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Showing papers on "Cognitive decline published in 2004"


Journal ArticleDOI
TL;DR: The clinical phenotype of SNCA duplication closely resembles idiopathic Parkinson's disease, which has a late age-of-onset, progresses slowly, and in which neither cognitive decline nor dementia are prominent, and suggest a direct relation between S NCA gene dosage and disease progression.

1,801 citations


Journal ArticleDOI
22 Sep 2004-JAMA
TL;DR: Long-term regular physical activity, including walking, is associated with significantly better cognitive function and less cognitive decline in older women.
Abstract: ContextPhysical activity may help maintain cognitive function in older adults.ObjectiveTo examine the relation of long-term regular physical activity, including walking, to cognitive function.DesignWomen reported participation in leisure-time physical activities on biennial mailed questionnaires beginning in 1986. We assessed long-term activity by averaging energy expenditures from questionnaires in 1986 through participants' baseline cognitive assessments (1995 to 2001). We used linear regression to estimate adjusted mean differences in baseline cognitive performance and cognitive decline over 2 years, across levels of physical activity and walking.Setting and ParticipantsNurses' Health Study, including 18 766 US women aged 70 to 81 years.Main Outcome MeasureValidated telephone assessments of cognition administered twice approximately 2 years apart (1995 to 2001 and 1997 to 2003), including tests of general cognition, verbal memory, category fluency, and attention.ResultsHigher levels of activity were associated with better cognitive performance. On a global score combining results of all 6 tests, women in the second through fifth quintiles of energy expenditure scored an average of 0.06, 0.06, 0.09, and 0.10 standard units higher than women in the lowest quintile (P for trend <.001). Compared with women in the lowest physical activity quintile, we found a 20% lower risk of cognitive impairment for women in the highest quintile of activity. Among women performing the equivalent of walking at an easy pace for at least 1.5 h/wk, mean global scores were 0.06 to 0.07 units higher compared with walking less than 40 min/wk (P≤.003). We also observed less cognitive decline among women who were more active, especially those in the 2 highest quintiles of energy expenditure. Women in the fourth and fifth quintiles had mean changes in global scores that were 0.04 (95% confidence interval, 0.02-0.10) and 0.06 (95% confidence interval, 0.02-0.11) standard units better than those in the lowest quintile.ConclusionLong-term regular physical activity, including walking, is associated with significantly better cognitive function and less cognitive decline in older women.

1,130 citations


Journal ArticleDOI
10 Nov 2004-JAMA
TL;DR: Findings support the hypothesis that the metabolic syndrome contributes to cognitive impairment in elders, but primarily in those with high level of inflammation.
Abstract: ContextSeveral studies have reported an association between the metabolic syndrome and cardiovascular disease Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there are few data on the metabolic syndrome and cognitionObjectiveTo determine if the metabolic syndrome is a risk factor for cognitive decline and if this association is modified by inflammationDesign and SettingA 5-year prospective observational study conducted from 1997 to 2002 at community clinics at 2 sitesParticipantsA total of 2632 black and white elders (mean age, 74 years)Main Outcome MeasuresAssociation of the metabolic syndrome (measured using National Cholesterol Education Program guidelines) and high inflammation (defined as above median serum level of interleukin 6 and C-reactive protein) with change in cognition (Modified Mini-Mental State Examination [3MS]) at 3 and 5 years Cognitive impairment was defined as at least a 5-point declineResultsCompared with those without the metabolic syndrome (n = 1616), elders with the metabolic syndrome (n = 1016) were more likely to have cognitive impairment (26% vs 21%, multivariate adjusted relative risk [RR], 120; 95% confidence interval [CI], 102-141) There was a statistically significant interaction with inflammation and the metabolic syndrome (P = 03) on cognitive impairment After stratifying for inflammation, those with the metabolic syndrome and high inflammation (n = 348) had an increased likelihood of cognitive impairment compared with those without the metabolic syndrome (multivariate adjusted RR, 166; 95% CI, 119-232) Those with the metabolic syndrome and low inflammation (n = 668) did not exhibit an increased likelihood of impairment (multivariate adjusted RR, 108; 95% CI, 089-130) Stratified multivariate random-effects models demonstrated that participants with the metabolic syndrome and high inflammation had greater 4-year decline on 3MS (P = 04) compared with those without the metabolic syndrome, whereas those with the metabolic syndrome and low inflammation did not (P = 44)ConclusionThese findings support the hypothesis that the metabolic syndrome contributes to cognitive impairment in elders, but primarily in those with high level of inflammation

938 citations


Journal ArticleDOI
TL;DR: A hypothetical model of Alzheimer's disease as a uniquely human brain disorder rooted in its exceptional process of myelination is presented, offering a framework that explains the anatomical distribution and progressive course of AD pathology, some of the failures of promising therapeutic interventions, and suggests further testable hypotheses as well as novel approaches for intervention efforts.

879 citations


Journal ArticleDOI
TL;DR: Cognitive recovery in the adult brain after successful surgery indicates functional compensation and, to some degree, functional reorganisation or a reactivation of functions previously suppressed by influence from distant but connected epileptogenic areas.
Abstract: Cognitive profiles in epilepsy are as heterogenous as the epileptic syndromes themselves; causes, topography of epileptogenic areas, pathogenetic mechanisms, and the diverse features characterising the clinical course all contribute to the effect on cognition. Chronic epilepsy generally impairs cognition, but it also induces processes of functional reorganisation and behavioural compensation. In most idiopathic epilepsies, cognition is only mildly deteriorated or even normal by clinical standards. Localisation-related cryptogenic and symptomatic epilepsy disorders are accompanied by focal deficits that mirror the specific functions of the respective areas. Poor cognitive outcome is generally associated with an early onset and a long duration of the disease and with poor seizure control. There is evidence that cognitive functions are already impaired at the onset of the disease, and that the maturation of cognitive functions in children is susceptible to the adverse influence of epilepsy. In adults, cognitive decline progresses very slowly over decades with an age regression similar to that of people without epilepsy. Successful epilepsy surgery can stop or partly reverse the unfavourable cognitive development, but left-temporal resections in particular have a high risk of additional postoperative verbal memory impairment. Cognitive recovery in the adult brain after successful surgery indicates functional compensation and, to some degree, functional reorganisation or a reactivation of functions previously suppressed by influence from distant but connected epileptogenic areas.

647 citations


Journal ArticleDOI
TL;DR: Cognitive function is now also recognised as an independent prognostic factor in the survival of glioma patients, and cognitive deterioration can be the first indicator of progressive disease after treatment.
Abstract: Summary Cognitive function, with survival and response on brain imaging, is increasingly regarded as an important outcome measure in patients with brain tumours. This measure provides us with information on a patient's clinical situation and adverse treatment effects. Radiotherapy has been regarded as the main cause of cognitive decline in these patients, because children with brain tumours can develop intellectual deterioration caused by radiotherapy. In long-term surviving patients, radiotherapy may indeed lead to cognitive deficits, or even dementia. Recent studies, however, have made clear that focal radiotherapy in patients with glioma is not the main reason for cognitive deficits. The tumour itself and other medical treatments contribute largely to the cognitive deficits. Cognitive function is now also recognised as an independent prognostic factor in the survival of glioma patients. Additionally, cognitive deterioration can be the first indicator of progressive disease after treatment.

638 citations


Journal ArticleDOI
TL;DR: A systematic search of the literature on the psychometric properties and validity of the IQCODE was carried out using three databases as mentioned in this paper, which showed that the questionnaire has high reliability and measures a single general factor of cognitive decline.
Abstract: Background and aims: The IQCODE is widely used as a screening test for dementia, particularly where the subject is unable to undergo direct cognitive testing or for screening in populations with low levels of education and literacy. This review draws together research on the psychometric properties and validity of the IQCODE. Method: A systematic search of the literature was carried out using three databases. Results: The review shows that the questionnaire has high reliability and measures a single general factor of cognitive decline. It validly reflects past cognitive decline, performs at least as well at screening as conventional cognitive screening tests, predicts incident dementia, and correlates with a wide range of cognitive tests. A particular strength is that the IQCODE is relatively unaffected by education and pre-morbid ability or by proficiency in the culture's dominant language. The disadvantage of the IQCODE is that it is affected by informant characteristics such as depression and anxiety in the informant and the quality of the relationship between the informant and the subject. Conclusions: Because the IQCODE provides information complementary to brief cognitive tests, harnessing them together can improve screening accuracy.

632 citations


Journal ArticleDOI
TL;DR: The results indicate that nondemented aging is characterized by significant changes in white matter most prominently in anterior brain regions, and the dissociation between the regional effects of age and dementia status suggests that the mechanisms underlying age-associated cognitive decline are likely distinct from those underlying DAT.
Abstract: White matter microstructural integrity was assessed using diffusion tensor imaging (DTI) in 25 young adults, 25 nondemented older adults, and 25 age-matched older adults with dementia of the Alzheimer type (DAT). For each individual, measures of anisotropy and diffusivity were obtained from atlas-transformed images in the anterior and posterior callosum and in the frontal, parietal, temporal and occipital white matter. These data revealed age differences in anisotropy and diffusivity in all assessed regions. Age effects were greater in the anterior as opposed to the posterior corpus callosum and greater in the frontal white matter than in the temporal, parietal and occipital white matter, suggesting age-associated differences in white matter that exhibit a roughly anterior-to-posterior gradient. In contrast, individuals with early-stage dementia exhibited minimal, if any, additional change in anterior regions but did show greater deterioration of white matter in posterior lobar regions. Taken collectively, these results indicate that nondemented aging is characterized by significant changes in white matter most prominently in anterior brain regions. The dissociation between the regional effects of age and dementia status suggests that the mechanisms underlying age-associated cognitive decline are likely distinct from those underlying DAT.

604 citations


Journal ArticleDOI
01 Jun 2004-Cancer
TL;DR: The most common domains of cognitive dysfunction were related to attention, learning, and processing speed in patients with non-metastatic breast carcinoma as discussed by the authors, and the importance of using prospective research designs, appropriate cognitive measures, and statistical methods to evaluate subgroup effects was discussed.
Abstract: BACKGROUND Retrospective trials have reported that chemotherapy-induced cognitive dysfunction was experienced by a subset of patients with breast carcinoma. However, recent evidence indicated that a subset also exhibited impaired cognitive function at baseline, before the start of chemotherapy. A prospective, longitudinal trial that incorporates baseline neuropsychologic evaluations is necessary to determine to what extent cognitive dysfunction is attributable to chemotherapy in this population. METHODS Eighteen women with breast carcinoma underwent a comprehensive neuropsychologic evaluation before treatment and at short-term and long-term intervals after chemotherapy. The incidence, nature, severity, and chronicity of cognitive dysfunction developing in patients with breast carcinoma treated with a standard dose of adjuvant chemotherapy were assessed. RESULTS Before the start of systemic therapy, 33% of women in the current cohort exhibited cognitive impairment. At the short-term postchemotherapy time point, 61% of the cohort exhibited a decline relative to baseline in 1 or more domains of cognitive functioning and reported greater difficulty in maintaining their ability to work. The most common domains of cognitive dysfunction were related to attention, learning, and processing speed. At the long-term postchemotherapy time point, approximately 50% of patients who experienced declines in cognitive function demonstrated improvement, whereas 50% remained stable. Self-reported ability to perform work-related activities also improved over this interval. Neither impairment at baseline nor subsequent treatment-related cognitive decline exhibited any statistically significant correlation with affective well-being or with demographic or clinical characteristics. CONCLUSIONS The current study is the first longitudinal trial to report evidence of an association between cognitive dysfunction and chemotherapy in a subgroup of women with nonmetastatic breast carcinoma. The importance of using prospective research designs, appropriate cognitive measures, and statistical methods to evaluate subgroup effects was discussed. Identification of mechanisms associated with cognitive dysfunction and of risk factors contributing to subgroup vulnerability is necessary. Cancer 2004. © 2004 by the American Cancer Society.

601 citations


Journal ArticleDOI
TL;DR: These quantitative, dynamic visualizations of hippocampal atrophy and ventricular expansion rates in aging and AD may provide a promising measure to track AD progression in drug trials.

598 citations


Journal ArticleDOI
TL;DR: The strongest predictors of both cognitive decline and mortality are age, APOE4, manifest vascular diseases, and diabetes, and the role of new potential predictors, feelings of loneliness and hypercalcemia, needs clinical testing.
Abstract: Background. The search for preventable and remediable risk conditions of cognitive decline is ongoing, but results have thus far been inconsistent. According to the hypothesis of our 10-year prospective study, the predictive values of different risk indicators change over time in a general 75þ population. Methods. A population-based sample of 75-, 80-, and 85-year-old individuals (n ¼ 650) underwent comprehensive clinical examinations in 1990 in Helsinki, Finland. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) and/or Clinical Dementia Rating (CDR) at baseline and after 1, 5, and 10 years. Results. At baseline, a low MMSE score was associated with age, history of stroke, apolipoprotein E allele e4 (APOE4), and intermittent claudication. After 1 year, cognitive decline was typical of participants suffering from vascular diseases, e.g., heart failure and intermittent claudication. Five-year decline was predicted by the presence of atrial fibrillation (RR [relative risk] 2.8), APOE4 (RR 2.4), elevated C-reactive protein (CRP) (RR 2.3), diabetes mellitus (RR 2.2), and heart failure (RR 1.8). They also tended to increase 5-year all-cause mortality. At 10 years, the decline associated with APOE4 (RR 3.3), slightly elevated serum ionized calcium (RR 3.3), and feelings of loneliness (RR 3.0). Conclusions. Long follow-up of a general aged population explains several inconsistencies of earlier reports. In 75þ individuals, general ill health is a strong associate of cognitive deficits. The strongest predictors of both cognitive decline and mortality are age, APOE4, manifest vascular diseases, and diabetes. The role of new potential predictors, feelings of loneliness and hypercalcemia, needs clinical testing.

Journal ArticleDOI
TL;DR: It is demonstrated that tau is cleaved at D421 (DeltaTau) by executioner caspases, and therapeutics aimed at inhibiting tau caspase-cleavage may prove beneficial not only in preventing NFT formation, but also in slowing cognitive decline.
Abstract: Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid β (Aβ) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Recent evidence also suggests that caspases are activated early in the progression of AD and may play a role in neuronal loss and NFT pathology. Here we demonstrate that tau is cleaved at D421 (ΔTau) by executioner caspases. Following caspase-cleavage, ΔTau facilitates nucleation-dependent filament formation and readily adopts a conformational change recognized by the early pathological tau marker MC1. ΔTau can be phosphorylated by glycogen synthase kinase-3β and subsequently recognized by the NFT antibody PHF-1. In transgenic mice and AD brains, ΔTau associates with both early and late markers of NFTs and is correlated with cognitive decline. Additionally, ΔTau colocalizes with Aβ1–42 and is induced by Aβ1–42 in vitro. Collectively, our data imply that Aβ accumulation triggers caspase activation, leading to caspase-cleavage of tau, and that this is an early event that may precede hyperphosphorylation in the evolution of AD tangle pathology. These results suggest that therapeutics aimed at inhibiting tau caspase-cleavage may prove beneficial not only in preventing NFT formation, but also in slowing cognitive decline.

Journal ArticleDOI
TL;DR: It is concluded that, in diabetic patients who achieve and maintain good glycemic control, type 2 diabetes only has a small impact on cognitive functions before the age of 70 years, and diabetes likely interacts with other dementing processes such as vascular disease and Alzheimer's disease to hasten cognitive decline.
Abstract: The present review integrates findings of published studies that have evaluated the cognitive function of treated and untreated type 2 diabetic patients and provides a detailed overview of the neuropsychological assessments conducted. Cognitive deficits are observed in older people with glucose intolerance or untreated diabetes but these deficits appear to be attenuated by treatments that improve glycemic control. Cognitive decrements in treated type 2 diabetic patients are most consistently observed on measures of verbal memory (35% of the measures) and processing speed (45% of the measures) while preserved function is observed on measures of visuospatial, attention, semantic and language function. Some studies suggest that deficits in cognitive functions are associated with poorer glycemic control. A number of other factors, such as depression, cardiovascular and cerebrovascular disease, increase these deficits. We conclude that, in diabetic patients who achieve and maintain good glycemic control, type 2 diabetes only has a small impact on cognitive functions before the age of 70 years. However, early onset of type 2 diabetes, poor glycemic control and the presence of micro- and macrovascular disease may interact to produce early cognitive deficits. In older adults (70 years and over), diabetes likely interacts with other dementing processes such as vascular disease and Alzheimer's disease to hasten cognitive decline.

Journal ArticleDOI
TL;DR: Stereotactic radiosurgery followed by EBRT and BCNU does not improve the outcome in patients with GBM nor does it change the general quality of life or cognitive functioning.
Abstract: Purpose Conventional treatment of glioblastoma multiforme (GBM) cures less than 5% of patients. We investigated the effect of stereotactic radiosurgery (SRS) added to conventional external beam radiation therapy (EBRT) with carmustine (BCNU) on the survival of patients with GBM. Methods and materials A total of 203 patients with supratentorial GBM (tumor ≤40 mm) were randomly assigned either to postoperative SRS followed by EBRT (60 Gy) plus BCNU (80 mg/m 2 Days 1–3 every 8 weeks for six cycles) or to EBRT with BCNU alone. The dose of radiosurgery was tumor size–dependent and ranged from 15 Gy for largest to 24 Gy for smallest tumors. RT and BCNU were identical in both arms. Results At a median follow-up time of 61 months, the median survival in the radiosurgery group was 13.5 months (95% confidence interval, 11.0–14.8) as compared with 13.6 months (95% confidence interval, 11.2–15.2, p = 0.5711) for the standard treatment group. There were also no significant differences in 2- and 3-year survival rates and in patterns of failure between the two arms. Quality of life deterioration and cognitive decline at the end of therapy, compared with baseline, were comparable and there was no difference in quality-adjusted survival between the arms. Conclusions Stereotactic radiosurgery followed by EBRT and BCNU does not improve the outcome in patients with GBM nor does it change the general quality of life or cognitive functioning.

Journal ArticleDOI
TL;DR: Greater social resources, as defined by social networks and social engagement, are associated with reduced cognitive decline in old age.
Abstract: Objective: To examine the relation of social resources and cognitive decline in older adults. Methods: Data are from the Chicago Health and Aging Project, an epidemiologic study of risk factors for Alzheimer disease (AD) and other common conditions in a geographically defined population of older persons. The sample consisted of 6,102 non-Hispanic African Americans (61.2%) and whites, aged ≥ 65, who underwent up to three interviews during an average of 5.3 years of follow-up. Each interview included administration of four cognitive function tests from which a composite measure of cognition was formed. Social networks were based on the number of children, relatives, and friends seen at least once a month. Social engagement was measured with four items related to social and productive activity. Results: Higher number of social networks and level of social engagement were positively correlated with initial level of cognitive function (networks estimate = 0.003, engagement estimate = 0.060, both p Conclusions: Greater social resources, as defined by social networks and social engagement, are associated with reduced cognitive decline in old age.

Journal ArticleDOI
TL;DR: The notion that subjective and objective evidence of cognitive decline is not normal and predicts conversion to dementia is strong, and Mild cognitive impairment, appropriately diagnosed, is a good measure with which to select subjects for disease modification studies.
Abstract: Objectives: Older people commonly present with memory loss although on assessment are not found to have a full dementia complex. Previous studies have suggested however that people with subjective and objective cognitive loss are at higher risk of dementia. We aimed to determine from the literature the rate of conversion from mild cognitive impairment to dementia. Methods: Systematic review of MedLine, PsychLit and EmBase. Results: We identified 19 longitudinal studies published between 1991 and 2001 that addressed conversion of mild cognitive impairment to dementia. Overall the rate of conversion was 10% but with large differences between studies. The single biggest variable accounting for between study heterogeneity was source of subjects, with self-selected clinic attenders having the highest conversion rate. The most important factor accounting for heterogeneity within studies was cognitive testing, with poor performance predicting conversion with a high degree of accuracy. Conclusions:These data strongly support the notion that subjective and objective evidence of cognitive decline is not normal and predicts conversion to dementia. The more stringent the measures of both variables the better the prediction of conversion. Mild cognitive impairment, appropriately diagnosed, is a good measure with which to select subjects for disease modification studies.

Journal ArticleDOI
TL;DR: A critical review of the extant literature that has focused on environmental influences on cognitive and brain plasticity over the adult life span and a number of factors that have been suggested to reduce age-related cognitive decline are reviewed.
Abstract: In the current article, we provide a critical review of the extant literature that has focused on environmental influences on cognitive and brain plasticity over the adult life span The review includes both human epidemiological, and human and nonhuman cross-sectional and longitudinal research We review a number of factors that have been suggested to reduce age-related cognitive decline including both formal and informal education, leisure pursuits, intellectual engagement, and expertise in different skill domains We also examine the literature on cognitive and physical fitness training We conclude with a discussion of the gaps in the literature and suggestions for future research

Journal ArticleDOI
TL;DR: Serial MRI could track disease progression and detect neurodegenerative diseases earlier to allow prompt and specific treatment, and the amount and pattern of excess atrophy might help to predict the underlying pathological process, allowing specific therapies to be started.

Journal ArticleDOI
01 Nov 2004-Stroke
TL;DR: Recent evidence is summarized why the receptor for advanced glycation end products and low-density lipoprotein receptor related protein 1 in the vascular CNS barriers are critical for regulation of A&bgr; homeostasis in the CNS and how altered activities in these 2 receptors at the blood–brain barrier may contribute to the CNS.
Abstract: Accumulation of amyloid beta-peptide (Abeta) in the central nervous system (CNS) may initiate pathogenic cascades mediating neurovascular and neuronal dysfunctions associated with the development of cerebral beta-amyloidosis and cognitive decline in patients with Alzheimer disease (AD) and with related familial cerebrovascular disorders. Whether Abeta-related pathology in the CNS is reversible or not and what key therapeutic targets are controlling Abeta/amyloid levels in the aging brain remain debatable. In this article, we summarize recent evidence why the receptor for advanced glycation end products and low-density lipoprotein receptor related protein 1 in the vascular CNS barriers are critical for regulation of Abeta homeostasis in the CNS and how altered activities in these 2 receptors at the blood-brain barrier may contribute to the CNS Abeta accumulation resulting in neuroinflammation, disconnect between the cerebral blood flow and metabolism, altered synaptic transmission, neuronal injury, and amyloid deposition into parenchymal and neurovascular lesions. We briefly discuss the potential of advanced glycation end products and low-density lipoprotein receptor related protein 1-based therapeutic strategies to control brain Abeta in animal models of AD and ultimately in patients with AD and related familial cerebrovascular beta-amyloidoses.

Journal ArticleDOI
TL;DR: The evidence suggests a relationship between delirium and cognitive impairment, although significant questions remain regarding the nature of this association and additional research onDelirium-related effects on long-term cognitive outcome is needed.
Abstract: Delirium is a common neurobehavioral syndrome that occurs across health care settings which is associated with adverse outcomes, including death. There are limited data on long-term cognitive outcomes following delirium. This report reviews the literature regarding relationships between delirium and cognitive impairment. Psych Info and Medline searches and investigation of secondary references for all English language articles on delirium and subsequent cognitive impairment were carried out. Nine papers met inclusion criteria and documented cognitive impairment in patients following delirium. Four papers reported greater cognitive impairment among patients with delirium than matched controls. Four papers reported higher incidence of dementia in patients with a history of delirium. One study found 1 of 3 survivors of critical illness with delirium developed cognitive impairment. The evidence suggests a relationship between delirium and cognitive impairment, although significant questions remain regarding the nature of this association. Additional research on delirium-related effects on long-term cognitive outcome is needed.

Journal ArticleDOI
TL;DR: To determine the association between vision and hearing impairment and subsequent cognitive and functional decline in community‐residing older women, a large sample of women aged 60 and over is studied.
Abstract: Author(s): Lin, Michael Y; Gutierrez, Peter R; Stone, Katie L; Yaffe, Kristine; Ensrud, Kristine E; Fink, Howard A; Sarkisian, Catherine A; Coleman, Anne L; Mangione, Carol M; Study of Osteoporotic Fractures Research Group | Abstract: ObjectivesTo determine the association between vision and hearing impairment and subsequent cognitive and functional decline in community-residing older womenDesignProspective cohort studySettingFour metropolitan areas of the United StatesParticipantsA total of 6,112 women aged 69 and older participating in the Study of Osteoporotic Fractures (SOF) between 1992 and 1994MeasurementsFive thousand three hundred forty-five participants had hearing measured, 1,668 had visual acuity measured, and 1,636 had both measured Visual impairment was defined as corrected vision worse than 20/40 Hearing impairment was defined as the inability to hear a tone of 40 dB or greater at 2,000 hertz Participants completed the modified Mini-Mental State Examination and/or a functional status assessment at baseline and follow-up Cognitive and functional decline were defined as the amount of decline from baseline to follow-up that exceeded the observed average change in scores by at least 1 standard deviationResultsAbout one-sixth (157%) of the sample had cognitive decline; 101% had functional decline In multivariate models adjusted for sociodemographic characteristics and chronic conditions, vision impairment at baseline was associated with cognitive (odds ratio (OR)=178, 95% confidence interval (CI)=121-261) and functional (OR=179, 95% CI=115-279) decline Hearing impairment was not associated with cognitive or functional decline Combined impairment was associated with the greatest odds for cognitive (OR=219, 95% CI=126-381) and functional (OR=187, 95% CI=101-347) declineConclusionSensory impairment is associated with cognitive and functional decline in older women Studies are needed to determine whether treatment of vision and hearing impairment can decrease the risk for cognitive and functional decline

Journal ArticleDOI
01 Nov 2004-Stroke
TL;DR: The vascular factors that might be responsible to cognitive decline in Alzheimer disease and vascular cognitive impairment are reviewed and the corresponding intervenvations that might prevent cognitive impairment as the authors age are reviewed.
Abstract: Alzheimer disease and vascular cognitive impairment are important causes of cognitive decline in the elderly. It has now been shown that vascular risk factors have measurable negative effects on the brain and are associated with cognitive impairment. We review vascular factors that might be responsible to cognitive decline in Alzheimer disease and vascular cognitive impairment and the corresponding intervenvations that might prevent cognitive impairment as we age.

Journal ArticleDOI
TL;DR: Evidence is added that inflammation against Aβ can cause vascular dysfunction, a potential mechanism for the toxic response recently observed in clinical trials of Aβ immunization.
Abstract: To explore the clinical effects of inflammation associated with vascular deposits of the amyloid beta peptide (A beta), we analyzed 42 consecutive patients with pathologically diagnosed cerebral amyloid angiopathy (CAA) for evidence of an inflammatory response. Inflammation with giant-cell reaction surrounding amyloid-laden vessels was identified in 7 of the 42 cases. The clinical symptoms in each of the seven were subacute cognitive decline or seizure rather than hemorrhagic stroke, the primary clinical presentation in 33 of 35 patients with noninflammatory CAA (p < 0.001). Inflammatory CAA also was associated with radiographic white matter abnormalities, significantly younger age at presentation, and a marked overrepresentation of the apolipoprotein E epsilon 4/epsilon 4 genotype (71% vs 4%, p < 0.001). Of the six inflammatory CAA patients with available follow-up information, five demonstrated clinical and radiographic improvement after immunosuppressive treatment. The syndrome of CAA-related perivascular inflammation appears to represent a subset of CAA with clinically distinct symptoms that may respond to immunosuppressive treatment. These data add to evidence that inflammation against A beta can cause vascular dysfunction, a potential mechanism for the toxic response recently observed in clinical trials of A beta immunization.

Journal ArticleDOI
TL;DR: Interestingly, reduced LTP paralleled plaque appearance and increased Aβ levels and abnormal short‐term memory (working memory) and progression of LTP impairment correlated with the deterioration of working memory, suggesting that percentage of potentiation might be an indicator of the cognitive decline and disease progression in the APP/PS1 mice.
Abstract: Increasing evidence points to synaptic plasticity impairment as one of the first events in Alzheimer's disease (AD). However, studies on synaptic dysfunction in different transgenic AD models that overexpress familial AD mutant forms of amyloid precursor protein (APP) and/or presenilin (PS) have provided conflicting results. Both long-term potentiation (LTP) and basal synaptic transmission (BST) have been found to be both unchanged and altered in different models and under differing experimental conditions. Because of their more robust amyloid-beta (Abeta) deposition, double transgenic mice currently are used by several laboratories as an AD model. Here, we report that mice overexpressing APP (K670N:M671L) together with PS1 (M146L) have abnormal LTP as early as 3 months of age. Interestingly, reduced LTP paralleled plaque appearance and increased Abeta levels and abnormal short-term memory (working memory). BST and long-term memory (reference memory) are impaired only later (approximately 6 months) as amyloid burden increases. Abeta pathology across different ages did not correlate with synaptic and cognitive deficits, suggesting that Abeta levels are not a marker of memory decline. In contrast, progression of LTP impairment correlated with the deterioration of working memory, suggesting that percentage of potentiation might be an indicator of the cognitive decline and disease progression in the APP/PS1 mice.

Journal ArticleDOI
TL;DR: Both experimental and epidemiological evidence demonstrate that flavonoid polyphenols, particularly from green tea and blueberries, improve age‐related cognitive decline and are neuroprotective in models of PD, AD and cerebral ischemia/reperfusion injuries.
Abstract: Accumulating evidence supports the hypothesis that brain iron misregulation and oxidative stress (OS), resulting in reactive oxygen species (ROS) generation from H2O2 and inflammatory processes, trigger a cascade of events leading to apoptotic/necrotic cell death in neurodegenerative disorders, such as Parkinson's (PD), Alzheimer's (AD) and Huntington's diseases, and amyotrophic lateral sclerosis (ALS). Thus, novel therapeutic approaches aimed at neutralization of OS-induced neurotoxicity, support the application of ROS scavengers, transition metals (e.g. iron and copper) chelators and non-vitamin natural antioxidant polyphenols, in monotherapy, or as part of antioxidant cocktail formulation for these diseases. Both experimental and epidemiological evidence demonstrate that flavonoid polyphenols, particularly from green tea and blueberries, improve age-related cognitive decline and are neuroprotective in models of PD, AD and cerebral ischemia/reperfusion injuries. However, recent studies indicate that the radical scavenger property of green tea polyphenols is unlikely to be the sole explanation for their neuroprotective capacity and in fact, a wide spectrum of cellular signaling events may well account for their biological actions. In this article, the currently established mechanisms involved in the beneficial health action and emerging studies concerning the putative novel molecular neuroprotective activity of green tea and its major polyphenol (-)-epigallocatechin-3-gallate (EGCG), will be reviewed and discussed.

Journal ArticleDOI
TL;DR: Findings suggest that relative folate deficiency may precede AD and VaD onset and Hyperhomocysteinemia might also be an early risk factor for cognitive decline in the elderly, but its role in dementia development must be addressed in future longitudinal studies.

Journal ArticleDOI
TL;DR: Even in old age, participation in activities with at least a medium-low intensity may postpone cognitive decline, and a decrease in duration orintensity of physical activity results in a stronger cognitive decline than maintaining duration or intensity.
Abstract: Background: Physical activity may be associated with better cognition. Objective: To investigate whether change in duration and intensity of physical activity is associated with 10-year cognitive decline in elderly men. Methods: Data of 295 healthy survivors, born between 1900 and 1920, from the Finland, Italy, and the Netherlands Elderly (FINE) Study were used. From 1990 onward, physical activity was measured with a validated questionnaire for retired men and cognitive functioning with the Mini-Mental State Examination (maximum score 30 points). Results: The rates of cognitive decline did not differ among men with a high or low duration of activity at baseline. However, a decrease in activity duration of >60 min/day over 10 years resulted in a decline of 1.7 points ( p p = 0.06). Men in the lowest intensity quartile at baseline had a 1.8 ( p = 0.07) to 3.5 ( p = 0.004) times stronger 10-year cognitive decline than those in the other quartiles. A decrease in intensity of physical activity of at least half a standard deviation was associated with a 3.6 times stronger decline than maintaining the level of intensity ( p = 0.003). Conclusions: Even in old age, participation in activities with at least a medium-low intensity may postpone cognitive decline. Moreover, a decrease in duration or intensity of physical activity results in a stronger cognitive decline than maintaining duration or intensity.

Journal ArticleDOI
TL;DR: The study confirms that dementia with grains is an age-associated tauopathy with relatively uniform distribution and may independently contribute to cognitive decline in the elderly and propose the following staging paradigm.
Abstract: We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age The distribution of AGs followed a stereotypic regional pattern Thus, we propose the following staging paradigm: stage I: AGs restricted to the ambient gyrus and its vicinity; stage II: AGs more apparent in the anterior and posterior medial temporal lobe, including the temporal pole, as well as the subiculum and entorhinal cortex; and stage III: abundant AGs in the septum, insular cortex, and anterior cingulate gyrus, accompanying spongy degeneration of the ambient gyrus Sixty-three of 65 (969%) argyrophilic grain stage III cases without other dementing pathology were classified as 05 or higher in the clinical dementia rating Forty-seven of 50 dementia with grains cases (94%) were stage III and 3 were stage II No association with apoE genotyping was detected Our study further confirms that dementia with grains is an age-associated tauopathy with relatively uniform distribution and may independently contribute to cognitive decline in the elderly

Journal ArticleDOI
TL;DR: These studies provide compelling evidence to support the view that people with type 2 diabetes are at increased risk of developing cognitive impairment in comparison with the general population.

Journal ArticleDOI
TL;DR: The results from the present study confirm the previous finding of significant neuronal losses in the CA1, hilus, and subiculum in AD, but did not observe a significant loss of neurons in CA1 or any of the other subdivisions of the hippocampus in preclinical AD.