing home stay.Method. Nine hundred and twenty-four individuals with MS in nursing homes were longitudinally studied. Of these, 121 had MS but no psychiatric or neurological co-morbidities, 169 had MS plus another neurological disorder (MS-Neuro), 269 had MS plus a psychiatric disorder (MS-Psych) and 365 had MS plus both psychiatric and neurological disorders (MS-Comb). Data were obtained from a large government data-set, the minimum data set (MDS), and cognition was rated on the MDS-Cognition Scale.Results. Data were analysed using a mixed-model ANOVA with a repeated factor of time and a fixed factor Group. We found a significant time effect with declines in cognition between each assessment, except 2000 and 2001, and a significant group effect so that the MS-Neuro and the MS-Comb groups had worse cognition than the MS-Psyc and the MS groups. A significant time × group interaction indicated differences in how the groups declined over time.Conclusions. Over the first 4 years of a nursing home stay, cognition deteriorates in individuals with MS. Though there are not different rates of decline, residents with MS-Neuro and MS-Comb perform worse than residents with MS or MS-Psyc.

Memory Changes in Normal and Pathological Aging

Declining memory abilities are reported by virtually all older adults and give rise to the greatest number of complaints about aging in older people. The important questions that arise clinically concern the differences between the so-called benign memory losses of healthy aging and the pathological losses associated with Alzheimer disease and other dementias. Also arising are questions such as to what extent can memory loss be used as a diagnostic tool, and (crucially) can anything be done about it? The 2 In Review articles survey what is known about age-related memory changes: first from the point of view of cognitive psychologists Dr Lin Luo and myself,1 and second from the perspective of a clinical neuropsychologist Dr Lars Backman.2 When does memory decline begin? A rather general answer could be that most people report some problems from their early sixties; however, a study by Park et al3 showed that some memory functions decline as early as the thirties. Two important points in this connection are first that memory is not one monolithic entity, and second that (paradoxically perhaps) memory is also intimately related to other cognitive functions. On the first point, the article by Dr Luo and myself1 describes ideas and evidence from cognitive psychology suggesting that there are at least 5 major memory systems, and that these systems show very different rates of decline in the course of aging. Episodic memory (for specific events) and working memory (for information held and manipulated in conscious awareness) typically fall off relatively rapidly, whereas memory for perceptual information, for highly practiced habits and procedures, and for general knowledge (semantic memory) hold up relatively well. The reasons behind these differential patterns of age-related losses are still under active debate; however, 2 suggestions at the cognitive level of analysis are that age-related problems are found especially in situations requiring large amounts of self-initiated processing and where access to highly specific information is required. The notion of self-initiated processing4 describes cognitive operations that are neither habitual nor well supported by the environmental context; rather, they must be initiated and performed in a conscious, effortful manner, often using new processing operations directed at the specific task. Such operations are typically considered to be frontal lobe functions, and the frontal lobes are known to decline in efficiency in the course of aging.5 Older people are also penalized when the information sought from memory is highly specific in nature-proper names are an obvious example, but specific episodes from the individual's autobiographical past are another. Older people are relatively unimpaired when retrieving general information about a topic, but do less well when specifics are required. One suggestion here is that knowledge is represented and organized hierarchically, with general commonalities easily accessible at the top, and increasingly specific pieces of information that are less easy to access at the bottom of the hierarchy.6 The point that memory is related to other cognitive functions is in line with Dr Backman's2 observation that other cognitive abilities such as attention, executive control, learning, and problem-solving also decline in the course of both normal and pathological aging. To some extent this general cognitive decline may reflect the growing inefficiency of general neurophysiological systems-blood supply, neural connectivity, dopamine depletion, poor glucose metabolism, and so forth-but it is also the case that memory integrity both affects and is affected by other cognitive abilities. Brief examples include: attention-paying attention, especially to the meaning and implication of perceived events, is an obvious prerequisite for subsequent memory performance; memory operations involving elaboration and organization are also crucial for good long-term learning; finally, good working memory abilities reflect good executive control functions (frontal lobes again) and affect such higher-level cognitive activities as problem-solving and planning. …

P-055: Longitudinal voxel based morphometry in AD: Optimizing the method to produce maps of gray matter change over time

Longitudinal Voxel-based morphometry (LVBM) provides a method to probe inter-group differences in rates of decline of gray matter (GM) density captured by serial MRI studies. To our knowledge, LVBM has not yet been used to study AD subjects, and possible variations of LVBM have not yet been explored. Our objective was to analyze a set of AD and control subjects using several variations of LVBM, and compare the results of each method. We selected 32 probable AD and 32 cognitively normal elderly control subjects from the Mayo Alzheimer's Disease Research Center and Alzheimer's Disease Patient Registry. Subjects had undergone two serial T1 weighted 3-D volumetric 1.5T MRI examinations, and were matched for age, gender, and inter-scan interval. We evaluated permutations of 2 different methodological implementations: the image used for normalization and segmentation (early image vs. soft-mean image); and modulation. This created 4 methods: early with or without modulation (methods 1–2); and soft-mean with or without modulation (methods 3–4). The basic steps of LVBM are: 1) Compute deformation from late to early image. 2) Create soft-mean of early and deformed-late images. 3) Create image of the deformation's Jacobian determinants. 4) Normalize and segment the early (methods 1–2), or soft-mean (methods 3–4) image, applying the normalization to the Jacobian image. 5) Multiply normalized Jacobian with segmented GM. 6) (methods 2,4) “Modulate” the normalized early and late GM images. 7) We generated and visually compared statistical maps from each method, showing areas where AD subjects had greater rates of GM loss than controls (p<0.005, uncorrected). Maps from methods 1–4 are displayed in 1-4, respectively. Results from each method are in agreement with general knowledge of neurofibrillary AD pathology. The hippocampus, medial and basal temporal lobe, posterior cingulate/precuneus, lateral temporal-parietal neocortex, and subfrontal regions were significantly affected. LVBM is a powerful tool. Using the soft-mean rather than the early image in step 4 slightly improves the results of group comparisons, and should therefore be used. Modulation slightly degrades the significance of the results, but gives a more accurate representation of GM volume, and should therefore be used.

Validation of the modified mini- mental state examination (3ms) in a German population

Post hoc analyses from clinical trials in Alzheimer's disease (AD) suggest that more cognitively impaired participants respond differently from less impaired on cognitive outcomes. We examined pooled clinical trials data to assess the utility of enriching trials using baseline cognition.We included 2882 participants with mild to moderate AD in seven studies from a meta-database. We used mixed effects models to estimate the rate of decline in Alzheimer's disease Assessment Scale-cognitive (ADAS-Cog) scores among Mini-Mental State Examination (MMSE) groups.Baseline MMSE category was associated with baseline scores and rate of decline on the ADAS-Cog, adjusting for age and education (both P < .001). Greater baseline cognitive impairment was associated with more rapid progression.Although we found significant differences in rate of decline, most differences between individuals were from baseline ADAS-Cog values. Since enrichment based on MMSE would reduce the recruitment pool while adding only slightly to detecting differences in rate of progression, it is not advised.

Patterns and Correlates of Muscle Strength Loss in Older Women

Background: The aging process is associated with progressive declines in muscle strength, resulting in functional disability and reduced quality of life. Objective: The purpose of this epidemiological study was to examine the age-related loss of grip strength both cross-sectionally and longitudinally and the risk factors associated with the decline in muscle strength in a large population of community-living older women (aged 65–91 years). Methods: Clinical visits, including physical examinations and lifestyle assessment, were conducted at baseline and biennially afterwards for a total of 10 years of follow-up. The upper-body muscle strength was measured by grip strength using a hand-held dynamometer. Results: The muscle strength decreased cross-sectionally (n = 9,372) as well as longitudinally (n = 5,214), as age increased, and the decline in muscle strength measured during follow-up was greater than that measured cross-sectionally at baseline. The average loss of grip strength during 10 years of follow-up was 5.1 kg, equivalent to a rate of 2.4% decline per year, with the greatest loss seen in the oldest age group (80 years or older). Cross-sectional analysis revealed that the correlates of lower muscle strength included older age, greater weight, greater height loss since age 25 years, lower protein intake, difficulties in functional tasks, and lower physical activity. In longitudinal analysis, older age, baseline strength, weight and height loss during follow-up, difficulties in functional tasks, and lower physical activity were found to be significantly and independently associated with greater loss in grip strength during follow-up. Conclusions: Cross-sectional and longitudinal analyses of age-related loss of muscle strength yielded different rates of decline. In addition to older age and difficulties in functional tasks, a number of modifiable factors, including weight and physical activity, are associated with increased decline in muscle strength among older women.