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Sample records for accelerated cognitive decline

  1. Cardiorespiratory Fitness and Accelerated Cognitive Decline With Aging

    PubMed Central

    2014-01-01

    Background. Growing evidence suggests that self-reported physical activity accounts for variability in cognitive function among older adults, and aerobic intervention may improve cognitive function in this population. However, much less is known about the longitudinal association between direct measures of cardiorespiratory fitness and cognitive function across the life span. The present study examined the prospective association between symptom-limited maximal oxygen consumption (VO2max) and longitudinal performance on a comprehensive neuropsychological battery. Methods. Up to 1,400 participants aged 19–94 years underwent initial VO2max assessment and completed subsequent tests of memory, attention, perceptuomotor speed, language, and executive function, in addition to cognitive screening measures, on up to six occasions (mean, M = 2; standard deviation, SD = 1) for up to 18 years (M = 7, SD = 3). Mixed-effects regression models were adjusted for demographic, biomedical, and behavioral confounders. Results. Analyses revealed significant longitudinal associations between baseline VO2max and trajectory of performance on multiple measures of verbal and visual memory, as well as on a cognitive screening test (all ps < .05). Individuals with lower VO2max demonstrated accelerated trajectories of cognitive decline over time. Conclusions. Baseline cardiorespiratory fitness is related to longitudinal neuropsychological performance, and memory appears to be a particularly vulnerable domain. Evidence that aerobic fitness is associated with accelerated cognitive decline emphasizes the possible importance of behavioral interventions to optimize cognitive aging over time. PMID:24192540

  2. Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

    PubMed Central

    Liu, Ganqiang; Boot, Brendon; Locascio, Joseph J.; Jansen, Iris E.; Winder‐Rhodes, Sophie; Eberly, Shirley; Elbaz, Alexis; Brice, Alexis; Ravina, Bernard; van Hilten, Jacobus J.; Cormier‐Dequaire, Florence; Corvol, Jean‐Christophe; Barker, Roger A.; Heutink, Peter; Marinus, Johan; Williams‐Gray, Caroline H.; Scherzer, C.; Hyman, B.T.; Ivinson, A.J.; Trisini‐Lipsanopoulos, A.; Franco, D.; Burke, K.; Sudarsky, L.R.; Hayes, M.T.; Umeh, C.C.; Growdon, J.H.; Schwarzschild, M.A.; Hung, A.Y.; Flaherty, A.W.; Wills, A.‐M.; Mejia, N.I.; Gomperts, S.N.; Khurana, V.; Selkoe, D.J.; Yi, T.; Page, K.; Liao, Z.; Barker, R.; Foltynie, T.; Williams‐Gray, C.H.; Mason, S.; Winder‐Rhodes, S.; Barker, R.; Williams‐Gray, C.H.; Breen, D.; Cummins, G.; Evans, J.; Winder‐Rhodes, S.; Corvol, J.‐C.; Brice, A.; Elbaz, A.; Mallet, A.; Vidailhet, M.; Bonnet, A.‐M.; Bonnet, C.; Grabli, D.; Hartmann, A.; Klebe, S.; Lacomblez, L.; Mangone, G.; Bourdain, F.; Brandel, J.‐P.; Derkinderen, P.; Durif, F.; Mesnage, V.; Pico, F.; Rascol, O.; Forlani, S.; Lesage, S.; Tahiri, K.; van Hilten, J.J.; Marinus, J.; Liao, Z.; Page, K.; Franco, D.; Duong, K.; Yi, T.; Trisini‐Lipsanopoulos, A.; Dong, X.; Sudarsky, L.R.; Hutten, S.J.; Amr, S.S.; Shoulson, I.; Tanner, C.M.; Lang, A.E.; Nalls, M.A.

    2016-01-01

    Objective We hypothesized that specific mutations in the β‐glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non‐neuropathic GD mutations confer intermediate progression rates. Methods A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models. Results Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60–6.25) and a hastened decline in Mini–Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18–8.73; p = 0.022). By contrast, the common, non‐neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92–4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89–2.05) did not reach significance. Interpretation Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into “high gear.” These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674–685 PMID:27717005

  3. Synergistic Interactions between Aβ, Tau, and α-Synuclein: Acceleration of Neuropathology and Cognitive Decline

    PubMed Central

    Clinton, Lani K.; Blurton-Jones, Mathew; Myczek, Kristoffer; Trojanowski, John Q.

    2010-01-01

    Alzheimer's disease (AD), the most prevalent age-related neurodegenerative disorder, is characterized pathologically by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles. Interestingly, up to 50% of AD cases exhibit a third prevalent neuropathology: the aggregation of α-synuclein into Lewy bodies. Importantly, the presence of Lewy body pathology in AD is associated with a more aggressive disease course and accelerated cognitive dysfunction. Thus, Aβ, tau, and α-synuclein may interact synergistically to promote the accumulation of each other. In this study, we used a genetic approach to generate a model that exhibits the combined pathologies of AD and dementia with Lewy bodies (DLB). To achieve this goal, we introduced a mutant human α-synuclein transgene into 3xTg-AD mice. As occurs in human disease, transgenic mice that develop both DLB and AD pathologies (DLB-AD mice) exhibit accelerated cognitive decline associated with a dramatic enhancement of Aβ, tau, and α-synuclein pathologies. Our findings also provide additional evidence that the accumulation of α-synuclein alone can significantly disrupt cognition. Together, our data support the notion that Aβ, tau, and α-synuclein interact in vivo to promote the aggregation and accumulation of each other and accelerate cognitive dysfunction. PMID:20505094

  4. Reduction of Endogenous Melatonin Accelerates Cognitive Decline in Mice in a Simulated Occupational Formaldehyde Exposure Environment

    PubMed Central

    Mei, Yufei; Duan, Chunli; Li, Xiaoxiao; Zhao, Yun; Cao, Fenghua; Shang, Shuai; Ding, Shumao; Yue, Xiangpei; Gao, Ge; Yang, Hui; Shen, Luxi; Feng, Xueyan; Jia, Jianping; Tong, Zhiqian; Yang, Xu

    2016-01-01

    Individuals afflicted with occupational formaldehyde (FA) exposure often suffer from abnormal behaviors such as aggression, depression, anxiety, sleep disorders, and in particular, cognitive impairments. Coincidentally, clinical patients with melatonin (MT) deficiency also complain of cognitive problems associated with the above mental disorders. Whether and how FA affects endogenous MT metabolism and induces cognitive decline need to be elucidated. To mimic occupational FA exposure environment, 16 healthy adult male mice were exposed to gaseous FA (3 mg/m3) for 7 consecutive days. Results showed that FA exposure impaired spatial memory associated with hippocampal neuronal death. Biochemical analysis revealed that FA exposure elicited an intensive oxidative stress by reducing systemic glutathione levels, in particular, decreasing brain MT concentrations. Inversely, intraperitoneal injection of MT markedly attenuated FA-induced hippocampal neuronal death, restored brain MT levels, and reversed memory decline. At tissue levels, injection of FA into the hippocampus distinctly reduced brain MT concentrations. Furthermore, at cellular and molecular levels, we found that FA directly inactivated MT in vitro and in vivo. These findings suggest that MT supplementation contributes to the rescue of cognitive decline, and may alleviate mental disorders in the occupational FA-exposed human populations. PMID:26938543

  5. Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair.

    PubMed

    Borgesius, Nils Z; de Waard, Monique C; van der Pluijm, Ingrid; Omrani, Azar; Zondag, Gerben C M; van der Horst, Gijsbertus T J; Melton, David W; Hoeijmakers, Jan H J; Jaarsma, Dick; Elgersma, Ype

    2011-08-31

    Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Δ/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.

  6. Accelerated postmenopausal cognitive decline is restricted to women with normal BMI: longitudinal evidence from the Betula project.

    PubMed

    Thilers, Petra P; Macdonald, Stuart W S; Nilsson, Lars-Göran; Herlitz, Agneta

    2010-05-01

    In order to determine whether cognitive performance is influenced by the menopausal transition, we tested cognitive performance at three time points, sampled women in earlier as well as later stages of the menopausal transition (40-65 years of age), and assessed the moderating influence of body mass index (BMI) on rate of change. Multilevel analyses were used to model change in cognitive performance as a function of number of years post menopause over and above chronological age. We investigated change in the menopausal transition for 10 cognitive outcomes in 193 women who were postmenopausal during the last test wave. The model, controlling for age and education, showed that postmenopausal women within the normal range of BMI (BMI 18.5-25) displayed more rapid decline than women with BMI above 25 for measures of visuospatial ability and episodic memory. In addition, there was an accelerated rate of change post menopause for all women on verbal fluency. The results support the notion that the diminished postmenopausal production of endogenous estrogen may have a slight negative influence on cognitive abilities, but mainly for women within a normal BMI range.

  7. Cognitive decline in Parkinson disease.

    PubMed

    Aarsland, Dag; Creese, Byron; Politis, Marios; Chaudhuri, K Ray; Ffytche, Dominic H; Weintraub, Daniel; Ballard, Clive

    2017-04-01

    Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition - or even reversal to normal cognition - is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.

  8. Dietary Factors and Cognitive Decline

    PubMed Central

    Smith, P.J.; Blumenthal, J.A.

    2015-01-01

    Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing ‘whole’ diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed. PMID:26900574

  9. Dietary Factors and Cognitive Decline.

    PubMed

    Smith, P J; Blumenthal, J A

    2016-03-01

    Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing 'whole' diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed.

  10. Trajectory of Cognitive Decline after Incident Stroke

    PubMed Central

    Levine, Deborah A.; Galecki, Andrzej T.; Langa, Kenneth M.; Unverzagt, Frederick W.; Kabeto, Mohammed U.; Giordani, Bruno; Wadley, Virginia G.

    2015-01-01

    .097); however, there was a significantly faster poststroke rate of incident cognitive impairment compared to the prestroke rate (odds ratio, 1.23 per year; 95% CI, 1.10–1.38; P<0.001). For a 70 year-old black woman, stroke at year 3 was associated with greater incident cognitive impairment: absolute difference (95% CI) of 4.0% (−1.2%–9.2%) at year 3 and 12.4% (7.7%–17.1% at year 6). Conclusion Incident stroke was associated with an acute decline in cognition and also accelerated and persistent cognitive decline over 6 years. PMID:26151265

  11. Cognitive Decline and the Default American Lifestyle

    PubMed Central

    2011-01-01

    Objectives. Upward trends in IQ, education, and mental work suggest that cognitive function among seniors should be rising strongly across cohorts. There is little sign of such improvement in recent decades, and some analyses find poorer function in the newer cohorts. This essay explores possible explanations of the anomaly. Methods. Major long-term trends that might increase cognitive impairment are reviewed, and their implications are considered. Results. Physical activity is declining, food is increasingly manufactured, body fat is increasing, diabetes and metabolic syndrome are on the rise, the number of prescription drugs per person is increasing, and the proportion of the population either old or obese is growing. Discussion. Technological and economic development may lower the cognitive function needed for survival. They also lower physical activity in daily life. Sedentary work, transportation, and leisure undermine the aerobic and metabolic fitness required for the brain to perform well. Some prescription drugs impair cognitive function, and others do so when taken for many years or in combination with others. The growing fraction of the population that is either old or obese may further lower physical activity norms and requirements and substitute medical intervention for health, accelerating a trend toward cognitive impairment. PMID:21743052

  12. Biomarkers of cognitive decline in Parkinson's disease.

    PubMed

    Lin, Chin-Hsien; Wu, Ruey-Meei

    2015-05-01

    Cognitive impairment is a frequent and devastating non-motor symptom of Parkinson's disease (PD). Impaired cognition has a major impact on either quality of life or mortality in patients with PD. Notably, the rate of cognitive decline and pattern of early cognitive deficits in PD are highly variable between individuals. Given that the underlying mechanisms of cognitive decline or dementia associated with PD remain unclear, there is currently no mechanism-based treatment available. Identification of biological markers, including neuroimaging, biofluids and common genetic variants, that account for the heterogeneity of PD related cognitive decline could provide important insights into the pathological processes that underlie cognitive impairment in PD. These combined biomarker approaches will enable early diagnosis and provide indicators of cognitive progression in PD patients. This review summarizes recent advances in the development of biomarkers for cognitive impairments in PD.

  13. Atrial Fibrillation, Cognitive Decline And Dementia

    PubMed Central

    Alonso, Alvaro; Arenas de Larriva, Antonio P.

    2016-01-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia. Growing evidence supports a role for AF as a risk factor for cognitive decline and dementia. In this review, we summarize epidemiologic observations linking AF with cognitive outcomes, describe potential mechanisms, and explore the impact of AF treatments on cognitive decline and dementia. Community-based, observational studies show a consistent higher rate of cognitive decline and risk of dementia in persons with AF. These associations are partly due to the increased risk of clinical stroke in AF, but other mechanisms, including incidence of silent cerebral infarcts, microbleeds, and cerebral hypoperfusion, are likely additional contributors. Adequate oral anticoagulation and improved management of the overall cardiovascular risk profile in persons with AF offer the promise of reducing the impact of AF on cognitive decline and dementia. PMID:27547248

  14. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    PubMed

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

  15. Cognitive deterioration in adult epilepsy: Does accelerated cognitive ageing exist?

    PubMed

    Breuer, L E M; Boon, P; Bergmans, J W M; Mess, W H; Besseling, R M H; de Louw, A; Tijhuis, A G; Zinger, S; Bernas, A; Klooster, D C W; Aldenkamp, A P

    2016-05-01

    A long-standing concern has been whether epilepsy contributes to cognitive decline or so-called 'epileptic dementia'. Although global cognitive decline is generally reported in the context of chronic refractory epilepsy, it is largely unknown what percentage of patients is at risk for decline. This review is focused on the identification of risk factors and characterization of aberrant cognitive trajectories in epilepsy. Evidence is found that the cognitive trajectory of patients with epilepsy over time differs from processes of cognitive ageing in healthy people, especially in adulthood-onset epilepsy. Cognitive deterioration in these patients seems to develop in a 'second hit model' and occurs when epilepsy hits on a brain that is already vulnerable or vice versa when comorbid problems develop in a person with epilepsy. Processes of ageing may be accelerated due to loss of brain plasticity and cognitive reserve capacity for which we coin the term 'accelerated cognitive ageing'. We believe that the concept of accelerated cognitive ageing can be helpful in providing a framework understanding global cognitive deterioration in epilepsy.

  16. Cholesterol and late-life cognitive decline.

    PubMed

    van Vliet, Peter

    2012-01-01

    High cholesterol levels are a major risk factor for cardiovascular disease, but their role in dementia and cognitive decline is less clear. This review highlights current knowledge on the role of cholesterol in late-life cognitive function, cognitive decline, and dementia. When measured in midlife, high cholesterol levels associate with an increased risk of late-life dementia and cognitive decline. However, when measured in late-life, high cholesterol levels show no association with cognitive function, or even show an inverse relation. Although statin treatment has been shown to associate with a lower risk of dementia and cognitive decline in observational studies, randomized controlled trials show no beneficial effect of statin treatment on late-life cognitive function. Lowering cholesterol levels may impair brain function, since cholesterol is essential for synapse formation and maturation and plays an important role in the regulation of signal transduction through its function as a component of the cell membrane. However, membrane cholesterol also plays a role in the formation and aggregation of amyloid-β. Factors that influence cholesterol metabolism, such as dietary intake, are shown to play a role in late-life cognitive function and the risk of dementia. In conclusion, cholesterol associates with late-life cognitive function, but the association is strongly age-dependent. There is no evidence that treatment with statins in late-life has a beneficial effect on cognitive function.

  17. Can exercise prevent cognitive decline?

    PubMed

    Behrman, Sophie; Ebmeier, Klaus P

    2014-01-01

    As the tolerability of pharmacological agents decreases with age, exercise may be particularly helpful as a possible treatment or stabiliser of mood and cognitive function in older age. Exercise has been most commonly evaluated for the treatment of depression. Exercise interventions designed primarily for treatment of physical conditions in the elderly do appear to confer psychological benefits as well, with reduction in depressive symptoms over the course of treatment. The effects of exercise on reducing depressive symptoms are not dissimilar to the effects of antidepressant drugs and cognitive behaviour therapy. Exercise may be a useful low-tech intervention for people with mild to moderate depression. In particular, exercise may be helpful in the elderly and in patients who have had insufficient response to, or are intolerant of, pharmacotherapy. Mastery of a new skill and positive feedback from others may increase feelings of self-esteem and improve mood. Exercise may distract participants from persistent negative thoughts. Exercise has been shown to improve executive function acutely in adults of all ages. It is possible that dance routines or other exercise regimens requiring some cognitive input may confer additional benefit to cognitive function. Exercise has a moderate effect on the ability of people with dementia to perform activities of daily living and may improve cognitive function. Midlife exercise may also have an impact on later cognitive function.

  18. Nutritional factors, cognitive decline, and dementia.

    PubMed

    Del Parigi, Angelo; Panza, Francesco; Capurso, Cristiano; Solfrizzi, Vincenzo

    2006-03-15

    Nutritional factors and nutritional deficiencies have been repeatedly associated with cognitive impairment. Most of the evidence is based on cross-sectional studies, which cannot prove whether a nutritional deficit is the cause or the consequence of an impaired cognitive status. In fact, cognitive impairment, in turn, can determine changes in dietary habits and consequent nutritional deficiencies. We reviewed clinical and epidemiological studies from January 1983 to June 2004. Several cross-sectional and fewer prospective studies reported an association between dietary or supplemental intake of antioxidants and protection from cognitive decline and dementia. There are negative reports as well and some methodological biases might have affected the consistencies across studies. Deficiencies of several B vitamins have been associated with cognitive dysfunction in many observational studies. More recently, deficiencies of folate (B9) and cobalamine (B12) have been studied in relation to hyperhomocysteinemia as potential determinants of cognitive impairment, dementia, and Alzheimer's disease (AD). A small number of studies assessed the association between intake of macronutrients and cognitive function or dementia. Among the others, the intake of fatty acids and cholesterol has received particular attention. Although the results are not always consistent, most studies have reported a protective role of dietary intakes of poly- and mono-unsaturated fatty acids against cognitive decline and AD. We point out that well designed intervention studies are warranted in order to establish specific levels of micro- and macronutrient deficiencies and to set general recommendations for the population.

  19. Antihypertensive treatments, cognitive decline, and dementia.

    PubMed

    Duron, Emmanuelle; Hanon, Olivier

    2010-01-01

    Chronic hypertension is associated with an increased risk of both vascular dementia and Alzheimer's disease (AD). In this context, the role of anti-hypertensive therapy for the prevention and delay of cognitive decline and dementia is of central importance. Most longitudinal studies have shown a significant inverse association between anti-hypertensive therapies and dementia incidence and for some of these, particularly in AD. Seven randomized, double blind placebo-controlled trials have evaluated the benefit of antihypertensive treatments on cognition. Three of them found positive results in term of prevention of dementia (SYST-EUR) or cognitive decline (PROGRESS, HOPE). Others disclosed non-significant results (MRC, SHEP, SCOPE, HYVET-COG). This discrepancy emphasizes the difficulty to perform such trials: the follow-up has to be long enough to disclose a benefit, a large number of patients is needed for these studies, and because of ethical reasons some anti-hypertensive treatments are often prescribed in the placebo group. Results of the two more recent meta-analyses are inconsistent, possibly due to methodological issues. Antihypertensive treatments could be beneficial to cognitive function by lowering blood pressure and/or by specific neuroprotective effect. Three main antihypertensive subclasses have been associated with a beneficial effect on cognitive function beyond blood pressure reduction (calcium channel blockers, angiotensin converting enzyme inhibitor, angiotensin-AT1-receptor-blockers). Further long-term randomized trials, designed especially to assess a link between antihypertensive therapy and cognitive decline or dementia are therefore needed with cognition as the primary outcome. A low blood pressure threshold that could be deleterious for cognitive function should also be determined.

  20. Reversal of cognitive decline in Alzheimer's disease

    PubMed Central

    Bredesen, Dale E.; Amos, Edwin C.; Canick, Jonathan; Ackerley, Mary; Raji, Cyrus; Fiala, Milan; Ahdidan, Jamila

    2016-01-01

    Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4−, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype. PMID:27294343

  1. Detection and Prevention of Cognitive Decline.

    PubMed

    Small, Gary W

    2016-12-01

    Current diagnostic and treatment strategies for cognitive decline can help patients maintain cognitive ability and higher levels of function longer. Despite advances in detection and early treatment strategies, many patients do not receive proper assessments and available therapies. A systematic assessment strategy will increase the likelihood of an accurate diagnosis, which can facilitate pharmacologic and non-pharmacologic treatment plans that can have a meaningful impact on prognosis. Available data support the integration of healthy lifestyle strategies in the treatment plan to help to stabilize symptoms and potentially delay future cognitive decline. While investigators continue to pursue more effective detection, treatment, and prevention strategies, the scientific data support the use of symptomatic drug treatments and recommendations for healthy lifestyle behaviors to improve quality of life and potentially stave off future cognitive decline. Success of such healthy lifestyle programs involves educating participants on the connection between lifestyle and disease prevention, offering enjoyable exercises that target the patient's skill level, and providing feedback that motivates participants to continue their healthy behaviors so they become habits.

  2. Cognition enhancers in age-related cognitive decline.

    PubMed

    Riedel, W J; Jolles, J

    1996-04-01

    A review of recently published studies on the effect of cognition enhancers in non-demented human study participants is presented. The heterogeneity of the therapeutic target, age-associated cognitive decline, can be improved by separately treating groups in whom age-extrinsic factors may underlie cognitive pathology. Standardisation of cognitive assessments is necessary, since many different tests are applied to answer the same question. Modelling cognitive dysfunction, either by pharmacological or nonpharmacological means, in humans is highly recommended since it allows hypotheses to be tested in a clearly operationalised way. Predictive validity of the currently applied models for the clinical situation remains a problem, however. The scopolamine (hyoscine) model has, to a reasonable extent, predictive validity for the cholinergic agents. The results of 67 single-dose studies and 30 multiple-dose studies are summarised. All single-dose studies and 14 multiple-dose studies were carried out in young or elderly human volunteers. In 45 of 81 volunteer studies, models of cognitive dysfunction were employed. The scopolamine model was the most used (n = 21); the other studies induced cognitive dysfunction by means of benzodiazepines (8), hypoxia (7), alcohol (5) and sleep-deprivation (4). The remaining 16 multiple-dose studies were clinical trials of a duration varying between 2 weeks and 1 year (average duration was 14 weeks). In these trials, the effects of cognition enhancers were assessed in elderly people in whom impairment of memory, psychomotor performance or cognitive function was determined. These included age-associated memory impairment (AAMI) and age-associated cognitive decline (AACD). There were many studies in which the cognition enhancing properties of substances in humans were reliably demonstrated. The cognition enhancing properties of substances that are widely used, such as caffeine, nicotine and vitamins, may already be active against AACD. New

  3. Depressed Mood Mediates Decline in Cognitive Processing Speed in Caregivers

    ERIC Educational Resources Information Center

    Vitaliano, Peter P.; Zhang, Jianping; Young, Heather M.; Caswell, Lisa W.; Scanlan, James M.; Echeverria, Diana

    2009-01-01

    Purpose: Very few studies have examined cognitive decline in caregivers versus noncaregivers, and only 1 study has examined mediators of such decline. We evaluated the relationship between caregiver status and decline on the digit symbol test (DST; a measure of processing speed, attention, cognitive-motor translation, and visual scanning) and…

  4. Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study.

    PubMed

    Nooyens, Astrid C J; Bueno-de-Mesquita, H Bas; van Gelder, Boukje M; van Boxtel, Martin P J; Verschuren, W M Monique

    2014-02-01

    Accelerated cognitive decline increases the risk of dementia. Slowing down the rate of cognitive decline leads to the preservation of cognitive functioning in the elderly, who can live independently for a longer time. Alcohol consumption may influence the rate of cognitive decline. The aim of the present study was to evaluate the associations between the total consumption of alcoholic beverages and different types of alcoholic beverages and cognitive decline at middle age. In 2613 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline (1995-2002), cognitive function (global cognitive function and the domains memory, speed and flexibility) was assessed twice, with a 5-year time interval. In linear regression analyses, the consumption of different types of alcoholic beverages was analysed in relation to cognitive decline, adjusting for confounders. We observed that, in women, the total consumption of alcoholic beverages was inversely associated with the decline in global cognitive function over a 5-year period (P for trend = 0·02), while no association was observed in men. Regarding the consumption of different types of alcoholic beverages in men and women together, red wine consumption was inversely associated with the decline in global cognitive function (P for trend < 0·01) as well as memory (P for trend < 0·01) and flexibility (P for trend = 0·03). Smallest declines were observed at a consumption of about 1·5 glasses of red wine per d. No other types of alcoholic beverages were associated with cognitive decline. In conclusion, only (moderate) red wine consumption was consistently associated with less strong cognitive decline. Therefore, it is most likely that non-alcoholic substances in red wine are responsible for any cognition-preserving effects.

  5. Folic Acid Supplements: Can They Slow Cognitive Decline?

    MedlinePlus

    ... slow cognitive decline? I've heard that folic acid supplements can improve cognitive function in older adults. ... those with Alzheimer's disease also benefit from folic acid? Answers from Paul Y. Takahashi, M.D. There's ...

  6. Sensorineural Organs Dysfunction and Cognitive Decline: A Review Article

    PubMed Central

    Wongrakpanich, Supakanya; Petchlorlian, Aisawan; Rosenzweig, Andrew

    2016-01-01

    Vision, hearing, olfaction, and cognitive function are essential components of healthy and successful aging. Multiple studies demonstrate relationship between these conditions with cognitive function. The present article focuses on hearing loss, visual impairment, olfactory loss, and dual sensory impairments in relation to cognitive declination and neurodegenerative disorders. Sensorineural organ impairment is a predictive factor for mild cognitive impairment and neurodegenerative disorders in the elderly. We recommend early detection of sensorineural dysfunction by history, physical examination, and screening tests. Assisted device and early cognitive rehabilitation may be beneficial. Future research is warranted in order to explore advanced treatment options and method to slow progression for cognitive declination and sensorineural organ impairment. PMID:28053826

  7. Healthy eating and reduced risk of cognitive decline

    PubMed Central

    Dehghan, Mahshid; O'Donnell, Martin; Anderson, Craig; Teo, Koon; Gao, Peggy; Sleight, Peter; Dagenais, Gilles; Probstfield, Jeffrey L.; Mente, Andrew; Yusuf, Salim

    2015-01-01

    Objective: We sought to determine the association of dietary factors and risk of cognitive decline in a population at high risk of cardiovascular disease. Methods: Baseline dietary intake and measures of the Mini-Mental State Examination were recorded in 27,860 men and women who were enrolled in 2 international parallel trials of the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) studies. We measured diet quality using the modified Alternative Healthy Eating Index. Cox proportional hazards regression was used to determine the association between diet quality and risk of ≥3-point decline in Mini-Mental State Examination score, and reported as hazard ratio with 95% confidence intervals with adjustment for covariates. Results: During 56 months of follow-up, 4,699 cases of cognitive decline occurred. We observed lower risk of cognitive decline among those in the healthiest dietary quintile of modified Alternative Healthy Eating Index compared with lowest quintile (hazard ratio 0.76, 95% confidence interval 0.66–0.86, Q5 vs Q1). Lower risk of cognitive decline was consistent regardless of baseline cognitive level. Conclusion: We found that higher diet quality was associated with a reduced risk of cognitive decline. Improved diet quality represents an important potential target for reducing the global burden of cognitive decline. PMID:25948720

  8. Inspection Time: A Biomarker for Cognitive Decline

    ERIC Educational Resources Information Center

    Gregory, Tess; Nettelbeck, Ted; Howard, Sara; Wilson, Carlene

    2008-01-01

    Inspection Time (IT) is a psychophysical speed measure that has been linked to a range of cognitive abilities with results finding that shorter IT is associated with superior performance in cognitive abilities. Following a recent suggestion by Nettelbeck and Wilson [Nettelbeck, T., & Wilson, C. (2004). The Flynn effect: Smarter not faster.…

  9. Cerebrospinal fluid biomarkers mirror rate of cognitive decline.

    PubMed

    Rolstad, Sindre; Berg, Anne Ingeborg; Bjerke, Maria; Johansson, Boo; Zetterberg, Henrik; Wallin, Anders

    2013-01-01

    The ability to predict future decline in cognitive systems using the cerebrospinal fluid (CSF) biomarkers 42 amino acid form of amyloid-β (Aβ42) and total tau (T-tau) is not fully understood. In a clinical sample ranging from cognitively healthy to dementia (n = 326), linear regression models were performed in order to investigate the ability of CSF biomarkers to predict cognitive decline in all cognitive domains from baseline to 2-year follow-up. Gender, age, and years of education were included as covariates. In patients with subjective cognitive impairment, T-tau had a small impact on executive functions (r2 = 0.07). T-tau had a small to moderate influence (r2 = 0.06-0.11) on all cognitive functions with the exception of visuospatial functions in patients with mild cognitive impairment (MCI). In patients with dementia, the impact of T-tau was large (r2 = 0.29) on semantic memory. Aβ42 had a small effect (r2 = 0.07) on speed and executive functions in MCI. In patients with dementia, Aβ42 had a moderate influence (r2 = 0.13-0.24) on semantic and verbal working memory/fluency. Our results speak in favor of the notion that CSF biomarkers reflect the rate of cognitive decline across the continuum of cognitive impairment from healthy to dementia. CSF predicted subsequent decline in more cognitive domains among MCI cases, but the impact was most pronounced in patients with dementia.

  10. Neuropsychological tests for predicting cognitive decline in older adults

    PubMed Central

    Baerresen, Kimberly M; Miller, Karen J; Hanson, Eric R; Miller, Justin S; Dye, Richelin V; Hartman, Richard E; Vermeersch, David; Small, Gary W

    2015-01-01

    Summary Aim To determine neuropsychological tests likely to predict cognitive decline. Methods A sample of nonconverters (n = 106) was compared with those who declined in cognitive status (n = 24). Significant univariate logistic regression prediction models were used to create multivariate logistic regression models to predict decline based on initial neuropsychological testing. Results Rey–Osterrieth Complex Figure Test (RCFT) Retention predicted conversion to mild cognitive impairment (MCI) while baseline Buschke Delay predicted conversion to Alzheimer’s disease (AD). Due to group sample size differences, additional analyses were conducted using a subsample of demographically matched nonconverters. Analyses indicated RCFT Retention predicted conversion to MCI and AD, and Buschke Delay predicted conversion to AD. Conclusion Results suggest RCFT Retention and Buschke Delay may be useful in predicting cognitive decline. PMID:26107318

  11. Nutritional management of older adults with cognitive decline and dementia.

    PubMed

    Ogawa, Sumito

    2014-04-01

    Age-related cognitive decline is a main predictor of disability among elderly people, and with the continued expansion of the aging population and the increase in life expectancy, the prevalence of mild cognitive impairment and dementia represented by Alzheimer's disease (AD), which is a multifactorial neurodegenerative disorder of older adults, have increased. Recent epidemiological and observational studies suggest a relationship exists between lifestyle factors, including nutrition and diet, and cognitive function in aging adults. It is also suggested that malnutrition and nutrient deficiencies are associated with cognitive decline in patients with dementia. There are a variety of nutritional factors, including nutritional status and dietary patterns, that might be associated with cognitive function, and specific micronutrients and dietary components have been suggested to have an association with cognitive function as well. Based on these findings and evidence, evaluation of nutritional state, as well as nutritional intervention, might be able to play a role in the management and prevention of dementia.

  12. Diagnosing early cognitive decline-When, how and for whom?

    PubMed

    Allan, Charlotte L; Behrman, Sophie; Ebmeier, Klaus P; Valkanova, Vyara

    2017-02-01

    Mild cognitive impairment (MCI) is a term used to describe cognitive impairment in one or more cognitive domains that is greater than any expected age-related changes, but not of the magnitude to warrant a diagnosis of dementia. This review considers how early cognitive decline is diagnosed, focusing on the use of neuropsychological tests and neuroimaging, as well as the differential diagnosis. Potential treatments, including secondary prevention, post-diagnostic support and self-help are discussed. Finally, medico-legal matters such as driving, lasting power of attorney and employment are outlined.

  13. Which factors predict cognitive decline in Parkinson's disease?

    PubMed Central

    Caparros-Lefebvre, D; Pécheux, N; Petit, V; Duhamel, A; Petit, H

    1995-01-01

    The study assessed cognitive decline in non-demented, non-depressed patients with well defined Parkinson's disease and determined the predictive value for cognitive decline of different motor symptoms. Motor disability was measured with the Unified Parkinson's disease rating scale, impairment in activities of daily living, levodopa test, and long term clinical follow up. Neuropsychological evaluations included modified mini mental state, fluency, Wechsler logical memory, Wisconsin card sorting test, and the Montgomery and Asberg depression rating scale. Fifty three patients fulfilling clinical criteria for idiopathic Parkinson's disease were studied. Cognitive performance on initial testing was significantly correlated with education and disease duration but not with age at disease onset. Cognitive performance on retesting after three years of follow up was significantly reduced. This reduction was significantly greater in the late onset group, in patients with isolated dystonic dyskinesiae, and in patients with a lower percentage of motor improvement on levodopa. Cognitive decline in idiopathic Parkinson's disease may depend on both the prevalence of non-dopaminergic lesions and the topography of dopaminergic denervation. Predictive factors for cognitive decline, especially in executive tasks, relate more to non-dopaminergic than to dopaminergic lesions. PMID:7823067

  14. Subtle Cognitive Decline and Biomarker Staging in Preclinical Alzheimer's Disease.

    PubMed

    Edmonds, Emily C; Delano-Wood, Lisa; Galasko, Douglas R; Salmon, David P; Bondi, Mark W

    2015-01-01

    The NIA-AA criteria for "preclinical" Alzheimer's disease (AD) propose a staging method in which AD biomarkers follow an invariable temporal sequence in accordance with the amyloid cascade hypothesis. However, recent findings do not align with the proposed temporal sequence and "subtle cognitive decline," which has not been definitively operationalized, may occur earlier than suggested in preclinical AD. We aimed to define "subtle cognitive decline" using sensitive and reliable neuropsychological tests, and to examine the number and sequence of biomarker abnormalities in the Alzheimer's Disease Neuroimaging Initiative (ADNI). 570 cognitively normal ADNI participants were classified based on NIA-AA criteria and separately based on the number of abnormal biomarkers/cognitive markers associated with preclinical AD that each individual possessed. Results revealed that neurodegeneration alone was 2.5 times more common than amyloidosis alone at baseline. For those who demonstrated only one abnormal biomarker at baseline and later progressed to mild cognitive impairment/AD, neurodegeneration alone was most common, followed by amyloidosis alone or subtle cognitive decline alone, which were equally common. Findings suggest that most individuals do not follow the temporal order proposed by NIA-AA criteria. We provide an operational definition of subtle cognitive decline that captures both cognitive and functional decline. Additionally, we offer a new approach for staging preclinical AD based on number of abnormal biomarkers, without regard to their temporal order of occurrence. This method of characterizing preclinical AD is more parsimonious than the NIA-AA staging system and does not presume that all patients follow a singular invariant expression of the disease.

  15. Cognitive decline, dietary factors and gut-brain interactions.

    PubMed

    Caracciolo, Barbara; Xu, Weili; Collins, Stephen; Fratiglioni, Laura

    2014-01-01

    Cognitive decline in elderly people often derives from the interaction between aging-related changes and age-related diseases and covers a large spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative disease. We reviewed the most recent findings in this rapidly expanding field. Some nutrients, such as vitamins and fatty acids, have been studied longer than others, but strong scientific evidence of an association is lacking even for these compounds. Specific dietary patterns, like the Mediterranean diet, may be more beneficial than a high consumption of single nutrients or specific food items. A strong link between vascular risk factors and dementia has been shown, and the association of diet with several vascular and metabolic diseases is well known. Other plausible mechanisms underlying the relationship between diet and cognitive decline, such as inflammation and oxidative stress, have been established. In addition to the traditional etiological pathways, new hypotheses, such as the role of the intestinal microbiome in cognitive function, have been suggested and warrant further investigation.

  16. Entorhinal cortex thickness predicts cognitive decline in Alzheimer's disease.

    PubMed

    Velayudhan, Latha; Proitsi, Petroula; Westman, Eric; Muehlboeck, J-Sebastian; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilkka; Spenger, Christian; Hodges, Angela; Powell, John; Lovestone, Simon; Simmons, Andrew

    2013-01-01

    Biomarkers for Alzheimer's disease (AD) based on non-invasive methods are highly desirable for diagnosis, disease progression, and monitoring therapeutics. We aimed to study the use of hippocampal volume, entorhinal cortex (ERC) thickness, and whole brain volume (WBV) as predictors of cognitive change in patients with AD. 120 AD subjects, 106 mild cognitive impairment (MCI), and 99 non demented controls (NDC) from the multi-center pan-European AddNeuroMed study underwent MRI scanning at baseline and clinical evaluations at quarterly follow-up up to 1 year. The rate of cognitive decline was estimated using cognitive outcomes, Mini-Mental State Examination (MMSE) and Alzheimer disease assessment scale-cognitive (ADAS-cog) by fitting a random intercept and slope model. AD subjects had smaller ERC thickness and hippocampal and WBV volumes compared to MCI and NDC subjects. Within the AD group, ERC > WBV was significantly associated with baseline cognition (MMSE, ADAS-cog) and disease severity (Clinical Dementia Rating). Baseline ERC thickness was associated with both longitudinal MMSE and ADAS-cog score changes and WBV with ADAS-cog decline. These data indicate that AD subjects with thinner ERC had lower baseline cognitive scores, higher disease severity, and predicted greater subsequent cognitive decline at one year follow up. ERC is a region known to be affected early in the disease. Therefore, the rate of atrophy in this structure is expected to be higher since neurodegeneration begins earlier. Focusing on structural analyses that predict decline can identify those individuals at greatest risk for future cognitive loss. This may have potential for increasing the efficacy of early intervention.

  17. Vascular risk factors, cognitive decline, and dementia.

    PubMed

    Duron, E; Hanon, Olivier

    2008-01-01

    Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer's disease) and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer's disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.

  18. Rapid cognitive decline: not always Creutzfeldt-Jakob disease.

    PubMed

    Randall, A; Ellis, R; Hywel, B; Davies, R R; Alusi, S H; Larner, A J

    2015-01-01

    A patient with rapidly progressive cognitive decline over an approximately four month period was suspected to have sporadic Creutzfeldt-Jakob disease. Features thought to support this diagnosis included psychiatric symptoms (anxiety and depression), visual hallucinations and a visual field defect. However, the finding of papilloedema broadened the differential diagnosis. Although standard brain imaging and electroencephalography had shown only non-specific abnormalities, subsequent cerebral angiography disclosed an intracranial dural arteriovenous fistula. Following embolisation, the patient made a good functional recovery. Intracranial dural arteriovenous fistula merits consideration in any patient with subacute cognitive decline, and should be included in the differential diagnosis of sporadic Creutzfeldt-Jakob disease.

  19. Both Financial and Cognitive Decline Predict Clinical Progression in MCI

    PubMed Central

    Gerstenecker, Adam; Triebel, Kristen L.; Martin, Roy; Snyder, Scott; Marson, Daniel C.

    2015-01-01

    We investigated the roles of financial/functional and cognitive abilities in predicting clinical progression in patients with mild cognitive impairment (MCI). In a longitudinal sample of 51 patients with consensus-conference diagnosed MCI likely due to Alzheimer’s disease (AD). Two-year change scores were calculated for a performance measure of functional ability, cognitive variables, and three outcome measures used to track progression in neurologic disorders. We examined patterns of financial and cognitive decline across the two-year study period, and used this data and the three outcome variables to construct discrete predictor models of clinical progression in MCI. We found that both financial skills and cognitive abilities declined over the two-year study period, were significantly associated with clinical progression, and contributed unique variance all three predictor models. The resulting models accounted for 40–75% of variance in clinical progression across outcome variables. Taken together, our results indicate that changes in both cognitive abilities and higher-order functional skills appear integral to understanding clinical progression in MCI likely due to AD. Specifically, declines in financial skills contribute unique variance to measures commonly used to track progression in neurological disorders associated with aging and thus represent an important functional marker of clinical progression in prodromal AD. PMID:26900988

  20. IANA task force on nutrition and cognitive decline with aging.

    PubMed

    Gillette Guyonnet, S; Abellan Van Kan, G; Andrieu, S; Barberger Gateau, P; Berr, C; Bonnefoy, M; Dartigues, J F; de Groot, L; Ferry, M; Galan, P; Hercberg, S; Jeandel, C; Morris, M C; Nourhashemi, F; Payette, H; Poulain, J P; Portet, F; Roussel, A M; Ritz, P; Rolland, Y; Vellas, B

    2007-01-01

    Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta

  1. Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.

    PubMed

    Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin L; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Chaibub Neto, Elias; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard J B; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Iyappan, Anandhi; Jiang, Qijia; Katsumata, Yuriko; Kauwe, John S K; Klein, Arno; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Ma, Tsung-Wei; Malhotra, Ashutosh; Mangravite, Lara M; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Peters, Mette A; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

    2016-06-01

    Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance.

  2. Dietary patterns, cognitive decline, and dementia: a systematic review.

    PubMed

    van de Rest, Ondine; Berendsen, Agnes Am; Haveman-Nies, Annemien; de Groot, Lisette Cpgm

    2015-03-01

    Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline.

  3. Dietary Patterns, Cognitive Decline, and Dementia: A Systematic Review12

    PubMed Central

    van de Rest, Ondine; Berendsen, Agnes AM; Haveman-Nies, Annemien; de Groot, Lisette CPGM

    2015-01-01

    Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline. PMID:25770254

  4. Visuomotor adaptability in older adults with mild cognitive decline.

    PubMed

    Schaffert, Jeffrey; Lee, Chi-Mei; Neill, Rebecca; Bo, Jin

    2017-02-01

    The current study examined the augmentation of error feedback on visuomotor adaptability in older adults with varying degrees of cognitive decline (assessed by the Montreal Cognitive Assessment; MoCA). Twenty-three participants performed a center-out computerized visuomotor adaptation task when the visual feedback of their hand movement error was presented in a regular (ratio=1:1) or enhanced (ratio=1:2) error feedback schedule. Results showed that older adults with lower scores on the MoCA had less adaptability than those with higher MoCA scores during the regular feedback schedule. However, participants demonstrated similar adaptability during the enhanced feedback schedule, regardless of their cognitive ability. Furthermore, individuals with lower MoCA scores showed larger after-effects in spatial control during the enhanced schedule compared to the regular schedule, whereas individuals with higher MoCA scores displayed the opposite pattern. Additional neuro-cognitive assessments revealed that spatial working memory and processing speed were positively related to motor adaptability during the regular scheduled but negatively related to adaptability during the enhanced schedule. We argue that individuals with mild cognitive decline employed different adaptation strategies when encountering enhanced visual feedback, suggesting older adults with mild cognitive impairment (MCI) may benefit from enhanced visual error feedback during sensorimotor adaptation.

  5. Can education rescue genetic liability for cognitive decline?

    PubMed

    Cook, C Justin; Fletcher, Jason M

    2015-02-01

    Although there is a vast literature linking education and later health outcomes, the mechanisms underlying these associations are relatively unknown. In the spirit of some medical literature that leverages developmental abnormalities to understand mechanisms of normative functioning, we explore the ability of higher educational attainments to "rescue" biological/genetic liabilities in brain function through inheritance of a variant of the APOE gene shown to lead to cognitive decline, dementia, and Alzheimer's disease in old age. Deploying a between-sibling design that allows quasi-experimental variation in genotype and educational attainment within a standard gene-environment interaction framework, we show evidence that the genetic effects of the "risky" APOE variant on old-age cognitive decline are absent in individuals who complete college (vs. high school graduates). Auxiliary analyses suggest that the likely mechanisms of education are most consistent through changing brain processes (i.e., "how we think") and potentially building cognitive reserves, rather than alleviating old age cognitive decline through the channels of higher socioeconomic status and resources over the life course.

  6. Exposure to Particulate Air Pollution and Cognitive Decline in Older Women

    PubMed Central

    Weuve, Jennifer; Puett, Robin C.; Schwartz, Joel; Yanosky, Jeff D.; Laden, Francine; Grodstein, Francine

    2013-01-01

    Background Chronic exposure to particulate air pollution may accelerate cognitive decline in older adults, although data on this association are limited. Our objective was to examine long-term exposure to particulate matter (PM) air pollution, both coarse ([PM 2.5–10 μm in diameter [PM2.5-10]) and fine (PM <2.5 μm in diameter [PM2.5]), in relation to cognitive decline. Methods The study population comprised the Nurses’ Health Study Cognitive Cohort, which included 19 409 US women aged 70 to 81 years. We used geographic information system–based spatiotemporal smoothing models to estimate recent (1 month) and long-term (7–14 years) exposures to PM2.5-10, and PM2.5 preceding base-line cognitive testing (1995–2001) of participants residing in the contiguous United States. We used generalized estimating equation regression to estimate differences in the rate of cognitive decline across levels of PM2.5-10 and PM2.5 exposures. The main outcome measure was cognition, via validated telephone assessments, administered 3 times at approximately 2-year intervals, including tests of general cognition, verbal memory, category fluency, working memory, and attention. Results Higher levels of long-term exposure to both PM2.5-10 and PM2.5 were associated with significantly faster cognitive decline. Two-year decline on a global score was 0.020 (95% CI, −0.032 to −0.008) standard units worse per 10 μg/m3 increment in PM2.5-10 exposure and 0.018 (95% CI, −0.035 to −0.002) units worse per 10 μg/m3 increment in PM2.5 exposure. These differences in cognitive trajectory were similar to those between women in our cohort who were approximately 2 years apart in age, indicating that the effect of a 10-μg/m3 increment in long-term PM exposure is cognitively equivalent to aging by approximately 2 years. Conclusion Long-term exposure to PM2.5-10 and PM2.5 at levels typically experienced by many individuals in the United States is associated with significantly worse cognitive

  7. Dynamic hub load predicts cognitive decline after resective neurosurgery

    PubMed Central

    Carbo, Ellen W. S.; Hillebrand, Arjan; van Dellen, Edwin; Tewarie, Prejaas; de Witt Hamer, Philip C.; Baayen, Johannes C.; Klein, Martin; Geurts, Jeroen J. G.; Reijneveld, Jaap C.; Stam, Cornelis J.; Douw, Linda

    2017-01-01

    Resective neurosurgery carries the risk of postoperative cognitive deterioration. The concept of ‘hub (over)load’, caused by (over)use of the most important brain regions, has been theoretically postulated in relation to symptomatology and neurological disease course, but lacks experimental confirmation. We investigated functional hub load and postsurgical cognitive deterioration in patients undergoing lesion resection. Patients (n = 28) underwent resting-state magnetoencephalography and neuropsychological assessments preoperatively and 1-year after lesion resection. We calculated stationary hub load score (SHub) indicating to what extent brain regions linked different subsystems; high SHub indicates larger processing pressure on hub regions. Dynamic hub load score (DHub) assessed its variability over time; low values, particularly in combination with high SHub values, indicate increased load, because of consistently high usage of hub regions. Hypothetically, increased SHub and decreased DHub relate to hub overload and thus poorer/deteriorating cognition. Between time points, deteriorating verbal memory performance correlated with decreasing upper alpha DHub. Moreover, preoperatively low DHub values accurately predicted declining verbal memory performance. In summary, dynamic hub load relates to cognitive functioning in patients undergoing lesion resection: postoperative cognitive decline can be tracked and even predicted using dynamic hub load, suggesting it may be used as a prognostic marker for tailored treatment planning. PMID:28169349

  8. Dynamic hub load predicts cognitive decline after resective neurosurgery.

    PubMed

    Carbo, Ellen W S; Hillebrand, Arjan; van Dellen, Edwin; Tewarie, Prejaas; de Witt Hamer, Philip C; Baayen, Johannes C; Klein, Martin; Geurts, Jeroen J G; Reijneveld, Jaap C; Stam, Cornelis J; Douw, Linda

    2017-02-07

    Resective neurosurgery carries the risk of postoperative cognitive deterioration. The concept of 'hub (over)load', caused by (over)use of the most important brain regions, has been theoretically postulated in relation to symptomatology and neurological disease course, but lacks experimental confirmation. We investigated functional hub load and postsurgical cognitive deterioration in patients undergoing lesion resection. Patients (n = 28) underwent resting-state magnetoencephalography and neuropsychological assessments preoperatively and 1-year after lesion resection. We calculated stationary hub load score (SHub) indicating to what extent brain regions linked different subsystems; high SHub indicates larger processing pressure on hub regions. Dynamic hub load score (DHub) assessed its variability over time; low values, particularly in combination with high SHub values, indicate increased load, because of consistently high usage of hub regions. Hypothetically, increased SHub and decreased DHub relate to hub overload and thus poorer/deteriorating cognition. Between time points, deteriorating verbal memory performance correlated with decreasing upper alpha DHub. Moreover, preoperatively low DHub values accurately predicted declining verbal memory performance. In summary, dynamic hub load relates to cognitive functioning in patients undergoing lesion resection: postoperative cognitive decline can be tracked and even predicted using dynamic hub load, suggesting it may be used as a prognostic marker for tailored treatment planning.

  9. Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice

    PubMed Central

    Feng, Xiaomei; Valdearcos, Martin; Uchida, Yosuke; Lutrin, David; Maze, Mervyn; Koliwad, Suneil K.

    2017-01-01

    Surgery can induce cognitive decline, a risk that increases with advancing age. In rodents, postoperative cognitive decline (POCD) is associated with the inflammatory activation of hippocampal microglia. To examine the role of microglia in POCD, we inhibited the colony-stimulating factor 1 receptor (CSF1R) in adult mice, effectively depleting CNS microglia. Surgical trauma (tibial fracture) reduced the ability of mice to remember a conditioned response learned preoperatively, a deficit more pronounced and persistent in mice with diet-induced obesity (DIO). Whereas microglial depletion by itself did not affect learning or memory, perioperative microglial depletion remarkably protected mice, including those with DIO, from POCD. This protection was associated with reduced hippocampal levels of inflammatory mediators, abrogation of hippocampal recruitment of CCR2+ leukocytes, and higher levels of circulating inflammation-resolving factors. Targeting microglia may thus be a viable strategy to mitigate the development of POCD, particularly in those with increased vulnerability.

  10. Nutrition, the brain and cognitive decline: insights from epigenetics.

    PubMed

    Dauncey, M J

    2014-11-01

    Nutrition affects the brain throughout life, with profound implications for cognitive decline and dementia. These effects are mediated by changes in expression of multiple genes, and responses to nutrition are in turn affected by individual genetic variability. An important layer of regulation is provided by the epigenome: nutrition is one of the many epigenetic regulators that modify gene expression without changes in DNA sequence. Epigenetic mechanisms are central to brain development, structure and function, and include DNA methylation, histone modifications and non-protein-coding RNAs. They enable cell-specific and age-related gene expression. Although epigenetic events can be highly stable, they can also be reversible, highlighting a critical role for nutrition in prevention and treatment of disease. Moreover, they suggest key mechanisms by which nutrition is involved in the pathogenesis of age-related cognitive decline: many nutrients, foods and diets have both immediate and long-term effects on the epigenome, including energy status, that is, energy intake, physical activity, energy metabolism and related changes in body composition, and micronutrients involved in DNA methylation, for example, folate, vitamins B6 and B12, choline, methionine. Optimal brain function results from highly complex interactions between numerous genetic and environmental factors, including food intake, physical activity, age and stress. Future studies linking nutrition with advances in neuroscience, genomics and epigenomics should provide novel approaches to the prevention of cognitive decline, and treatment of dementia and Alzheimer's disease.

  11. Flavonol Intake and Cognitive Decline in Middle-Aged Adults.

    PubMed

    Root, Martin; Ravine, Erin; Harper, Anne

    2015-12-01

    Cognitive decline occurs with age and may be slowed by dietary measures, including increased intake of dietary phytochemicals. However, evidence from large and long-term studies of flavonol intake is limited. Dietary intakes of flavonols were assessed from a large biracial study of 10,041 subjects, aged 45-64, by analysis of a food frequency questionnaire administered at visit 1 of triennial visits. Cognitive function was assessed at visits 2 and 4 with the following three cognitive performance tests: the delayed word recall test, the revised Wechsler Adult Intelligence Scale digit symbol subtest, and the word fluency test of the Multilingual Aphasia Examination. The change in each score over 6 years was calculated, and a combined standardized change score was calculated. Generalized linear models controlled for age, ethnicity, gender, education level, energy intake, current smoking, physical activity, body mass index, diabetes, and vitamin C intake. Total flavonols across quintiles of intake were positively associated with preserved combined cognitive function (P<.001). This pattern with preserved combined cognitive function was consistent for the three major individual flavonols in the diet, myricetin, kaempferol, and quercetin (each P<.001). The positive association with total flavonols was strongest for the digit symbol subtest (P<.001). In this cohort, flavonol intake was correlated with protected cognitive function over time.

  12. Neuroanatomical substrates of age-related cognitive decline

    PubMed Central

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure, and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the age-related cognitive changes. Although this conclusion may well be true, it is widely recognized that simple correlations are not sufficient to warrant causal conclusions, and other types of correlational information, such as mediation and correlations between longitudinal brain changes and longitudinal cognitive changes, also have limitations with respect to causal inferences. These issues are discussed, and the existing results on relations of regional volume, white matter hyperintensities, and DTI measures of white matter integrity to age and to measures of cognitive functioning are reviewed. It is concluded that at the current time the evidence that these aspects of brain structure are neuroanatomical substrates of age-related cognitive decline is weak. The final section contains several suggestions concerned with measurement and methodology that may lead to stronger conclusions in the future. PMID:21463028

  13. Faith-based cognitive behavioral therapy: easing depression in the elderly with cognitive decline.

    PubMed

    Ceramidas, Dagmar M

    2012-01-01

    Minimizing depression in residential aged care facilities is a formidable challenge but doing so may improve quality of life and protect against dementia. A pilot project with residents with cognitive decline and concurrent depression tested the suitability of a faith-based cognitive behavioral therapy (CBT) intervention in reducing participant levels of depression, offering promising results.

  14. Cognitive decline and dementia in the oldest-old.

    PubMed

    Kravitz, Efrat; Schmeidler, James; Beeri, Michal Schnaider

    2012-10-01

    The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer's disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out everyday activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology is accumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life.

  15. The Addenbrooke's Cognitive Examination-Revised accurately detects cognitive decline in Huntington's disease.

    PubMed

    Begeti, Faye; Tan, Adrian Y K; Cummins, Gemma A; Collins, Lucy M; Guzman, Natalie Valle; Mason, Sarah L; Barker, Roger A

    2013-11-01

    Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington's disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke's Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington's disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington's disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington's disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington's disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington's disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.

  16. Citicoline, use in cognitive decline: vascular and degenerative.

    PubMed

    García-Cobos, Rocío; Frank-García, Ana; Gutiérrez-Fernández, María; Díez-Tejedor, Exuperio

    2010-12-15

    CDP-choline has been widespread used in humans for decades as a treatment for many types of cognitive impairment. Despite this, its mechanism of action still remains unclear, but several experimental models in acute cerebral ischaemia suggest that it could have a brain repair action. Due to the lack of significant adverse effects and its high tolerability, there has been a growing interest for this molecule in recent years. In this article, a review of the most significant published clinical trials in cognitive decline has been made. A few Citicoline trials have studied its effects at medium and long-term on vascular cognitive impairment and Alzheimer's disease. Results show that Citicoline seems to have beneficial impact on several cognitive domains, but the methodological heterogeneity of the these studies makes it difficult to draw conclusions about these effects. New trials with a greater number of patients, uniform diagnostic criteria for inclusion and standardized neuropsychological assessment are needed to evidence with much more consistency Citicoline efficacy upon cognitive disorders. The use of new neuroimaging procedures in current trials could be of great interest.

  17. Patterns of Cognitive Decline Prior to Dementia in Persons with Mild Cognitive Impairment

    PubMed Central

    Cloutier, Simon; Chertkow, Howard; Kergoat, Marie-Jeanne; Gauthier, Serge; Belleville, Sylvie

    2015-01-01

    Abstract Only a limited number of studies have investigated the decline of discrete cognitive domains as individuals progress from mild cognitive impairment (MCI) to dementia. Thus, the goal of this longitudinal study was to evaluate the cognitive changes underway during the years preceding a diagnosis of probable Alzheimer’s disease (AD), and to compare these changes to those found in MCI participants who do not progress to dementia. Participants were compared as a function of whether they later converted to AD (n = 47) or not (n = 74). Cognitive change was assessed prior to the conversion year, using that year as a starting point. A combination of polynomial regression analyses and mixed ANOVAs assessed 1) the trajectory of cognitive decline for each domain and 2) the differences between non-progressors and those who had converted to AD. The different cognitive domains demonstrated very different patterns of decline in the group of MCI progressors. A quadratic function, i.e., many years of stable performance followed by a rapid decline just prior to diagnosis, was observed for delayed recall, working memory, and spatial memory. In contrast, a gradual linear decline was observed for immediate recall, executive function, and visuo-spatial abilities. Finally, language in progressors was impaired on all time periods relative to non-progressors, but there was no further change between the first assessments and conversion to AD. Individuals with MCI who progress to AD show abnormal cognition at least two years prior to their dementia diagnosis. The pattern of symptom change observed appears to depend upon the cognitive domain and thus, clinical studies should not assume similar rate of decline across domains. In contrast and, apart from verbal memory, the non-progressors present a performance similar to that of healthy older adults. PMID:26401770

  18. Cognitive training and Bacopa monnieri: Evidence for a combined intervention to alleviate age associated cognitive decline.

    PubMed

    McPhee, Grace M; Downey, Luke A; Noble, Anthony; Stough, Con

    2016-10-01

    As the elderly population grows the impact of age associated cognitive decline as well as neurodegenerative diseases such as Alzheimer's disease and dementia will increase. Ageing is associated with consistent impairments in cognitive processes (e.g., processing speed, memory, executive function and learning) important for work, well-being, life satisfaction and overall participation in society. Recently, there has been increased effort to conduct research examining methods to improve cognitive function in older citizens. Cognitive training has been shown to improve performance in some cognitive domains; including memory, processing speed, executive function and attention in older adults. These cognitive changes are thought to be related to improvements in brain connectivity and neural circuitry. Bacopa monnieri has also been shown to improve specific domains of cognition, sensitive to age associated cognitive decline (particularly processing speed and memory). These Bacopa monnieri dependent improvements may be due to the increase in specific neuro-molecular mechanisms implicated in the enhancement of neural connections in the brain (i.e. synaptogenesis). In particular, a number of animal studies have shown Bacopa monnieri consumption upregulates calcium dependent kinases in the synapse and post-synaptic cell, crucial for strengthening and growing connections between neurons. These effects have been shown to occur in areas important for cognitive processes, such as the hippocampus. As Bacopa monnieri has shown neuro-molecular mechanisms that encourage synaptogenesis, while cognitive training enhances brain connectivity, Bacopa monnieri supplementation could theoretically enhance and strengthen synaptic changes acquired through cognitive training. Therefore, the current paper hypothesises that the combination of these two interventions could improve cognitive outcomes, over and above the effects of administrating these interventions independently, as an effective

  19. Reversal of cognitive decline: A novel therapeutic program

    PubMed Central

    Bredesen, Dale E.

    2014-01-01

    This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system. PMID:25324467

  20. Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy

    PubMed Central

    Mukerji, Shibani S.; Locascio, Joseph J.; Misra, Vikas; Lorenz, David R.; Holman, Alex; Dutta, Anupriya; Penugonda, Sudhir; Wolinsky, Steven M.; Gabuzda, Dana

    2016-01-01

    Background. Dyslipidemia and apolipoprotein E4 (APOE ϵ4) allele are risk factors for age-related cognitive decline, but how these risks are modified by human immunodeficiency virus (HIV) infection is unclear. Methods. In a longitudinal nested study from the Multicenter AIDS Cohort Study, 273 HIV type 1–infected (HIV+) men aged 50–65 years with baseline HIV RNA <400 copies/mL and on continuous antiretroviral therapy (ART) in ≥95% of follow-up visits were matched by sociodemographic variables to 516 HIV-uninfected (HIV–) controls. The association between lipid markers (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), APOE genotype, and cognitive decline in HIV infection was examined using mixed-effects models. Results. The median baseline age of participants was 51, 81% were white, and 89% had education >12 years. HIV+ men had similar baseline total cholesterol and LDL-C, but lower HDL-C and higher triglycerides than controls (P < .001). Higher total cholesterol and LDL-C were associated with faster rates of cognitive decline (P < .01), whereas higher HDL-C attenuated decline (P = .02) in HIV+ men. In HIV+ men with elevated cholesterol, statin use was associated with a slower estimated rate of decline (P = .02). APOE ϵ4 genotype accelerated cognitive decline in HIV+ but not HIV– men (P = .01), with trajectories diverging from HIV– ε4 carriers after age 50. Total cholesterol levels did not modify the association of ϵ4 genotype with decline (P = .9). Conclusions. Elevated cholesterol and APOE ϵ4 genotype are independent risk factors for cognitive decline in ART-adherent HIV+ men aged >50 years. Treatment of dyslipidemia may be an effective strategy to reduce cognitive decline in older HIV+ individuals. PMID:27448678

  1. From mild cognitive impairment to subjective cognitive decline: conceptual and methodological evolution

    PubMed Central

    Cheng, Yu-Wen; Chen, Ta-Fu; Chiu, Ming-Jang

    2017-01-01

    Identification of subjects at the early stages of Alzheimer’s disease (AD) is fundamental for drug development and possible intervention or prevention of cognitive decline. The concept of mild cognitive impairment (MCI) evolved during the past two decades to define subjects at the transitional stage between normal aging and dementia. Evidence from cross-sectional and longitudinal studies has shown that MCI is associated with an increased risk of positive AD biomarkers and an increased annual conversion rate of 5%–17% to AD. The presence of AD biomarkers in subjects with MCI was associated with an even higher risk of progression to dementia. However, earlier clinical trials for pharmacotherapy in subjects with MCI were disappointing. To extend the spectrum of AD to an earlier stage before MCI, subjective cognitive decline (SCD) was introduced and was defined as self-reported cognitive decline before the deficits could be detected by cognitive tests. Subjects with SCD have an increased risk of underlying AD pathology. However, SCD can also develop secondary to other heterogeneous etiologies, including other neurodegenerative and psychiatric diseases, personality traits, physical conditions, and medication use. Several clinical and biomarker features were proposed to predict risk of conversion to AD in subjects with SCD. Further longitudinal studies are needed to support the validity of these high-risk features. PMID:28243102

  2. From mild cognitive impairment to subjective cognitive decline: conceptual and methodological evolution.

    PubMed

    Cheng, Yu-Wen; Chen, Ta-Fu; Chiu, Ming-Jang

    2017-01-01

    Identification of subjects at the early stages of Alzheimer's disease (AD) is fundamental for drug development and possible intervention or prevention of cognitive decline. The concept of mild cognitive impairment (MCI) evolved during the past two decades to define subjects at the transitional stage between normal aging and dementia. Evidence from cross-sectional and longitudinal studies has shown that MCI is associated with an increased risk of positive AD biomarkers and an increased annual conversion rate of 5%-17% to AD. The presence of AD biomarkers in subjects with MCI was associated with an even higher risk of progression to dementia. However, earlier clinical trials for pharmacotherapy in subjects with MCI were disappointing. To extend the spectrum of AD to an earlier stage before MCI, subjective cognitive decline (SCD) was introduced and was defined as self-reported cognitive decline before the deficits could be detected by cognitive tests. Subjects with SCD have an increased risk of underlying AD pathology. However, SCD can also develop secondary to other heterogeneous etiologies, including other neurodegenerative and psychiatric diseases, personality traits, physical conditions, and medication use. Several clinical and biomarker features were proposed to predict risk of conversion to AD in subjects with SCD. Further longitudinal studies are needed to support the validity of these high-risk features.

  3. Multivariable network associated with cognitive decline and dementia.

    PubMed

    Licastro, Federico; Porcellini, Elisa; Chiappelli, Martina; Forti, Paola; Buscema, Massimo; Ravaglia, Giovanni; Grossi, Enzo

    2010-02-01

    Data mining of a large data base from the population longitudinal study named "The Conselice Study" has been the focus of the present investigation. Initially, 65 years old or older participants were interviewed, underwent medical and cognitive examination, and were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 35 genetic and/or phenotypic factors with incident cognitive decline and dementia were investigated. The new mathematical approach, called the Auto Contractive Map (AutoCM), was able to show the differential importance of each variables. This new variable processing created a semantic connectivity map that: (a) preserved non-linear associations; (b) showed connection schemes; (c) captured the complex dynamics of adaptive interactions. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Few variables resulted to be aggregation points and were considered as major biological hubs. Three hubs were identified in the hydroxyl-methyl-gutaryl-CoA reductase (HMGCR) enzyme, plasma cholesterol levels and age. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. This data analysis method was compared with another mathematical model called mutual information relevance network and results are presented and discussed.

  4. Decline in renal functioning is associated with longitudinal decline in global cognitive functioning, abstract reasoning and verbal memory

    PubMed Central

    Davey, Adam; Elias, Merrill F.; Robbins, Michael A.; Seliger, Stephen L.; Dore, Gregory A.

    2013-01-01

    Background Decreased estimated glomerular filtration rate (eGFR) and higher serum creatinine (sCR) levels have been associated with longitudinal decline in global mental status measures. Longitudinal data describing change in multiple domains of cognitive functioning are needed in order to determine which specific abilities are most affected in individuals with impaired renal function. Methods We conducted a 5-year longitudinal study with 590 community-living individuals (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus, mean eGFR 78.4 mL/min/1.73 m²) free from dementia, acute stroke and end-stage renal disease. To measure longitudinal change-over-time, cognitive performance measures were regressed on eGFR adjusting for baseline eGFR and cognitive performance, comorbidity and vascular risk factors. Outcome measures were scores from 17 separate tests of cognitive abilities that were used to index 5 theoretically relevant domains: verbal episodic memory, visual-spatial organization and memory, scanning and tracking, working memory and similarities (abstract reasoning). Results Declines in eGFR values were associated with cognitive declines, when adjusted for eGFR and cognitive function scores at baseline. Change in renal functioning over time was related to change observed in global cognitive ability [b = 0.21SD decline per unit ln(eGFR), 95% CI: 0.04–0.38, P = .018], verbal episodic memory [b = 0.28 SD decline per unit ln(eGFR), 95% CI: 0.02–0.54, P = 0.038] and abstract reasoning [b = 0.36 SD decline per unit ln(eGFR), 95% CI: 0.04–0.67, P = 0.025]. Decline in cognitive functioning in association with declining renal functioning was observed despite statistical adjustment for demographic variables and CVD risk factors and the exclusion of persons with dementia or a history of acute stroke. Conclusions Early detection of mild to moderate kidney disease is an important public health concern with regard to cognitive decline. PMID

  5. Higher brain BDNF gene expression is associated with slower cognitive decline in older adults

    PubMed Central

    Yu, Lei; Boyle, Patricia A.; Schneider, Julie A.; De Jager, Philip L.; Bennett, David A.

    2016-01-01

    Objectives: We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults. Methods: Five hundred thirty-five older participants underwent annual cognitive assessments and brain autopsy at death. BDNF gene expression was measured in the dorsolateral prefrontal cortex. Linear mixed models were used to examine whether BDNF expression was associated with cognitive decline adjusting for age, sex, and education. An interaction term was added to determine whether this association varied with clinical diagnosis proximate to death (no cognitive impairment, mild cognitive impairment, or dementia). Finally, we examined the extent to which the association of Alzheimer disease (AD) pathology with cognitive decline varied by BDNF expression. Results: Higher brain BDNF expression was associated with slower cognitive decline (p < 0.001); cognitive decline was about 50% slower with the 90th percentile BDNF expression vs 10th. This association was strongest in individuals with dementia. The level of BDNF expression was lower in individuals with pathologic AD (p = 0.006), but was not associated with macroscopic infarcts, Lewy body disease, or hippocampal sclerosis. BDNF expression remained associated with cognitive decline in a model adjusting for age, sex, education, and neuropathologies (p < 0.001). Furthermore, the effect of AD pathology on cognitive decline varied by BDNF expression such that the effect was strongest for high levels of AD pathology (p = 0.015); thus, in individuals with high AD pathology (90th percentile), cognitive decline was about 40% slower with the 90th percentile BDNF expression vs 10th. Conclusions: Higher brain BDNF expression is associated with slower cognitive decline and may also reduce the deleterious effects of AD pathology on cognitive decline. PMID:26819457

  6. Oxidative stress and aberrant signaling in aging and cognitive decline

    PubMed Central

    Dröge, Wulf; Schipper, Hyman M

    2007-01-01

    Brain aging is associated with a progressive imbalance between antioxidant defenses and intracellular concentrations of reactive oxygen species (ROS) as exemplified by increases in products of lipid peroxidation, protein oxidation, and DNA oxidation. Oxidative conditions cause not only structural damage but also changes in the set points of redox-sensitive signaling processes including the insulin receptor signaling pathway. In the absence of insulin, the otherwise low insulin receptor signaling is strongly enhanced by oxidative conditions. Autophagic proteolysis and sirtuin activity, in turn, are downregulated by the insulin signaling pathway, and impaired autophagic activity has been associated with neurodegeneration. In genetic studies, impairment of insulin receptor signaling causes spectacular lifespan extension in nematodes, fruit flies, and mice. The predicted effects of age-related oxidative stress on sirtuins and autophagic activity and the corresponding effects of antioxidants remain to be tested experimentally. However, several correlates of aging have been shown to be ameliorated by antioxidants. Oxidative damage to mitochondrial DNA and the electron transport chain, perturbations in brain iron and calcium homeostasis, and changes in plasma cysteine homeostasis may altogether represent causes and consequences of increased oxidative stress. Aging and cognitive decline thus appear to involve changes at multiple nodes within a complex regulatory network. PMID:17517043

  7. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats

    PubMed Central

    Latimer, Caitlin S.; Brewer, Lawrence D.; Searcy, James L.; Chen, Kuey-Chu; Popović, Jelena; Kraner, Susan D.; Thibault, Olivier; Blalock, Eric M.; Landfield, Philip W.; Porter, Nada M.

    2014-01-01

    Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues, including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5–6 mo, middle-aged F344 rats were fed diets containing low, medium (typical amount), or high (100, 1,000, or 10,000 international units/kg diet, respectively) vitamin D3, and hippocampal-dependent learning and memory were then tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication, and G protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced, corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function, and they suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging. PMID:25267625

  8. Decline in changing Montreal Cognitive Assessment (MoCA) scores is associated with post-stroke cognitive decline determined by a formal neuropsychological evaluation

    PubMed Central

    Teoh, Hock Luen; Chan, Bernard Poon-Lap; Seet, Raymond Chee Seong; Venketasubramanian, Narayanaswarmy; Sharma, Vijay Kumar; Chen, Christopher Li-Hsian; Dong, YanHong

    2017-01-01

    Objectives We aimed to examine changes in the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores within a one-year period after stroke/transient ischemic attack (TIA) in associating cognitive decline determined by a formal neuropsychological test battery. Methods Patients with ischemic stroke/TIA received MoCA and MMSE at baseline within 14 days after stroke/TIA, at 3–6 months and 1-year follow-ups. The scores of MoCA and MMSE were considered to have declined if there were a reduction of ≥2 points in the respective scores measured across two time points. The decline in neuropsychological diagnosis transitional status was defined by a category transition from no cognitive impairment or any cognitive impairment to a more severe cognitive impairment or dementia. Results 275 patients with a mean age of 59.8 ± 11.6 years, and education of 7.7 ± 4.3 years completed all the assessments at baseline, 3–6 months and 1-year follow-ups. A decline in MoCA scores from 3–6 months to 1 year was associated with higher risk of decline in diagnosis transitional status (odd ratio = 3.21, p = 0.004) in the same time period whereas there was no association with a decline in MMSE scores. Conclusions The decline in MoCA scores from 3–6 months to 1 year after stroke/TIA has three times higher risk for decline in the diagnosis transitional status. The decline of MoCA scores (reduction ≥ 2points) is associated with the decline in neuropsychological diagnosis transitional status. PMID:28346532

  9. A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.

    PubMed

    Dacks, Penny A; Armstrong, Joshua J; Brannan, Stephen K; Carman, Aaron J; Green, Allan M; Kirkman, M Sue; Krakoff, Lawrence R; Kuller, Lewis H; Launer, Lenore J; Lovestone, Simon; Merikle, Elizabeth; Neumann, Peter J; Rockwood, Kenneth; Shineman, Diana W; Stefanacci, Richard G; Velentgas, Priscilla; Viswanathan, Anand; Whitmer, Rachel A; Williamson, Jeff D; Fillit, Howard M

    2016-08-20

    Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

  10. The potential effects of meditation on age-related cognitive decline: a systematic review

    PubMed Central

    Gard, Tim; Hölzel, Britta K.; Lazar, Sara W.

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. PMID:24571182

  11. The potential effects of meditation on age-related cognitive decline: a systematic review.

    PubMed

    Gard, Tim; Hölzel, Britta K; Lazar, Sara W

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

  12. The Roles of Exercise and Yoga in Ameliorating Depression as a Risk Factor for Cognitive Decline

    PubMed Central

    Rosenbaum, Simon

    2016-01-01

    Currently, there are no effective pharmaceutical treatments to reduce cognitive decline or prevent dementia. At the same time, the global population is aging, and rates of dementia and mild cognitive impairment (MCI) are on the rise. As such, there is an increasing interest in complementary and alternative interventions to treat or reduce the risk of cognitive decline. Depression is one potentially modifiable risk factor for cognitive decline and dementia. Notably, exercise and yoga are two interventions known to both reduce symptoms of depression and improve cognitive function. The current review discusses the efficacy of exercise and yoga to ameliorate depression and thereby reduce the risk of cognitive decline and potentially prevent dementia. Potential mechanisms of change, treatment implications, and future directions are discussed. PMID:28044084

  13. Walking ability to predict future cognitive decline in old adults: A scoping review.

    PubMed

    Kikkert, Lisette H J; Vuillerme, Nicolas; van Campen, Jos P; Hortobágyi, Tibor; Lamoth, Claudine J

    2016-05-01

    Early identification of individuals at risk for cognitive decline may facilitate the selection of those who benefit most from interventions. Current models predicting cognitive decline include neuropsychological and/or biological markers. Additional markers based on walking ability might improve accuracy and specificity of these models because motor and cognitive functions share neuroanatomical structures and psychological processes. We reviewed the relationship between walking ability at one point of (mid) life and cognitive decline at follow-up. A systematic literature search identified 20 longitudinal studies. The average follow-up time was 4.5 years. Gait speed quantified walking ability in most studies (n=18). Additional gait measures (n=4) were step frequency, variability and step-length. Despite methodological weaknesses, results revealed that gait slowing (0.68-1.1 m/sec) preceded cognitive decline and the presence of dementia syndromes (maximal odds and hazard ratios of 10.4 and 11.1, respectively). The results indicate that measures of walking ability could serve as additional markers to predict cognitive decline. However, gait speed alone might lack specificity. We recommend gait analysis, including dynamic gait parameters, in clinical evaluations of patients with suspected cognitive decline. Future studies should focus on examining the specificity and accuracy of various gait characteristics to predict future cognitive decline.

  14. Bereavement and behavioral changes as risk factors for cognitive decline in adults with Down syndrome

    PubMed Central

    Fonseca, Luciana Mascarenhas; de Oliveira, Melaine Cristina; de Figueiredo Ferreira Guilhoto, Laura Maria; Cavalheiro, Esper Abrao; Bottino, Cássio MC

    2014-01-01

    Background Cognitive decline and Alzheimer’s disease often affect older adults with Down syndrome (DS) much earlier than those in the general population. There is also growing evidence of the effects of negative life events on the mental health and behavior of individuals with intellectual disability. However, to our knowledge, this is the first study investigating objective cognitive decline following bereavement in aging individuals with DS. Objective The objective of this study was to determine whether cognitive decline correlates with bereavement following the recent loss of a caregiver or with behavioral changes in a sample of adult individuals with DS who do not meet the criteria for dementia or depression, using the longitudinal assessment of the Cambridge Cognitive Examination (CAMCOG), together with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Methods We evaluated 18 subjects at baseline and over a follow-up period of 14–22 months, attempting to determine whether cognitive decline correlates with bereavement following the recent loss of the main caregiver or with behavioral changes (as assessed with the Neuropsychiatric Inventory). Results The mean rate of change in CAMCOG was −1.83 (standard deviation 4.51). Behavioral changes had a significant direct influence on cognitive decline. When bereavement was accompanied by behavioral changes, the probability of cognitive decline was 87% (odds ratio 3.82). Conclusion The occurrence of behavioral changes attributed to bereavement following the loss of the primary caregiver significantly increases the probability of cognitive decline in individuals with DS. Longitudinal comparison of the CAMCOG and use of the IQCODE appear to enrich the analysis of cognitive decline in individuals with DS. Further studies involving larger samples are needed in order to corroborate and expand upon our findings, which can have implications for the clinical management of older adults with DS. PMID

  15. Changes in physical activity and cognitive decline in older adults living in the community.

    PubMed

    Lee, Yunhwan; Kim, Jinhee; Han, Eun Sook; Chae, Songi; Ryu, Mikyung; Ahn, Kwang Ho; Park, Eun Ju

    2015-01-01

    Accumulating evidence suggests that physical activity may be beneficial in preserving cognition in late life. This study examined the association between baseline and changes in physical activity and cognitive decline in community-dwelling older people. Data were from the Korean Longitudinal Study of Aging, with 2605 aged 65 years and older subjects interviewed in 2006 and followed up for 2 years. Cognitive decline was defined by calculating the Reliable Change Index using the Mini-Mental State Examination. Physical activity levels were categorized as sedentary, low, or high. Changes in physical activity were classified as inactive, decreaser, increaser, or active. Logistic regression analysis of baseline and changes in physical activity with cognitive decline was performed. Compared with the sedentary group at baseline, both the low and high activity groups were less likely to experience cognitive decline. The active (odds ratio [OR] = 0.40, 95 % confidence interval [CI] 0.23-0.68) and increaser (OR = 0.45, 95 % CI 0.27-0.74) group, compared with the inactive counterpart, demonstrated a significantly lower likelihood of cognitive decline. Older adults who remained active or increased activity over time had a reduced risk of cognitive decline. Engagement in physical activity in late life may have cognitive health benefits.

  16. Effects of Diabetes Mellitus on Cognitive Decline in Patients with Alzheimer Disease: A Systematic Review.

    PubMed

    Li, Jun; Cesari, Matteo; Liu, Fei; Dong, Birong; Vellas, Bruno

    2017-02-01

    Basic and clinical research support a link between diabetes mellitus and Alzheimer disease (AD). However, the relationship with AD progression is unclear. This review focuses on the association between diabetes and cognitive decline in patients with AD. The literature published through May 2015 was searched in 3 databases: PubMed, Embase and Cochrane. Studies evaluating the effects of diabetes on patients with AD or cognitive decline were included, and extracted data were analyzed. A total of 10 articles met the inclusion criteria for review. The results of these studies were inconsistent in terms of the association between diabetes and cognitive decline. Only 2 studies demonstrated that the presence of diabetes was independently related to the progression of cognitive decline in the patients with AD, and 3 studies suggested that histories of diabetes were not correlated with the changes in cognitive function in patients with AD. Half of the included studies even indicated that histories of diabetes were associated with lesser declines in cognitive function in patients with AD. Current evidence indicates that the link between diabetes and cognitive decline in patients with AD is uncertain. Further clinical studies are needed, with larger samples, long-term follow up and an extended battery of cognitive assessments.

  17. Decline of cognition in multiple sclerosis: dissociable deficits.

    PubMed Central

    Jennekens-Schinkel, A; Sanders, E A

    1986-01-01

    Three female patients (ages 32, 37 and 27 years) developed progressive deficits of cognition in stages of multiple sclerosis in which physical disability ratings were low. Neuropsychological examination revealed severe cognitive impairments in the first two patients. Cognitive functioning was essentially intact in the third patient, although her work pace was significantly slowed. CT scanning of the brain showed cortical atrophy as well as white matter lesions in patients 1 and 2, and multiple lesions and oedema of predominantly white matter in patient 3. The differences of cognitive dysfunction between the third and the first two patients may be related to involvement of different anatomical structures. Images PMID:3806111

  18. Roles of Arterial Stiffness and Blood Pressure in Hypertension-Associated Cognitive Decline in Healthy Adults.

    PubMed

    Hajjar, Ihab; Goldstein, Felicia C; Martin, Greg S; Quyyumi, Arshed A

    2016-01-01

    Although there is strong evidence that hypertension leads to cognitive decline, especially in the executive domain, the relationship between blood pressure and cognition has been conflicted. Hypertension is characterized by blood pressure elevation and increased arterial stiffness. We aimed at investigating whether arterial stiffness would be superior to blood pressure in predicting cognitive decline and explaining the hypertension-executive decline association. A randomly selected asymptomatic population (n=591, age=49.2 years, 70% women, 27% black, and education=18 years) underwent annual vascular and cognitive assessments. Cognition was assessed using computerized versions commonly used cognitive tests, and principal component analysis was used for deriving cognitive scores for executive function, memory, and working memory. Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV). Higher PWV, but not blood pressure, was associated with a steeper decline in executive (P=0.0002), memory (P=0.05), and working memory (P=0.02) scores after adjusting for demographics, education, and baseline cognitive performance. This remained true after adjusting for hypertension. Hypertension was associated with greater decline in executive score (P=0.0029) and those with combined hypertension and elevated PWV (>7 m/s) had the greatest decline in executive score (P value hypertension×PWV=0.02). PWV explained the association between hypertension and executive function (P value for hypertension=0.0029 versus 0.24 when adjusting for PWV). In healthy adults, increased arterial stiffness is superior to blood pressure in predicting cognitive decline in all domains and in explaining the hypertension-executive function association. Arterial stiffness, especially in hypertension, may be a target in the prevention of cognitive decline.

  19. The emerging role of dietary fructose in obesity and cognitive decline

    PubMed Central

    2013-01-01

    The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer’s disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet. PMID:23924506

  20. Neuroanatomical Substrates of Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

  1. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease.

    PubMed

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice.

  2. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease

    PubMed Central

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice. PMID:27190672

  3. FDG-PET and CSF phospho-tau for prediction of cognitive decline in mild cognitive impairment.

    PubMed

    Fellgiebel, Andreas; Scheurich, Armin; Bartenstein, Peter; Müller, Matthias J

    2007-07-15

    Specific patterns of cortical glucose metabolism disturbances and increased CSF phospho-tau (p-tau(181)) concentrations could be demonstrated to predict cognitive decline and shift to dementia in amnestic mild cognitive impairment (MCI). But comparisons of both diagnostic tools have not been undertaken so far. The aim of the study was to compare (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) findings and CSF phospho-tau (p-tau(181)) measurements in the prediction of cognitive deterioration and conversion to dementia in MCI. During follow-up (mean 19 months) eight of 16 patients (50%) showed progressive cognitive decline, and four patients shifted to dementia. Pathological FDG-PET and elevated p-tau(181) levels both predicted deterioration. While p-tau(181) was highly sensitive for cognitive decline, FDG-PET was superior in predicting conversion to clinical dementia in MCI patients.

  4. Foreign language training as cognitive therapy for age-related cognitive decline: a hypothesis for future research.

    PubMed

    Antoniou, Mark; Gunasekera, Geshri M; Wong, Patrick C M

    2013-12-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline-Alzheimer's disease and other dementias-hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis.

  5. Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

    PubMed Central

    Lawrence, Andrew J.; Brookes, Rebecca L.; Zeestraten, Eva A.; Barrick, Thomas R.; Morris, Robin G.; Markus, Hugh S.

    2015-01-01

    Objectives Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline. Methods 121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George’s Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points. Results Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up. Conclusions The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease. PMID:26273828

  6. Obstructive Sleep Apnea and 15-Year Cognitive Decline: The Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Lutsey, Pamela L.; Bengtson, Lindsay G.S.; Punjabi, Naresh M.; Shahar, Eyal; Mosley, Thomas H.; Gottesman, Rebecca F.; Wruck, Lisa M.; MacLehose, Richard F.; Alonso, Alvaro

    2016-01-01

    Study Objectives: Prospective data evaluating abnormal sleep quality and quantity with cognitive decline are limited because most studies used subjective data and/or had short follow-up. We hypothesized that, over 15 y of follow-up, participants with objectively measured obstructive sleep apnea (OSA) and other indices of poor sleep quantity and quality would experience greater decline in cognitive functioning than participants with normal sleep patterns. Methods: ARIC participants (n = 966; mean age 61 y, 55% women) with in-home polysomnography (1996–1998) and repeated cognitive testing were followed for 15 y. Three cognitive tests (Delayed Word Recall, Word Fluency, and Digit Symbol Substitution) were administered at two time points (1996–1998 and 2011–2013). Ten additional cognitive tests were administered at the 2011–2013 neurocognitive examination. OSA was modeled using established clinical OSA severity categories. Multivariable linear regression was used to explore associations of OSA and other sleep indices with change in cognitive tests between the two assessments. Results: A median of 14.9 y (max: 17.3) passed between the two cognitive assessments. OSA category and additional indices of sleep (other measures of hypoxemia and disordered breathing, sleep fragmentation, sleep duration) were not associated with change in any cognitive test. Analyses of OSA severity categories and 10 cognitive tests administered only in 2011–2013 also showed little evidence of an association. Conclusions: Overall, abnormal sleep quality and quantity at midlife was not related to cognitive decline and later-life cognition. The effect of adverse sleep quality and quantity on cognitive decline among the elderly remains to be determined. Citation: Lutsey PL, Bengtson LG, Punjabi NM, Shahar E, Mosley TH, Gottesman RF, Wruck LM, MacLehose RF, Alonso A. Obstructive sleep apnea and 15-year cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study. SLEEP 2016

  7. Relationship between changes of body mass index (BMI) and cognitive decline in Parkinson's disease (PD).

    PubMed

    Kim, Hyun Jung; Oh, Eung Seok; Lee, Ji Hee; Moon, Jung Soo; Oh, Ji Eun; Shin, Jong Wook; Lee, Kyung Jae; Baek, In Chul; Jeong, Seong-Hae; Song, Hee-Jung; Sohn, Eun Hee; Lee, Ae Young

    2012-01-01

    Decreased BMI has been reported that it may be associated with cognitive decline in the elderly. Weight loss is common in patients with PD. However, studies comparing cognitive changes according to BMI changes in PD have not been done yet. We performed this study to know a relationship between BMI changes and the rate of cognitive decline in PD. PD patients were recruited retrospectively. The patients (n=104) were divided into two groups according to BMI changes during initial 6 months of follow-up: decreased (n=52) vs. stable BMI groups (n=52). Cognitive functions were repeated until 36 months of follow-up using the Korean version of the Mini-Mental State Examination (K-MMSE) and the modified Mini-Mental State (3MS) test. We calculated the rate of cognitive decline (K-MMSE and 3MS score changes/month) and compared it between the two groups. The decreased BMI group showed lower level of cognitive function than that of stable BMI group, especially at the 36th month of follow-up (p<0.05). In addition, the rate of cognitive decline was also significantly faster in the decreased BMI group, particularly at the 36th month of follow-up (p<0.05). This study suggests that decreased BMI during initial 6 months of follow-up in PD might be a useful indicator for future risk of dementia and let clinicians predict faster rate of cognitive decline in patients with PD.

  8. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

    PubMed Central

    Cho, Kyung-Ok; Lybrand, Zane R.; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G.; Birnbaum, Shari G.; Scharfman, Helen E.; Eisch, Amelia J.; Hsieh, Jenny

    2015-01-01

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult. PMID:25808087

  9. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline.

    PubMed

    Cho, Kyung-Ok; Lybrand, Zane R; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G; Birnbaum, Shari G; Scharfman, Helen E; Eisch, Amelia J; Hsieh, Jenny

    2015-03-26

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.

  10. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease

    PubMed Central

    Alosco, Michael L.; Forman, Daniel E.

    2015-01-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns. PMID:25750853

  11. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease.

    PubMed

    Hayes, Scott M; Alosco, Michael L; Forman, Daniel E

    2014-12-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns.

  12. Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: systematic review of the literature.

    PubMed

    Coyle, Hannah; Traynor, Victoria; Solowij, Nadia

    2015-04-01

    The aim of this study was to assess the efficacy of cognitive training, specifically computerized cognitive training (CCT) and virtual reality cognitive training (VRCT), programs for individuals living with mild cognitive impairment (MCI) or dementia and therefore at high risk of cognitive decline. After searching a range of academic databases (CINHAL, PSYCinfo, and Web of Science), the studies evaluated (N = 16) were categorized as CCT (N = 10), VRCT (N = 3), and multimodal interventions (N = 3). Effect sizes were calculated, but a meta-analysis was not possible because of the large variability of study design and outcome measures adopted. The cognitive domains of attention, executive function, and memory (visual and verbal) showed the most consistent improvements. The positive effects on psychological outcomes (N = 6) were significant reductions on depressive symptoms (N = 3) and anxiety (N = 2) and improved perceived use of memory strategy (N = 1). Assessments of activities of daily living demonstrated no significant improvements (N = 8). Follow-up studies (N = 5) demonstrated long-term improvements in cognitive and psychological outcomes (N = 3), and the intervention groups showed a plateau effect of cognitive functioning compared with the cognitive decline experienced by control groups (N = 2). CCT and VRCT were moderately effective in long-term improvement of cognition for those at high risk of cognitive decline. Total intervention time did not mediate efficacy. Future research needs to improve study design by including larger samples, longitudinal designs, and a greater range of outcome measures, including functional and quality of life measures, to assess the wider effect of cognitive training on individuals at high risk of cognitive decline.

  13. Post-concussion cognitive declines and symptomatology are not related to concussion biomechanics in high school football players.

    PubMed

    Broglio, Steven P; Eckner, James T; Surma, Tyler; Kutcher, Jeffrey S

    2011-10-01

    Concussion is a major public health concern with nearly 4 million injuries occurring each year in the United States. In the acute post-injury stage, concussed individuals demonstrate cognitive function and motor control declines as well as reporting increased symptoms. Researchers have hypothesized that the severity of these impairments is related to impact magnitude. Using the Head Impact Telemetry System (HITS) to record head impact biomechanics, we sought to correlate pre- and post-concussive impact characteristics with declines in cognitive performance and increases in concussion-related symptoms. Over four seasons, 19 high school football athletes wearing instrumented helmets sustained 20 diagnosed concussions. Each athlete completed a baseline computer-based symptom and cognitive assessment during the pre-season and a post-injury assessment within 24 h of injury. Correlational analyses identified no significant relationships between symptoms and cognitive performance change scores and impact biomechanics (i.e., time from session start until injury, time from the previous impact, peak linear acceleration, peak rotational acceleration, and HIT severity profile [HITsp]). Nor were there any significant relationships between change scores and the number of impacts, cumulative linear acceleration, cumulative rotational acceleration, or cumulative HITsp values associated with all impacts prior to or following the injury. This investigation is the first to examine the relationship between concussion impact characteristics, including cumulative impact profiles, and post-morbid outcomes in high school athletes. There appears to be no association between head impact biomechanics and post-concussive outcomes. As such, the use of biomechanical variables to predict injury severity does not appear feasible at this time.

  14. Body mass and cognitive decline are indirectly associated via inflammation among aging adults.

    PubMed

    Bourassa, Kyle; Sbarra, David A

    2017-02-01

    Inflammatory models of neurodegeneration suggest that higher circulating levels of inflammation can lead to cognitive decline. Despite established independent associations between greater body mass, increased inflammation, and cognitive decline, no prior research has explored whether markers of systemic inflammation might mediate the association between body mass and changes in cognitive functioning. To test such a model, we used two longitudinal subsamples (ns=9066; 12,561) of aging adults from the English Longitudinal Study of Ageing (ELSA) study, which included two cognitive measures components of memory and executive functioning, as well as measurements of body mass and systemic inflammation, assessed via C-reactive protein (CRP). Greater body mass was indirectly associated with declines in memory and executive functioning over 6years via relatively higher levels of CRP. Our results suggest that systemic inflammation is one biologically plausible mechanism through which differences in body mass might influence changes in cognitive functioning among aging adults.

  15. Rate of Cognitive Decline Before and After the Onset of Functional Limitations in Older Persons

    PubMed Central

    Rajan, Kumar B.; Hebert, Liesi E.; Scherr, Paul A.; Mendes de Leon, Carlos F.; Evans, Denis A.

    2015-01-01

    Background: Loss in physical function is indicative of deterioration in physiological health that may also be associated with deterioration in neurological health. The objective of this study was to examine whether the onset of functional limitations and their severity is associated with increases in cognitive decline among older adults. Methods: The study sample consists of 3825 (65% African Americans and 53% females) participants over the age of 65 with no functional limitations. Cognitive function was assessed using a standardized global cognitive score, and functional limitations using a summary measure of 8 Rosow-Breslau and Nagi limitations (ROS-B/Nagi). Cognitive decline before and after the onset of limitations were analyzed using a linear piecewise change point model. Results: During follow-up, 2682 (70%) participants reported limitations in ROS-B/Nagi measure. The rate of cognitive decline was 0.053-units per year before any limitations, and increased to 0.069-units per year after one or more limitations in ROS-B/Nagi measure. This was about 30% (95% Confidence Interval [CI]: 18 – 42%) increase in the rate of cognitive decline comparing before and after the onset of limitations in ROS-B/Nagi measure. Also, higher number of limitations in ROS-B/Nagi measure at the time of onset was associated with faster cognitive decline. Conclusions: The rate of cognitive decline was significantly higher following functional limitations. This study suggests that self-reported measures of functional limitations may serve as an important marker of cognitive decline. PMID:25934994

  16. Effect of plasma lipids and APOE genotype on cognitive decline.

    PubMed

    Yasuno, Fumihiko; Asada, Takashi

    2013-03-01

    A central tenet of brain aging is that "what is good for the heart is good for the brain." We examined the combined effect of plasma lipids and APOE genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein, triglyceride, total cholesterol, and apolipoprotein E (apoE) were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids and cognitive function in APOE4 carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma apoE levels in both E4- and E4+, and HDL level in E4-. Our findings suggest that an interaction between apoE and HDL is facilitated by APOE4, and is possibly linked with an enhancement of neuroplasticity and with resultant protective effects on cognitive function in later life. Preservation of higher plasma apoE and HDL from early life is proposed as a possible strategy for maintaining cognitive function in later life, especially for APOE4-positive individuals.

  17. Education and Age-Related Cognitive Decline: The Contribution of Mental Workload.

    ERIC Educational Resources Information Center

    Bosma, H.; van Boxtel, M. P. J.; Ponds, R. W. H. M.; Houx, P. J. H.; Jolles, J.

    2003-01-01

    Longitudinal data from a Dutch study of 708 older adults showed that persons with low educational attainment experienced more decline in information processing speed, memory, and cognitive function. About 42% of the variance was explained by low stimulus or challenge in work. Decline was independent of crystallized intelligence. (Contains 24…

  18. Genetic architecture of age-related cognitive decline in African Americans

    PubMed Central

    Raj, Towfique; Chibnik, Lori B.; McCabe, Cristin; Wong, Andus; Replogle, Joseph M.; Yu, Lei; Gao, Sujuan; Unverzagt, Frederick W.; Stranger, Barbara; Murrell, Jill; Barnes, Lisa; Hendrie, Hugh C.; Foroud, Tatiana; Krichevsky, Anna; Bennett, David A.; Hall, Kathleen S.; Evans, Denis A.

    2016-01-01

    Objective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD. PMID:28078323

  19. Effects of NSAID treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: Findings from the randomized controlled ADAPT trial

    PubMed Central

    Leoutsakos, Jeannie-Marie S.; Muthen, Bengt O.; Breitner, John C.S.; Lyketsos, Constantine G.

    2011-01-01

    Objective We examined effects of non-steroidal anti-inflammatory drugs (NSAID) on cognitive decline as a function of phase of pre-clinical Alzheimer’s disease (AD). Methods Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer’s disease. We fit growth mixture models of Modified Mini-Mental State Examination (3MS) trajectories with data from 2,388 participants in the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT), and included class-specific effects of naproxen and celecoxib. Results We identified 3 classes: “no-decline”, “slow-decline”, and “fast-decline”, and examined effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (−2 log likelihood difference: 369.23; p<0.001), but resulted in reversal of effects over time. Over four years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, while those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), while those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Conclusions Our results appeared statistically robust, but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then to attenuate change in fast decliners. PMID:21560159

  20. The role of B-vitamins in preventing and treating cognitive impairment and decline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many epidemiologic studies have considered the question of whether markers of B-vitamin status are associated with cognitive function and cognitive decline. This avenue of research was sparked by the homocysteine (Hcy) theory of cardiovascular disease (CVD), which was extended to Alzheimer’s disease...

  1. C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline. Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) tri...

  2. An Evaluation of the Evidence that Methamphetamine Abuse Causes Cognitive Decline in Humans

    PubMed Central

    Dean, Andy C; Groman, Stephanie M; Morales, Angelica M; London, Edythe D

    2013-01-01

    Methamphetamine (MA) is one of the most commonly abused illicit substances worldwide. Among other problems, abuse of the drug has been associated with reduced cognitive function across several domains. However, much of the literature has not attempted to differentiate cognitive difficulties caused by MA abuse from preexisting cognitive difficulties that are likely caused by other factors. Here, we address this question, evaluating evidence for a priori hypotheses pertaining to six lines of research: (a) animal studies; (b) cross-sectional human studies; (c) a twin study; (d) studies of changes in cognition with abstinence from MA; (e) studies of changes in brain structure and function with abstinence from MA; and (f) studies of the relationship between the severity of MA abuse and the extent of cognitive deficits observed. Overall the findings were mixed, with some support for a causal relationship between MA abuse and cognitive decline, and other findings suggesting that there is no relationship. The preponderance of the data, however, does support the possibility that MA abuse causes cognitive decline, of unknown duration, in at least some users of the drug. When averaged across individuals, this decline is likely to be mild in early-to-middle adulthood. However, moderator variables are likely to contribute to the presence and/or severity of cognitive decline exhibited by a given individual. PMID:22948978

  3. Prevention of Age-Related Cognitive Decline: Which Strategies, When, and for Whom?

    PubMed

    Shatenstein, Bryna; Barberger-Gateau, Pascale; Mecocci, Patrizia

    2015-01-01

    Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level.

  4. Clinical workout for the early detection of cognitive decline and dementia.

    PubMed

    Tsolaki, M

    2014-11-01

    Aging is the major risk factor for the development of human neurodegenerative maladies such as Alzheimer's, Huntington's and Parkinson's diseases (PDs) and prion disorders, all of which stem from toxic protein aggregation. All of these diseases are correlated with cognitive decline. Cognitive Decline is a dynamic state from normal cognition of aging to dementia. According to the original criteria for Alzheimer's Disease (AD) (1984), a clinical diagnosis was possible only when someone was already demented. The prevalence rates of Cognitive Decline (mild cognitive impairment plus dementia) are very high now and will be higher in future because of the increasing survival time of people. Many neurological and psychiatric diseases are correlated with cognitive decline. Diagnosis of cognitive decline is mostly clinical (clinical criteria), but there are multiple biomarkers that could help us mostly in research programs such as short or long, paper and pencil or computerized neuropsychological batteries for cognition, activities of daily living and behavior, electroencephalograph, event-related potentials, and imaging-structural magnetic resonance imaging (MRI) and functional (fMRI, Pittsburgh bound positron emission tomography, FDG-PET, single photon emission computerized tomography and imaging of tau pathology)-cerebrospinal fluid proteins (Abeta, tau and phospho-tau in AD and α-synuclein (αSyn) for PD). Blood biomarkers need more studies to confirm their usefulness. Genetic markers are also studied but until now are not used in clinical praxis. Finally, in everyday clinical praxis and in research workout for early detection of cognitive decline, the combination of biomarkers is useful.

  5. Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline

    PubMed Central

    Harrison, Fiona E.; Bowman, Gene L.; Polidori, Maria Cristina

    2014-01-01

    This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer’s disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. PMID:24763117

  6. A systematic review of cognitive decline in dementia with Lewy bodies versus Alzheimer’s disease

    PubMed Central

    2014-01-01

    Introduction The aim of this review was to investigate whether there is a faster cognitive decline in dementia with Lewy bodies (DLB) than in Alzheimer’s disease (AD) over time. Methods PsycINFO and Medline were searched from 1946 to February 2013. A quality rating from 1 to 15 (best) was applied to the included studies. A quantitative meta-analysis was done on studies with mini mental state examination (MMSE) as the outcome measure. Results A total of 18 studies were included. Of these, six (36%) reported significant differences in the rate of cognitive decline. Three studies reported a faster cognitive decline on MMSE in patients with mixed DLB and AD compared to pure forms, whereas two studies reported a faster decline on delayed recall and recognition in AD and one in DLB on verbal fluency. Mean quality scores for studies that did or did not differ were not significantly different. Six studies reported MMSE scores and were included in the meta-analysis, which showed no significant difference in annual decline on MMSE between DLB (mean 3.4) and AD (mean 3.3). Conclusions Our findings do not support the hypothesis of a faster rate of cognitive decline in DLB compared to AD. Future studies should apply recent diagnostic criteria, as well as extensive diagnostic evaluation and ideally autopsy diagnosis. Studies with large enough samples, detailed cognitive tests, at least two years follow up and multivariate statistical analysis are also needed. PMID:25478024

  7. ω-3 fatty acids and cognitive decline: modulation by ApoEε4 allele and depression.

    PubMed

    Samieri, Cécilia; Féart, Catherine; Proust-Lima, Cécile; Peuchant, Evelyne; Dartigues, Jean-François; Amieva, Hélène; Barberger-Gateau, Pascale

    2011-12-01

    Long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may slow cognitive decline. The ε4 allele of the ApolipoproteinE (ApoE), the main genetic risk factor for Alzheimer's disease, and depressive symptoms, which are frequently associated with cognitive impairment in older persons, may modify this relationship. We estimated the associations between EPA and DHA plasma levels and subsequent cognitive decline over 7 years, taking into account ApoE-ε4 status and depressive symptoms, in a prospective population-based cohort. Participants (≥ 65 years, n = 1,228 nondemented at baseline) were evaluated at least once over three follow-up visits using four cognitive tests. Plasma EPA was associated with slower decline on Benton Visual Retention Test (BVRT) performances in ApoE-ε4 carriers, or in subjects with high depressive symptoms at baseline. Plasma DHA was associated with slower decline on BVRT performances in ApoE-ε4 carriers only. EPA and DHA may contribute to delaying decline in visual working memory in ApoE-ε4 carriers. In older depressed subjects, EPA, but not DHA, may slow cognitive decline.

  8. Fish intake is associated with slower cognitive decline in Chinese older adults.

    PubMed

    Qin, Bo; Plassman, Brenda L; Edwards, Lloyd J; Popkin, Barry M; Adair, Linda S; Mendez, Michelle A

    2014-10-01

    Modifiable lifestyle changes, including dietary changes, could translate into a great reduction in the global burden of cognitive impairment and dementia. Few studies evaluated the benefits of fish intake for delaying cognitive decline, and no studies were conducted in a Chinese population, which may differ with respect to types, amounts, and correlates of fish consumption compared with Western populations. We hypothesized that higher consumption of fish would predict slower decline in cognitive function, independent of a wide range of potential confounders. This prospective cohort study comprised 1566 community-dwelling adults aged ≥ 55 y who completed a cognitive screening test at ≥2 waves of the China Health and Nutrition Survey in 1997, 2000, or 2004, with a mean follow-up of 5.3 y [age at entry (mean ± SD): 63 ± 6 y]. Diet was measured by 3-d 24-h recalls at baseline. Outcomes included repeated measures of global cognitive scores (baseline mean ± SD: 19 ± 6 points), composite cognitive Z-scores (standardized units), and standardized verbal memory scores (standardized units). Multivariable-adjusted linear mixed-effects models were used to evaluate the relation of fish intake with changes in cognitive scores. Age was found to significantly modify the association between fish consumption and cognitive change (P = 0.007). Among adults aged ≥ 65 y, compared with individuals who consumed <1 serving/wk (i.e., 100 g) fish, the mean annual rate of global cognitive decline was reduced by 0.35 point (95% CI: 0.13, 0.58) among those consuming ≥ 1 serving/wk, equivalent to the disparity associated with 1.6 y of age. Fish consumption was also associated with a slower decline in composite and verbal memory scores. No associations were observed among adults aged 55-64 y. Our findings suggest a potential role of fish consumption as a modifiable dietary factor to reduce the rate of cognitive decline in later life.

  9. Association between tooth loss and cognitive decline: A 13-year longitudinal study of Chinese older adults

    PubMed Central

    Li, Juan; Xu, Hanzhang; Pan, Wei; Wu, Bei

    2017-01-01

    Objectives To examine the association between the number of teeth remaining and cognitive decline among Chinese older adults over a 13-year period. Design A large national longitudinal survey of Chinese older adults Setting The Chinese Longitudinal Healthy Longevity Survey (CLHLS) (1998–2011). Participants A total of 8,153 eligible participants aged 60+ interviewed in up to six waves. Measurements Cognitive function and teeth number were measured at each interview. Cognitive function was measured by the Mini-Mental Status Examination (MMSE). Number of natural teeth was self-reported. Individuals with severe cognitive impairment were excluded. Covariates included demographic characteristics, adult socioeconomic status characteristics, childhood socioeconomic status, health conditions, and health behaviors. Linear mixed models were applied in the analysis. Results The mean teeth number at baseline was 17.5(SD = 0.1), and the mean of baseline cognitive function was 27.3(SD = 0.0). Cognitive function declined over time (β = -0.19, P < .001) after controlling covariates. But, regardless of time, more teeth were associated with better cognitive function (β = 0.01, P < .001). The interaction of teeth number and time was significant (β = 0.01, P < .001), suggesting that the participants who had more teeth showed a slower pace of cognitive decline over time than those with fewer teeth after controlling for other covariates. Conclusion This study showed that tooth loss was associated with cognitive decline among Chinese older adults. Further studies are needed to examine the linkages between cognitive decline and oral health status using clinical examination data. PMID:28158261

  10. Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

    PubMed

    Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

    2012-05-22

    The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

  11. Education does not slow cognitive decline with aging: 12-year evidence from the victoria longitudinal study.

    PubMed

    Zahodne, Laura B; Glymour, M Maria; Sparks, Catharine; Bontempo, Daniel; Dixon, Roger A; MacDonald, Stuart W S; Manly, Jennifer J

    2011-11-01

    Although the relationship between education and cognitive status is well-known, evidence regarding whether education moderates the trajectory of cognitive change in late life is conflicting. Early studies suggested that higher levels of education attenuate cognitive decline. More recent studies using improved longitudinal methods have not found that education moderates decline. Fewer studies have explored whether education exerts different effects on longitudinal changes within different cognitive domains. In the present study, we analyzed data from 1014 participants in the Victoria Longitudinal Study to examine the effects of education on composite scores reflecting verbal processing speed, working memory, verbal fluency, and verbal episodic memory. Using linear growth models adjusted for age at enrollment (range, 54-95 years) and gender, we found that years of education (range, 6-20 years) was strongly related to cognitive level in all domains, particularly verbal fluency. However, education was not related to rates of change over time for any cognitive domain. Results were similar in individuals older or younger than 70 at baseline, and when education was dichotomized to reflect high or low attainment. In this large longitudinal cohort, education was related to cognitive performance but unrelated to cognitive decline, supporting the hypothesis of passive cognitive reserve with aging.

  12. Foreign language training as cognitive therapy for age-related cognitive decline: A hypothesis for future research

    PubMed Central

    Antoniou, Mark; Gunasekera, Geshri; Wong, Patrick C. M.

    2014-01-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline—Alzheimer's disease and other dementias—hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. PMID:24051310

  13. Literature review on the role of dietary protein and amino acids in cognitive functioning and cognitive decline.

    PubMed

    van de Rest, Ondine; van der Zwaluw, Nikita L; de Groot, Lisette C P G M

    2013-11-01

    As the population of elderly people is growing rapidly, the number of individuals with dementia and cognitive impairment is also increasing. One of the preventive measures against cognitive decline is diet and different dietary factors have already been investigated. This review provides an overview of studies on dietary protein and cognitive functioning and cognitive decline. Also studies on the individual amino acids that are related to brain function, tryptophan and tyrosine, are discussed. Overall, the role of dietary protein intake on cognitive functioning as well as cognitive decline has hardly been studied; we found eight observational studies and three intervention studies. More studies investigated the role of tryptophan (14 studies) and tyrosine (nine studies) in relation to cognitive functioning, but all these studies were performed in young adult populations and mostly under special conditions. Research in elderly populations, in particular, is warranted. Also more research is needed to come to definitive conclusions and specific recommendations regarding protein intake or intake of specific amino acids for maintaining optimal cognitive functioning.

  14. Cognitive decline is associated with risk aversion and temporal discounting in older adults without dementia.

    PubMed

    James, Bryan D; Boyle, Patricia A; Yu, Lei; Han, S Duke; Bennett, David A

    2015-01-01

    Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that

  15. Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline.

    PubMed

    Bilbo, Staci D

    2010-07-01

    There is significant individual variability in cognitive decline during aging, suggesting the existence of "vulnerability factors" for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or Escherichia coli, and then tested for learning and memory at 2 or 16months of age, using two fear-conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16months. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHCII on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity.

  16. Caffeine and cognitive decline in elderly women at high vascular risk

    PubMed Central

    Vercambre, Marie-Noël; Berr, Claudine; Ritchie, Karen; Kang, Jae H.

    2013-01-01

    Background Persons with vascular disorders are at higher risk of cognitive decline. Objective To determine whether caffeine may be associated with cognitive decline reduction in elderly at high vascular risk. Methods We included 2475 women aged 65+ years in the Women’s Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vitamins for cardiovascular disease secondary prevention. We ascertained regular caffeine intake at baseline (1995–1996) using a validated 116 item-food frequency questionnaire. From 1998–2000 to 2005–2006, we administered four telephone cognitive assessments at two-year intervals evaluating global cognition, verbal memory and category fluency. The primary outcome was the change in global cognitive score, which was the average of the z-scores of all tests. We used generalized linear models for repeated measures that were adjusted for various sociodemographic, health and lifestyle factors to evaluate the difference in cognitive decline rates across quintiles of caffeine intake. Results We observed significantly slower rates of cognitive decline with increasing caffeine intake (p-trend=0.02). The rate difference between the highest and lowest quintiles of usual caffeine intake (> 371 versus < 30 mg/day) was equivalent to that observed between those who were 7 years apart in age (p=0.006). Consumption of caffeinated coffee was significantly related to slower cognitive decline (p-trend=0.05), but not other caffeinated products (e.g., decaf, tea, cola, chocolate). We conducted interaction analyses and observed stronger associations in women assigned to vitamin B supplementation (p-interaction = 0.02). Conclusions Caffeine intake was related to moderately better cognitive maintenance over 5 years in older women with vascular disorders. PMID:23422357

  17. Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases?

    PubMed Central

    Yau, Suk-yu; Christie, Brian R.; So, Kwok-fai

    2014-01-01

    Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain. PMID:24818140

  18. The Hippocampal Neuroproteome with Aging and Cognitive Decline: Past Progress and Future Directions

    PubMed Central

    VanGuilder, Heather D.; Freeman, Willard M.

    2011-01-01

    Although steady progress on understanding brain aging has been made over recent decades through standard anatomical, immunohistochemical, and biochemical techniques, the biological basis of non-neurodegenerative cognitive decline with aging remains to be determined. This is due in part to technical limitations of traditional approaches, in which only a small fraction of neurobiologically relevant proteins, mRNAs or metabolites can be assessed at a time. With the development and refinement of proteomic technologies that enable simultaneous quantitative assessment of hundreds to thousands of proteins, neuroproteomic studies of brain aging and cognitive decline are becoming more widespread. This review focuses on the contributions of neuroproteomic investigations to advances in our understanding of age-related deficits of hippocampus-dependent spatial learning and memory. Accumulating neuroproteomic data demonstrate that hippocampal aging involves common themes of dysregulated metabolism, increased oxidative stress, altered protein processing, and decreased synaptic function. Additionally, growing evidence suggests that cognitive decline does not represent a “more aged” phenotype, but rather is associated with specific neuroproteomic changes that occur in addition to age-related alterations. Understanding if and how age-related changes in the hippocampal neuroproteome contribute to cognitive decline and elucidating the pathways and processes that lead to cognitive decline are critical objectives that remain to be achieved. Progress in the field and challenges that remain to be addressed with regard to animal models, behavioral testing, and proteomic reporting are also discussed. PMID:21647399

  19. Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease.

    PubMed

    Weintraub, Daniel; Dietz, Nicole; Duda, John E; Wolk, David A; Doshi, Jimit; Xie, Sharon X; Davatzikos, Christos; Clark, Christopher M; Siderowf, Andrew

    2012-01-01

    Research suggests overlap in brain regions undergoing neurodegeneration in Parkinson's and Alzheimer's disease. To assess the clinical significance of this, we applied a validated Alzheimer's disease-spatial pattern of brain atrophy to patients with Parkinson's disease with a range of cognitive abilities to determine its association with cognitive performance and decline. At baseline, 84 subjects received structural magnetic resonance imaging brain scans and completed the Dementia Rating Scale-2, and new robust and expanded Dementia Rating Scale-2 norms were applied to cognitively classify participants. Fifty-nine non-demented subjects were assessed annually with the Dementia Rating Scale-2 for two additional years. Magnetic resonance imaging scans were quantified using both a region of interest approach and voxel-based morphometry analysis, and a method for quantifying the presence of an Alzheimer's disease spatial pattern of brain atrophy was applied to each scan. In multivariate models, higher Alzheimer's disease pattern of atrophy score was associated with worse global cognitive performance (β = -0.31, P = 0.007), including in non-demented patients (β = -0.28, P = 0.05). In linear mixed model analyses, higher baseline Alzheimer's disease pattern of atrophy score predicted long-term global cognitive decline in non-demented patients [F(1, 110) = 9.72, P = 0.002], remarkably even in those with normal cognition at baseline [F(1, 80) = 4.71, P = 0.03]. In contrast, in cross-sectional and longitudinal analyses there was no association between region of interest brain volumes and cognitive performance in patients with Parkinson's disease with normal cognition. These findings support involvement of the hippocampus and parietal-temporal cortex with cognitive impairment and long-term decline in Parkinson's disease. In addition, an Alzheimer's disease pattern of brain atrophy may be a preclinical biomarker of cognitive decline in

  20. Recognition of Famous Names Predicts Episodic Memory Decline in Cognitively Intact Elders

    PubMed Central

    Seidenberg, Michael; Kay, Christina; Woodard, John L.; Nielson, Kristy A.; Smith, J. Carson; Kandah, Cassandra; Guidotti Breting, Leslie M.; Novitski, Julia; Lancaster, Melissa; Matthews, Monica; Hantke, Nathan; Butts, Alissa; Rao, Stephen M.

    2013-01-01

    Objective: Semantic memory impairment is common in both Mild Cognitive Impairment (MCI) and early Alzheimer’s disease (AD), and the ability to recognize familiar people is particularly vulnerable. A time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently is also reported in both AD and MCI. In this study, we hypothesized that the TG pattern on a famous name recognition task (FNRT) administered to cognitively intact elders would predict future episodic memory decline, and would also show a significant correlation with hippocampal volume. Methods: 78 healthy elders (ages 65-90) with normal cognition and episodic memory at baseline were administered a FNRT. Follow-up episodic memory testing 18 months later produced two groups: Declining (≥ 1 SD reduction in episodic memory) and Stable (< 1 SD). Results: The Declining group (N=27) recognized fewer recent famous names than the Stable group (N=51), while recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampus was significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining versus Stable) independent of chronological age and APOE ε4 inheritance. Conclusions: Famous name recognition may serve as an early pre-clinical cognitive marker of episodic memory decline in older individuals. PMID:23688215

  1. Association of Lifetime Intellectual Enrichment with Cognitive Decline in the Older Population

    PubMed Central

    Vemuri, Prashanthi; Lesnick, Timothy G.; Przybelski, Scott A.; Machulda, Mary; Knopman, David S.; Mielke, Michelle M.; Roberts, Rosebud O.; Geda, Yonas E.; Rocca, Walter A.; Petersen, Ronald C.; Jack, Clifford R.

    2014-01-01

    IMPORTANCE Intellectual lifestyle enrichment throughout life is increasingly viewed as a protective strategy against commonly observed cognitive decline in the elderly. OBJECTIVE To investigate the association of lifetime intellectual enrichment with baseline cognitive performance and rate of cognitive decline in a non-demented elderly population and to estimate difference (in years) associated with lifetime intellectual enrichment to the onset of cognitive impairment. DESIGN, SETTING, PARTICIPANTS Prospective analysis of subjects enrolled in the Mayo Clinic Study of Aging (MCSA), a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We studied 1995 non-demented (1718 cognitively normal, 277 MCI) participants in MCSA who completed intellectual lifestyle measures at baseline and underwent at least one follow-up visit. MAIN OUTCOMES AND MEASURES We studied the effect of lifetime intellectual enrichment by separating the variables into two non-overlapping principal components: education/occupation-score and mid/late-life cognitive activity measure based on self-report questionnaires. A global cognitive Z-score served as our summary cognition measure. We used linear mixed-effects models to investigate the associations of demographic and intellectual enrichment measures with global cognitive Z-score trajectories. RESULTS Baseline cognitive performance was lower in older subjects and in those with lower education/occupation, lower mid/late-life cognitive activity, apolipoprotein E4 (APOE) genotype, and in men. The interaction between the two intellectual enrichment measures was significant such that the beneficial effect of mid/late-life cognitive activity on baseline cognitive performance was reduced with increasing education/occupation. Only baseline age, mid/late-life cognitive activity, and APOE4 genotype were significantly associated with longitudinal change in cognitive performance from baseline. For APOE4 carriers with high

  2. Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China

    PubMed Central

    Peng, Dantao; Shi, Zhihong; Xu, Jun; Shen, Lu; Xiao, Shifu; Zhang, Nan; Li, Yi; Jiao, Jinsong; Wang, Yan-Jiang; Liu, Shuai; Zhang, Meilin; Wang, Meng; Liu, Shuling; Zhou, Yuying; Zhang, Xiao; Gu, Xiao-hua; Yang, Ce-ce; Wang, Yu; Jiao, Bin; Tang, Beisha; Wang, Jinhuan; Yu, Tao; Ji, Yong

    2016-01-01

    Abstract Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China. We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year. The mean age at diagnosis was 72.0 ± 10.0 years (range 38–96 years), and the mean age at onset of AD was 69.8 ± 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ± 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11–2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09–3.06). Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset. PMID:27367978

  3. Telmisartan prevented cognitive decline partly due to PPAR-{gamma} activation

    SciTech Connect

    Mogi, Masaki; Li Jianmei; Tsukuda, Kana; Iwanami, Jun; Min, Li-Juan; Sakata, Akiko; Fujita, Teppei; Iwai, Masaru; Horiuchi, Masatsugu

    2008-10-24

    Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-{gamma}. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of A{beta} 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-{gamma} antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-{gamma} agonistic effect, also inhibited A{beta}-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was not affected by GW9662. Immunohistochemical staining for A{beta} showed the reduced A{beta} deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-{gamma} activation, could exert a stronger effect.

  4. Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline.

    PubMed

    Moreira, Afonso; Diógenes, Maria José; de Mendonça, Alexandre; Lunet, Nuno; Barros, Henrique

    2016-05-06

    Cocoa-related products like chocolate have taken an important place in our food habits and culture. In this work, we aim to examine the relationship between chocolate consumption and cognitive decline in an elderly cognitively healthy population. In the present longitudinal prospective study, a cohort of 531 participants aged 65 and over with normal Mini-Mental State Examination (MMSE; median 28) was selected. The median follow-up was 48 months. Dietary habits were evaluated at baseline. The MMSE was used to assess global cognitive function at baseline and at follow-up. Cognitive decline was defined by a decrease ≥ 2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95% CI) estimates were adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes. Chocolate intake was associated with a lower risk of cognitive decline (RR = 0.59, 95% CI 0.38-0.92). This protective effect was observed only among subjects with an average daily consumption of caffeine lower than 75 mg (69% of the participants; RR = 0.50, 95% CI 0.31-0.82). To our knowledge, this is the first prospective cohort study to show an inverse association between regular long-term chocolate consumption and cognitive decline in humans.

  5. The LonDownS adult cognitive assessment to study cognitive abilities and decline in Down syndrome

    PubMed Central

    2016-01-01

    Background: Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with an ultra-high risk of developing Alzheimer’s disease. However, there is individual variability in the onset of clinical dementia and in baseline cognitive abilities prior to decline, particularly in memory, executive functioning, and motor coordination. The LonDownS Consortium aims to determine risk and protective factors for the development of dementia and factors relating to cognitive abilities in people with DS. Here we describe our cognitive test battery and related informant measures along with reporting data from our baseline cognitive and informant assessments. Methods: We developed a cognitive test battery to assess general abilities, memory, executive function, and motor coordination abilities in adults with DS, with informant ratings of similar domains also collected, designed to allow for data on a broad range of participants. Participants (n=305) had a range of ages and abilities, and included adults with and without a clinical diagnosis of dementia. Results: Results suggest the battery is suitable for the majority of adults with DS, although approximately half the adults with dementia were unable to undertake any cognitive task. Many test outcomes showed a range of scores with low floor and ceiling effects. Non-verbal age-adjusted IQ scores had lower floor effects than verbal IQ scores. Before the onset of any cognitive decline, females aged 16-35 showed better verbal abilities compared to males. We also identified clusters of cognitive test scores within our battery related to visuospatial memory, motor coordination, language abilities, and processing speed / sustained attention. Conclusions: Our further studies will use baseline and longitudinal assessments to explore factors influencing cognitive abilities and cognitive decline related to ageing and onset of dementia in adults with DS. PMID:28018980

  6. Deep brain stimulation and cognitive decline in Parkinson's disease: The predictive value of electroencephalography.

    PubMed

    Markser, A; Maier, Franziska; Lewis, C J; Dembek, T A; Pedrosa, D; Eggers, C; Timmermann, L; Kalbe, E; Fink, G R; Burghaus, Lothar

    2015-10-01

    Some Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) develop new-onset cognitive decline. We examined whether clinical EEG recordings can be used to predict cognitive deterioration in PD patients undergoing STN-DBS. In this retrospective study, we used the Grand Total EEG (GTE)-score (short and total) to evaluate pre- and postoperative EEGs. In PD patients undergoing STN-DBS (N = 30), cognitive functioning was measured using Mini-Mental State Test and DemTect before and after surgery. Severity of motor impairment was assessed using the Unified Parkinson's Disease Rating Scale-III. Patients were classified into patients with or without cognitive decline after STN-DBS surgery. Epidemiological data, pre- and postoperative EEG recordings as well as neuropsychological and neurological data, electrode positions and the third ventricle width were compared. A logistic regression model was used to identify predictors of cognitive decline. Motor deficits significantly improved from pre- to post-surgery, while the mean GTE-scores increased significantly. Six patients developed cognitive deterioration 4-12 months postoperatively. These patients had significantly higher preoperative GTE-scores than patients without cognitive deterioration, although preoperative cognitive functioning was comparable. Electrode positions, brain atrophy and neurological data did not differ between groups. Logistic regression analysis identified the GTE-score as a significant predictor of postoperative cognitive deterioration. Data suggest that the preoperative GTE-score can be used to identify PD patients that are at high risk for developing cognitive deterioration after STN-DBS surgery even though their preoperative cognitive state was normal.

  7. Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline

    PubMed Central

    Desler, Claus; Frederiksen, Jane H.; Angleys, Maria; Maynard, Scott; Keijzers, Guido; Fagerlund, Birgitte; Mortensen, Erik Lykke; Osler, Merete; Lauritzen, Martin; Bohr, Vilhelm A.; Rasmussen, Lene Juel

    2016-01-01

    Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer’s disease (AD). Utilizing relative decline of cognitive ability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement. We show that relative cognitive decline is associated with higher PBMC content of deoxythymidine-triphosphate (dTTP) (20%), but not mitochondrial bioenergetics parameters measured in this study or mitochondrial ROS. Levels of dTTP in PBMCs are indicators of relative cognitive change suggesting a role of deoxyribonucleotides in the etiology of AD. PMID:26408413

  8. Age-related decline in cognitive control: the role of fluid intelligence and processing speed

    PubMed Central

    2014-01-01

    Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034

  9. Metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline

    PubMed Central

    Wang, Maggie; Norman, Jennifer E; Srinivasan, Vivek J; Rutledge, John C

    2016-01-01

    White Matter Disease is increasingly being recognized as an important cause of cognitive decline and dementia. Various investigations have linked chronic diet-related conditions to the development of white matter lesions, which appear as white matter hyperintensities on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Thus, it can be postulated that the metabolic, inflammatory, and microvascular changes accompanying a western diet, hyperlipidemia, hypertension, and diabetes mellitus type II (DMII) are potential mediators in the development and progression of white matter disease, which in turn contributes to the development and progression of cognitive decline. This review will examine evidence for potential metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline. Specifically, we will focus on the effects of altered insulin signaling in diabetes, obesity-induced oxidative stress, neuroinflammation, arterial stiffness due to hypertension, ischemia secondary to cerebral small vessel disease, and blood brain barrier disturbances. PMID:28078193

  10. Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline.

    PubMed

    Leal, Stephanie L; Landau, Susan M; Bell, Rachel K; Jagust, William J

    2017-02-08

    The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer's disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baseline was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.

  11. Traditional used Plants against Cognitive Decline and Alzheimer Disease

    PubMed Central

    Eckert, Gunter Peter

    2010-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory deficits, impaired cognitive function, and altered and inappropriate behavior. Aging represents the most important risk factor for AD and the global trend in the phenomenon of population aging has dramatic consequences for public health, healthcare financing, and delivery systems in the word and, especially in developing countries. Mounting evidence obtained in in vitro and in vivo studies, suggests that various traditionally used plants in Asia, India, and Europe significantly affect key metabolic alterations culminating in AD-typical neurodegeneration. The present article aims to bring the reader up-to-date on the most recent studies and advances describing the direct and indirect activities of traditional used plants and its constituents possibly relieving features of AD. A variety of traditional used plants and its extracts exerted activities on AD related drug targets including AChE activity, antioxidative activity, modulation of Aβ-producing secretase activities, Aβ-degradation, heavy metal chelating, induction of neurotrophic factors, and cell death mechanisms. Although pre-clinical investigations identified promising drug candidates for AD, clinical evidences are still pending. PMID:21833177

  12. Prediction of Cognitive Decline in Healthy Older Adults using fMRI

    PubMed Central

    Woodard, John L.; Seidenberg, Michael; Nielson, Kristy A.; Smith, J. Carson; Antuono, Piero; Durgerian, Sally; Guidotti, Leslie; Zhang, Qi; Butts, Alissa; Hantke, Nathan; Lancaster, Melissa; Rao, Stephen M.

    2010-01-01

    Few studies have examined the extent to which structural and functional MRI, alone and in combination with genetic biomarkers, can predict future cognitive decline in asymptomatic elders. This prospective study evaluated individual and combined contributions of demographic information, genetic risk, hippocampal volume, and fMRI activation for predicting cognitive decline after an 18-month retest interval. Standardized neuropsychological testing, an fMRI scans semantic memory task (famous name discrimination), and structural MRI (sMRI) were performed on 78 healthy elders (73% female; mean age = 73 years, range = 65 to 88 years). Positive family history of dementia and presence of one or both apolipoprotein E (APOE) ε4 alleles occurred in 51.3% and 33.3% of the sample, respectively. Hippocampal volumes were traced from sMRI scans. At follow-up, all participants underwent a repeat neuropsychological examination. At 18 months, 27 participants (34.6%) declined by at least 1 SD on one of three neuropsychological measures. Using logistic regression, demographic variables (age, years of education, gender) and family history of dementia did not predict future cognitive decline. Greater fMRI activity, absence of an APOE ε4 allele, and larger hippocampal volume were associated with reduced likelihood of cognitive decline. The most effective combination of predictors involved fMRI brain activity and APOE ε4 status. Brain activity measured from task-activated fMRI, in combination with APOE ε4 status, was successful in identifying cognitively intact individuals at greatest risk for developing cognitive decline over a relatively brief time period. These results have implications for enriching prevention clinical trials designed to slow AD progression. PMID:20634590

  13. Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly

    PubMed Central

    Lesnick, Timothy G.; Przybelski, Scott A.; Knopman, David S.; Preboske, Greg M.; Kantarci, Kejal; Raman, Mekala R.; Machulda, Mary M.; Mielke, Michelle M.; Lowe, Val J.; Senjem, Matthew L.; Gunter, Jeffrey L.; Rocca, Walter A.; Roberts, Rosebud O.; Petersen, Ronald C.; Jack, Clifford R.

    2015-01-01

    Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-β load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-β load of ≥1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load ≥1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with

  14. Critical levels of brain atrophy associated with homocysteine and cognitive decline.

    PubMed

    de Jager, Celeste A

    2014-09-01

    Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of beneficial effects on cognition in older adults with cognitive impairment or Alzheimer's disease. This article reviews the role of Hcy in cognitive decline. It also considers some reasons why meta-analyses have failed to find effects of B-vitamin treatment. Findings from the successful VITACOG trial are examined from a new perspective of critical levels of Hcy and brain atrophy that may impact on the efficacy of B-vitamin treatment. It appears that there is a critical level of brain shrinkage, possibly mediated by elevated Hcy, which when reached, results in cognitive decline, especially in episodic memory performance. Supplements, food sources, and effects of folic acid fortification are discussed in relation to B12 deficiency.

  15. Hot Topics in Research: Preventive Neuroradiology in Brain Aging and Cognitive Decline.

    PubMed

    Raji, C A; Eyre, H; Wei, S H; Bredesen, D E; Moylan, S; Law, M; Small, G; Thompson, P M; Friedlander, R M; Silverman, D H; Baune, B T; Hoang, T A; Salamon, N; Toga, A W; Vernooij, M W

    2015-10-01

    Preventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment, and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking, and physical activity. In studying this link between lifestyle and cognitive decline, brain imaging markers may be instrumental as quantitative measures or even indicators of early disease. The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition aging. In this hot topics review, we will specifically focus on obesity and physical activity.

  16. Long-term digital mobile phone use and cognitive decline in the elderly.

    PubMed

    Ng, Tze Pin; Lim, May Li; Niti, Mathew; Collinson, Simon

    2012-02-01

    Research on long-term exposure to electromagnetic fields on cognition is lacking. We investigated the associations between frequent digital mobile phone use and global and domain-specific cognitive changes in older persons, a vulnerable group experiencing age-associated cognitive decline. We assessed 871 non-demented Chinese participants in the Singapore Longitudinal Ageing Studies cohort on the frequency of digital mobile phone use, neurocognitive performance and confounding variables at baseline, and neurocognitive performance at the 4-year follow-up. Findings showed that digital mobile phone users were typically self-selected to possess characteristics favoring better cognitive functioning and concomitantly demonstrate better performance on cognitive tasks. There was evidently no significant deleterious effect of digital mobile phone use on cognitive functioning in older people. Findings suggest, however, that digital mobile phone use may have an independent facilitating effect on global and executive functioning.

  17. Does Intensive Glucose Control Prevent Cognitive Decline in Diabetes? A Meta-Analysis

    PubMed Central

    Peñaherrera-Oviedo, Carlos; Moreno-Zambrano, Daniel; Palacios, Michael; Duarte-Martinez, María Carolina; Cevallos, Carlos; Gamboa, Ximena; Jurado, María Beatriz; Tamariz, Leonardo; Palacio, Ana; Santibañez, Rocío

    2015-01-01

    Diabetes mellitus is associated with cognitive decline and impaired performance in cognitive function tests among type 1 and type 2 diabetics. Even though the use of tight glucose control has been limited by a reported higher mortality, few reports have assessed the impact of treatment intensity on cognitive function. We conducted a meta-analysis to evaluate if an intensive glucose control in diabetes improves cognitive function, in comparison to standard therapy. We included 7 studies that included type 1 or type 2 diabetics and used standardized tests to evaluate various cognitive function domains. Standardized mean differences (SMDs) were calculated for each domain. We found that type 1 diabetics get no cognitive benefit from a tight glucose control, whereas type 2 diabetics get some benefit on processing speed and executive domains but had worse performances in the memory and attention domains, along with a higher incidence of mortality when using intensive glucose control regimes. PMID:26464871

  18. Caffeine intake is associated with a lower risk of cognitive decline: a cohort study from Portugal.

    PubMed

    Santos, Catarina; Lunet, Nuno; Azevedo, Ana; de Mendonça, Alexandre; Ritchie, Karen; Barros, Henrique

    2010-01-01

    Alzheimer's disease has emerged in recent decades as a major health problem and the role of lifestyles in the modulation of risk has been increasingly recognized. Recent epidemiological studies suggest a protective effect for caffeine intake in dementia. We aimed to quantify the association between caffeine dietary intake and cognitive decline, in a cohort of adults living in Porto. A cohort of 648 subjects aged > or =65 years was recruited between 1999-2003. Follow-up evaluation (2005-2008) was carried out on 58.2% of the eligible participants and 10.9% were deceased. Caffeine exposure in the year preceding baseline evaluation was assessed with a validated food frequency questionnaire. Cognitive evaluation consisted of baseline and follow-up Mini-Mental State Examination (MMSE). Cognitive decline was defined by a decrease > or =2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95%CI) estimates adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes were computed using Poisson regression. Caffeine intake (> 62 mg/day [3rd third] vs. < 22 mg/day [1st third]) was associated with a lower risk of cognitive decline in women (RR=0.49, 95%CI 0.24-0.97), but not significantly in men (RR=0.65, 95%CI 0.27-1.54). Our study confirms the negative association between caffeine and cognitive decline in women.

  19. Community-level education accelerates the cultural evolution of fertility decline.

    PubMed

    Colleran, Heidi; Jasienska, Grazyna; Nenko, Ilona; Galbarczyk, Andrzej; Mace, Ruth

    2014-03-22

    Explaining why fertility declines as populations modernize is a profound theoretical challenge. It remains unclear whether the fundamental drivers are economic or cultural in nature. Cultural evolutionary theory suggests that community-level characteristics, for example average education, can alter how low-fertility preferences are transmitted and adopted. These assumptions have not been empirically tested. Here, we show that community-level education accelerates fertility decline in a way that is neither predicted by individual characteristics, nor by the level of economic modernization in a population. In 22 high-fertility communities in Poland, fertility converged on a smaller family size as average education in the community increased-indeed community-level education had a larger impact on fertility decline than did individual education. This convergence was not driven by educational levels being more homogeneous, but by less educated women having fewer children than expected, and more highly educated social networks, when living among more highly educated neighbours. The average level of education in a community may influence the social partners women interact with, both within and beyond their immediate social environments, altering the reproductive norms they are exposed to. Given a critical mass of highly educated women, less educated neighbours may adopt their reproductive behaviour, accelerating the pace of demographic transition. Individual characteristics alone cannot capture these dynamics and studies relying solely on them may systematically underestimate the importance of cultural transmission in driving fertility declines. Our results are inconsistent with a purely individualistic, rational-actor model of fertility decline and suggest that optimization of reproduction is partly driven by cultural dynamics beyond the individual.

  20. Sub-Clinical Cognitive Decline and Resting Cerebral Blood Flow in Middle Aged Men

    PubMed Central

    Henriksen, Otto Mølby; Hansen, Naja Liv; Osler, Merete; Mortensen, Erik Lykke; Hallam, Dorte Merete; Pedersen, Esben Thade; Chappell, Michael; Lauritzen, Martin Johannes; Rostrup, Egill

    2017-01-01

    Background Although dementia is associated with both global and regional cerebral blood flow (CBF) changes, little is known about cerebral perfusion in the early pre-clinical stages of cognitive decline preceding overt cognitive dysfunction. The aim of this study was to investigate the association of early sub-clinical cognitive decline with CBF. Materials and Methods The study participants were recruited from a cohort of Danish men born in 1953. Based on a regression model we selected men who performed better (Group A, n = 94) and poorer (Group B, n = 95) on cognitive testing at age 57 than expected from testing at age 20. Participants underwent supplementary cognitive testing, blood sampling and MRI including measurements of regional and global CBF. Results Regional CBF was lower in group B than in group A in the posterior cingulate gyrus and the precuneus. The associations were attenuated when corrected for global atrophy, but remained significant in regions of interest based analysis adjusting for regional gray matter volume and vascular risk factors. No influence of group on global CBF was observed. Conclusions We conclude that early sub-clinical cognitive decline is associated with reduced perfusion in the precuneus and posterior cingulate gyrus independently of regional atrophy and vascular risk factors, but cannot be statistically separated from an association with global atrophy. PMID:28095458

  1. Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues

    PubMed Central

    Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K.

    2016-01-01

    Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets. PMID:27114845

  2. Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline

    PubMed Central

    Roberts, Katherine L.; Allen, Harriet A.

    2016-01-01

    Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age. PMID:26973514

  3. Development and validation of risk index for cognitive decline using blood-derived markers

    PubMed Central

    Ayonayon, Hilsa; Harris, Tamara; Phillips, Caroline; Rosano, Caterina; Satterfield, Suzanne; Yaffe, Kristine

    2015-01-01

    Objective: We sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers. Methods: The index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma β-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index. Results: The risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: −0.46, −0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: −0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: −0.85, −0.54). Using the secondary index, which included β-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: −0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: −0.72, −0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: −1.14, −0.51). Conclusions: A risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary. PMID:25609760

  4. Role of physical activity in reducing cognitive decline in older Mexican-American adults.

    PubMed

    Ottenbacher, Allison J; Snih, Soham Al; Bindawas, Saad M; Markides, Kyriakos S; Graham, James E; Samper-Ternent, Rafael; Raji, Mukaila; Ottenbacher, Kenneth J

    2014-09-01

    The effect of physical activity on cognitive function in older adults from minority and disadvantaged populations is not well understood. This study examined the longitudinal association between physical activity and cognition in older Mexican Americans. The study methodology included a prospective cohort with longitudinal analysis of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly. General linear mixed models were used to assess the associations and interactions between physical activity and cognitive function over 14 years. Community-based assessments were performed in participants' homes. Physical activity was recorded for 1,669 older Mexican Americans using the Physical Activity Scale for the Elderly. Cognition was measured using the Mini-Mental State Examination (MMSE) and separated into memory and nonmemory components. A statistically significant positive association was observed between levels of physical activity and cognitive function after adjusting for age, sex, marital status, education, and comorbid health conditions. There was a statistically significant difference in MMSE scores over time between participants in the third (β = 0.11, standard error (SE) = 0.05) and fourth (β = 0.10, SE = 0.2) quartiles of physical activity and those in the first. The protective effect of physical activity on cognitive decline was evident for the memory component of the MMSE but not the nonmemory component after adjusting for covariates. Greater physical activity at baseline was associated with less cognitive decline over 14 years in older Mexican Americans. The reduction in cognitive decline appeared to be related to the memory components of cognitive function.

  5. Vestibular Performance During High-Acceleration Stimuli Correlates with Clinical Decline in SCA6.

    PubMed

    Huh, Young Eun; Kim, Ji-Soo; Kim, Hyo-Jung; Park, Seong-Ho; Jeon, Beom Seok; Kim, Jong-Min; Cho, Jin Whan; Zee, David S

    2015-06-01

    In spinocerebellar ataxia type 6 (SCA6), the vestibular dysfunction and its correlation with other clinical parameters require further exploration. We determined vestibular responses over a broad range of stimulus acceleration in 11 patients with SCA6 (six men, age range=33-72 years, mean age±SD=59±12 years) using bithermal caloric irrigations, rotary chair, and head impulse tests. Correlations were also pursued among disability scores, as measured using the International Cooperative Ataxia Rating Scale, disease duration, age at onset, cytosine-adenine-guanine (CAG) repeat length, and the gain of the vestibulo-ocular reflex (VOR). In response to relatively low-acceleration, low-frequency rotational and bithermal caloric stimuli, the VOR gains were normal or increased regardless of the severity of disease. On the other hand, with relatively high-acceleration, high-frequency head impulses, there was a relative increase in gain in the mildly affected patients and a decrease in gain in the more severely affected patients and gains were negatively correlated with the severity of disease (Spearman correlation, R=-0.927, p<0.001). Selective decrease of the vestibular responses during high-acceleration, high-frequency stimuli may be ascribed to degeneration of either the flocculus or vestibular nuclei. The performance of the VOR during high-acceleration, high-frequency head impulses may be a quantitative indicator of clinical decline in SCA6.

  6. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  7. B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study

    PubMed Central

    Hughes, Catherine F.; Ward, Mary; Tracey, Fergal; Hoey, Leane; Molloy, Anne M.; Pentieva, Kristina; McNulty, Helene

    2017-01-01

    Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60–88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9–1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28–13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing. PMID:28075382

  8. Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline

    ERIC Educational Resources Information Center

    Pakhomov, Serguei V. S.; Hemmy, Laura S.; Lim, Kelvin O.

    2012-01-01

    The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer's disease and mild cognitive impairment are…

  9. Beneficial Effects of Yogasanas and Pranayama in limiting the Cognitive decline in Type 2 Diabetes

    PubMed Central

    Rajani, Santhakumari; Archana, Rajagopalan; Indla, Yogananda Reddy; Rajesh, P

    2016-01-01

    Background Out of many complications that were observed in type 2 diabetes, cognitive impairment is the most neglected. Aim and Objectives The aim of the present study is to assess the cognitive decline in type 2 diabetes and to observe the role of yogasanas and pranayama in ameliorating the cognitive decline. Materials and methods Sixty eight type 2 diabetic subjects were recruited in the study, 34 of them did specific yogasanas and pranayama (test group) for six months and the remaining age and sex matched 34 subjects were recruited as (control group) who were not on any specific exercise regimen. Glycaemic index was estimated by measuring the glycosylated haemoglobin (HbA1c) concentration with Bio-Rad apparatus and cognition was assessed by using Addenbrook’s Cognitive Examination-Revised (ACE-R), which is a neuropsychological battery. Statistical analysis Data was analysed with unpaired student t test. P value<0.05 is considered as statistically significant. Validity was assessed by receiver operating characteristics Results Analysis of data indicated more cognitive scores in the test group when compared with the control group. In test group six months practice of yogasanas and pranayama has also significantly brought down the high glycaemic values which were observed in the control group. Conclusion These findings allow the study to conclude that regular practice of yogasanas and pranayama has a beneficial effect on cognitive performance in type 2 diabetic subjects by stabilizing blood glucose.

  10. Recent Advances in Berry Supplementation and Age-Related Cognitive Decline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effe...

  11. Use it or lose it! Cognitive activity as a protec-tive factor for cognitive decline associated with Alzheimer's disease.

    PubMed

    Mistridis, Panagiota; Mata, Jutta; Neuner-Jehle, Stefan; Annoni, Jean-Marie; Biedermann, Andreas; Bopp-Kistler, Irene; Brand, Dominique; Brioschi Guevara, Andrea; Decrey-Wick, Hedi; Démonet, Jean-François; Hemmeter, Ulrich; Kressig, Reto W; Martin, Brian; Rampa, Luca; Savaskan, Egemen; Stuck, Andreas; Tschopp, Philipp; Zekry, Dina; Monsch, Andreas

    2017-03-21

    Because of the worldwide aging of populations, Alzheimer's disease and other dementias constitute a devastating experience for patients and families as well as a major social and economic burden for both healthcare systems and society. Multiple potentially modifiable cardiovascular and lifestyle risk factors have been associated with this disease. Thus, modifying these risk factors and identifying protective factors represent important strategies to prevent and delay disease onset and to decrease the social burden. Based on the cognitive reserve hypothesis, evidence from epidemiological studies shows that low education and cognitive inactivity constitute major risk factors for dementia. This indicates that a cognitively active lifestyle may protect against cognitive decline or delay the onset of dementia. We describe a newly developed preventive programme, based on this evidence, to stimulate and increase cognitive activity in older adults at risk for cognitive decline. This programme, called "BrainCoach", includes the technique of "motivational interviewing" to foster behaviour change. If the planned feasibility study is successful, we propose to add BrainCoach as a module to the already existing "Health Coaching" programme, a Swiss preventive programme to address multiple risk factors in primary care.

  12. Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia

    PubMed Central

    Gao, Yang; O'Caoimh, Rónán; Healy, Liam; Kerins, David M; Eustace, Joseph; Guyatt, Gordon; Sammon, David; Molloy, D William

    2013-01-01

    Objectives There is growing evidence that antihypertensive agents, particularly centrally acting ACE inhibitors (CACE-Is), which cross the blood–brain barrier, are associated with a reduced rate of cognitive decline. Given this, we compared the rates of cognitive decline in clinic patients with dementia receiving CACE-Is (CACE-I) with those not currently treated with CACE-Is (NoCACE-I), and with those who started CACE-Is, during their first 6 months of treatment (NewCACE-I). Design Observational case–control study. Setting 2 university hospital memory clinics. Participants 817 patients diagnosed with Alzheimer's disease, vascular or mixed dementia. Of these, 361 with valid cognitive scores were included for analysis, 85 CACE-I and 276 NoCACE-I. Measurements Patients were included if the baseline and end-point (standardised at 6 months apart) Standardised Mini-Mental State Examination (SMMSE) or Quick Mild Cognitive Impairment (Qmci) scores were available. Patients with comorbid depression or other dementia subtypes were excluded. The average 6-month rates of change in scores were compared between CACE-I, NoCACE-I and NewCACE-I patients. Results When the rate of decline was compared between groups, there was a significant difference in the median, 6-month rate of decline in Qmci scores between CACE-I (1.8 points) and NoCACE-I (2.1 points) patients (p=0.049), with similar, non-significant changes in SMMSE. Median SMMSE scores improved by 1.2 points in the first 6 months of CACE treatment (NewCACE-I), compared to a 0.8 point decline for the CACE-I (p=0.003) group and a 1 point decline for the NoCACE-I (p=0.001) group over the same period. Multivariate analysis, controlling for baseline characteristics, showed significant differences in the rates of decline, in SMMSE, between the three groups, p=0.002. Conclusions Cognitive scores may improve in the first 6 months after CACE-I treatment and use of CACE-Is is associated with a reduced rate of cognitive

  13. A review of new insights on the association between hearing loss and cognitive decline in ageing.

    PubMed

    Fortunato, S; Forli, F; Guglielmi, V; De Corso, E; Paludetti, G; Berrettini, S; Fetoni, A R

    2016-06-01

    Age-related hearing loss (ARHL) has a multifactorial pathogenesis and it is an inevitable hearing impairment associated with reduction of communicative skills related to ageing. Increasing evidence has linked ARHL to more rapid progression of cognitive decline and incidental dementia. Many aspects of daily living of elderly people have been associated to hearing abilities, showing that hearing loss (HL) affects the quality of life, social relationships, motor skills, psychological aspects and function and morphology in specific brain areas. Epidemiological and clinical studies confirm the assumption of a relationship between these conditions. However, the mechanisms are still unclear and are reviewed herein. Long-term hearing deprivation of auditory inputs can impact cognitive performance by decreasing the quality of communication leading to social isolation and depression and facilitate dementia. On the contrary, the limited cognitive skills may reduce the cognitive resources available for auditory perception, increasing the effects of HL. In addition, hearing loss and cognitive decline may reflect a 'common cause' on the auditory pathway and brain. In fact, some pathogenetic factors are recongised in common microvascular disease factors such as diabetes, atherosclerosis and hypertension. Interdisciplinary efforts to investigate and address HL in the context of brain and cognitive ageing are needed. Surprisingly, few studies have been adressed on the effectiveness of hearing aids in changing the natural history of cognitive decline. Effective interventions with hearing aids or cochlear implant may improve social and emotional function, communication, cognitive function and positively impact quality of life. The aim of this review is to overview new insights on this challenging topic and provide new ideas for future research.

  14. Periodic Limb Movements in Sleep are Associated with Greater Cognitive Decline in Older Men without Dementia

    PubMed Central

    Leng, Yue; Blackwell, Terri; Stone, Katie L.; Hoang, Tina D.; Redline, Susan; Yaffe, Kristine

    2016-01-01

    Study Objectives: To examine the association between periodic limb movements in sleep (PLMS) and change in selected aspects of cognition in community-dwelling older men. Methods: We studied 2,636 older men without dementia who underwent in-home polysomnography with measurement of the periodic limb movement index (PLMI) and periodic limb movement arousal index (PLMAI) using piezoelectric sensors. Random-effects models and logistic regression were used to examine the association between PLMI, PLMAI, and 3- to 4-y change in cognition. Results: After multivariable adjustment, men with a high PLMI had greater decline on the Trail Making Test – Part B (P trend = 0.02); those with a PLMI ≥ 30 were 48% more likely (odds ratio = 1.48, 95% confidence interval = 1.05–2.07) to experience the development of significant cognitive impairment (≥ 1 SD above mean change). Further adjustment for sleep efficiency, nocturnal hypoxemia, or dopaminergic medication use and analysis among men without Parkinson disease (n = 2,607) showed similar findings. No significant association was found for PLMAI or for Modified Mini-Mental State Examination scores. Conclusions: Among older men without dementia, higher PLMS frequency was associated with greater decline in cognition, particularly in executive function. Citation: Leng Y, Blackwell T, Stone KL, Hoang TD, Redline S, Yaffe K. Periodic limb movements in sleep are associated with greater cognitive decline in older men without dementia. SLEEP 2016;39(10):1807–1810. PMID:27568800

  15. Use of the Internet as a prevention tool against cognitive decline in normal aging

    PubMed Central

    Klimova, Blanka

    2016-01-01

    Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed. PMID:27672317

  16. Epidemiologic Evidence of a Relationship between Tea, Coffee, or Caffeine Consumption and Cognitive Decline12

    PubMed Central

    Arab, Lenore; Khan, Faraz; Lam, Helen

    2013-01-01

    A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men. PMID:23319129

  17. Epidemiologic evidence of a relationship between tea, coffee, or caffeine consumption and cognitive decline.

    PubMed

    Arab, Lenore; Khan, Faraz; Lam, Helen

    2013-01-01

    A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men.

  18. Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer's disease, through angiotensin II.

    PubMed

    Nakagawa, Takashi; Hasegawa, Yu; Uekawa, Ken; Kim-Mitsuyama, Shokei

    2017-01-01

    Epidemiological studies suggest that chronic kidney disease (CKD) is a significant risk factor in the development of cognitive decline. However, the exact role of CKD in cognitive impairment or dementia is unclear. This work was performed to examine the potential impact of CKD on cognitive impairment in Alzheimer's disease (AD), focusing on angiotensin II. (1) CKD was induced in 5XFAD mice, an AD model mouse, and wild-type mice by feeding an adenine-containing diet and the effect on cognitive function was compared between both strains. There was no significant difference regarding the severity of CKD induced by adenine between the strains. In 5XFAD mice, the CKD group exhibited significant cognitive impairment while the control group (control diet-fed group) did not, as evidenced by a passive avoidance test. On the other hand, in wild-type mice, neither the CKD group nor the control group showed cognitive impairment. Thus, CKD itself appears to accelerate cognitive impairment in AD mice. (2) We also examined the effect of olmesartan, an angiotensin II receptor blocker, on 5XFAD mice with CKD to elucidate the potential involvement of angiotensin II. As evidenced by the findings of the water maze test, olmesartan treatment significantly ameliorated the impairment of spatial learning and memory function induced by CKD in 5XFAD mice. Olmesartan treatment significantly ameliorated blood-brain barrier (BBB) disruption induced by CKD in 5XFAD mice. Furthermore, olmesartan reduced hippocampal oxidative stress in 5XFAD with CKD to similar levels to the control group of 5XFAD fed standard diet. Hence, the amelioration of CKD-induced cognitive impairment in 5XFAD mice by olmesartan appears to be mediated by the suppression of BBB disruption or oxidative stress. In conclusion, we obtained the evidence suggesting that CKD itself accelerates cognitive impairment in AD mice, through angiotensin II. Thus, our work provides a novel insight into the underlying mechanism of the link

  19. Gender differences in tea, coffee, and cognitive decline in the elderly: the Cardiovascular Health Study.

    PubMed

    Arab, Lenore; Biggs, Mary L; O'Meara, Ellen S; Longstreth, W T; Crane, Paul K; Fitzpatrick, Annette L

    2011-01-01

    Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study.

  20. Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

    NASA Astrophysics Data System (ADS)

    Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

    2016-08-01

    In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

  1. Vitamin D as a marker of cognitive decline in elderly Indian population

    PubMed Central

    Vedak, Tejal Kanhaiya; Ganwir, Vaishali; Shah, Arun B.; Pinto, Charles; Lele, Vikram R.; Subramanyam, Alka; Shah, Hina; Deo, Sudha Shrikant

    2015-01-01

    Objectives: Very few studies in India have addressed the role of vitamin D in cognitive function. The present study was conducted to assess the serum levels of 25-hydroxyvitamin D (25(OH)D) and its association with markers of cognitive impairment and homocysteine levels in the elderly Indian population. Materials and Methods: The study population consisted of patients with dementia (Group A, n = 32), mild cognitive impairment (MCI; Group B, n = 24), and elderly age-matched controls (Group C, n = 30). Measurement of serum levels of 25(OH)D and total homocysteine were done. Results: Significant decreased concentration of 25(OH)D and increased concentration of homocysteine was observed. Association of serum levels of vitamin D with markers of cognitive decline as well as serum homocysteine levels was observed in patients with dementia and MCI when compared to controls. Conclusion: Correlation of vitamin D with markers of cognitive decline and homocysteine opens a new door for early diagnosis of cognitive impairment. PMID:26425010

  2. Preventing cognitive decline in older African Americans with mild cognitive impairment: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Leiby, Benjamin E

    2012-07-01

    Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society.

  3. Preventing Cognitive Decline in Older African Americans with Mild Cognitive Impairment: Design and Methods of a Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Leiby, Benjamin E.

    2012-01-01

    Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society. PMID:22406101

  4. Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

    PubMed

    Lorius, Natacha; Locascio, Joseph J; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Viswanathan, Anand; Marshall, Gad A

    2015-01-01

    We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E ε4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E ε4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.

  5. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering

    PubMed Central

    Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.

    2014-01-01

    The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  6. Rate of cognitive decline in relation to sex after 60 years-of-age: a systematic review.

    PubMed

    Ferreira, Leandro; Ferreira Santos-Galduróz, Ruth; Ferri, Cleusa Pinheiro; Fernandes Galduróz, José Carlos

    2014-01-01

    Some studies have shown differences in specific cognitive ability domains between the sexes at 60 years-of-age. However is important to analyze whether the rate of cognitive decline is also similar between the sexes after this age. The present study examined previously published literature to investigate whether cognitive decline is distinct between men and women after the age of 60 years. A systematic review was carried out with the PubMed, LILACS and PsycINFO databases (2001-2011) using the following search terms: aging, aged, cognitive function, mild cognitive impairment, mental health and cognition. We analyzed longitudinal research that used neuropsychological tests for evaluating cognitive function, showed results separated by sex and that excluded participants with dementia. Elderly women showed better performance in tests of episodic memory, whereas elderly men had a better visuospatial ability. Only one study detected distinct rates of cognitive decline in specific tests between the sexes. Despite differences observed in some domains, most of the studies showed that this rate is similar between the sexes until the age of 80 years. It is unclear whether sex influences the rate of cognitive decline after the age of 80 years. The present review observed that sex does not determine the rate of cognitive decline between 60 and 80 years-of-age. The contextual and cultural factors that involve men and women might determine a distinct decline between them, rather than sex alone.

  7. Optimizing Cognitive Development over the Life Course and Preventing Cognitive Decline: Introducing the Cognitive Health Environment Life Course Model (CHELM)

    ERIC Educational Resources Information Center

    Anstey, Kaarin J.

    2014-01-01

    Optimal cognitive development is defined in this article as the highest level of cognitive function reached in each cognitive domain given a person's biological and genetic disposition, and the highest possible maintenance of cognitive function over the adult life course. Theoretical perspectives underpinning the development of a framework…

  8. Decreased Self-Appraisal Accuracy on Cognitive Tests of Executive Functioning Is a Predictor of Decline in Mild Cognitive Impairment

    PubMed Central

    Scherling, Carole S.; Wilkins, Sarah E.; Zakrezewski, Jessica; Kramer, Joel H.; Miller, Bruce L.; Weiner, Michael W.; Rosen, Howard J.

    2016-01-01

    Objective: Mild cognitive impairment (MCI) in older individuals is associated with increased risk of progression to dementia. The factors predicting progression are not yet well established, yet cognitive performance, particularly for memory, is known to be important. Anosognosia, meaning lack of awareness of one’s impaired function, is commonly reported in dementia and is often also a feature of MCI, but its association with risk of progression is not well understood. In particular, self-appraisal measures provide an autonomous measure of insight abilities, without the need of an informant. Methods: The present study examined the utility of self-appraisal accuracy at baseline for predicting cognitive decline in 51 patients using an informant-free assessment method. Baseline task performance scores were compared to self-assessments of performance to yield a discrimination score (DS) for tasks tapping into memory and executive functions. Results: Linear regression revealed that a larger DS for executive function tasks in MCI predicted functional decline, independent of age, education, and baseline memory and executive task scores. Conclusion: These findings indicate that objective estimates of self-appraisal can be used to quantify anosognosia and increase predictive accuracy for decline in MCI. PMID:27458368

  9. Attention capacity and self-report of subjective cognitive decline: a P3 ERP study.

    PubMed

    Smart, Colette M; Segalowitz, Sidney J; Mulligan, Bryce P; MacDonald, Stuart W S

    2014-12-01

    Subjective cognitive decline (SCD) has recently been proposed as the earliest stage of pathologic cognitive decline in older adults. Longitudinal research suggests that many individuals with SCD go on to develop mild cognitive impairment or Alzheimer's disease. However, those with SCD typically appear normal on standardized neuropsychological testing, and as of yet there are no reliable objective measures discriminating those with SCD from healthy peers. Two groups of healthy older adults (ages 65-80), who self-identified as being with (n=17) or without SCD (n=23), completed self-report measures and objective measures of cognition. Groups did not differ on demographic variables, estimated cognitive reserve, or clinical neuropsychological testing. However, self-identifying as having SCD predicted clear differences in the P3 event-related potential in response to an attention control task, over and above any contributions from mood, anxiety, or neuroticism. Results suggest that using direct neural measures of information processing might be useful where standardized clinical tools are insensitive in those with SCD.

  10. Sex-specific risk of cardiovascular disease and cognitive decline: pregnancy and menopause

    PubMed Central

    2013-01-01

    Understanding the biology of sex differences is integral to personalized medicine. Cardiovascular disease and cognitive decline are two related conditions, with distinct sex differences in morbidity and clinical manifestations, response to treatments, and mortality. Although mortality from all-cause cardiovascular diseases has declined in women over the past five years, due in part to increased educational campaigns regarding the recognition of symptoms and application of treatment guidelines, the mortality in women still exceeds that of men. The physiological basis for these differences requires further research, with particular attention to two physiological conditions which are unique to women and associated with hormonal changes: pregnancy and menopause. Both conditions have the potential to impact life-long cardiovascular risk, including cerebrovascular function and cognition in women. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of hypertensive pregnancy disorders on cardiovascular disease and cognitive function later in life, and examines the effects of post-menopausal hormone treatments on cardiovascular risk and cognition in midlife women. We suggest that hypertensive pregnancy disorders and menopause activate vascular components, i.e., vascular endothelium and blood elements, including platelets and leukocytes, to release cell-membrane derived microvesicles that are potential mediators of changes in cerebral blood flow, and may ultimately affect cognition in women as they age. Research into specific sex differences for these disease processes with attention to an individual’s sex chromosomal complement and hormonal status is important and timely. PMID:23537114

  11. Can training in a real-time strategy video game attenuate cognitive decline in older adults?

    PubMed

    Basak, Chandramallika; Boot, Walter R; Voss, Michelle W; Kramer, Arthur F

    2008-12-01

    Declines in various cognitive abilities, particularly executive control functions, are observed in older adults. An important goal of cognitive training is to slow or reverse these age-related declines. However, opinion is divided in the literature regarding whether cognitive training can engender transfer to a variety of cognitive skills in older adults. In the current study, the authors trained older adults in a real-time strategy video game for 23.5 hr in an effort to improve their executive functions. A battery of cognitive tasks, including tasks of executive control and visuospatial skills, were assessed before, during, and after video-game training. The trainees improved significantly in the measures of game performance. They also improved significantly more than the control participants in executive control functions, such as task switching, working memory, visual short-term memory, and reasoning. Individual differences in changes in game performance were correlated with improvements in task switching. The study has implications for the enhancement of executive control processes of older adults.

  12. Neuropsychological Markers of Cognitive Decline in Persons With Alzheimer Disease Neuropathology.

    PubMed

    Hassenstab, Jason; Monsell, Sarah E; Mock, Charles; Roe, Catherine M; Cairns, Nigel J; Morris, John C; Kukull, Walter

    2015-11-01

    To evaluate cognitive performance among persons who did and did not develop clinical Alzheimer disease (AD) but had AD neuropathology at autopsy, we examined neuropsychological performance in cognitively healthy (Clinical Dementia Rating [CDR] = 0) participants who returned for at least 1 follow-up and died within 2 years of their last assessment. Nonprogressors remained at CDR = 0 until death; progressors developed symptomatic AD during life (CDR > 0). Cognitive performance at baseline was compared between progressors and nonprogressors on a global cognitive composite and 4 domain-specific composites (episodic memory, language, attention/working memory, and executive function). Models adjusted for age, education, sex, and non-AD neuropathology. Progressors (n = 173) had worse performance than nonprogressors (n = 141) in nearly all cognitive domains. Progressors scored lower on composites of global cognition (P < 0.001), executive function (P = 0.0006), language (P < 0.0001), and episodic memory (P = 0.0006) but not on attention/working memory (P = 0.91). These data indicate that individuals with underlying AD neuropathology who are clinically healthy but who later develop symptomatic AD have worse performance in a wide range of domains versus individuals with underlying AD neuropathology who are clinically healthy but do not become symptomatic during life. Therefore, subtle cognitive decline at baseline may indicate an increased risk of progression to symptomatic AD.

  13. Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

    PubMed

    Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why.

  14. Adverse Vascular Risk is Related to Cognitive Decline in Older Adults

    PubMed Central

    Jefferson, Angela L.; Hohman, Timothy J.; Liu, Dandan; Haj-Hassan, Shereen; Gifford, Katherine A.; Benson, Elleena M.; Skinner, Jeannine S.; Lu, Zengqi; Sparling, Jamie; Sumner, Emily C.; Bell, Susan; Ruberg, Frederick L.

    2014-01-01

    Background Cardiovascular disease (CVD) and related risk factors are associated with Alzheimer’s disease (AD). This association is less well-defined in normal cognition (NC) or prodromal AD (mild cognitive impairment (MCI)). Objective Cross-sectionally and longitudinally relate a vascular risk index to cognitive outcomes among elders free of clinical dementia. Methods 3117 MCI (74±8 years, 56% female) and 6603 NC participants (72±8 years, 68% female) were drawn from the National Alzheimer’s Coordinating Center. A composite measure of vascular risk was defined using the Framingham Stroke Risk Profile (FSRP) score (i.e., age, systolic blood pressure, anti-hypertensive medication, diabetes, cigarette smoking, CVD history, atrial fibrillation). Ordinary linear regressions and generalized linear mixed models related baseline FSRP to cross-sectional and longitudinal cognitive outcomes, separately for NC and MCI, adjusting for age, sex, race, education, and follow-up time (in longitudinal models). Results In NC participants, increasing FSRP was related to worse baseline global cognition, information processing speed, and sequencing abilities (p-values<0.0001) and a worse longitudinal trajectory on all cognitive measures (p-values<0.0001). In MCI, increasing FSRP correlated with worse longitudinal delayed memory (p=0.004). In secondary models using an age-excluded FSRP score, associations persisted in NC participants for global cognition, naming, information processing speed, and sequencing abilities. Conclusions An adverse vascular risk profile is associated with worse cognitive trajectory, especially global cognition, naming, and information processing speed, among NC elders. Future studies are needed to understand how effective management of CVD and related risk factors can modify cognitive decline to identify the ideal timeframe for primary prevention implementation. PMID:25471188

  15. Cancer, Coping, and Cognition: A Model for the Role of Stress Reactivity in Cancer-Related Cognitive Decline

    PubMed Central

    Andreotti, Charissa; Root, James C.; Ahles, Tim A.; McEwen, Bruce S.; Compas, Bruce E.

    2014-01-01

    Cognitive decline and accompanying neurological changes associated with non-CNS cancer diagnosis and treatment have been increasingly identified in a subset of patients. Initially believed to be due to neurotoxic effects of chemotherapy exposure, observation of cognitive decline in patients not treated with chemotherapy, cancer-diagnosed individuals prior to treatment, and patients receiving alternative treatment modalities (surgery, endocrine therapy, radiation), has led to investigation of additional potential etiologies and moderating factors. Stressful experiences have long been posited as a contributor to these cognitive changes. Through reciprocal connectivity with peripheral systems, the brain maintains a dynamic circuitry to adapt to stress (allostasis). However, overuse of this system leads to dysregulation and contributes to pathophysiology (allostatic load). At this time, little research has been conducted to systematically examine the role of allostatic load in cancer-related cognitive dysfunction. Here we integrate theories of stress biology, neuropsychology, and coping and propose a model through which individuals with a high level of allostatic load at diagnosis may be particularly vulnerable to the neurocognitive effects of cancer. Opportunities for future research to test and extend proposed mechanisms are discussed in addition to points of prevention and intervention based on individual variation in stress reactivity and coping skills. PMID:25286084

  16. ω-3 fatty acids in the prevention of cognitive decline in humans.

    PubMed

    Cederholm, Tommy; Salem, Norman; Palmblad, Jan

    2013-11-01

    The brain is a lipid-rich organ where docosahexaenoic acid (DHA) is enriched and where eicosapentaenoic acid (EPA) may have anti-inflammatory effects. The potential role for n-3 (ω-3) fatty acids such as DHA and EPA in the prevention of cognitive decline, including Alzheimer's disease (AD) has attracted major interest for the past 20 y. This review presents our understanding of recent observational, interventional, and experimental studies, with the aim of providing some answers to the following question: Can n-3 FA intake modulate cognitive function during aging? In longitudinal observation studies we mainly observe inverse relations between fish intake or serum concentrations of DHA and cognitive impairment. Intervention studies of EPA and DHA supplementation in healthy old individuals have been negative so far (i.e., after up to 2 years of treatment, no differences in cognitive decline between treated and nontreated participants have been observed). In studies that provided EPA and DHA to adults with mild cognitive impairment or age-related cognitive impairment the data seem to be positive. However, when patients with established AD were supplemented with EPA and DHA it appears no benefit was gained. For studies on healthy individuals, a major concern is that the treatment periods may have been too short. There might also be subgroup effects because of the carriage of apolipoprotein Eε4 alleles or risk factor burden. Experimental studies appear to be consistently positive (i.e., n-3 FA supplementation in rodents over a substantial portion of their lives reduces amyloid-β deposition and hippocampal neuron loss and improves cognitive functioning). We are getting closer to providing evidence-based recommendations on fish and fish oil intake to facilitate memory function during old age. In the meantime it is advised to follow the general CDC dietary recommendations of 2-3 fish meals per week or the equivalent intake of long chain n-3 fatty acids, particularly DHA.

  17. The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study

    NASA Astrophysics Data System (ADS)

    Kent, Shia T.; Kabagambe, Edmond K.; Wadley, Virginia G.; Howard, Virginia J.; Crosson, William L.; Al-Hamdan, Mohammad Z.; Judd, Suzanne E.; Peace, Fredrick; McClure, Leslie A.

    2014-04-01

    Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.

  18. Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

    PubMed Central

    Leal, Stephanie L; Landau, Susan M; Bell, Rachel K; Jagust, William J

    2017-01-01

    The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baseline was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline. DOI: http://dx.doi.org/10.7554/eLife.22978.001 PMID:28177283

  19. Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline

    PubMed Central

    Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.

    2015-01-01

    Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

  20. Ascorbic Acid and Rates of Cognitive Decline in Alzheimer’s Disease

    PubMed Central

    Bowman, Gene L.; Dodge, Hiroko; Frei, Balz; Calabrese, Carlo; Oken, Barry S.; Kaye, Jeffrey A.; Quinn, Joseph F.

    2009-01-01

    The brain maintains high levels of ascorbic acid (AA) despite a concentration gradient favoring diffusion from brain to peripheral tissues. Dietary antioxidants, including AA, appear to modify the risk of Alzheimer’s disease (AD). The objective of this study was to test the hypothesis that neurodegeneration in AD is modified by brain levels of AA. Thirty-two patients with mild to moderate AD participated in a biomarker study involving standardized clinical assessments over one year. Cerebrospinal fluid (CSF) and serum were collected at baseline for AA and albumin content. Cognitive measures were collected at baseline and one year. CSF and plasma AA failed to predict cognitive decline independently, however, CSF: plasma AA ratio did. After adding CSF Albumin Index (an established marker of blood-brain barrier integrity) to the regression models the effect of CSF: plasma AA ratio as a predictor of cognitive decline was weakened. CSF: plasma AA ratio predicts rate of decline in AD. This relationship may indicate that the CSF: plasma AA ratio is an index of AA availability to the brain or may be an artifact of a relationship between blood-brain barrier impairment and neurodegeneration. PMID:19158425

  1. Cerebral small vessel disease: Capillary pathways to stroke and cognitive decline

    PubMed Central

    Engedal, Thorbjørn S; Moreton, Fiona; Hansen, Mikkel B; Wardlaw, Joanna M; Dalkara, Turgay; Markus, Hugh S; Muir, Keith W

    2015-01-01

    Cerebral small vessel disease (SVD) gives rise to one in five strokes worldwide and constitutes a major source of cognitive decline in the elderly. SVD is known to occur in relation to hypertension, diabetes, smoking, radiation therapy and in a range of inherited and genetic disorders, autoimmune disorders, connective tissue disorders, and infections. Until recently, changes in capillary patency and blood viscosity have received little attention in the aetiopathogenesis of SVD and the high risk of subsequent stroke and cognitive decline. Capillary flow patterns were, however, recently shown to limit the extraction efficacy of oxygen in tissue and capillary dysfunction therefore proposed as a source of stroke-like symptoms and neurodegeneration, even in the absence of physical flow-limiting vascular pathology. In this review, we examine whether capillary flow disturbances may be a shared feature of conditions that represent risk factors for SVD. We then discuss aspects of capillary dysfunction that could be prevented or alleviated and therefore might be of general benefit to patients at risk of SVD, stroke or cognitive decline. PMID:26661176

  2. Visuospatial deficits predict rate of cognitive decline in autopsy-verified dementia with Lewy bodies.

    PubMed

    Hamilton, Joanne M; Salmon, David P; Galasko, Douglas; Raman, Rema; Emond, Jenn; Hansen, Lawrence A; Masliah, Eliezer; Thal, Leon J

    2008-11-01

    Dementia with Lewy bodies (DLB) is often characterized by pronounced impairment in visuospatial skills, attention, and executive functions. However, the strength of the phenotypic expression of DLB varies and may be weaker in patients with extensive concomitant Alzheimer's disease (AD). To determine whether strength of the DLB clinical phenotype impacts cognitive decline, visuospatial and language tests were retrospectively used to predict 2-year rate of global cognitive decline in 22 autopsy-confirmed DLB patients (21 with concomitant AD) and 44 autopsy-confirmed "pure" AD patients. Generalized estimating equations (GEE) revealed a significant interaction such that poor baseline performances on tests of visuospatial skills were strongly associated with a rapid rate of cognitive decline in DLB but not AD (p < .001). No effect of confrontation naming was found. DLB patients with poor visuospatial skills had fewer neurofibrillary tangles and were more likely to experience visual hallucinations than those with better visuospatial skills. These results suggest that the severity of visuospatial deficits in DLB may identify those facing a particularly malignant disease course and may designate individuals whose clinical syndrome is impacted more by Lewy body formation than AD pathology.

  3. Bilingualism Does Not Alter Cognitive Decline or Dementia Risk among Spanish-Speaking Immigrants

    PubMed Central

    Zahodne, Laura B.; Schofield, Peter W.; Farrell, Meagan T.; Stern, Yaakov; Manly, Jennifer J.

    2013-01-01

    Objective Clinic-based studies suggest that dementia is diagnosed at older ages in bilinguals compared to monolinguals. The current study sought to test this hypothesis in a large, prospective, community-based study of initially non-demented Hispanic immigrants living in a Spanish-speaking enclave of Northern Manhattan. Method Participants included 1,067 participants in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were tested in Spanish and followed at 18–24 month intervals for up to 23 years. Spanish-English bilingualism was estimated via both self-report and an objective measure of English reading level. Multilevel models for change estimated the independent effects of bilingualism on cognitive decline in four domains: episodic memory, language, executive function, and speed. Over the course of the study, 282 participants developed dementia. Cox regression was used to estimate the independent effect of bilingualism on dementia conversion. Covariates included country of origin, gender, education, time spent in the United States, recruitment cohort, and age at enrollment. Results Independent of the covariates, bilingualism was associated with better memory and executive function at baseline. However bilingualism was not independently associated with rates of cognitive decline or dementia conversion. Results were similar whether bilingualism was measured via self-report or an objective test of reading level. Conclusions This study does not support a protective effect of bilingualism on age-related cognitive decline or the development of dementia. In this sample of Hispanic immigrants, bilingualism is related to higher initial scores on cognitive tests and higher educational attainment and may not represent a unique source of cognitive reserve. PMID:24188113

  4. Network Optimization of Functional Connectivity within Default Mode Network Regions to Detect Cognitive Decline.

    PubMed

    Chaovalitwongse, Wanpracha Art; Won, Daehan; Seref, Onur; Borghesani, Paul; Askren, Mary Katie; Willis, Sherry; Grabowski, Tom

    2017-03-07

    The rapid aging of the world's population is causing an increase in the prevalence of cognitive decline and degenerative brain disease in the elderly. Current diagnoses of amnestic and nonamnestic Mild Cognitive Impairment (MCI), which may represent early stage Alzheimer's disease or related degenerative conditions, are based on clinical grounds. The recent emergence of advanced network analyses of functional Magnetic Resonance Imaging (fMRI) data taken at cognitive rest has provided insight that declining functional connectivity of the default mode network (DMN) may be correlated with neurological disorders, and particularly prodromal Alzheimer's disease. The goal of this paper is to develop a network analysis technique using fMRI data to characterize transition stages from healthy brain aging to cognitive decline. Previous studies primarily focused on internodal connectivity of the DMN and often assume functional homogeneity within each DMN region. In this paper, we develop a technique that focuses on identifying critical intra-nodal DMN connectivity by incorporating sparsity into connectivity modeling of the k-cardinality tree (KCT) problem. Most biological networks are efficient and formed by sparse connections, and the KCT can potentially reveal sparse connectivity patterns that are biologically informative. The KCT problem is NP-hard, and existing solution approaches are mostly heuristic. Mathematical formulations of the KCT problem in the literature are not compact and do not provide good solution bounds. This paper presents new KCT formulations and a fast heuristic approach to efficiently solve the KCT models for large DMN regions. The results in this study demonstrate that traditional fMRI group analysis on DMN regions cannot detect any statistically significant connectivity differences between normal aging and cognitively impaired subjects in DMN regions, and the proposed KCT approaches are more sensitive than the state-of-the-art regional homogeneity

  5. Early-Stage White Matter Lesions Detected by Multispectral MRI Segmentation Predict Progressive Cognitive Decline

    PubMed Central

    Jokinen, Hanna; Gonçalves, Nicolau; Vigário, Ricardo; Lipsanen, Jari; Fazekas, Franz; Schmidt, Reinhold; Barkhof, Frederik; Madureira, Sofia; Verdelho, Ana; Inzitari, Domenico; Pantoni, Leonardo; Erkinjuntti, Timo

    2015-01-01

    White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a “pre-visible” stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65–84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment. PMID:26696814

  6. Age-related cognitive decline during normal aging: the complex effect of education.

    PubMed

    Ardila, A; Ostrosky-Solis, F; Rosselli, M; Gómez, C

    2000-08-01

    The purpose of this study was to further analyze the effects of education on cognitive decline during normal aging. An 806-subject sample was taken from five different Mexican regions. Participants ranged in age from 16 to 85 years. Subjects were grouped into four educational levels: illiterate, 1-4, 5-9, and 10 or more years of education, and four age ranges: 16-30, 31-50, 51-65, and 66-85 years. A brief neuropsychological test battery (NEUROPSI), standardized and normalized in Spanish, was administered. The NEUROPSI test battery includes assessment of orientation, attention, memory, language, visuoperceptual abilities, motor skills, and executive functions. In general, test scores were strongly associated with level of educational, and differences among age groups were smaller than differences among education groups. However, there was an interaction between age and education such as that among illiterate individuals scores of participants 31-50 years old were higher than scores of participants 16-30 years old for over 50% of the tests. Different patterns of interaction among educational groups were distinguished. It was concluded that: (a) The course of life-span changes in cognition are affected by education. Among individuals with a low level of education, best neuropsychological test performance is observed at an older age than among higher-educated subjects; and (b) there is not a single relationship between age-related cognitive decline and education, but different patterns may be found, depending upon the specific cognitive domain.

  7. Relationship between Inflammation and Oxidative Stress and Cognitive Decline in the Institutionalized Elderly

    PubMed Central

    Baierle, Marília; Nascimento, Sabrina N.; Moro, Angela M.; Brucker, Natália; Freitas, Fernando; Gauer, Bruna; Durgante, Juliano; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M.; Duarte, Marta M. M. F.; Grune, Tilman; Breusing, Nicolle; Garcia, Solange C.

    2015-01-01

    Objective. Cognitive impairment reduces quality of life and is related to vascular and neurodegenerative disorders. However, there is also a close relationship between these diseases and oxidative stress. Thus, the purpose of this study was to assess whether inflammation and oxidative damage are associated with low cognitive performance in the elderly with different housing conditions. Methods. The study groups consisted of 32 institutionalized and 25 noninstitutionalized Brazilian elderly subjects. Oxidative damage, inflammation markers, and cognitive function were evaluated. Results. The results demonstrated pronounced oxidative stress in the institutionalized elderly group, which also had a lower antioxidant status compared to noninstitutionalized subjects. High levels of proinflammatory cytokines were also observed in the institutionalized elderly. Furthermore, the raised levels of inflammatory markers were correlated with increased oxidative stress, and both were associated with low cognitive performance. However, based on multiple linear regression analysis, oxidative stress appears to be the main factor responsible for the cognitive decline. Conclusions. The findings suggest that individuals with lower antioxidant status are more vulnerable to oxidative stress, which is associated with cognitive function, leading to reduced life quality and expectancy. PMID:25874023

  8. Daily stress magnifies the association between cognitive decline and everyday memory problems: an integration of longitudinal and diary methods.

    PubMed

    Rickenbach, Elizabeth Hahn; Almeida, David M; Seeman, Teresa E; Lachman, Margie E

    2014-12-01

    We examined whether long-term fluid cognitive decline was associated with memory problems in everyday life, and whether stress plays a moderating role. We expected that the association between cognitive decline and everyday memory problems would be magnified in the context of self-reported and physiological stress. Data are from the Boston Longitudinal Study, a subsample of the Midlife in the United States study. Participants in the current study (n = 112) completed a battery of tests measuring fluid cognitive functioning at Time 1 (T1) and 2 (T2) over 10 years. At T2, participants completed weekly diaries of self-reported daily stressors and everyday memory problems for 12 consecutive weeks. Also at T2, participants provided 4 saliva samples over the course of 1 day to assess physiological stress using diurnal cortisol profiles [cortisol awakening response (CAR) and diurnal cortisol slope (DCS)]. Self-reported daily stressors and a less healthy DCS were associated with more everyday memory problems, and participants with greater cognitive decline reported more memory problems compared to those with less or no decline. Self-reported daily stressors and CAR moderated the relationship of cognitive decline and memory problems. As expected, more cognitive decline was associated with greater increases in memory problems on weeks when individuals reported more daily stressors and for individuals with a less healthy CAR. The current findings can inform interventions aimed to identify factors, such as daily stress, that contribute to daily functioning in the context of cognitive decline.

  9. Daily Stress Magnifies the Association between Cognitive Decline and Everyday Memory Problems: An Integration of Longitudinal and Diary Methods

    PubMed Central

    Rickenbach, Elizabeth H.; Almeida, David M.; Seeman, Teresa E.; Lachman, Margie E.

    2014-01-01

    We examined whether long-term fluid cognitive decline was associated with memory problems in everyday life, and whether stress plays a moderating role. We expected that the association between cognitive decline and everyday memory problems would be magnified in the context of self-reported and physiological stress. Data are from the Boston Longitudinal Study, a subsample of the Midlife in the United States study. Participants in the current study (n=112) completed a battery of tests measuring fluid cognitive functioning at Time 1 (T1) and 2 (T2) over ten years. At T2, participants completed weekly diaries of self-reported daily stressors and everyday memory problems for twelve consecutive weeks. Also at T2, participants provided four saliva samples over the course of one day to assess physiological stress using diurnal cortisol profiles [cortisol awakening response (CAR) and diurnal cortisol slope (DCS)]. Self-reported daily stressors and a less healthy DCS were associated with more everyday memory problems, and participants with greater cognitive decline reported more memory problems compared to those with less or no decline. Self-reported daily stressors and CAR moderated the relationship of cognitive decline and memory problems. As expected, more cognitive decline was associated with greater increases in memory problems on weeks when individuals reported more daily stressors and for individuals with a less healthy CAR. The current findings can inform interventions aimed to identify factors, such as daily stress, that contribute to daily functioning in the context of cognitive decline. PMID:25365691

  10. Age-associated losses of brain volume predict longitudinal cognitive declines over 8 to 20 years.

    PubMed

    Rabbitt, Patrick; Ibrahim, Said; Lunn, Mary; Scott, Marietta; Thacker, Neil; Hutchinson, Charles; Horan, Michael; Pendleton, Neil; Jackson, Alan

    2008-01-01

    Absolute differences in global brain volume predict differences in cognitive ability among healthy older adults. However, absolute differences confound lifelong differences in brain size with amounts of age-related shrinkage. Measurements of cerebrospinal fluid (CSF) volume were made to estimate age-related shrinkage in 93 healthy volunteers aged 63 to 86 years. Their current levels of brain shrinkage predicted their amounts of decline over the previous 8 to 20 years on repeated assessments during a longitudinal study on the Cattell "Culture Fair" Intelligence Test, on two tests of information processing speed, and marginally on the Wechsler Adult Intelligence Scale (D. Wechsler, 1981), but not on three memory tests. Loss of brain volume is an effective marker both for current cognitive status and for amounts and rates of previous age-related cognitive losses.

  11. Hippocampal and Amygdala Gray Matter Loss in Elderly Controls with Subtle Cognitive Decline

    PubMed Central

    Zanchi, Davide; Giannakopoulos, Panteleimon; Borgwardt, Stefan; Rodriguez, Cristelle; Haller, Sven

    2017-01-01

    In contrast to the idea that hippocampal and amygdala volume loss occur in late phases of neurodegeneration, recent contributions point to the relevance of preexisting structural deficits that are associated with aging and are independent of amyloid deposition in preclinical Alzheimer disease cases. The present work explores GM hippocampal and amygdala volumes in elderly controls displaying the first signs of cognitive decline. 455 subjects (263 females), including 374 controls (228 females) and 81 middle cognitive impairment subjects (35 females), underwent two neuropsychological evaluations (baseline and 18 months follow-up) and a MRI-T1 examination (only baseline). Clinical assessment included Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale, Hospitalized Anxiety and Depression scale, the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery and RI-48 Cued Recall Test (RI-48) for episodic memory. Based on their cognitive performance, we defined the controls as stable controls (sCON) and deteriorating controls (dCONs). Analyses included volumetric assessment, shape analyses and linear regressions between GM volume loss and differences in clinical scores between baseline and follow-up. Significant GM volume decrease in hippocampus bilaterally and right amygdala was found in dCON compared to sCON (p < 0.05). Lower right amygdala volumes were measured in mild cognitive impairment (MCI) compared to sCON (p < 0.05). Shape analyses revealed that atrophy was more pronounced at the superior- posterior lateral side of the hippocampus and amygdala. Significant correlations were found between GM volume of left hippocampus and the delta of MMSE and RI-48 scores in dCON and MCI groups separately. Decreased hippocampal and right amygdala volumes precede the first signs of cognitive decline in healthy elderly controls at the pre-MCI state. Left hippocampus volume may also predict short-term changes of overall cognition in

  12. Prospective memory on a novel clinical task in older adults with mild cognitive impairment and subjective cognitive decline

    PubMed Central

    Rabin, Laura A.; Chi, Susan Y.; Wang, Cuiling; Fogel, Joshua; Kann, Sarah J.; Aronov, Avner

    2014-01-01

    Despite the relevance of prospective memory to everyday functioning and the ability to live independently, prospective memory tasks are rarely incorporated into clinical evaluations of older adults. We investigated the validity and clinical utility of a recently developed measure, the Royal Prince Alfred Prospective Memory Test (RPA-ProMem), in a demographically diverse, non-demented, community-dwelling sample of 257 older adults (mean age = 80.78 years, 67.7% female) with amnestic mild cognitive impairment (aMCI, n = 18), non-amestic mild cognitive impairment (naMCI, n = 38), subjective cognitive decline (SCD, n = 83) despite intact performance on traditional episodic memory tests, and healthy controls (HC, n = 118). Those with aMCI and naMCI performed significantly worse than controls on the RPA-ProMem and its subtasks (time-based, event-based, short-term, long-term). Also, those with SCD scored significantly lower than controls on long-term, more naturalistic subtasks. Additional results supported the validity and inter-rater reliability of the RPA-ProMem and demonstrated a relation between test scores and informant reports of real-world functioning. The RPA-ProMem may help detect subtle cognitive changes manifested by individuals in the earliest stages of dementia, which may be difficult to capture with traditional episodic memory tests. Also, assessment of prospective memory can help guide the development of cognitive interventions for older adults at risk for dementia. PMID:24875614

  13. Longitudinal Attentional Engagement Rescues Mice from Age-Related Cognitive Declines and Cognitive Inflexibility

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

    2011-01-01

    Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm…

  14. Effects of a computer-based cognitive exercise program on age-related cognitive decline.

    PubMed

    Bozoki, Andrea; Radovanovic, Mirjana; Winn, Brian; Heeter, Carrie; Anthony, James C

    2013-01-01

    We developed a 'senior friendly' suite of online 'games for learning' with interactive calibration for increasing difficulty, and evaluated the feasibility of a randomized clinical trial to test the hypothesis that seniors aged 60-80 can improve key aspects of cognitive ability with the aid of such games. Sixty community-dwelling senior volunteers were randomized to either an online game suite designed to train multiple cognitive abilities, or to a control arm with online activities that simulated the look and feel of the games but with low level interactivity and no calibration of difficulty. Study assessment included measures of recruitment, retention and play-time. Cognitive change was measured with a computerized assessment battery administered just before and within two weeks after completion of the six-week intervention. Impediments to feasibility included: limited access to in-home high-speed internet, large variations in the amount of time devoted to game play, and a reluctance to pursue more challenging levels. Overall analysis was negative for assessed performance (transference effects) even though subjects improved on the games themselves. Post hoc analyses suggest that some types of games may have more value than others, but these effects would need to be replicated in a study designed for that purpose. We conclude that a six-week, moderate-intensity computer game-based cognitive intervention can be implemented with high-functioning seniors, but the effect size is relatively small. Our findings are consistent with Owen et al. (2010), but there are open questions about whether more structured, longer duration or more intensive 'games for learning' interventions might yield more substantial cognitive improvement in seniors.

  15. Towards an index of cognitive efficacy EEG-based estimation of cognitive load among individuals experiencing cancer-related cognitive decline.

    PubMed

    Mathan, Santosh; Smart, Andrew; Ververs, Trish; Feuerstein, Michael

    2010-01-01

    This paper describes an effort to estimate variations in cognitive effort among cancer survivors experiencing treatment related cognitive decline. EEG-based cognitive state sensing algorithms were validated in the context of an experiment with 5 brain cancer and 5 breast cancer survivors. Workload was manipulated by varying text complexity and time pressure. Analysis indicates that EEG-based cognitive state sensing algorithms were able to distinguish between high and low cognitive workload with an average classification accuracy of 0.84. Results suggest that 5 to 10 channels of EEG can provide enough information to achieve classification accuracies exceeding 0.80. The highest density of informative sites were over the left temporal and mid to inferior frontal regions in the left hemisphere - regions that play a major role in language.

  16. Cognitive decline in short and long sleepers: A prospective population-based study (NEDICES)

    PubMed Central

    Benito-León, Julián; Louis, Elan D.; Bermejo-Pareja, Félix

    2013-01-01

    Background It is not clear whether cognitive decline progresses more quickly in long sleepers than in short sleepers or than in participants with usual sleep duration. We assessed cognitive decline as a function of self-reported sleep duration in a prospective population-based cohort (NEDICES). Methods Participants were evaluated at baseline and 3 years later. Baseline demographic variables were recorded and participants indicated their daily sleep usual duration as the sum of nighttime sleep and daytime napping. The average daily total usual sleep duration was grouped into three categories: ≤5 hours (short sleepers), 6 to 8 hours (reference category), and ≥9 hours (long sleepers). At baseline and at follow-up, a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered. Results The final sample, 2,715 participants (72.9±6.1 years), comprised 298 (11%) short sleepers, 1,086 (40%) long sleepers, and 1,331 (49%) in the reference group (6 to 8 hours). During the three year follow-up period, the 37-MMSE declined by 0.5±4.0 points in short sleepers, 0.6±4.3 points in long sleepers, and 0.2±3.8 points in the reference group (p=0.08). The difference between short sleepers and the reference group was not significant (p=0.142); however, the difference between long sleepers and the reference group was significant (p=0.040). In analyses adjusted for baseline age and other potential confounders, this difference remained robust. Conclusions In this study, cognitive test scores among long sleepers declined more rapidly than observed in a reference group. Additional studies are needed to confirm these results. PMID:24094933

  17. Ipsilateral foetal-type posterior cerebral artery is associated with cognitive decline after carotid revascularisation

    PubMed Central

    2014-01-01

    Background Stenosis of the internal carotid artery has been associated with cognitive impairment and decline. However, studies testing the effect of carotid revascularisation on cognition have had conflicting results. This may in part be explained by variation in the flow territory of the carotid artery. In 12 to 36% of the patients, the posterior cerebral artery is mainly or exclusively supplied by the internal carotid artery via a foetal-type posterior cerebral artery. In these patients, ipsilateral carotid artery stenosis is likely to result in a larger area with hypoperfusion than in case of a normal posterior cerebral artery. Patients with a foetal-type posterior cerebral artery could therefore benefit more from revascularisation. We compared the effects of carotid revascularisation on cognition between patients with a foetal-type and those with a normal posterior cerebral artery. Methods Patients with symptomatic internal carotid artery stenosis ≥ 50%, enrolled in the International Carotid Stenting Study (ICSS) at a single centre, underwent detailed neuropsychological examinations before and 6 months after revascularisation. Cognitive test results were standardized into z-scores, from which a cognitive sumscore was calculated. The primary outcome was the change in cognitive sumscore between baseline and follow-up. Changes in cognitive sumscore were compared between patients with an ipsilateral foetal-type and those with a normal posterior cerebral artery, as assessed with CT or MR angiography. Results Of 145 patients enrolled in ICSS at the centre during the study period, 98 had both angiography at baseline and neuropsychological examination at baseline and at 6-months follow-up. The cognitive sum score decreased by 0.28 (95% confidence interval, 0.10 to 0.45) in 13 patients with an ipsilateral foetal-type posterior cerebral artery and by 0.07 (95% CI, 0.002 to 0.15) in 85 patients with a normal posterior cerebral artery (mean difference, -0.20; 95% CI

  18. A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline

    PubMed Central

    Zitzelberger, T.; Oken, B.S.; Howieson, D.; Kaye, J.

    2009-01-01

    Objective To assess the feasibility, safety, and efficacy of Ginkgo biloba extract (GBE) on delaying the progression to cognitive impairment in normal elderly aged 85 and older. Methods Randomized, placebo-controlled, double-blind, 42-month pilot study with 118 cognitively intact subjects randomized to standardized GBE or placebo. Kaplan-Meier estimation, Cox proportional hazard, and random-effects models were used to compare the risk of progression from Clinical Dementia Rating (CDR) = 0 to CDR = 0.5 and decline in episodic memory function between GBE and placebo groups. Results In the intention-to-treat analysis, there was no reduced risk of progression to CDR = 0.5 (log-rank test, p = 0.06) among the GBE group. There was no less of a decline in memory function among the GBE group (p = 0.05). In the secondary analysis, where we controlled the medication adherence level, the GBE group had a lower risk of progression from CDR = 0 to CDR = 0.5 (HR = 0.33, p = 0.02), and a smaller decline in memory scores (p = 0.04). There were more ischemic strokes and TIAs in the GBE group (p = 0.01). Conclusions In unadjusted analyses, Ginkgo biloba extract (GBE) neither altered the risk of progression from normal to Clinical Dementia Rating (CDR) = 0.5, nor protected against a decline in memory function. Secondary analysis taking into account medication adherence showed a protective effect of GBE on the progression to CDR = 0.5 and memory decline. Results of larger prevention trials taking into account medication adherence may clarify the effectiveness of GBE. More stroke and TIA cases observed among the GBE group requires further study to confirm. PMID:18305231

  19. Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition

    PubMed Central

    Meyers, Emily A.; Gobeske, Kevin T.; Bond, Allison M.; Jarrett, Jennifer C.; Peng, Chian-Yu; Kessler, John A.

    2015-01-01

    Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. PMID:26827654

  20. Comparison of semantic and episodic memory BOLD fMRI activation in predicting cognitive decline in older adults

    PubMed Central

    Hantke, Nathan; Nielson, Kristy A.; Woodard, John L.; Guidotti Breting, Leslie M.; Butts, Alissa; Seidenberg, Michael; Smith, J. Carson; Durgerian, Sally; Lancaster, Melissa; Matthews, Monica; Sugarman, Michael A.; Rao, Stephen M.

    2013-01-01

    Previous studies suggest that task-activated fMRI can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively “Stable” or “Declining” based on ≥1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with APOE ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R2 = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R2 = .285; C index = .787), whereas the addition of EM did not (R2 = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer’s disease. PMID:23199565

  1. Macronutrients, aluminium from drinking water and foods, and other metals in cognitive decline and dementia.

    PubMed

    Solfrizzi, Vincenzo; Colacicco, Anna Maria; D'Introno, Alessia; Capurso, Cristiano; Parigi, Angelo Del; Capurso, Sabrina A; Torres, Francesco; Capurso, Antonio; Panza, Francesco

    2006-11-01

    A possible role of the macronutrients and the basic elements of carbohydrates (glucose administration or depletion), proteins (amino acids such as tryptophan and tyrosine), and fat (unsaturated fatty acids) was recently proposed for age-related changes of cognitive function, and the cognitive decline of degenerative (AD) or vascular origin. The availability and utilization of glucose has been implicated in cognitive function not only as a result of nutritional and systemic metabolic conditions, but also, although speculatively, as a crucial phase of the mechanism of action of molecules used as cognitive-enhancers. Furthermore, many lines of evidence have focused on the importance of oxidative stress mechanisms and free radical damage in AD pathogenesis. In addition, epidemiological studies have recently reported an association between alcohol and the incidence of AD and predementia syndromes. Foods with large amounts of aluminium-containing additives or aluminium from drinking water may affect the risk of developing AD, aluminium more likely acting as a cofactor somewhere in the cascade of events leading to the demented brain. A role for other metals in dementia have been speculated, given the encouraging results reported from studies on peripheral zinc concentrations, zinc supplementation, serum copper, either bound with ceruloplasmin or not, and iron metabolism in AD. Nonetheless, more data are needed to support a possible role of these metals in dementing diseases. Healthy diets, antioxidant supplements, and the prevention of nutritional deficiencies or exposure to foods and water with high content of metals could be considered the first line of defence against the development and progression of cognitive decline.

  2. Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease.

    PubMed

    Carrasquillo, Minerva M; Crook, Julia E; Pedraza, Otto; Thomas, Colleen S; Pankratz, V Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G; Ma, Li; Bisceglio, Gina D; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Machulda, Mary M; Graff-Radford, Neill R; Petersen, Ronald C; Younkin, Steven G; Ertekin-Taner, Nilüfer

    2015-01-01

    We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease.

  3. Relation between acute and long-term cognitive decline after surgery: Influence of metabolic syndrome☆

    PubMed Central

    Gambús, P.L; Trocóniz, I.F.; Feng, X.; Gimenez-Milá, M.; Mellado, R.; Degos, V.; Vacas, S.; Maze, M.

    2015-01-01

    Introduction The relationship between persistent postoperative cognitive decline and the more common acute variety remains unknown; using data acquired in preclinical studies of postoperative cognitive decline we attempted to characterize this relationship. Methods Low capacity runner (LCR) rats, which have all the features of the metabolic syndrome, were compared postoperatively with high capacity runner (HCR) rats for memory, assessed by trace fear conditioning (TFC) on the 7th postoperative day, and learning and memory (probe trial [PT]) assessed by the Morris water-maze (MWM) at three months postoperatively. Rate of learning (AL) data from the MWM test, were estimated by non-linear mixed effects modeling. The individual rat's TFC result at postoperative day (POD) 7 was correlated with its AL and PT from the MWM data sets at postoperative day POD 90. Results A single exponential decay model best described AL in the MWM with LCR and surgery (LCR–SURG) being the only significant covariates; first order AL rate constant was 0.07 s−1 in LCR–SURG and 0.16 s−1 in the remaining groups (p<0.05). TFC was significantly correlated with both AL (R = 0.74; p < 0.0001) and PT (R = 0.49; p < 0.01). Conclusion Severity of memory decline at 1 week after surgery presaged long-lasting deteriorations in learning and memory. PMID:26164200

  4. Does a physically active lifestyle attenuate decline in all cognitive functions in old age?

    PubMed

    Ballesteros, Soledad; Mayas, Julia; Reales, Jose Manuel

    2013-07-01

    In this study, the performance of a group of 20 physically active older adults was compared with that of a group of 20 sedentary healthy older adults while performing a series of cognitive tasks. These tasks were designed to assess processes that deteriorate most with age, namely executive control (assessed with the Wisconsin Card Sorting Task) and processing speed (simple and choice reaction time tasks). A repetition priming task that does not decline with age, involving attended and unattended picture outlines at encoding, was also included as a control task. The results show that a physically active lifestyle has a positive influence on executive control, processing speed, and controlled processing. As expected, a physically active lifestyle did not enhance repetition priming for attended stimuli, nor did it produce priming for unattended stimuli at encoding. Both groups exhibited robust priming for attended stimuli and no priming for unattended ones. Executive control functions are of vital importance for independent living in old age. These results have practical implications for enhancing the cognitive processes that decline most in old age. Promoting a physically active lifestyle throughout adulthood could significantly reduce the decline of effortful executive control functions in old age.

  5. Computerized assessment of communication for cognitive stimulation for people with cognitive decline using spectral-distortion measures and phylogenetic inference.

    PubMed

    Pham, Tuan D; Oyama-Higa, Mayumi; Truong, Cong-Thang; Okamoto, Kazushi; Futaba, Terufumi; Kanemoto, Shigeru; Sugiyama, Masahide; Lampe, Lisa

    2015-01-01

    Therapeutic communication and interpersonal relationships in care homes can help people to improve their mental wellbeing. Assessment of the efficacy of these dynamic and complex processes are necessary for psychosocial planning and management. This paper presents a pilot application of photoplethysmography in synchronized physiological measurements of communications between the care-giver and people with dementia. Signal-based evaluations of the therapy can be carried out using the measures of spectral distortion and the inference of phylogenetic trees. The proposed computational models can be of assistance and cost-effectiveness in caring for and monitoring people with cognitive decline.

  6. Moving Forward: Age Effects on the Cerebellum Underlie Cognitive and Motor Declines

    PubMed Central

    Bernard, Jessica A.; Seidler, Rachael D.

    2014-01-01

    Though the cortical contributions to age-related declines in motor and cognitive performance are well-known, the potential contributions of the cerebellum are less clear. The diverse functions of the cerebellum make it an important structure to investigate in aging. Here, we review the extant literature on this topic. To date, there is evidence to indicate that there are morphological age differences in the cerebellum that are linked to motor and cognitive behavior. Cerebellar morphology is often as good as -- or even better -- at predicting performance than the prefrontal cortex. We also touch on the few studies using functional neuroimaging and connectivity analyses that further implicate the cerebellum in age-related performance declines. Importantly, we provide a conceptual framework for the cerebellum influencing age differences in performance, centered on the notion of degraded internal models. The evidence indicating that cerebellar age differences associate with performance highlights the need for additional work in this domain to further elucidate the role of the cerebellum in age differences in movement control and cognitive function. PMID:24594194

  7. Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

    PubMed Central

    Lipnicki, Darren M.; Crawford, John D.; Thalamuthu, Anbupalam; Castro-Costa, Erico; Stephan, Blossom C. M.; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C. W.; Fung, Ada W. T.; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S.

    2017-01-01

    Background The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0

  8. Functional magnetic resonance imaging in aging and dementia: detection of age-related cognitive changes and prediction of cognitive decline.

    PubMed

    Woodard, John L; Sugarman, Michael A

    2012-01-01

    Functional magnetic resonance imaging (fMRI) allows for dynamic observation of the neural substrates of cognitive processing, which makes it a valuable tool for studying brain changes that may occur with both normal and pathological aging. fMRI studies have revealed that older adults frequently exhibit a greater magnitude and extent activation of the blood-oxygen-level-dependent signal compared to younger adults. This additional activation may reflect compensatory recruitment associated with functional and structural deterioration of neural resources. Increased activation has also been associated with several risk factors for Alzheimer's disease (AD), including the apolipoprotein ε4 allele. Longitudinal studies have also demonstrated that fMRI may have predictive utility in determining which individuals are at the greatest risk of developing cognitive decline. This chapter will review the results of a number of task-activated fMRI studies of older adults, focusing on both healthy aging and neuropathology associated with AD. We also discuss models that account for cognitive aging processes, including the hemispheric asymmetry reduction in older adults (HAROLD) and scaffolding theory of aging and cognition (STAC) models. Finally, we discuss methodological issues commonly associated with fMRI research in older adults.

  9. Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a study of 20 years of cognitive decline.

    PubMed

    Amieva, Hélène; Mokri, Hind; Le Goff, Mélanie; Meillon, Céline; Jacqmin-Gadda, Hélène; Foubert-Samier, Alexandra; Orgogozo, Jean-Marc; Stern, Yaakov; Dartigues, Jean-François

    2014-04-01

    A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimer's dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimer's disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimer's dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up. The sample comprises 442 participants with incident Alzheimer's disease (27.2% were male)--171 with low education (mean age=86.2 years; standard deviation=5.3 years) and 271 with higher education (mean age=86.5; standard deviation=5.4)--and 442 control subjects matched according to age, sex and education. At each visit and up to the 20-year follow-up visit, several cognitive and clinical measures were collected and incident cases of Alzheimer's disease clinically diagnosed. The evolution of clinical measures in pre-demented subjects and matched controls was analysed with a semi-parametric extension of the mixed effects linear model. The results show that the first signs of cognitive decline occurred 15 to 16 years before achieving dementia threshold in higher-educated subjects whereas signs occurred at 7 years before dementia in low-educated subjects. There seemed to be two successive periods of decline in higher-educated subjects. Decline started ∼15 to 16 years before dementia with subtle impairment restricted to some cognitive tests and with no impact during the first 7 to 8 years on global cognition, cognitive complaints, or activities of daily living scales. Then, ∼7 years before dementia, global cognitive abilities begin to deteriorate, along with difficulties dealing with complex activities of daily living, the increase in self-perceived difficulties and depressive symptoms. By contrast, lower-educated subjects presented a single period of decline lasting ∼7 years, characterized by

  10. Autoimmune encephalitis: A potentially reversible cause of status epilepticus, epilepsy, and cognitive decline

    PubMed Central

    Pandit, Awadh Kishor; Ihtisham, Kavish; Garg, Ajay; Gulati, Sheffali; Padma, Madakasira Vasantha; Tripathi, Manjari

    2013-01-01

    Objectives: To review clinical characteristics and response to immunomodulation therapy in autoimmune encephalitis presenting with status epilepticus (SE), epilepsy, and cognitive decline. Design: Observational, prospective case series. Setting: All India Institute of Medical Sciences, New Delhi, India. Materials and Methods: Prospective analysis of 15 patients, who presented with SE, epilepsy, cognitive decline, and other neurological symptoms with positive autoantibodies. Demographic and clinical characteristics were recorded. Brain magnetic resonance imaging (MRI), cerebrospinal-fluid analysis (CSF), and tumor screening were done periodically. Treatment received and responses (categorized as per patients and treating doctor's information) were noted. Results: There were 15 (males = 10) patients of autoimmune encephalitis. The mean age of presentation was 24 years (range: 2-64 years). The most common onset was subacute (64%) and four (29%) patients presented as SE. Predominant clinical presentations were seizures (100%) almost of every semiology. CSF was done in 10 patients; it was normal in 60%. Brain MRI was done in all patients, in six (40%) it was normal, six (40%) showed T2W and FLAIR hyperintensities in bilateral limbic areas. Antibodies found were the N-methyl-D-aspartate receptor antibody in seven (50%), voltage-gated potassium channel antibody in five (36%), two of antiglutamic acid decarboxylase, and one patient with double stranded DNA (dsDNA) antibodies. None showed evidence of malignancy. Patients received immunotherapy, either steroids, intravenous immunoglobulin, or both. Follow-up showed significant improvement in majority of cases, neither further seizures nor relapse in nine (67%) cases. One death occurred, due to delayed presentation. Conclusions: Uncommon but potentially reversible causes of SE, epilepsy, and cognitive decline may be immune-related and high index of suspicion will prevent missing the diagnosis. PMID:24339583

  11. The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study.

    PubMed

    Kent, Shia T; Kabagambe, Edmond K; Wadley, Virginia G; Howard, Virginia J; Crosson, William L; Al-Hamdan, Mohammad Z; Judd, Suzanne E; Peace, Fredrick; McClure, Leslie A

    2014-04-01

    Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.

  12. Cognitive decline impairs financial and health literacy among community-based older persons without dementia.

    PubMed

    Boyle, Patricia A; Yu, Lei; Wilson, Robert S; Segawa, Eisuke; Buchman, Aron S; Bennett, David A

    2013-09-01

    Literacy is an important determinant of health and well-being across the life span but is critical in aging, when many influential health and financial decisions are made. Prior studies suggest that older persons exhibit lower literacy than younger persons, particularly in the domains of financial and health literacy, but the reasons why remain unknown. The objectives of this study were to: (a) examine pathways linking diverse resources (i.e., education, word knowledge, cognitive function, and decision making style) to health and financial literacy among older persons and determine the extent to which the relation of age with literacy represents a direct effect versus an indirect effect due to decrements in specific cognitive functions (i.e., executive functions and episodic memory); and (b) test the hypothesis that declines in executive function and episodic memory are associated with lower literacy among older persons without dementia. Six-hundred and forty-five community-based older persons without dementia underwent detailed assessments of diverse resources, including education, word knowledge, cognitive function (i.e., executive function, episodic memory) and decision making style (i.e., risk aversion), and completed a measure of literacy that included items similar to those used in the Health and Retirement Study, such as numeracy, financial concepts such as compound inflation and knowledge of stocks and bonds, and important health concepts such as understanding of drug risk and Medicare Part D. Path analysis revealed a strong effect of age on literacy, with about half of the effect of age on literacy due to decrements in executive functions and episodic memory. In addition, executive function had an indirect effect on literacy via decision making style (i.e., risk aversion), and education and word knowledge had independent effects on literacy. Finally, among (n = 447) persons with repeated cognitive assessments available for up to 14 years, regression

  13. Exploring Experiences and Perceptions of Aging and Cognitive Decline Across Diverse Racial and Ethnic Groups

    PubMed Central

    Schuh, Holly; Sherzai, Dean; Belliard, Juan Carlos; Montgomery, Susanne B.

    2015-01-01

    Objective: To explore how older adults from three prominent ethnoracial groups experience cognitive decline and aging. Method: Semistructured key informant interviews (KIIs) and focus groups (FGs) were conducted with caregivers, experts, and older adults. Results: (N = 75). Fifteen KIIs regarding cognitive aging issues were conducted among health care professionals and community-based agencies serving older adults. Eight FGs included family caregivers and physicians, and six FGs with Latino, African American, and White older adult community members. Major themes included (a) personal expectations about aging, (b) societal value of older adults, (c) model of care preferred, and (d) community concerns. An overarching theme was a sense of loss associated with aging; however, how this loss was experienced and dealt with varied. Discussion: Distinct patterns of concerns and views are important to understand for the development of programs aimed at meeting the needs of diverse older adult community members to improve health outcomes. PMID:26925436

  14. Network functional connectivity and whole-brain functional connectomics to investigate cognitive decline in neurodegenerative conditions.

    PubMed

    Dipasquale, O; Cercignani, Mara

    Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain's intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC. In this paper we provide an overview of these two techniques and some examples of their clinical applications in the most common neurodegenerative disorders associated with cognitive decline, including mild cognitive impairment, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies and behavioral variant frontotemporal dementia.

  15. Network functional connectivity and whole-brain functional connectomics to investigate cognitive decline in neurodegenerative conditions

    PubMed Central

    Dipasquale, Ottavia; Cercignani, Mara

    2016-01-01

    Summary Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain’s intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC. In this paper we provide an overview of these two techniques and some examples of their clinical applications in the most common neurodegenerative disorders associated with cognitive decline, including mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, dementia with Lewy Bodies and behavioral variant frontotemporal dementia. PMID:28072380

  16. Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

    PubMed Central

    Febo, Marcelo; Foster, Thomas C.

    2016-01-01

    Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline. PMID:27468264

  17. Neurogenesis in a rat model of age-related cognitive decline.

    PubMed

    Bizon, J L; Lee, H J; Gallagher, M

    2004-08-01

    Age-related decrements in hippocampal neurogenesis have been suggested as a basis for learning impairment during aging. In the current study, a rodent model of age-related cognitive decline was used to evaluate neurogenesis in relation to hippocampal function. New hippocampal cell survival was assessed approximately 1 month after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Correlational analyses between individual measures of BrdU-positive cells and performance on the Morris water maze task provided no indication that this measure of neurogenesis was more preserved in aged rats with intact cognitive abilities. On the contrary, among aged rats, higher numbers of BrdU-positive cells in the granule cell layer were associated with a greater degree of impairment on the learning task. Double-labelling studies confirmed that the majority of the BrdU+ cells were of the neuronal phenotype; the proportion of differentiated neurons was not different across a broad range of cognitive abilities. These data demonstrate that aged rats that maintain cognitive function do so despite pronounced reductions in hippocampal neurogenesis. In addition, these findings suggest the interesting possibility that impaired hippocampal function is associated with greater survival of newly generated hippocampal neurons at advanced ages.

  18. Increased non-protein bound iron in Down syndrome: contribution to lipid peroxidation and cognitive decline.

    PubMed

    Manna, Caterina; Officioso, Arbace; Trojsi, Francesca; Tedeschi, Gioacchino; Leoncini, Silvia; Signorini, Cinzia; Ciccoli, Lucia; De Felice, Claudio

    2016-12-01

    Down syndrome (DS, trisomy 21) is the leading cause of chromosomal-related intellectual disability. At an early age, adults with DS develop with the neuropathological hallmarks of Alzheimer's disease, associated with a chronic oxidative stress. To investigate if non-protein bound iron (NPBI) can contribute to building up a pro-oxidative microenvironment, we evaluated NPBI in both plasma and erythrocytes from DS and age-matched controls, together with in vivo markers of lipid peroxidation (F2-isoprostanes, F2-dihomo-isoprostanes, F4-neuroprostanes) and in vitro reactive oxygen species (ROS) formation in erythrocytes. The serum iron panel and uric acid were also measured. Second, we explored possible correlation between NPBI, lipid peroxidation and cognitive performance. Here, we report NPBI increase in DS, which correlates with increased serum ferritin and uric acid. High levels of lipid peroxidation markers and intraerythrocyte ROS formations were also reported. Furthermore, the scores of Raven's Colored Progressive Matrices (RCPM) test, performed as a measure of current cognitive function, are inversely related to NPBI, serum uric acid, and ferritin. Likewise, ROS production, F2-isoprostanes, and F4-neuroprostanes were also inversely related to cognitive performance, whereas serum transferrin positively correlated to RCPM scores. Our data reveal that increased availability of free redox-active iron, associated with enhanced lipid peroxidation, may be involved in neurodegeneration and cognitive decline in DS. In this respect, we propose chelation therapy as a potential preventive/therapeutic tool in DS.

  19. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients.

    PubMed

    Damjanovic, Amanda K; Yang, Yinhua; Glaser, Ronald; Kiecolt-Glaser, Janice K; Nguyen, Huy; Laskowski, Bryon; Zou, Yixiao; Beversdorf, David Q; Weng, Nan-ping

    2007-09-15

    Caregivers of Alzheimer's disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-alpha and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.

  20. Ageing and apoE change DHA homeostasis: relevance to age-related cognitive decline.

    PubMed

    Hennebelle, Marie; Plourde, Mélanie; Chouinard-Watkins, Raphaël; Castellano, Christian-Alexandre; Barberger-Gateau, Pascale; Cunnane, Stephen C

    2014-02-01

    Epidemiological studies fairly convincingly suggest that higher intakes of fatty fish and n-3 fatty acids are associated with reduced risk of Alzheimer's disease (AD). DHA in plasma is normally positively associated with DHA intake. However, despite being associated with lower fish and DHA intake, unexpectedly, plasma (or brain) DHA is frequently not lower in AD. This review will highlight some metabolic and physiological factors such as ageing and apoE polymorphism that influence DHA homeostasis. Compared with young adults, blood DHA is often slightly but significantly higher in older adults without any age-related cognitive decline. Higher plasma DHA in older adults could be a sign that their fish or DHA intake is higher. However, our supplementation and carbon-13 tracer studies also show that DHA metabolism, e.g. transit through the plasma, apparent retroconversion and β-oxidation, is altered in healthy older compared with healthy young adults. ApoE4 increases the risk of AD, possibly in part because it too changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may tend to obscure the relationship between DHA intake and plasma DHA which, in turn, may contribute to making older adults more susceptible to cognitive decline despite older adults having similar or sometimes higher plasma DHA than in younger adults. In conclusion, recent development of new tools such as isotopically labelled DHA to study DHA metabolism in human subjects highlights some promising avenues to evaluate how and why DHA metabolism changes during ageing and AD.

  1. Protective effect of betulin on cognitive decline in streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Ma, Chunhua; Long, Hongyan

    2016-12-01

    Betulin is extracted from birch tree bark and exerts diverse pharmacological activities. The present study was designed to investigate the protective effect of betulin (BE) on cognitive decline in streptozotocin (STZ)-induced diabetic rats. The diabetic model was built by streptozotocin (STZ) (30mg/kg, ip). After 4 weeks, the diabetic rats were treated with vehicle or BE (20mg/kg, 40mg/kg) for 4 weeks. The oral glucose tolerance (OGTT) and serum insulin were detected. Three days later, Morris water maze (MWM) test was used to evaluate memory function. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in hippocampus were examined. Inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in serum and hippocampus were measured. The protein expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NF-κB pathways-related molecules in hippocampus were examined. As a results, BE could improve glucose intolerance and modify basal learning performance. Treatment with BE significantly restored SOD activity and decreased MDA content in hippocampus. BE also markedly reduced the contents of inflammatory cytokines in serum and hippocampus. Furthermore, administration of BE effectively upregulated the expressions of Nrf2, HO-1 and blocked the phosphorylations of IκB, NF-κB. In summary, BE might exhibit protective effect on cognitive decline in STZ-induced diabetic rats through HO-1/Nrf-2/NF-κB pathway.

  2. Decline in the negative association between low birth weight and cognitive ability

    PubMed Central

    Özcan, Berkay; Myrskylä, Mikko

    2017-01-01

    Low birth weight predicts compromised cognitive ability. We used data from the 1958 National Child Development Study (NCDS), the 1970 British Cohort Study (BCS), and the 2000–2002 Millennium Cohort Study (MCS) to analyze how this association has changed over time. Birth weight was divided into two categories, <2,500 g (low) and 2,500–4,500 g (normal) and verbal cognitive ability was measured at the age of 10 or 11 y. A range of maternal and family characteristics collected at or soon after the time of birth were considered. Linear regression was used to analyze the association between birth weight and cognitive ability in a baseline model and in a model that adjusted for family characteristics. The standardized difference (SD) in cognitive scores between low-birth-weight and normal-birth-weight children was large in the NCDS [−0.37 SD, 95% confidence interval (CI): −0.46, −0.27] and in the BCS (−0.34, 95% CI: −0.43, −0.25) cohorts, and it was more than halved for children born in the MCS cohort (−0.14, 95% CI: −0.22, −0.06). The adjustment for family characteristics did not explain the cross-cohort differences. The results show that the association between low birth weight and decreased cognitive ability has declined between the 1950s and 1970s birth cohorts and the 2000--2002 birth cohort, despite a higher proportion of the low-birth-weight babies having a very low birth weight (<1,500 g) in the more recent birth cohort. Advancements in obstetric and neonatal care may have attenuated the negative consequences associated with being born small. PMID:27994141

  3. Cerebrospinal Fluid α-Synuclein Predicts Cognitive Decline in Parkinson Disease Progression in the DATATOP Cohort

    PubMed Central

    Stewart, Tessandra; Liu, Changqin; Ginghina, Carmen; Cain, Kevin C.; Auinger, Peggy; Cholerton, Brenna; Shi, Min; Zhang, Jing

    2015-01-01

    Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of −0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, −0.12 (P = 0.037); delayed recall, −0.05 (P = 0.002); New Dot Test, −0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation. PMID:24625392

  4. Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers

    PubMed Central

    Ulvestad, B; Bakke, B; Eduard, W; Kongerud, J; Lund, M

    2001-01-01

    most important risk factor for respiratory symptoms. The finding of accelerated decline in lung function in tunnel workers suggests that better control of exposures is needed.


Keywords: heavy construction; respirable dust; lung function PMID:11555688

  5. Effects of education and race on cognitive decline: An integrative study of generalizability versus study-specific results.

    PubMed

    Gross, Alden L; Mungas, Dan M; Crane, Paul K; Gibbons, Laura E; MacKay-Brandt, Anna; Manly, Jennifer J; Mukherjee, Shubhabrata; Romero, Heather; Sachs, Bonnie; Thomas, Michael; Potter, Guy G; Jones, Richard N

    2015-12-01

    The objective of the study was to examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. We compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: (a) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N = 4,115), (b) Spanish and English Neuropsychological Assessment Scales (N = 525), (c) Duke Memory, Health, and Aging study (N = 578), and (d) Neurocognitive Outcomes of Depression in the Elderly (N = 585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. The results found that for baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. In this diverse set of datasets, non-Hispanic Whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed.

  6. Ventral striatal volume is associated with cognitive decline in older people: a population based MR-study.

    PubMed

    de Jong, L W; Wang, Y; White, L R; Yu, B; van Buchem, M A; Launer, L J

    2012-02-01

    Striatal degeneration may contribute to cognitive impairment in older people. Here, we examine the relation of degeneration of the striatum and substructures to cognitive decline and dementia in subjects with a wide range of cognitive function. Data are from the prospective community-based Honolulu Asia Aging Study of Japanese American men born 1900-1919. Brain magnetic resonance imaging (MRI) (1.5 T) was acquired on a stratified subsample (n = 477) that included four groups defined by cognitive status relative to the scan date: subjects without dementia (n = 347), subjects identified as demented 2-3 years before brain scanning (n = 30), at the time of scanning (n = 58), and 3-5 years after scanning (n = 42). Volumes of the striatum, including the accumbens, putamen, and caudate nucleus were automatically estimated from T1 MR images. Global cognitive function was measured with the cognitive ability screening instrument (CASI), at four examinations spanning an 8-year interval. Trajectories of cognitive decline were estimated for each quartile of striatal volume using mixed models, controlling for demographic variables, measures of cerebro-vascular damage, global brain atrophy, and hippocampal volume. Diagnosis of dementia before, during, and after brain scanning was associated with smaller volumes of n. accumbens and putamen, but not with caudate nucleus volume. Subjects in the lowest quartile of n. accumbens volume, both in the total sample and in the subjects not diagnosed with dementia during the study, had a significantly (p < 0.0001) steeper decline in cognitive performance compared with those in the highest quartile. In conclusion, volumes of the n. accumbens and putamen are closely associated with the occurrence of dementia and n. accumbens volume predicts cognitive decline in older people. These associations were found independent of the magnitude of other pivotal markers of cognitive decline, i.e. cerebro-vascular damage and hippocampal volume. The present

  7. Effects of education and race on cognitive decline: An integrative analysis of generalizability versus study-specific results

    PubMed Central

    Gross, Alden L.; Mungas, Dan M.; Crane, Paul K.; Gibbons, Laura E.; MacKay-Brandt, Anna; Manly, Jennifer J.; Mukherjee, Shubhabrata; Romero, Heather; Sachs, Bonnie; Thomas, Michael; Potter, Guy G.; Jones, Richard N.

    2015-01-01

    Objective To examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. Method To compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: 1) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N=4,115), 2) Spanish and English Neuropsychological Assessment Scales (N=525), 3) Duke Memory, Health, and Aging study (N=578), and 4) Neurocognitive Outcomes of Depression in the Elderly (N=585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. Results For baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. Discussion In this diverse set of datasets, non-Hispanic whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed. PMID:26523693

  8. Relative value of diverse brain MRI and blood-based biomarkers for predicting cognitive decline in the elderly

    NASA Astrophysics Data System (ADS)

    Madsen, Sarah K.; Ver Steeg, Greg; Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Nir, Talia M.; Hua, Xue; Gutman, Boris A.; Galstyan, Aram; Thompson, Paul M.

    2016-03-01

    Cognitive decline accompanies many debilitating illnesses, including Alzheimer's disease (AD). In old age, brain tissue loss also occurs along with cognitive decline. Although blood tests are easier to perform than brain MRI, few studies compare brain scans to standard blood tests to see which kinds of information best predict future decline. In 504 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we first used linear regression to assess the relative value of different types of data to predict cognitive decline, including 196 blood panel biomarkers, 249 MRI biomarkers obtained from the FreeSurfer software, demographics, and the AD-risk gene APOE. A subset of MRI biomarkers was the strongest predictor. There was no specific blood marker that increased predictive accuracy on its own, we found that a novel unsupervised learning method, CorEx, captured weak correlations among blood markers, and the resulting clusters offered unique predictive power.

  9. Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome.

    PubMed

    Merke, Deborah P; Giedd, Jay N; Keil, Margaret F; Mehlinger, Sarah L; Wiggs, E A; Holzer, Stuart; Rawson, Erin; Vaituzis, A Catherine; Stratakis, Constantine A; Chrousos, George P

    2005-05-01

    Adults with Cushing syndrome frequently develop brain atrophy, memory impairment, and depression, with partial to complete resolution after cure. The effect of excess glucocorticoid exposure on the brain of children has not been systematically studied. Eleven children (six girls, five boys; ages, 8-16 yr) with endogenous Cushing syndrome seen at the National Institutes of Health Clinical Center from 1999-2000 and 10 healthy age- and sex-matched control subjects were studied. Cognitive and psychological evaluations and magnetic resonance imaging of the brain were done before and 1 yr after cure for patients with Cushing syndrome and once for controls. The estimated duration of Cushing syndrome was 4.4 +/- 1.2 yr. When compared with control subjects, children with Cushing syndrome had significantly smaller cerebral volumes (P < 0.001), larger ventricles (P = 0.02), and smaller amygdala (P = 0.004). At baseline, there were no significant differences in IQ between the two groups, and no psychopathology was identified. Despite reversal of cerebral atrophy 1 yr after surgical cure (total cerebral volume, 947 +/- 94 vs.1050 +/- 74 ml, P < 0.001; ventricular volume, 21.4 +/- 12.5 vs. 14.5 +/- 11.6 ml, P < 0.001), children with Cushing syndrome experienced a significant (P < 0.05) decline in Wechsler IQ scores (Full Scale, 112 +/- 19 vs. 98 +/- 14) and a decline in school performance, without any associated psychopathology. The effect of glucocorticoid excess on the brain of children appears to be different from adults. Despite rapid reversibility of cerebral atrophy, children experience a significant decline in cognitive function 1 yr after correction of hypercortisolism.

  10. Enriched childhood experiences moderate age-related motor and cognitive decline

    PubMed Central

    Metzler, Megan J.; Saucier, Deborah M.; Metz, Gerlinde A.

    2012-01-01

    Aging is associated with deterioration of skilled manual movement. Specifically, aging corresponds with increased reaction time, greater movement duration, segmentation of movement, increased movement variability, and reduced ability to adapt to external forces and inhibit previously learned sequences. Moreover, it is thought that decreased lateralization of neural function in older adults may point to increased neural recruitment as a compensatory response to deterioration of key frontal and intra-hemispheric networks, particularly of callosal structures. However, factors that mediate age-related motor decline are not well understood. Here we show that music training in childhood is associated with reduced age-related decline of bimanual and unimanual motor skills in a MIDI keyboard motor learning task. Compared to older adults without music training, older adults with more than a year of music training demonstrated proficient bimanual and unimanual movement, evidenced by enhanced speed and decreased movement errors. Further, this group demonstrated significantly better implicit learning in the weather prediction task, a non-motor task. The performance of older adults with music training in those tasks was comparable to young adults. Older adults, however, displayed greater verbal ability compared to young adults irrespective of a past history of music training. Our results indicate that music training early in life may reduce age-associated decline of neural motor and cognitive networks. PMID:23423702

  11. Cognitive declines in healthy aging: evidence from multiple aspects of interference resolution.

    PubMed

    Pettigrew, Corinne; Martin, Randi C

    2014-06-01

    The present study tested the hypothesis that older adults show age-related deficits in interference resolution, also referred to as inhibitory control. Although oftentimes considered as a unitary aspect of executive function, various lines of work support the notion that interference resolution may be better understood as multiple constructs, including resistance to proactive interference (PI) and response-distractor inhibition (e.g., Friedman & Miyake, 2004). Using this dichotomy, the present study assessed whether older adults (relative to younger adults) show impaired performance across both, 1, or neither of these interference resolution constructs. To do so, we used multiple tasks to tap each construct and examined age effects at both the single task and latent variable levels. Older adults consistently demonstrated exaggerated interference effects across resistance to PI tasks. Although the results for the response-distractor inhibition tasks were less consistent at the individual task level analyses, age effects were evident on multiple tasks, as well as at the latent variable level. However, results of the latent variable modeling suggested declines in interference resolution are best explained by variance that is common to the 2 interference resolution constructs measured herein. Furthermore, the effect of age on interference resolution was found to be both distinct from declines in working memory, and independent of processing speed. These findings suggest multiple cognitive domains are independently sensitive to age, but that declines in the interference resolution constructs measured herein may originate from a common cause.

  12. White matter degeneration in subjective cognitive decline: a diffusion tensor imaging study

    PubMed Central

    Li, Xuan-yu; Tang, Zhen-chao; Sun, Yu; Tian, Jie; Liu, Zhen-yu; Han, Ying

    2016-01-01

    Subjective cognitive decline (SCD) may be an at-risk stage of Alzheimer's disease (AD) occurring prior to amnestic mild cognitive impairment (aMCI). To examine white matter (WM) defects in SCD, diffusion images from 27 SCD (age=65.3±8.0), 35 aMCI (age=69.2±8.6) and 25 AD patients (age=68.3±9.4) and 37 normal controls (NC) (age=65.1±6.8) were compared using Tract-Based Spatial Statistics (TBSS). WM impairments common to the three patient groups were extracted, and fractional anisotropy (FA) values were averaged in each group. As compared to NC subjects, SCD patients displayed widespread WM alterations represented by decreased FA (p<0.05), increased mean diffusivity (MD; p<0.05), and increased radial diffusivity (RD; p<0.05). In addition, localized WM alterations showed increased axial diffusivity (AxD; p<0.05) similar to what was observed in aMCI and AD patients (p<0.05). In the shared WM impairment tracts, SCD patients had FA values between the NC group and the other two patient groups. In the NC and SCD groups, the AVLT-delayed recall score correlated with higher AxD (r=−0.333, p=0.045), MD (r=−0.351, p=0.03) and RD (r=−0.353, p=0.025). In both the aMCI and AD groups the diffusion parameters were highly correlated with cognitive scores. Our study suggests that SCD patients present with widespread WM changes, which may contribute to the early memory decline they experience. PMID:27384675

  13. Multi-Scale Glycemic Variability: A Link to Gray Matter Atrophy and Cognitive Decline in Type 2 Diabetes

    PubMed Central

    Cui, Xingran; Abduljalil, Amir; Manor, Brad D.; Peng, Chung-Kang; Novak, Vera

    2014-01-01

    Objective Type 2 diabetes mellitus (DM) accelerates brain aging and cognitive decline. Complex interactions between hyperglycemia, glycemic variability and brain aging remain unresolved. This study investigated the relationship between glycemic variability at multiple time scales, brain volumes and cognition in type 2 DM. Research Design and Methods Forty-three older adults with and 26 without type 2 DM completed 72-hour continuous glucose monitoring, cognitive tests and anatomical MRI. We described a new analysis of continuous glucose monitoring, termed Multi-Scale glycemic variability (Multi-Scale GV), to examine glycemic variability at multiple time scales. Specifically, Ensemble Empirical Mode Decomposition was used to identify five unique ultradian glycemic variability cycles (GVC1–5) that modulate serum glucose with periods ranging from 0.5–12 hrs. Results Type 2 DM subjects demonstrated greater variability in GVC3–5 (period 2.0–12 hrs) than controls (P<0.0001), during the day as well as during the night. Multi-Scale GV was related to conventional markers of glycemic variability (e.g. standard deviation and mean glycemic excursions), but demonstrated greater sensitivity and specificity to conventional markers, and was associated with worse long-term glycemic control (e.g. fasting glucose and HbA1c). Across all subjects, those with greater glycemic variability within higher frequency cycles (GVC1–3; 0.5–2.0 hrs) had less gray matter within the limbic system and temporo-parietal lobes (e.g. cingulum, insular, hippocampus), and exhibited worse cognitive performance. Specifically within those with type 2 DM, greater glycemic variability in GVC2–3 was associated with worse learning and memory scores. Greater variability in GVC5 was associated with longer DM duration and more depression. These relationships were independent of HbA1c and hypoglycemic episodes. Conclusions Type 2 DM is associated with dysregulation of glycemic variability over multiple

  14. Lifelong bilingualism contributes to cognitive reserve against white matter integrity declines in aging.

    PubMed

    Gold, Brian T; Johnson, Nathan F; Powell, David K

    2013-11-01

    Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N=20) and monolinguals (N=20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging.

  15. Lifelong Bilingualism Contributes to Cognitive Reserve against White Matter Integrity Declines in Aging

    PubMed Central

    Gold, Brian T.; Johnson, Nathan F.; Powell, David K.

    2013-01-01

    Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N = 20) and monolinguals (N = 20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging. PMID:24103400

  16. Cardiovascular Risk Factors Promote Brain Hypoperfusion Leading to Cognitive Decline and Dementia

    PubMed Central

    de la Torre, Jack C.

    2012-01-01

    Heart disease is the major leading cause of death and disability in the world. Mainly affecting the elderly population, heart disease and its main outcome, cardiovascular disease, have become an important risk factor in the development of cognitive decline and Alzheimer's disease (AD). This paper examines the evidence linking chronic brain hypoperfusion induced by a variety of cardiovascular deficits in the development of cognitive impairment preceding AD. The evidence indicates a strong association between AD and cardiovascular risk factors, including ApoE4, atrial fibrillation, thrombotic events, hypertension, hypotension, heart failure, high serum markers of inflammation, coronary artery disease, low cardiac index, and valvular pathology. In elderly people whose cerebral perfusion is already diminished by their advanced age, additional reduction of cerebral blood flow stemming from abnormalities in the heart-brain vascular loop ostensibly increases the probability of developing AD. Evidence also suggests that a neuronal energy crisis brought on by relentless brain hypoperfusion may be responsible for protein synthesis abnormalities that later result in the classic neurodegenerative lesions involving the formation of amyloid-beta plaques and neurofibrillary tangles. Insight into how cardiovascular risk factors can induce progressive cognitive impairment offers an enhanced understanding of the multifactorial pathophysiology characterizing AD and ways at preventing or managing the cardiovascular precursors of this dementia. PMID:23243502

  17. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline

    PubMed Central

    Schwarz, Flavio; Springer, Stevan A.; Altheide, Tasha K.; Varki, Nissi M.; Gagneux, Pascal; Varki, Ajit

    2016-01-01

    The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer’s dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer’s disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin. PMID:26621708

  18. The Relationship between Cognitive Decline and Psychopathology in Patients with Schizophrenia and Bipolar Disorder

    PubMed Central

    Kim, Moon-Doo; Seo, Hye-Jin; Yun, Hyunju; Jung, Young-Eun; Park, Joon Hyuk; Lee, Chang-In; Moon, Ji Hyun; Hong, Seong-Chul; Yoon, Bo-Hyun; Bahk, Won-Myong

    2015-01-01

    Objective The primary goals of the present study were to assess intellectual function in participants with schizophrenia or bipolar disorder (BD) and to investigate the relationships between cognitive decline and the severity of each type of psychopathology. Methods The present study included 51 patients with schizophrenia and 42 with BD who were recruited from the psychiatry outpatient clinic of Jeju University Hospital between March 2011 and March 2014. The Korean Wechsler Adult Intelligence Scale (K-WAIS) was administered to each of the 93 participants, and they were categorized into two groups based on their current intelligence quotient (IQ) and their estimated premorbid IQ: severely impaired group (SIG) and mildly impaired group (MIG). The Minnesota Multiple Personality Inventory (MMPI) and the Brief Psychiatric Rating Scale (BPRS) were used to assess psychopathology. Results The SIG schizophrenia participants exhibited significantly higher scores on the frequent (F) and schizophrenia (Sc) subscales of the MMPI, but significantly lower scores on the correction (K) and psychopathic deviate (Pd) subscales compared with the MIG schizophrenia participants. Furthermore, the BPRS scores were significantly higher in the SIG schizophrenia participants relative to the MIG schizophrenia participants. The SIG BD participants had significantly higher F, masculinity-femininity (Mf), paranoia (Pa), and Sc but significantly lower Pd scores compared with the MIG BD participants. Conclusion The present findings revealed a significant discrepancy between the estimated premorbid levels of cognitive function and current cognitive function in participants with schizophrenia or BD. Moreover, this discrepancy was correlated with severity of psychopathology in both groups. PMID:25912543

  19. Cohort Differences in Cognitive Aging and Terminal Decline in the Seattle Longitudinal Study

    PubMed Central

    Gerstorf, Denis; Ram, Nilam; Hoppmann, Christiane; Willis, Sherry L.; Schaie, K. Warner

    2011-01-01

    Life span researchers have long been interested in how and why fundamental aspects of human ontogeny differ between cohorts of people who have lived through different historical epochs. When examined at the same age, later born cohorts are often cognitively and physically fitter than earlier born cohorts. Less is known, however, about cohort differences in the rate of cognitive aging and if, at the very end of life, pervasive mortality-related processes overshadow and minimize cohort differences. We used data on 5 primary mental abilities from the Seattle Longitudinal Study (Schaie, 2005) to compare both age-related and mortality-related changes between earlier born cohorts (1886–1913) and later born cohorts (1914–1948). Our models covary for several individual and cohort differences in central indicators of life expectancy, education, health, and gender. Age-related growth models corroborate and extend earlier findings by documenting level differences at age 70 of up to 0.50 SD and less steep rates of cognitive aging on all abilities between 50 and 80 years of age favoring the later born cohort. In contrast, mortality-related models provide limited support for positive cohort differences. The later born cohort showed steeper mortality-related declines. We discuss possible reasons why often reported positive secular trends in age-related processes may not generalize to the vulnerable segment of the population that is close to death and suggest routes for further inquiry. PMID:21517155

  20. Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin.

    PubMed

    Zenaro, Elena; Pietronigro, Enrica; Della Bianca, Vittorina; Piacentino, Gennj; Marongiu, Laura; Budui, Simona; Turano, Ermanna; Rossi, Barbara; Angiari, Stefano; Dusi, Silvia; Montresor, Alessio; Carlucci, Tommaso; Nanì, Sara; Tosadori, Gabriele; Calciano, Lucia; Catalucci, Daniele; Berton, Giorgio; Bonetti, Bruno; Constantin, Gabriela

    2015-08-01

    Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune cells have been shown to contribute to disease pathogenesis. In two transgenic models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated and were present in areas with amyloid-β (Aβ) deposits, where they released neutrophil extracellular traps (NETs) and IL-17. Aβ42 peptide triggered the LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS and intraparenchymal motility. In transgenic Alzheimer's disease models, neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade reduced Alzheimer's disease-like neuropathology and improved memory in mice already showing cognitive dysfunction. Temporary depletion of neutrophils for 1 month at early stages of disease led to sustained improvements in memory. Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from cognitive decline and had reduced gliosis. In humans with Alzheimer's disease, neutrophils adhered to and spread inside brain venules and were present in the parenchyma, along with NETs. Our results demonstrate that neutrophils contribute to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease.

  1. Administration of bovine casein-derived peptide prevents cognitive decline in Alzheimer disease model mice

    PubMed Central

    Tsukuda, Kana; Yamada, Akio; Yamauchi, Koji; Abe, Fumiaki; Iwanami, Jun; Xiao, Jin-Zhong; Horiuchi, Masatsugu

    2017-01-01

    There is a growing interest in identifying natural food ingredients that may serve to prevent dementia such as that due to Alzheimer disease (AD). Peptides derived from food proteins have been demonstrated to have various physiological activities such as a hypotensive action. Recent findings have indicated possible associations of hypertension with AD progression, and suggest that angiotensin converting enzyme (ACE) inhibitors with potential to pass through the blood brain barrier (BBB) may reduce the risk of AD. In this study, we investigated the effect of milk peptide (CH-3) on cognitive function in AD model mice. CH-3 contains a tripeptide (methionine-lysine-proline, MKP) that has been found to have a strong ACE inhibitory effect and the potential to pass through the BBB. Adult male ddY mice were used in this study, and an animal model of AD was induced by intracerebroventricular (ICV) injection of Aβ1–42. CH-3 (250 mg/kg/day) or MKP (0.5 mg/kg/day) was orally administered every day starting 2 days before ICV injection. At 3 weeks after ICV injection, cognitive function was evaluated by the Morris water maze test. Brain samples were obtained after behavioral testing, and expression of inflammatory cytokines and NADPH oxidase subunits was measured by real-time quantitative RT-PCR. ICV injection of Aβ1–42 significantly impaired cognitive function compared with that in PBS-injected mice. Daily administration of CH-3 markedly attenuated this Aβ1-42-induced cognitive decline. Aβ1–42 injection significantly enhanced the expression of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and p22phox in the mouse hippocampus compared with PBS injection, and showed a tendency to increase the expression of monocyte chemoattractant protein-1 (MCP-1), p47phox and gp91phox, whereas CH-3 treatment markedly reduced Aβ1-42-induced TNF-α, MCP-1, iNOS, p47phox and gp91phox expression. Finally, administration of MKP also attenuated Aβ1-42-induced

  2. Non-Pharmacologic Interventions for Older Adults with Subjective Cognitive Decline: Systematic Review, Meta-Analysis, and Preliminary Recommendations.

    PubMed

    Smart, Colette M; Karr, Justin E; Areshenkoff, Corson N; Rabin, Laura A; Hudon, Carol; Gates, Nicola; Ali, Jordan I; Arenaza-Urquijo, Eider M; Buckley, Rachel F; Chetelat, Gael; Hampel, Harald; Jessen, Frank; Marchant, Natalie L; Sikkes, Sietske A M; Tales, Andrea; van der Flier, Wiesje M; Wesselman, Linda

    2017-03-07

    In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

  3. Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

    PubMed

    Santiago, Jose A; Potashkin, Judith A

    2015-01-01

    Early diagnosis of Parkinson's disease (PD) continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two independent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA biomarkers in blood samples from 99 untreated PD patients and 101 HC nested in the cross-sectional Parkinson's Progression Markers Initiative by quantitative real-time PCR. One biomarker out of ten, COPZ1 trended toward significance (nominal p = 0.009) when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs correlated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA) score. Levels of EFTUD2 and PTBP1 were significantly higher in cognitively normal PD patients (PD-CN) compared to cognitively impaired PD patients (PD-MCI). Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients (≥ 100 mg/dL, pre-diabetes) compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical features including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted.

  4. Evidence of an association between brain cellular injury and cognitive decline after non-cardiac surgery

    PubMed Central

    Rappold, T.; Laflam, A.; Hori, D.; Brown, C.; Brandt, J.; Mintz, C. D.; Sieber, F.; Gottschalk, A.; Yenokyan, G.; Everett, A.; Hogue, C. W.

    2016-01-01

    Background. Postoperative cognitive dysfunction (POCD) is common after non-cardiac surgery, but the mechanism is unclear. We hypothesized that decrements in cognition 1 month after non-cardiac surgery would be associated with evidence of brain injury detected by elevation of plasma concentrations of S100β, neuron-specific enolase (NSE), and/or the brain-specific protein glial fibrillary acid protein (GFAP). Methods. One hundred and forty-nine patients undergoing shoulder surgery underwent neuropsychological testing before and then 1 month after surgery. Plasma was collected before and after anaesthesia. We determined the relationship between plasma biomarker concentrations and individual neuropsychological test results and a composite cognitive functioning score (mean Z-score). Results. POCD (≥−1.5 sd decrement in Z-score from baseline) was present in 10.1% of patients 1 month after surgery. There was a negative relationship between higher plasma GFAP concentrations and lower postoperative composite Z-scores {estimated slope=−0.14 [95% confidence interval (CI) −0.24 to −0.04], P=0.005} and change from baseline in postoperative scores on the Rey Complex Figure Test copy trial (P=0.021), delayed recall trial (P=0.010), and the Symbol Digit Modalities Test (P=0.004) after adjustment for age, sex, history of hypertension and diabetes. A similar relationship was not observed with S100β or NSE concentrations. Conclusions. Decline in cognition 1 month after shoulder surgery is associated with brain cellular injury as demonstrated by elevated plasma GFAP concentrations. PMID:26675953

  5. Do Changes in Lifestyle Engagement Moderate Cognitive Decline in Normal Aging? Evidence from the Victoria Longitudinal Study

    PubMed Central

    Small, Brent J.; Dixon, Roger A.; McArdle, John J.; Grimm, Kevin J.

    2013-01-01

    Objective Do lifestyle activities buffer normal aging-related declines in cognitive performance? The emerging literature will benefit from theoretically broader measurement of both lifestyle activities and cognitive performance, and longer-term longitudinal designs complemented with dynamic statistical analyses. We examine the temporal ordering of changes in lifestyle activities and changes in cognitive neuropsychological performance in older adults. Method We assembled data (n = 952) across a 12-year (5-wave) period from the Victoria Longitudinal Study. Latent Change Score models were applied to examine whether (and in which temporal order) changes in physical, social, or cognitive lifestyle activities were related to changes in three domains of cognitive performance. Results Two main results reflect the dynamic coupling among changes in lifestyle activities and cognition. First, reductions in cognitive lifestyle activities were associated with subsequent declines in measures of verbal speed, episodic memory, and semantic memory. Second, poorer cognitive functioning was related to subsequent decrements in lifestyle engagement, especially in social activities. Conclusions The results support the dual contention that (a) lifestyle engagement may buffer some of the cognitive changes observed in late life, and (b) persons who are exhibiting poorer cognitive performance may also relinquish some lifestyle activities. PMID:22149165

  6. Vascular brain lesions, brain atrophy, and cognitive decline. The Second Manifestations of ARTerial disease--Magnetic Resonance (SMART-MR) study.

    PubMed

    Kooistra, Minke; Geerlings, Mirjam I; van der Graaf, Yolanda; Mali, Willem P T M; Vincken, Koen L; Kappelle, L Jaap; Muller, Majon; Biessels, Geert Jan

    2014-01-01

    We examined the association between brain atrophy and vascular brain lesions (i.e., white matter lesions [WMLs] or brain infarcts), alone or in combination, with decline in memory and executive functioning over 4 years of follow-up in 448 patients (57 ± 9.5 years) with symptomatic atherosclerotic disease from the Second Manifestations of ARTerial disease--Magnetic Resonance SMART-MR study. Automated brain segmentation was used to quantify volumes of total brain, ventricles, cortical gray matter, and WMLs on 1.5-T magnetic resonance imaging (MRI). Brain infarcts were rated visually. WML volume was associated with significant decline in z score of executive functioning. No independent associations between MRI measures and memory decline were found. Significant declines in z scores of memory performance and of executive functioning were observed in patients with a combination of severe atrophy (upper quartile) and most vascular brain lesions (upper quartile) compared with those with minimal atrophy (lowest quartile) and fewest vascular brain lesions (lowest quartile). Our findings suggest that in patients with symptomatic atherosclerotic disease, the combination of brain atrophy and WMLs or brain infarcts accelerates cognitive decline over 4 years.

  7. Acute parietal lobe infarction presenting as Gerstmann's syndrome and cognitive decline mimicking senile dementia.

    PubMed

    Chen, Tien-Yu; Chen, Chun-Yen; Yen, Che-Hung; Kuo, Shin-Chang; Yeh, Yi-Wei; Chang, Serena; Huang, San-Yuan

    2013-01-01

    Gerstmann's syndrome encompasses the tetrad of finger agnosia, agraphia, acalculia, and right-left confusion. An elderly man with a history of several cardiovascular diseases was initially brought to the psychiatric outpatient department by his family because of worsening of recent memory, executive function, and mixed anxious-depressive mood. Gerstmann's syndrome without obvious motor function impairment and dementia-like features could be observed at first. Emergent brain computed tomography scan revealed new left-middle cerebral artery infarction over the left posterior parietal lobe. This case reminds us that acute cerebral infarction involving the parietal lobe may present as Gerstmann's syndrome accompanied by cognitive decline mimicking dementia. As a result, emergent organic workups should be arranged, especially for elderly patients at high risk for cerebral vascular accident.

  8. Acute parietal lobe infarction presenting as Gerstmann’s syndrome and cognitive decline mimicking senile dementia

    PubMed Central

    Chen, Tien-Yu; Chen, Chun-Yen; Yen, Che-Hung; Kuo, Shin-Chang; Yeh, Yi-Wei; Chang, Serena; Huang, San-Yuan

    2013-01-01

    Gerstmann’s syndrome encompasses the tetrad of finger agnosia, agraphia, acalculia, and right-left confusion. An elderly man with a history of several cardiovascular diseases was initially brought to the psychiatric outpatient department by his family because of worsening of recent memory, executive function, and mixed anxious-depressive mood. Gerstmann’s syndrome without obvious motor function impairment and dementia-like features could be observed at first. Emergent brain computed tomography scan revealed new left-middle cerebral artery infarction over the left posterior parietal lobe. This case reminds us that acute cerebral infarction involving the parietal lobe may present as Gerstmann’s syndrome accompanied by cognitive decline mimicking dementia. As a result, emergent organic workups should be arranged, especially for elderly patients at high risk for cerebral vascular accident. PMID:23847420

  9. Shared Neuropathological Characteristics of Obesity, Type 2 Diabetes and Alzheimer's Disease: Impacts on Cognitive Decline.

    PubMed

    Walker, Jennifer M; Harrison, Fiona E

    2015-09-01

    In the past few decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM), as well as older individuals at risk for Alzheimer's disease (AD), has increased. While the consumption of diets high in fat (total and saturated) have been linked to increased risk of AD, diets rich in antioxidants, polyunsaturated fats, and omega-3 fatty acids are associated with decreased risk. Additionally, AD patients are at increased risk for developing T2DM. Recent research suggests that there are stronger similarities between AD and T2DM than have previously been considered. Here we review the neurocognitive and inflammatory effects of high-fat diet consumption, its relationship to AD, and the treatment potential of dietary interventions that may decrease risk of cognitive decline and other associated neuropathological changes, such as insulin resistance, oxidative stress, and chronic inflammatory processes.

  10. Hearing loss and cognitive decline in older adults: questions and answers.

    PubMed

    Bernabei, Roberto; Bonuccelli, Ubaldo; Maggi, Stefania; Marengoni, Alessandra; Martini, Alessandro; Memo, Maurizio; Pecorelli, Sergio; Peracino, Andrea P; Quaranta, Nicola; Stella, Roberto; Lin, Frank R

    2014-12-01

    The association between hearing impairment, the diagnosis of dementia, and the role of sensory therapy has been proposed for some time, but further research is needed. Current understanding of this association requires the commitment of those experts who can integrate experience and research from several fields to be able to understand the link from hearing to dementia. A workshop whose panelists included experts from many areas, ranging from ear, nose and throat (ENT) to dementia's specialists, was promoted and organized by the Giovanni Lorenzini Medical Science Foundation (Milan, Italy; Houston, TX, USA) to increase the awareness of the relationship between hearing loss and dementia, and included questions and comments following a presentation from the clinical researcher, Frank Lin, who has been evaluating the relationship between hearing loss and cognitive decline since 2009.

  11. Anti-Ca/anti-ARHGAP26 antibodies associated with cerebellar atrophy and cognitive decline.

    PubMed

    Doss, Sarah; Nümann, Astrid; Ziegler, Annerose; Siebert, Eberhard; Borowski, Kathrin; Stöcker, Winfried; Prüss, Harald; Wildemann, Brigitte; Endres, Matthias; Jarius, Sven

    2014-02-15

    Recently, we identified a novel Purkinje cell-specific autoantibody (termed anti-Ca) targeting rhoGTPase-activating-protein-26 (ARHGAP26) in a patient with cerebellar ataxia. Here we describe a new case of anti-Ca/ARHGAP26 antibody-positive cerebellar ataxia. Cerebellar ataxia was associated with signs of possible limbic encephalitis in this case. The 24-year-old man presented with subacute pancerebellar ataxia, flattened affect, and cognitive decline. Neuropsychological testing revealed working memory deficits, compromised verbal learning and recall, attention deficits, slowed information processing, interference difficulty, and reduced spatial recognition. MRI showed severe pancerebellar atrophy. Serological examinations revealed high-titre anti-Ca/anti-ARHGAP26 antibodies. The antibodies belonged to the IgG1 subclass and were produced intrathecally. This case further corroborates the association of anti-Ca antibodies with cerebellar ataxia, expands the clinical spectrum, and highlights the necessity of antigen-specific diagnostic testing in immune-mediated cerebellar ataxia.

  12. Early Age-Related Functional Connectivity Decline in High-Order Cognitive Networks

    PubMed Central

    Siman-Tov, Tali; Bosak, Noam; Sprecher, Elliot; Paz, Rotem; Eran, Ayelet; Aharon-Peretz, Judith; Kahn, Itamar

    2017-01-01

    As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established. Here, an extensive cross-sectional sample (21–85 years old, N = 887) from a public fcMRI database was used to characterize adult lifespan connectivity dynamics within and between seven brain networks: the default mode, salience, dorsal attention, fronto-parietal control, auditory, visual and motor networks. The entire cohort was divided into young (21–40 years, mean ± SD: 25.5 ± 4.8, n = 543); middle-aged (41–60 years, 50.6 ± 5.4, n = 238); and old (61 years and above, 69.0 ± 6.3, n = 106) subgroups. Correlation matrices as well as a mixed model analysis of covariance indicated that within high-order cognitive networks a considerable connectivity decline is already evident by middle adulthood. In contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline. Additionally, alterations in inter-network interactions are noticeable primarily in the transition between young and middle adulthood. These results provide evidence that aging-related neural changes start early in adult life. PMID:28119599

  13. Alcohol Consumption, Dementia and Cognitive Decline: An Overview of Systematic Reviews.

    PubMed

    Ilomaki, Jenni; Jokanovic, Natali; Tan, Edwin C K; Lonnroos, Eija

    2015-01-01

    There is uncertainty in relation to the effect of alcohol consumption on the incidence of dementia and cognitive decline. This review critically evaluated published systematic reviews on the epidemiology of alcohol consumption and the risk of dementia or cognitive decline. MEDLINE, EMBASE and PsycINFO were searched from inception to February 2014. Systematic reviews of longitudinal observational studies were considered. Two reviewers independently completed the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) tool to assess the quality. We identified three moderate quality systematic reviews (AMSTAR score 4-6) that included a total of 45 unique studies. Two of the systematic reviews encompassed a meta-analysis. Light to moderate drinking may decrease the risk of Alzheimer's disease (AD) (pooled risk ratio [RR] 0.72; 95% confidence interval [CI] 0.61-0.86) and dementia (RR 0.74; 95%CI 0.61-0.91) whereas heavy to excessive drinking does not affect the risk (RR 0.92; 95%CI 0.59-1.45 and RR 1.04; 95%CI 0.69-1.56, respectively). One systematic review identified two studies that reported a link between alcohol consumption and the development of AD. No systematic review categorised former drinkers separately from lifetime abstainers in their analysis. Definitions of alcohol consumption, light to moderate drinking and heavy-excessive drinking varied and drinking patterns were not considered. Moderate quality (AMSTAR score 4-6) systematic reviews indicate that light to moderate alcohol consumption may protect against AD and dementia. However, the importance of drinking patterns and specific beverages remain unknown. There is insufficient evidence to suggest abstainers should initiate alcohol consumption to protect against dementia.

  14. Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.

    PubMed

    Doan, Ryan N; Bae, Byoung-Il; Cubelos, Beatriz; Chang, Cindy; Hossain, Amer A; Al-Saad, Samira; Mukaddes, Nahit M; Oner, Ozgur; Al-Saffar, Muna; Balkhy, Soher; Gascon, Generoso G; Nieto, Marta; Walsh, Christopher A

    2016-10-06

    Comparative analyses have identified genomic regions potentially involved in human evolution but do not directly assess function. Human accelerated regions (HARs) represent conserved genomic loci with elevated divergence in humans. If some HARs regulate human-specific social and behavioral traits, then mutations would likely impact cognitive and social disorders. Strikingly, rare biallelic point mutations-identified by whole-genome and targeted "HAR-ome" sequencing-showed a significant excess in individuals with ASD whose parents share common ancestry compared to familial controls, suggesting a contribution in 5% of consanguineous ASD cases. Using chromatin interaction sequencing, massively parallel reporter assays (MPRA), and transgenic mice, we identified disease-linked, biallelic HAR mutations in active enhancers for CUX1, PTBP2, GPC4, CDKL5, and other genes implicated in neural function, ASD, or both. Our data provide genetic evidence that specific HARs are essential for normal development, consistent with suggestions that their evolutionary changes may have altered social and/or cognitive behavior. PAPERCLIP.

  15. Aging process, cognitive decline and Alzheimer`s disease: can strength training modulate these responses?

    PubMed

    Portugal, Eduardo Matta Mello; Vasconcelos, Poliane Gomes Torres; Souza, Renata; Lattari, Eduardo; Monteiro-Junior, Renato Sobral; Machado, Sergio; Deslandes, Andrea Camaz

    2015-01-01

    Some evidence shows that aerobic training can attenuate the aging effects on the brain structures and functions. However, the strength exercise effects are poorly discussed. Thus, in the present study, the effects of strength training on the brain in elderly people and Alzheimer`s disease (AD) patients were revised. Furthermore, it a biological explanation relating to strength training effects on the brain is proposed. Brain atrophy can be related to neurotransmission dysfunction, like oxidative stress, that generates mitochondrial damage and reduced brain metabolism. Another mechanism is related to amyloid deposition and amyloid tangles, that can be related to reductions on insulin-like growth factor I concentrations. The brain-derived neurotrophic factor also presents reduction during aging process and AD. These neuronal dysfunctions are also related to cerebral blood flow decline that influence brain metabolism. All of these alterations contribute to cognitive impairment and AD. After a long period of strength training, the oxidative stress can be reduced, the brain-derived neurotrophic factor and insulin-like growth factor I serum concentrations enhance, and the cognitive performance improves. Considering these results, we can infer that strength training can be related to increased neurogenesis, neuroplasticity and, consequently, counteracts aging effects on the brain. The effect of strength training as an additional treatment of AD needs further investigation.

  16. Deep Brain Stimulation and Cognitive Decline in Parkinson’s Disease: A Clinical Review

    PubMed Central

    Massano, João; Garrett, Carolina

    2012-01-01

    Parkinson’s disease is a common and often debilitating disorder, with a growing prevalence accompanying global population aging. Current drug therapy is not satisfactory enough for many patients, especially after a few years of symptom progression. This is mainly due to the motor complications that frequently emerge as disease progresses. Deep brain stimulation (DBS) is a useful therapeutic option in carefully selected patients that significantly improves motor symptoms, functional status, and quality of life. However, cognitive impairment may limit patient selection for DBS, as patients need to have sufficient mental capabilities in order to understand the procedure, as well as its benefits and limitations, and cooperate with the medical team throughout the process of selection, surgery, and postsurgical follow-up. On the other hand it has been observed that certain aspects of cognitive performance may decline after DBS, namely when the therapeutic target is the widely used subthalamic nucleus. These are important pieces of information for patients, their families, and health care professionals. This manuscript reviews these aspects and their clinical implications. PMID:22557991

  17. Risk Factors Associated with Cognitive Decline after Cardiac Surgery: A Systematic Review

    PubMed Central

    Patel, Nikil; Minhas, Jatinder S.; Chung, Emma M. L.

    2015-01-01

    Modern day cardiac surgery evolved upon the advent of cardiopulmonary bypass machines (CPB) in the 1950s. Following this development, cardiac surgery in recent years has improved significantly. Despite such advances and the introduction of new technologies, neurological sequelae after cardiac surgery still exist. Ischaemic stroke, delirium, and cognitive impairment cause significant morbidity and mortality and unfortunately remain common complications. Postoperative cognitive decline (POCD) is believed to be associated with the presence of new ischaemic lesions originating from emboli entering the cerebral circulation during surgery. Cardiopulmonary bypass was thought to be the reason of POCD, but randomised controlled trials comparing with off-pump surgery show contradictory results. Attention has now turned to the growing evidence that perioperative risk factors, as well as patient-related risk factors, play an important role in early and late POCD. Clearly, identifying the mechanism of POCD is challenging. The purpose of this systematic review is to discuss the literature that has investigated patient and perioperative risk factors to better understand the magnitude of the risk factors associated with POCD after cardiac surgery. PMID:26491558

  18. Environmental enrichment lessens cognitive decline in APP23 mice without affecting brain sirtuin expression.

    PubMed

    Polito, Letizia; Chierchia, Armando; Tunesi, Marta; Bouybayoune, Ihssane; Kehoe, Patrick Gavin; Albani, Diego; Forloni, Gianluigi

    2014-01-01

    Environmental enrichment (EE) is a non-pharmacological intervention reported to counteract pathological signs in models of Alzheimer's disease (AD). We developed EE protocols in APP23 mice and evaluated how they influenced cognitive decline and brain amyloid-β (Aβ) burden. We also investigated the involvement of sirtuins (SIRTs) as a possible molecular mediator of EE, by assessing hippocampal and cortical mRNA and protein levels of the SIRT family members (SIRT1 to SIRT7). APP23 transgenic mice were moved to EE cages (TG-EEs) starting from 3 months of age. TG-EEs were compared to transgenic mice housed in standard cages (TG-SHs) and to wild-type littermates in the two housing conditions (WT-EEs and WT-SHs). At 7 months of age, all mice were tested for behavioral performance with Morris Water Maze (MWM) and visual novel Object Recognition Test (vORT). After a month, a group underwent biochemical analyses, while another group continued in the EE environment till 18 months of age, when Aβ plaque load was assessed. At 7 months, TG-SHs had impaired behavioral performance in MWM and vORT. In contrast, TG-EE mice had restored behavioral performance. At 8 months, EE did not affect AβPP expression or processing, Aβ40/42, pGlu-Aβ3-40/3-42, or Aβ oligomer level. The expression of two Aβ degrading enzymes (insulin degrading enzyme and neprilysin) was not modulated by EE. Brain sirtuin mRNA and protein levels were unchanged, while brain-derived neurotrophic factor expression increased after EE. Aβ deposition was attenuated in 18-month-old TG-EE mice, without apparent reduction of neuroinflammatory signs. We suggest that EE had a beneficial effect on cognitive performance and lessened long-term Aβ accumulation, but brain sirtuin expression was not modulated when cognitive impairment was restored.

  19. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective.

    PubMed

    Baumgart, Matthew; Snyder, Heather M; Carrillo, Maria C; Fazio, Sam; Kim, Hye; Johns, Harry

    2015-06-01

    An estimated 47 million people worldwide are living with dementia in 2015, and this number is projected to triple by 2050. In the absence of a disease-modifying treatment or cure, reducing the risk of developing dementia takes on added importance. In 2014, the World Dementia Council (WDC) requested the Alzheimer's Association evaluate and report on the state of the evidence on modifiable risk factors for cognitive decline and dementia. This report is a summary of the Association's evaluation, which was presented at the October 2014 WDC meeting. The Association believes there is sufficient evidence to support the link between several modifiable risk factors and a reduced risk for cognitive decline, and sufficient evidence to suggest that some modifiable risk factors may be associated with reduced risk of dementia. Specifically, the Association believes there is sufficiently strong evidence, from a population-based perspective, to conclude that regular physical activity and management of cardiovascular risk factors (diabetes, obesity, smoking, and hypertension) reduce the risk of cognitive decline and may reduce the risk of dementia. The Association also believes there is sufficiently strong evidence to conclude that a healthy diet and lifelong learning/cognitive training may also reduce the risk of cognitive decline.

  20. Association between Exposure to the Chinese Famine in Different Stages of Early Life and Decline in Cognitive Functioning in Adulthood

    PubMed Central

    Wang, Chao; An, Yu; Yu, Huanling; Feng, Lingli; Liu, Quanri; Lu, Yanhui; Wang, Hui; Xiao, Rong

    2016-01-01

    Objective: To investigate whether exposure to the Chinese Famine in different life stages of early life is associated with cognitive functioning decline in adulthood. Methods: We recruited 1366 adults born between 1950 and 1964 and divided them into fetal-exposed, early childhood-exposed (1–3 years old during the famine), mid childhood-exposed (4–6 years old during the famine), late childhood-exposed (7–9 years old during the famine), and non-exposed groups. A selection of cognitive tests was administered to assess their cognitive performance. Association between malnutrition in different famine exposure periods and adult cognitive performance was estimated by multivariate logistic and multiple linear regression analyses. Results: There were significant differences in cognitive performance between subjects exposed to famine during different life stages. For the general cognitive tests, fetal-exposed period was associated with decreased scores of the Mini-Mental State Examination (MMSE), and late childhood-exposed with decreased scores of the Montreal Cognitive Assessment (MoCA). We also found exposure to famine during mid and late childhood was associated with worse performance on the Stroop color and word test. Conclusion: Famine exposure in utero and during childhood is associated with overall and specific cognitive decline, affecting selective attention and response inhibition particularly. PMID:27471454

  1. The Impact of Motivational "World-View" on Engagement in a Cognitive Acceleration Programme

    ERIC Educational Resources Information Center

    McLellan, Ros

    2006-01-01

    Cognitive Acceleration through Science Education (CASE) is an intervention programme conducted during Years 7 and 8 in the United Kingdom (aged 11-13 years), which has reported remarkable success in enhancing cognitive development and in raising academic achievement. Critics, however, have questioned whether a purely cognitive mechanism can…

  2. Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline.

    PubMed

    Lista, Simone; Molinuevo, Jose L; Cavedo, Enrica; Rami, Lorena; Amouyel, Philippe; Teipel, Stefan J; Garaci, Francesco; Toschi, Nicola; Habert, Marie-Odile; Blennow, Kaj; Zetterberg, Henrik; O'Bryant, Sid E; Johnson, Leigh; Galluzzi, Samantha; Bokde, Arun L W; Broich, Karl; Herholz, Karl; Bakardjian, Hovagim; Dubois, Bruno; Jessen, Frank; Carrillo, Maria C; Aisen, Paul S; Hampel, Harald

    2015-09-24

    There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials.

  3. Insulin-Like Growth Factor-1 but Not Insulin Predicts Cognitive Decline in Huntington’s Disease

    PubMed Central

    Youssov, Katia; Dolbeau, Guillaume; Cleret, Laurent; Bourhis, Marie-Laure; Azulay, Jean-Philippe; Krystkowiak, Pierre; Verny, Christophe; Morin, Françoise; Moutereau, Stéphane; Bachoud-Lévi, Anne-Catherine; Maison, Patrick

    2016-01-01

    Background Huntington's disease (HD) is one of several neurodegenerative disorders that have been associated with metabolic alterations. Changes in Insulin Growth Factor 1 (IGF-1) and/or insulin input to the brain may underlie or contribute to the progress of neurodegenerative processes. Here, we investigated the association over time between changes in plasma levels of IGF-1 and insulin and the cognitive decline in HD patients. Methods We conducted a multicentric cohort study in 156 patients with genetically documented HD aged from 22 to 80 years. Among them, 146 patients were assessed at least twice with a follow-up of 3.5 ± 1.8 years. We assessed their cognitive decline using the Unified Huntington’s Disease Rating Scale, and their IGF-1 and insulin plasmatic levels, at baseline and once a year during the follow-up. Associations were evaluated using a mixed-effect linear model. Results In the cross-sectional analysis at baseline, higher levels of IGF-1 and insulin were associated with lower cognitive scores and thus with a higher degree of cognitive impairment. In the longitudinal analysis, the decrease of all cognitive scores, except the Stroop interference, was associated with the IGF-1 level over time but not of insulin. Conclusions IGF-1 levels, unlike insulin, predict the decline of cognitive function in HD. PMID:27627435

  4. Gait dyspraxia as a clinical marker of cognitive decline in Down syndrome: A review of theory and proposed mechanisms.

    PubMed

    Anderson-Mooney, Amelia J; Schmitt, Frederick A; Head, Elizabeth; Lott, Ira T; Heilman, Kenneth M

    2016-04-01

    Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimer's disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Early detection may allow for appropriate preparation by caregivers. Recent literature suggests that declines in gait may serve as an early marker of AD-related cognitive disorders; however, this relationship has not been examined in individuals with DS. The theory regarding gait dyspraxia and cognitive decline in the general population is reviewed, and potential applications to the population with individuals with DS are highlighted. Challenges and benefits in the line of inquiry are discussed. In particular, it appears that gait declines in aging individuals with DS may be associated with known declines in frontoparietal gray matter, development of AD-related pathology, and white matter losses in tracts critical to motor control. These changes are also potentially related to the cognitive and functional changes often observed during the same chronological period as gait declines in adults with DS. Gait declines may be an early marker of cognitive change, related to the development of underlying AD-related pathology, in individuals with DS. Future investigations in this area may provide insight into the clinical changes associated with development of AD pathology in both the population with DS and the general population, enhancing efforts for optimal patient and caregiver support and propelling investigations regarding safety/quality of life interventions and disease-modifying interventions.

  5. Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension

    PubMed Central

    Uiterwijk, Renske; van Oostenbrugge, Robert J.; Huijts, Marjolein; De Leeuw, Peter W.; Kroon, Abraham A.; Staals, Julie

    2016-01-01

    Objectives: Hypertension is a major risk factor for white matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces, which are MRI markers of cerebral small vessel disease (SVD). Studies have shown associations between these individual MRI markers and cognitive functioning and decline. Recently, a “total SVD score” was proposed in which the different MRI markers were combined into one measure of SVD, to capture total SVD-related brain damage. We investigated if this SVD score was associated with cognitive decline over 4 years in patients with hypertension. Methods: In this longitudinal cohort study, 130 hypertensive patients (91 patients with uncomplicated hypertension and 39 hypertensive patients with a lacunar stroke) were included. They underwent a neuropsychological assessment at baseline and after 4 years. The presence of WMH, lacunes, cerebral microbleeds, and perivascular spaces were rated on baseline MRI. Presence of each individual marker was added to calculate the total SVD score (range 0–4) in each patient. Results: Uncorrected linear regression analyses showed associations between SVD score and decline in overall cognition (p = 0.017), executive functioning (p < 0.001) and information processing speed (p = 0.037), but not with memory (p = 0.911). The association between SVD score and decline in overall cognition and executive function remained significant after adjustment for age, sex, education, anxiety and depression score, potential vascular risk factors, patient group, and baseline cognitive performance. Conclusion: Our study shows that a total SVD score can predict cognitive decline, specifically in executive function, over 4 years in hypertensive patients. This emphasizes the importance of considering total brain damage due to SVD. PMID:28018214

  6. Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension.

    PubMed

    Uiterwijk, Renske; van Oostenbrugge, Robert J; Huijts, Marjolein; De Leeuw, Peter W; Kroon, Abraham A; Staals, Julie

    2016-01-01

    Objectives: Hypertension is a major risk factor for white matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces, which are MRI markers of cerebral small vessel disease (SVD). Studies have shown associations between these individual MRI markers and cognitive functioning and decline. Recently, a "total SVD score" was proposed in which the different MRI markers were combined into one measure of SVD, to capture total SVD-related brain damage. We investigated if this SVD score was associated with cognitive decline over 4 years in patients with hypertension. Methods: In this longitudinal cohort study, 130 hypertensive patients (91 patients with uncomplicated hypertension and 39 hypertensive patients with a lacunar stroke) were included. They underwent a neuropsychological assessment at baseline and after 4 years. The presence of WMH, lacunes, cerebral microbleeds, and perivascular spaces were rated on baseline MRI. Presence of each individual marker was added to calculate the total SVD score (range 0-4) in each patient. Results: Uncorrected linear regression analyses showed associations between SVD score and decline in overall cognition (p = 0.017), executive functioning (p < 0.001) and information processing speed (p = 0.037), but not with memory (p = 0.911). The association between SVD score and decline in overall cognition and executive function remained significant after adjustment for age, sex, education, anxiety and depression score, potential vascular risk factors, patient group, and baseline cognitive performance. Conclusion: Our study shows that a total SVD score can predict cognitive decline, specifically in executive function, over 4 years in hypertensive patients. This emphasizes the importance of considering total brain damage due to SVD.

  7. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study

    PubMed Central

    Carrière, Isabelle; Fourrier-Reglat, Annie; Dartigues, Jean-François; Rouaud, Olivier; Pasquier, Florence; Ritchie, Karen; Ancelin, Marie-Laure

    2009-01-01

    Objective To examine the association between use of medications with anticholinergic properties, cognitive decline and incident dementia in a large community-based sample of subjects aged 65 years and over. Methods Participants were 4128 women and 2784 men from a population-based cohort recruited from three French cities. Cognitive performance, clinical diagnosis of dementia and anticholinergic use were evaluated at base-line, 2 and 4 year later. Results 7.5% of subjects reported anticholinergic drug use at base-line. Multivariate adjusted logistic regression indicated that women reporting anticholinergic drugs at base-line showed greater decline over four years in verbal fluency scores (OR=1.41, CI=1.11–1.79) and in global cognitive functioning (OR=1.22, CI=0.96–1.55) than women not using anticholinergic drugs. In men, an association was found with decline in visual memory (OR=1.63, CI=1.08–2.47) and to a lesser extent in executive function (OR=1.47, CI=0.89–2.44). Significant interactions were observed in women between anticholinergic use and age, apolipoprotein E, or hormone replacement therapy. A significantly 1.4–2 fold higher risk of cognitive decline was observed for continuous anticholinergic users but not for those having discontinued. The risk of incident dementia over the four-year followup was also increased in continuous users (HR=1.65, CI=1.00–2.73) but not in those having discontinued anticholinergic drugs (HR=1.28, CI=0.59–2.76). Conclusions Elderly people taking anticholinergic drugs were at increased risk for cognitive decline and dementia. Discontinuing anticholinergic treatment was associated with a decreased risk. Physicians should carefully consider prescription of anticholinergic drugs in elderly people especially in the oldest old and persons at high genetic risk of cognitive disorder. PMID:19636034

  8. Review of information and communication technology devices for monitoring functional and cognitive decline in Alzheimer's disease clinical trials.

    PubMed

    Pillai, Jagan A; Bonner-Jackson, Aaron

    2015-01-01

    Detecting and monitoring early cognitive impairment in Alzheimer's disease (AD) is a significant need in the field of AD therapeutics. Successful AD clinical trial designs have to overcome challenges related to the subtle nature of early cognitive changes. Continuous unobtrusive assessments using Information and Communication Technology (ICT) devices to capture markers of intra-individual change over time to assess cognitive and functional disability therefore offers significant benefits. We review the literature and provide an overview on randomized clinical trials in AD that use intelligent systems to monitor functional decline, as well as strengths, weaknesses, and future directions for the use of ICTs in a new generation of AD clinical trials.

  9. Is It Possible to Delay or Prevent Age-Related Cognitive Decline?

    PubMed Central

    2016-01-01

    Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published. PMID:27688858

  10. Needs in Nursing Homes and Their Relation with Cognitive and Functional Decline, Behavioral and Psychological Symptoms

    PubMed Central

    Ferreira, Ana Rita; Dias, Cláudia Camila; Fernandes, Lia

    2016-01-01

    Unmet needs are becoming acknowledged as better predictors of the worst prognostic outcomes than common measures of functional or cognitive decline. Their accurate assessment is a pivotal component of effective care delivery, particularly in institutionalized care where little is known about the needs of its residents, many of whom suffer from dementia and show complex needs. The aims of this study were to describe the needs of an institutionalized sample and to analyze its relationship with demographic and clinical characteristics. A cross-sectional study was conducted with a sample from three nursing homes. All residents were assessed with a comprehensive protocol that included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI) and Adults and Older Adults Functional Inventory (IAFAI). To identify needs, the Camberwell Assessment of Need for the Elderly (CANE) was used. The final sample included 175 residents with a mean age of 81 standard deviation (SD = 10) years. From these, 58.7% presented cognitive deficit (MMSE) and 45.2% depressive symptoms (GDS). Statistically significant negative correlations were found between MMSE score and met (rs = −0.425), unmet (rs = −0.369) and global needs (rs = −0.565). Data also showed significant correlations between depressive symptoms and unmet (rs = 0.683) and global needs (rs = 0.407), and between behavioral and psychological symptoms (BPSD) and unmet (rs = 0.181) and global needs (rs = 0.254). Finally, significant correlations between functional impairment and met (rs = 0.642), unmet (rs = 0.505) and global needs (rs = 0.796) were also found. These results suggest that in this sample, more unmet needs are associated with the worst outcomes measured. This is consistent with previous findings and seems to demonstrate that the needs of those institutionalized elderly remain under-diagnosed and untreated. PMID:27148044

  11. Phytoestrogen consumption and risk for cognitive decline and dementia: With consideration of thyroid status and other possible mediators.

    PubMed

    Soni, M; White, L R; Kridawati, A; Bandelow, S; Hogervorst, E

    2016-06-01

    It is predicted that around 20% of the worlds population will be age 60 or above by 2050. Prevalence of cognitive decline and dementia is high in older adults and modifiable dietary factors may be able to reduce risk for these conditions. Phytoestrogens are bioactive plant chemicals found in soy, which have a similarity in structure to natural estradiol (the most abundant circulating estrogen). This structural likeness enables phytoestrogens to interact with estrogen receptors in the brain, potentially affecting cognition. However, findings in this domain are largely inconsistent, with approximately 50% of studies showing positive effects of phytoestrogens on cognition and the other half resulting in null/negative findings. This paper provides an updated review of the relationship between consumption of phytoestrogens and risk for cognitive decline and/or dementia. In particular, possible mediators were identified to explain discrepant findings and for consideration in future research. A case can be made for a link between phytoestrogen consumption, thyroid status and cognition in older age, although current findings in this area are very limited. Evidence suggests that inter-individual variants that can affect phytoestrogen bioavailability (and thus cognitive outcome) include age and ability to breakdown ingested phytoestrogens into their bioactive metabolites. Factors of the study design that must be taken into account are type of soy product, dosage, frequency of dietary intake and type of cognitive test used. Guidelines regarding optimal phytoestrogen dosage and frequency of intake are yet to be determined.

  12. Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

    PubMed

    Baierle, Marília; Charão, Mariele F; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Avila, Daiana S; Gioda, Adriana; Garcia, Solange C

    2014-10-17

    Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation.

  13. Are Delta-Aminolevulinate Dehydratase Inhibition and Metal Concentrations Additional Factors for the Age-Related Cognitive Decline?

    PubMed Central

    Baierle, Marília; Charão, Mariele F.; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C.; Rocha, Rafael C. C.; Saint’Pierre, Tatiana D.; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M.; Ávila, Daiana S.; Gioda, Adriana; Garcia, Solange C.

    2014-01-01

    Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation. PMID:25329536

  14. Omega-3 fatty acids and risk of cognitive decline in the elderly: a meta-analysis of randomized controlled trials.

    PubMed

    Zhang, Xiao-Wei; Hou, Wen-Shang; Li, Min; Tang, Zhen-Yu

    2016-02-01

    Evidence has demonstrated that omega-3 fatty acids intake may be associated with age-related cognitive decline. However, randomized controlled trials (RCTs) have drawn inconsistent conclusions. We performed a meta-analysis to assess the association between omega-3 fatty acids and risk of cognitive decline in the elderly. A strategic literature search of PubMed, EMBASE, and Cochrane Library (updated to December 2014) was performed. We retrieved six randomized controlled studies as eligible for our meta-analysis. Among these six studies, the duration time ranged from 3 to 40 months. The dose of omega-3 fatty acids (DHA + EPA) ranged from 400 to 1800 mg. The result of our meta-analysis expressed that omega-3 fatty acids statistically decrease the rate of cognitive decline in MMSE score (WMD = 0.15, [0.05, 0.25]; p = 0.003). In conclusion, our meta-analysis indicated that omega-3 fatty acids may help to prevent cognitive decline in the elderly.

  15. Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

    2008-01-01

    Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…

  16. A[Beta] Deposits in Older Non-Demented Individuals with Cognitive Decline Are Indicative of Preclinical Alzheimer's Disease

    ERIC Educational Resources Information Center

    Villemagne, V. L.; Pike, K. E.; Darby, D.; Maruff, P.; Savage, G.; Ng, S.; Ackermann, U.; Cowie, T. F.; Currie, J.; Chan, S. G.; Jones, G.; Tochon-Danguy, H.; O'Keefe, G.; Masters, C. L.; Rowe, C. C.

    2008-01-01

    Approximately 30% of healthy persons aged over 75 years show A[beta] deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between A[beta] burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and…

  17. Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons

    PubMed Central

    Lauretani, F.; Bandinelli, S.; Benedetta, B.; Cherubini, A.; Iorio, A. D.; Blè, A.; Giacomini, V.; Corsi, A. M.; Guralnik, J. M.; Ferrucci, L.

    2009-01-01

    Pre-clinical studies suggest that both omega-6 and omega-3 fatty acids have beneficial effects on peripheral nerve function. Rats feed a diet rich in polyunsaturated fatty acids (PUFAs) showed modification of phospholipid fatty acid composition in nerve membranes and improvement of sciatic nerve conduction velocity (NCV). We tested the hypothesis that baseline plasma omega-6 and omega-3 fatty acids levels predict accelerated decline of peripheral nerve function. Changes between baseline and the 3-year follow-up in peripheral nerve function was assessed by standard surface ENG of the right peroneal nerve in 384 male and 443 female participants of the InCHIANTI study (age range: 24–97 years). Plasma concentrations of selected fatty acids assessed at baseline by gas chromatography. Independent of confounders, plasma omega-6 fatty acids and linoleic acid were significantly correlated with peroneal NCV at enrollment. Lower plasma PUFA, omega-6 fatty acids, linoleic acid, ratio omega-6/omega-3, arachidonic acid and docosahexanoic acid levels were significantly predicted a steeper decline in nerve function parameters over the 3-year follow-up. Low plasma omega-6 and omega-3 fatty acids levels were associated with accelerated decline of peripheral nerve function with aging. PMID:17594339

  18. A retrospective investigation of energy efficiency standards: policies may have accelerated long term declines in appliance costs

    NASA Astrophysics Data System (ADS)

    Van Buskirk, R. D.; Kantner, C. L. S.; Gerke, B. F.; Chu, S.

    2014-11-01

    We perform a retrospective investigation of multi-decade trends in price and life-cycle cost (LCC) for home appliances in periods with and without energy efficiency (EE) standards and labeling polices. In contrast to the classical picture of the impact of efficiency standards, the introduction and updating of appliance standards is not associated with a long-term increase in purchase price; rather, quality-adjusted prices undergo a continued or accelerated long-term decline. In addition, long term trends in appliance LCCs—which include operating costs—consistently show an accelerated long term decline with EE policies. We also show that the incremental price of efficiency improvements has declined faster than the baseline product price for selected products. These observations are inconsistent with a view of EE standards that supposes a perfectly competitive market with static supply costs. These results suggest that EE policies may be associated with other forces at play, such as innovation and learning-by-doing in appliance production and design, that can affect long term trends in quality-adjusted prices and LCCs.

  19. Omega-3 fatty acids, cognitive decline, and Alzheimer's disease: a critical review and evaluation of the literature.

    PubMed

    Huang, Tina L

    2010-01-01

    The precipitous decline of memory and independence associated with cognitive decline, dementia, and Alzheimer's disease is emotionally and financially devastating to patients, their families, and caretakers. Studies from animal models and cell cultures have shown that omega-3 fatty acids (n-3 FAs) are neuroprotective during development and aging. Numerous epidemiologic, postmortem, and clinical trials have been published on fish or n-3 FAs and Alzheimer's disease, dementia, or cognitive decline. Yet results across the literature in humans are inconsistent and thus difficult to interpret. This review provides background and context needed for interpretation of the findings, summaries of the literature grouped by longitudinal studies of fish, dietary n-3 FAs, blood levels of fatty acids, postmortem studies, and clinical trials, and subsequent interpretation of findings. Possible reasons for discrepancies in the literature are presented throughout, and conclusions suggest directions for future research.

  20. Obesity and diabetes as accelerators of functional decline: can lifestyle interventions maintain functional status in high risk older adults?

    PubMed

    Anton, Stephen D; Karabetian, Christy; Naugle, Kelly; Buford, Thomas W

    2013-09-01

    Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and treatment of physical disability in these persons have become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes.

  1. Cognitive Decline in Patients with Chronic Hydrocephalus and Normal Aging: ‘Growing into Deficits’

    PubMed Central

    de Beer, Marlijn H.; Scheltens, Philip

    2016-01-01

    Background/Aim To explore the theory of ‘growing into deficits’, a concept known from developmental neurology, in a series of cases with chronic hydrocephalus (CH). Methods Patients were selected from the Amsterdam Dementia Cohort and underwent extensive dementia screening. Results Twelve patients with CH were selected, in whom Alzheimer's disease was considered unlikely, based on biomarker information and follow-up. Mean Mini-Mental State Examination score was 24 (range 7-30). Most patients were functioning on a level of mild dementia [Clinical Dementia Rating score of 0.5 in 8/11 (66.7%) patients]. On neuropsychological examination, memory and executive functions, as well as processing speed were most frequently impaired. Conclusion In our opinion, the theory of ‘growing into deficits’ shows a parallel with the clinical course of CH and normal aging when Alzheimer's disease was considered very unlikely, because most of these patients were functioning well for a very large part of their lives. The altered cerebrospinal fluid dynamics might make the brain more vulnerable to aging-related changes, leading to a faster cognitive decline in CH patients compared to healthy subjects, especially in case of concomitant brain damage such as traumatic brain injury or meningitis. PMID:27920793

  2. Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I.

    PubMed

    Nestrasil, Igor; Shapiro, Elsa; Svatkova, Alena; Dickson, Patricia; Chen, Agnes; Wakumoto, Amy; Ahmed, Alia; Stehel, Edward; McNeil, Sarah; Gravance, Curtis; Maher, Elizabeth

    2017-03-01

    Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood-brain barrier (BBB) which limits treatment effects of intravenously applied α-L-iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progressive cognitive decline. Neuropsychological testing and MRIs were performed twice prior (baseline, at 1 year) and twice after initiating IT rhIDU (at 2nd and 3rd years). The difference between pre- and post-treatment means was evaluated as a percentage of the change. Neurocognitive performance improved particularly in memory tests and resulted in improved school performance after IT rhIDU treatment. White matter (WM) integrity improved together with an increase of WM and corpus callosum volumes. Hippocampal and gray matter volume decreased which may either parallel reduction of glycosaminoglycan storage or reflect typical longitudinal brain changes in early adulthood. In conclusion, our outcomes suggest neurological benefits of IT rhIDU compared to the intravenous administration on brain structure and function in a single MPS IA patient.© 2017 Wiley Periodicals, Inc.

  3. Predictive Factors of Rapid Cognitive Decline in Patients with Alzheimer Disease

    PubMed Central

    Barbe, Coralie; Morrone, Isabella; Novella, J.L.; Dramé, Moustapha; Wolak-Thierry, Aurore; Aquino, Jean-Pierre; Ankri, Joël; Jolly, Damien; Mahmoudi, Rachid

    2016-01-01

    Aim To determine predictive factors associated with rapid cognitive decline (RCD) in elderly patients suffering from Alzheimer disease (AD). Methods Patients suffering from mild to moderate AD were included. RCD was defined as the loss of at least 3 points on the Mini-Mental State Examination (MMSE) over 12 months. Factors associated with RCD were identified by logistic regression. Results Among 123 patients included, 61 were followed up until 12 months. RCD occurred in 46% of patients (n = 28). Polymedication (p < 0.0001), the fact that the caregiver was the child or spouse of the patient (p < 0.0001) and autonomy for washing (p < 0.0001) were protective factors against RCD, while the presence of caregiver burden (p < 0.0001) was shown to be a risk factor for RCD. Conclusion Early detection of the RCD risk in AD patients could make it possible to anticipate the patient's medical needs and adjust the care plan for caregiver burden. PMID:28101101

  4. CEREBRAL ATROPHY, APOLIPOPROTEIN E ε4, AND RATE OF DECLINE IN EVERYDAY FUNCTION AMONG PATIENTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT

    PubMed Central

    Okonkwo, Ozioma C.; Alosco, Michael L.; Jerskey, Beth A.; Sweet, Lawrence H.; Ott, Brian R.; Tremont, Geoffrey

    2010-01-01

    BACKGROUND Patients with amnestic mild cognitive impairment (MCI) demonstrate decline in everyday function. In this study, we investigated whether whole brain atrophy and apolipoprotein E (APOE) genotype are associated with the rate of functional decline in MCI. METHODS Participants were 164 healthy controls, 258 MCI patients, and 103 patients with mild Alzheimer’s disease (AD), enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). They underwent brain MRI scans, APOE genotyping, and completed up to 6 biannual Functional Activities Questionnaire (FAQ) assessments. Random effects regressions were used to examine trajectories of decline in FAQ across diagnostic groups, and to test the effects of ventricle-to-brain ratio (VBR) and APOE genotype on FAQ decline among MCI patients. RESULTS Rate of decline in FAQ among MCI patients was intermediate between that of controls and mild AD patients. Patients with MCI who converted to mild AD declined faster than those who remained stable. Among MCI patients, increased VBR and possession of any APOE ε4 allele were associated with faster rate of decline in FAQ. In addition, there was a significant VBR by APOE ε4 interaction such that patients who were APOE ε4 positive and had increased atrophy experienced the fastest decline in FAQ. CONCLUSIONS Functional decline occurs in MCI, particularly among patients who progress to mild AD. Brain atrophy and APOE ε4 positivity are associated with such declines, and patients who have elevated brain atrophy and are APOE ε4 positive are at greatest risk of functional degradation. These findings highlight the value of genetic and volumetric MRI information as predictors of functional decline, and thus disease progression, in MCI. PMID:20813341

  5. Resting-state networks associated with cognitive processing show more age-related decline than those associated with emotional processing.

    PubMed

    Nashiro, Kaoru; Sakaki, Michiko; Braskie, Meredith N; Mather, Mara

    2017-03-11

    Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual-regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all 5 identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory), and right and left frontoparietal networks, whereas such age effects were not observed in the 3 identified emotion networks. In addition, we observed age-related decline in functional connectivity in 3 visual and 3 motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside 4 out of the 5 identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based functional magnetic resonance imaging studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging.

  6. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition

    PubMed Central

    Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn

    2015-01-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  7. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition.

    PubMed

    Pichora-Fuller, M Kathleen; Mick, Paul; Reed, Marilyn

    2015-08-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging.

  8. Citizen Science Program Shows Urban Areas Have Lower Occurrence of Frog Species, but Not Accelerated Declines.

    PubMed

    Westgate, Martin J; Scheele, Ben C; Ikin, Karen; Hoefer, Anke Maria; Beaty, R Matthew; Evans, Murray; Osborne, Will; Hunter, David; Rayner, Laura; Driscoll, Don A

    2015-01-01

    Understanding the influence of landscape change on animal populations is critical to inform biodiversity conservation efforts. A particularly important goal is to understand how urban density affects the persistence of animal populations through time, and how these impacts can be mediated by habitat provision; but data on this question are limited for some taxa. Here, we use data from a citizen science monitoring program to investigate the effect of urbanization on patterns of frog species richness and occurrence over 13 years. Sites surrounded by a high proportion of bare ground (a proxy for urbanization) had consistently lower frog occurrence, but we found no evidence that declines were restricted to urban areas. Instead, several frog species showed declines in rural wetlands with low-quality habitat. Our analysis shows that urban wetlands had low but stable species richness; but also that population trajectories are strongly influenced by vegetation provision in both the riparian zone and the wider landscape. Future increases in the extent of urban environments in our study area are likely to negatively impact populations of several frog species. However, existing urban areas are unlikely to lose further frog species in the medium term. We recommend that landscape planning and management focus on the conservation and restoration of rural wetlands to arrest current declines, and the revegetation of urban wetlands to facilitate the re-expansion of urban-sensitive species.

  9. Citizen Science Program Shows Urban Areas Have Lower Occurrence of Frog Species, but Not Accelerated Declines

    PubMed Central

    Westgate, Martin J.; Scheele, Ben C.; Ikin, Karen; Hoefer, Anke Maria; Beaty, R. Matthew; Evans, Murray; Osborne, Will; Hunter, David; Rayner, Laura; Driscoll, Don A.

    2015-01-01

    Understanding the influence of landscape change on animal populations is critical to inform biodiversity conservation efforts. A particularly important goal is to understand how urban density affects the persistence of animal populations through time, and how these impacts can be mediated by habitat provision; but data on this question are limited for some taxa. Here, we use data from a citizen science monitoring program to investigate the effect of urbanization on patterns of frog species richness and occurrence over 13 years. Sites surrounded by a high proportion of bare ground (a proxy for urbanization) had consistently lower frog occurrence, but we found no evidence that declines were restricted to urban areas. Instead, several frog species showed declines in rural wetlands with low-quality habitat. Our analysis shows that urban wetlands had low but stable species richness; but also that population trajectories are strongly influenced by vegetation provision in both the riparian zone and the wider landscape. Future increases in the extent of urban environments in our study area are likely to negatively impact populations of several frog species. However, existing urban areas are unlikely to lose further frog species in the medium term. We recommend that landscape planning and management focus on the conservation and restoration of rural wetlands to arrest current declines, and the revegetation of urban wetlands to facilitate the re-expansion of urban-sensitive species. PMID:26580412

  10. The mismatch negativity as an index of cognitive decline for the early detection of Alzheimer’s disease

    PubMed Central

    Ruzzoli, Manuela; Pirulli, Cornelia; Mazza, Veronica; Miniussi, Carlo; Brignani, Debora

    2016-01-01

    Evidence suggests that Alzheimer’s disease (AD) is part of a continuum, characterized by long preclinical phases before the onset of clinical symptoms. In several cases, this continuum starts with a syndrome, defined as mild cognitive impairment (MCI), in which daily activities are preserved despite the presence of cognitive decline. The possibility of having a reliable and sensitive neurophysiological marker that can be used for early detection of AD is extremely valuable because of the incidence of this type of dementia. In this study, we aimed to investigate the reliability of auditory mismatch negativity (aMMN) as a marker of cognitive decline from normal ageing progressing from MCI to AD. We compared aMMN elicited in the frontal and temporal locations by duration deviant sounds in short (400 ms) and long (4000 ms) inter-trial intervals (ITI) in three groups. We found that at a short ITI, MCI showed only the temporal component of aMMN and AD the frontal component compared to healthy elderly who presented both. At a longer ITI, aMMN was elicited only in normal ageing subjects at the temporal locations. Our study provides empirical evidence for the possibility to adopt aMMN as an index for assessing cognitive decline in pathological ageing. PMID:27616726

  11. Vascular Risk as a Predictor of Cognitive Decline in a Cohort of Elderly Patients with Mild to Moderate Dementia

    PubMed Central

    Curiati, Pedro K.; Magaldi, Regina M.; Suemoto, Claudia K.; Bottino, Cassio M.C.; Nitrini, Ricardo; Farfel, José Marcelo; Jacob-Filho, Wilson

    2014-01-01

    Background/Aims The purpose of our study was to evaluate vascular risk factors and other clinical variables as predictors of cognitive and functional decline in elderly patients with mild to moderate dementia. Methods The clinical characteristics of 82 elderly patients (mean age 79.0 ± 5.9 years; 67.1% females) with mild to moderate dementia were obtained at baseline, including years of education, Framingham Coronary Heart Disease Risk score, Hachinski Ischemic Score (HIS), Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE) score, Functional Activities Questionnaire (FAQ) score, Burden Interview Scale score, and Neuropsychiatric Inventory (NPI) score. Changes in MMSE and FAQ scores over time were assessed annually. The association between baseline clinical variables and cognitive and functional decline was investigated during 3 years of follow-up through the use of generalized linear mixed effects models. Results A trend was found towards steeper cognitive decline in patients with less vascular burden according to the HIS (β = 0.056, p = 0.09), better cognitive performance according to the CDR score (β = 0.313, p = 0.06) and worse caregiver burden according to the Burden Interview Scale score (β = −0.012, p = 0.07) at baseline. Conclusion Further studies with larger samples are necessary to confirm and expand our findings. PMID:25493090

  12. Age-dependent cognitive decline in the APP23 model precedes amyloid deposition.

    PubMed

    Van Dam, Debby; D'Hooge, Rudi; Staufenbiel, Matthias; Van Ginneken, Chris; Van Meir, Frans; De Deyn, Peter P

    2003-01-01

    Heterozygous APP23 mice, expressing human amyloid-precursor protein with the Swedish double mutation and control littermates, were subjected to behavioral and neuromotor tasks at the age of 6-8 weeks, 3 and 6 months. A hidden-platform Morris-type water maze showed an age-dependent decline of spatial memory capacities in the APP23 model. From the age of 3 months onwards, the APP23 mice displayed major learning and memory deficits as demonstrated by severely impaired learning curves during acquisition and impaired probe trial performance. In addition to the cognitive deficit, APP23 mice displayed disturbed activity patterns. Overnight cage-activity recording showed hyperactivity in the transgenics for the three age groups tested. However, a short 2-h recording during dusk phase demonstrated lower activity levels in 6-month-old APP23 mice as compared to controls. Moreover, at this age, APP23 mice differed from control littermates in exploration and activity levels in the open-field paradigm. These findings are reminiscent of disturbances in circadian rhythms and activity observed in Alzheimer patients. Determination of plaque-associated human amyloid-beta 1-42 peptides in brain revealed a fivefold increase in heterozygous APP23 mice at 6 months as compared to younger transgenics. This increase coincided with the first appearance of plaques in hippocampus and neocortex. Spatial memory deficits preceded plaque formation and increase in plaque-associated amyloid-beta 1-42 peptides, but probe trial performance did correlate negatively with soluble amyloid-beta brain concentration in 3-month-old APP23 mutants. Detectable plaque formation is not the (only) causal factor contributing to memory defects in the APP23 model.

  13. Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly – Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe)

    PubMed Central

    Roehr, Susanne; Luck, Tobias; Heser, Kathrin; Fuchs, Angela; Ernst, Annette; Wiese, Birgitt; Werle, Jochen; Bickel, Horst; Brettschneider, Christian; Koppara, Alexander; Pentzek, Michael; Lange, Carolin; Prokein, Jana; Weyerer, Siegfried; Mösch, Edelgard; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin

    2016-01-01

    Objective Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer’s disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. Methods Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. Results Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8–1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7–1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. Conclusion Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases. PMID:26766555

  14. Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies

    PubMed Central

    Rabin, Laura A.; Smart, Colette M.; Crane, Paul K.; Amariglio, Rebecca E.; Berman, Lorin M.; Boada, Mercè; Buckley, Rachel F.; Chételat, Gaël; Dubois, Bruno; Ellis, Kathryn A.; Gifford, Katherine A.; Jefferson, Angela L.; Jessen, Frank; Katz, Mindy J.; Lipton, Richard B.; Luck, Tobias; Maruff, Paul; Mielke, Michelle M.; Molinuevo, José Luis; Naeem, Farnia; Perrotin, Audrey; Petersen, Ronald C.; Rami, Lorena; Reisberg, Barry; Rentz, Dorene M.; Riedel-Heller, Steffi G.; Risacher, Shannon L.; Rodriguez, Octavio; Sachdev, Perminder S.; Saykin, Andrew J.; Slavin, Melissa J.; Snitz, Beth E.; Sperling, Reisa A.; Tandetnik, Caroline; van der Flier, Wiesje M.; Wagner, Michael; Wolfsgruber, Steffen; Sikkes, Sietske A.M.

    2015-01-01

    Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844–852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures—approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes. PMID:26402085

  15. Acceleration of oxygen decline in the tropical Pacific over the past decades by aerosol pollutants

    NASA Astrophysics Data System (ADS)

    Ito, T.; Nenes, A.; Johnson, M. S.; Meskhidze, N.; Deutsch, C.

    2016-06-01

    Dissolved oxygen in the mid-depth tropical Pacific Ocean has declined in the past several decades. The resulting expansion of the oxygen minimum zone has consequences for the region's ecosystem and biogeochemical cycles, but the causes of the oxygen decline are not yet fully understood. Here we combine models of atmospheric chemistry, ocean circulation and biogeochemical cycling to test the hypothesis that atmospheric pollution over the Pacific Ocean contributed to the redistribution of oxygen in deeper waters. We simulate the pollution-induced enhancement of atmospheric soluble iron and fixed nitrogen deposition, as well as its impacts on ocean productivity and biogeochemical cycling for the late twentieth century. The model reproduces the magnitude and large-scale pattern of the observed oxygen changes from the 1970s to the 1990s, and the sensitivity experiments reveal the reinforcing effects of pollution-enhanced iron deposition and natural climate variability. Despite the aerosol deposition being the largest in mid-latitudes, its effect on oceanic oxygen is most pronounced in the tropics, where ocean circulation transports added iron to the tropics, leading to an increased regional productivity, respiration and subsurface oxygen depletion. These results suggest that anthropogenic pollution can interact and amplify climate-driven impacts on ocean biogeochemistry, even in remote ocean biomes.

  16. ZiBuPiYin recipe improves cognitive decline by regulating gut microbiota in Zucker diabetic fatty rats.

    PubMed

    Gu, Chunyan; Zhou, Wen; Wang, Wang; Xiang, Hong; Xu, Huiying; Liang, Lina; Sui, Hua; Zhan, Libin; Lu, Xiaoguang

    2017-01-12

    Numerous researches supported that microbiota can influence behavior and modulate cognitive function through "microbiota-gut-brain" axis. Our previous study has demonstrated that ZiBuPiYin recipe (ZBPYR) possesses excellent pharmacological effects against diabetes-associated cognitive decline. To elucidate the role of ZBPYR in regulating the balance of gut microbiota to improve psychological-stress-induced diabetes-associated cognitive decline (PSDACD), we compared blood glucose, behavioral and cognitive functions and diversity of the bacterial community among experimental groups. The Zucker diabetic fatty (ZDF) rats with PSDACD exhibited behavioral and cognitive anomalies showing as increased anxiety- and depression-like behaviors and decreased learning and memory abilities. High-throughput sequencing of the bacterial 16S rRNA gene revealed that Roseburia and Coprococcus were decreased in ZDF rats with PSDACD compared with control group. Notably, these changes were reversed by ZBPYR treatment. Our findings indicate that ZBPYR might prevent PSDACD by maintaining the compositions of gut microbiota, which could be developed as a new therapy for T2D with PSDACD.

  17. Mechanism of Isoflavone Aglycone's Effect on Cognitive Performance of Senescence-Accelerated Mice

    ERIC Educational Resources Information Center

    Yang, Hong; Jin, Guifang; Ren, Dongdong; Luo, Sijing; Zhou, Tianhong

    2011-01-01

    This study investigated the effect of isoflavone aglycone (IA) on the learning and memory performance of senescence-accelerated mice, and explored its neural protective mechanism. Results showed that SAM-P/8 senescence-accelerated mice treated with IA performed significantly better in the Y-maze cognitive test than the no treatment control (P less…

  18. Digital Tracking of Cognitive Decline: Researchers Are Co-opting Computers in their Efforts to Detect Early Signs of Dementia.

    PubMed

    Solis, Michele

    2017-01-01

    Pinpointing where healthy brain aging leaves off and dementia begins is difficult. Is a slip in memory an expected outcome for a too-busy person or a warning of something else? If an empty-nester loses the motivation to cook, is it a sign that the person is enjoying retirement after a lifetime spent cooking or an early sign of a cognitive decline?

  19. Apathy and cognitive and functional decline in community-dwelling older adults: Results from the Baltimore ECA longitudinal study

    PubMed Central

    Clarke, Diana E.; Ko, Jean Y.; Lyketsos, Constantine; Rebok, George W.; Eaton, William W.

    2010-01-01

    Background Apathy, a complex neuropsychiatric syndrome, commonly affects patients with Alzheimer’s disease. Prevalence estimates for apathy range widely and are based on cross-sectional data and / or clinic samples. This study examines the relationships between apathy and cognitive and functional declines in non-depressed community-based older adults. Methods Data on 1,136 community-dwelling adults age 50 and older from the Baltimore Epidemiologic Catchment Area (ECA) study, with 1 and 13 years of follow-up, were used. Apathy was assessed with a subscale of items from the General Health Questionnaire. Chi-square, t-tests, logistic regression, and Generalized Estimating Equations were used to accomplish the study’s objectives. Results The prevalence of apathy at Wave 1 was 23.7%. Compared to those without, individuals with apathy were on average older, more likely to be female, and have lower MMSE scores and impairments in basic and instrumental functioning at baseline. Apathy was significantly associated with cognitive decline (OR = 1.65, 95% CI = 1.06, 2.60) and declines in instrumental (OR = 4.42; 95% CI = 2.65, 7.38) and basic (OR=2.74; 95%CI= 1.35, 5.57) function at 1 year follow-up, even after adjustment for baseline age, level of education, race, and depression at follow-up. At 13 years of follow-up, apathetic individuals were not at greater risk for cognitive decline but were 2-fold more likely to have functional decline. Incidence of apathy at 1- year follow up and 13- year follow-up was respectively, 22.6% and 29.4%. Conclusions These results underline the public health importance of apathy and the need for further population-based studies in this area. PMID:20478091

  20. Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer’s Disease and Vascular Dementia: a Retrospective Study

    PubMed Central

    Pilon, Marie-Hélène; Poulin, Stéphane; Fortin, Marie-Pierre; Houde, Michèle; Verret, Louis; Bouchard, Rémi W.; Laforce, Robert

    2016-01-01

    Few studies have explored the rate of cognitive decline and caregiver burden within the context of a specialized memory clinic. When this was done, the focus was largely on functional decline related to Alzheimer’s disease (AD). Our goal was to compare the longitudinal decline of AD patients to those with Vascular Dementia (VaD) on Mini-Mental State Examination (MMSE). We further explored the differential impact on caregiver burden. We retrospectively studied 237 charts from patients seen at our Memory Clinic between 2006 and 2012. The data was collected over 17 years. Cohorts were formed by excluding conditions other than AD and VaD, and including patients who had been assessed at least twice with the MMSE (AD: n = 83; mean age: 67.7 yo; VaD: n = 32; mean age: 73.3yo). A small group of 36 caregivers was surveyed by phone to explore caregiver burden. Results indicated that the natural history of MMSE changes in AD patients differed significantly from that of patients with VaD (F = 10.41, p<0.0014), with AD patients showing more cognitive decline over time. Sadness, stress/anxiety, fatigue, and sleep disorders were reported as the main preoccupations by caregivers and its impact was rated as ‘severe’ in 50% of cases. Altogether, this study provides further insight into the natural history of cognitive decline in AD and VaD. Future studies should explore the progression of dementing disorders in larger cohorts using prospective methodological designs. PMID:27747317

  1. Impact of Physical Activity on Cognitive Decline, Dementia, and Its Subtypes: Meta-Analysis of Prospective Studies

    PubMed Central

    Ibrahim, Noor A.; Adam, Mohd B.; Said, Salmiah Md

    2017-01-01

    The association of physical activity with dementia and its subtypes has remained controversial in the literature and has continued to be a subject of debate among researchers. A systematic review and meta-analysis of longitudinal studies on the relationship between physical activity and the risk of cognitive decline, all-cause dementia, Alzheimer's disease, and vascular dementia among nondemented subjects are considered. A comprehensive literature search in all available databases was conducted up until April 2016. Well-defined inclusion and exclusion criteria were developed with focus on prospective studies ≥ 12 months. The overall sample from all studies is 117410 with the highest follow-up of 28 years. The analyses are performed with both Bayesian parametric and nonparametric models. Our analysis reveals a protective effect for high physical activity on all-cause dementia, odds ratio of 0.79, 95% CI (0.69, 0.88), a higher and better protective effect for Alzheimer's disease, odds ratio of 0.62, 95% CI (0.49, 0.75), cognitive decline odds ratio of 0.67, 95% CI (0.55, 0.78), and a nonprotective effect for vascular dementia of 0.92, 95% CI (0.62, 1.30). Our findings suggest that physical activity is more protective against Alzheimer's disease than it is for all-cause dementia, vascular dementia, and cognitive decline. PMID:28271072

  2. VENTRICULAR MAPS IN 804 SUBJECTS CORRELATE WITH COGNITIVE DECLINE, CSF PATHOLOGY, AND IMMINENT ALZHEIMER’S DISEASE

    PubMed Central

    Chou, Yi-Yu; Leporé, Natasha; Madsen, Sarah K.; Saharan, Priya; Hua, Xue; Jack, Clifford R.; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Toga, Arthur W.; Thompson, Paul M.

    2017-01-01

    There is an urgent need for neuroimaging biomarkers of Alzheimer’s disease (AD) that correlate with cognitive decline, and with accepted measures of pathology detectable in cerebrospinal fluid (CSF). Ideal biomarkers should also be able to predict future decline, and should be computable automatically from hundreds to thousands of images without user intervention. Here we used our multi-atlas fluid image alignment method (MAFIA [1]), to automatically segment parametric 3D surface models of the lateral ventricles in brain MRI scans from 184 AD, 391 MCI, and 229 healthy elderly controls. Radial expansion of the ventricles, computed pointwise, was correlated with measures of (1) clinical decline, (2) pathology from CSF, and (3) future deterioration. Surface–based correlation maps were assessed using a cumulative distribution function method to rank influential covariates according to their effect sizes. The resulting approach is highly automated, and boosts the power of fluid image registration by integrating multiple independent registrations to reduce segmentation errors.

  3. Daytime somnolence as an early sign of cognitive decline in a community-based study of older people

    PubMed Central

    Tsapanou, Angeliki; Gu, Yian; O’Shea, Deirdre; Eich, Teal; Tang, Ming-Xin; Schupf, Nicole; Manly, Jennifer; Zimmerman, Molly; Scarmeas, Nikolaos; Stern, Yaakov

    2017-01-01

    Objective This study aimed to examine the association between self-reported sleep problems and cognitive decline in community-dwelling older people. We hypothesized that daytime somnolence predicts subsequent cognitive decline. Methods This is a longitudinal study in a 3.2-year follow-up, with 18-month intervals. The setting is the Washington Heights-Inwood Community Aging Project. There were 1098 participants, who were over 65 years old and recruited from the community. Sleep problems were estimated using five sleep categories derived from the RAND Medical Outcome Study Sleep Scale: sleep disturbance, snoring, awaken short of breath/with a headache, sleep adequacy, and daytime somnolence. Four distinct cognitive composite scores were calculated: memory, language, speed of processing, and executive functioning. We used generalized estimating equations analyses with cognitive scores as the outcome, and time, sleep categories and their interactions as the main predictors. Models were initially unadjusted and then adjusted for age, gender, education, ethnicity, depression, and apolipoprotein E-ε4 genotype. Results Increased daytime somnolence (including feeling drowsy/sleepy, having trouble staying awake, and taking naps during the day) was linked to slower speed of processing both cross-sectionally (B = −0.143, p = 0.047) and longitudinally (B = −0.003, p = 0.027). After excluding the demented participants at baseline, the results remained significant (B = −0.003, p = 0.021). Conclusions Our findings suggest that daytime somnolence may be an early sign of cognitive decline in the older population. Copyright # 2015 John Wiley & Sons, Ltd. PMID:26081795

  4. Exploring patients' reasons for declining contact in a cognitive behavioural therapy randomised controlled trial in primary care

    PubMed Central

    Barnes, Maria; Wiles, Nicola; Morrison, Jill; Kessler, David; Williams, Chris; Kuyken, Willem; Lewis, Glyn; Turner, Katrina

    2012-01-01

    Background The difficulties of recruiting individuals into mental health trials are well documented. Few studies have collected information from those declining to take part in research, in order to understand the reasons behind this decision. Aim To explore patients' reasons for declining to be contacted about a study of the effectiveness of cognitive behavioural therapy as a treatment for depression. Design and setting Questionnaire and telephone interview in general practices in England and Scotland. Method Patients completed a short questionnaire about their reasons for not taking part in research. Semi-structured telephone interviews were conducted with a purposive sample to further explore reasons for declining. Results Of 4552 patients responding to an initial invitation to participate in research involving a talking therapy, 1642 (36%) declined contact. The most commonly selected reasons for declining were that patients did not want to take part in a research study (n = 951) and/or did not want to have a talking therapy (n = 688) (more than one response was possible). Of the decliners, 451 patients agreed to an interview about why they declined. Telephone interviews were completed with 25 patients. Qualitative analysis of the interview data indicated four main themes regarding reasons for non-participation: previous counselling experiences, negative feelings about the therapeutic encounter, perceived ineligibility, and misunderstandings about the research. Conclusion Collecting information about those who decline to take part in research provides information on the acceptability of the treatment being studied. It can also highlight concerns and misconceptions about the intervention and research, which can be addressed by researchers or recruiting GPs. This may improve recruitment to studies and thus ultimately increase the evidence base. PMID:22546597

  5. Neuroanatomical and Neuropsychological Markers of Amnestic MCI: A Three-Year Longitudinal Study in Individuals Unaware of Cognitive Decline

    PubMed Central

    Goerlich, Katharina S.; Votinov, Mikhail; Dicks, Ellen; Ellendt, Sinika; Csukly, Gábor; Habel, Ute

    2017-01-01

    Structural brain changes underlying mild cognitive impairment (MCI) have been well-researched, but most previous studies required subjective cognitive complaints (SCC) as a diagnostic criterion, diagnosed MCI based on a single screening test or lacked analyses in relation to neuropsychological impairment. This longitudinal voxel-based morphometry study aimed to overcome these limitations: The relationship between regional gray matter (GM) atrophy and behavioral performance was investigated over the course of 3 years in individuals unaware of cognitive decline, identified as amnestic MCI based on an extensive neuropsychological test battery. Region of interest analyses revealed GM atrophy in the left amygdala, hippocampus, and parahippocampus in MCI individuals compared to normally aging participants, which was specifically related to verbal memory impairment and evident already at the first measurement point. These findings demonstrate that GM atrophy is detectable in individuals with amnestic MCI despite unawareness of beginning cognitive decline. Thus, individuals with GM atrophy in regions associated with verbal memory impairment do not necessarily need to experience SCC before meeting neuropsychological criteria for MCI. These results have important implications for future research and diagnostic procedures of MCI. PMID:28275349

  6. Nicotinamide Forestalls Pathology and Cognitive Decline in Alzheimer Mice: Evidence for Improved Neuronal Bioenergetics and Autophagy Procession

    PubMed Central

    Liu, Dong; Pitta, Michael; Jiang, Haiyang; Lee, Jong-Hwan; Zhang, Guofeng; Chen, Xinzhi; Kawamoto, Elisa M.; Mattson, Mark P.

    2012-01-01

    Impaired brain energy metabolism and oxidative stress are implicated in cognitive decline and the pathological accumulations of amyloid β-peptide (Aβ) and hyperphosphorylated Tau (p-Tau) in Alzheimer's disease (AD). To determine whether improving brain energy metabolism will forestall disease progress in AD, the impact of the NAD+ precursor nicotinamide on brain cell mitochondrial function and macroautophagy, bioenergetics-related signaling and cognitive performance were studied in cultured neurons and in a mouse model of AD. Oxidative stress resulted in decreased mitochondrial mass, mitochondrial degeneration and autophagosome accumulation in neurons. Nicotinamide preserved mitochondrial integrity and autophagy function, and reduced neuronal vulnerability to oxidative/metabolic insults and Aβ toxicity. NAD+ biosynthesis, autophagy and PI3K signaling were required for the neuroprotective action of nicotinamide. Treatment of 3xTgAD mice with nicotinamide for 8 months resulted in improved cognitive performance, and reduced Aβ and p-Tau pathologies in hippocampus and cerebral cortex. Nicotinamide treatment preserved mitochondrial integrity, and improved autophagy-lysosome procession by enhancing lysosome/autolysosome acidification to reduce autophagosome accumulation. Treatment of 3xTgAD mice with nicotinamide resulted in elevated levels of activated neuroplasticity-related kinases (Akt and ERKs) and the transcription factor cyclic AMP response element-binding protein in the hippocampus and cerebral cortex. Thus, nicotinamide suppresses AD pathology and cognitive decline in a mouse model of AD by a mechanism involving improved brain bioenergetics with preserved functionality of mitochondria and the autophagy system. PMID:23273573

  7. Graph theoretical analysis of functional networks and its relationship to cognitive decline in patients with carotid stenosis

    PubMed Central

    Chang, Ting-Yu; Huang, Kuo-Lun; Ho, Meng-Yang; Ho, Pei-Shan; Chang, Chien-Hung; Liu, Chi-Hung; Chang, Yeu-Jhy; Wong, Ho-Fai; Hsieh, I-Chang; Lee, Tsong-Hai

    2015-01-01

    Significant carotid stenosis compromises hemodynamics and impairs cognitive functions. The interplay between these changes and brain connectivity has rarely been investigated. We aimed to discover the changes of functional connectivity and its relation to cognitive decline in carotid stenosis patients. Twenty-seven patients with unilateral carotid stenosis (≥60%) and 20 age- and sex-matched controls underwent neuropsychological tests and resting-state functional magnetic resonance imaging. The patients also received perfusion magnetic resonance imaging. The relationships between cognitive function and functional networks among the patients and controls were evaluated. Graph theory was applied on resting-state functional magnetic resonance imaging network analysis, which revealed that the hemispheres ipsilateral to the stenosis were significantly impaired in “degree” and “global efficiency.” The neuropsychological performances were positively correlated with degree, clustering coefficient, local efficiency, and global efficiency, and negatively correlated with characteristic path length, modularity, and small-worldness in the patients, whereas these relationships were not observed in the controls. In this study, we identified the networks that were impaired in the affected hemispheres in patients with carotid stenosis. Specific indices (global efficiency, characteristic path length, and modularity) were highly correlated with neuropsychological performance in our patients. Analysis of brain connectivity may help to elucidate the relationship between hemodynamic impairment and cognitive decline. PMID:26661184

  8. Potential of N-acetylated-para-aminosalicylic Acid to Accelerate Manganese Enhancement Decline for Long-term MEMRI in Rodent Brain

    PubMed Central

    Bade, Aditya N; Zhou, Biyun; McMillan, JoEllyn; Narayanasamy, Prabagaran; Veerubhotla, Ram; Gendelman, Howard E; Boska, Michael D; Liu, Yutong

    2015-01-01

    Background Manganese (Mn2+)-enhanced MRI (MEMRI) is a valuable imaging tool to study brain structure and function in normal and diseased small animals. The brain retention of Mn2+ is relatively long with a half-life (t1/2) of 51 to 74 days causing a slow decline of MRI signal enhancement following Mn2+ administration. Such slow decline limits using repeated MEMRI to follow the central nervous system longitudinally in weeks or months. This is because residual Mn2+ from preceding administrations can confound the interpretation of imaging results. We investigated whether the Mn2+ enhancement decline could be accelerated thus enabling repeated MEMRI, and as a consequence broadens the utility of MEMRI tests. New Methods We investigated whether N-acetyl-para-aminosalicylic acid (AcPAS), a chelator of Mn2+, could affect the decline of Mn2+ induced MRI enhancement in brain. Results and Conclusion Two-week treatment with AcPAS (200 mg/kg/dose × 3 daily) accelerated the decline of Mn2+ induced enhancement in MRI. In the whole brain on average the enhancement declined from 100% to 17% in AcPAS treated mice, while in PBS controls the decline is from 100% to 27%. We posit that AcPAS could enhance MEMRI utility for evaluating brain biology in small animals. Comparison with Existing Methods To the best of our knowledge, no method exists to accelerate the decline of the Mn2+ induced MRI enhancement for repeated MEMRI tests. PMID:26004847

  9. Addiction, cognitive decline and therapy: seeking ways to escape a vicious cycle.

    PubMed

    Perry, C J; Lawrence, A J

    2017-01-01

    Any type of behavioral change is an effortful process. Thus, the process of behavioral therapy, where clients seek to change maladaptive behavioral patterns, requires high-level cognitive engagement. It is unfortunate, then, that cognitive impairment is a feature of substance use disorders (SUDs), and especially because the domains that tend to be impaired are the very ones involved in the process of therapeutic behavioral change. In this review, we compare the cognitive profile that is frequently observed with chronic SUD with the skills that are required to initiate and sustain behavioral change during rehabilitation. Furthermore, we look to new therapeutic developments that seek to improve cognitive function. We propose that the use of these cognitive enhancing agents as adjuncts to behavioral therapy should help to overcome some of the cognitive barriers imposed by the disorder itself, and hence reduce the chance of relapse.

  10. Carriers of a common variant in the dopamine transporter gene have greater dementia risk, cognitive decline, and faster ventricular expansion

    PubMed Central

    Roussotte, Florence F.; Gutman, Boris A.; Hibar, Derrek P.; Madsen, Sarah K.; Narr, Katherine L.; Thompson, Paul M.

    2015-01-01

    Background Genetic variants in DAT1, the gene encoding the dopamine transporter protein (DAT), have been implicated in many brain disorders. In a recent case-control study of Alzheimer’s disease (AD), a regulatory polymorphism in DAT1 showed a significant association with the clinical stages of dementia. Methods We tested whether this variant was associated with increased AD risk, and with measures of cognitive decline and longitudinal ventricular expansion, in a large sample of elderly participants with genetic, neurocognitive, and neuroimaging data from the Alzheimer’s Disease Neuroimaging Initiative. Results The minor allele – previously linked with increased DAT expression in vitro – was More common in AD patients than in both individuals with mild cognitive impairment and Healthy elderly controls. The same allele was also associated with poorer cognitive performance and faster ventricular expansion, independently of diagnosis. Conclusion These results may be due to reduced dopaminergic transmission in carriers of the DAT1 mutation. PMID:25496873

  11. Parkinson's disease accelerates age-related decline in haptic perception by altering somatosensory integration.

    PubMed

    Konczak, Jürgen; Sciutti, Alessandra; Avanzino, Laura; Squeri, Valentina; Gori, Monica; Masia, Lorenzo; Abbruzzese, Giovanni; Sandini, Giulio

    2012-11-01

    This study investigated how Parkinson's disease alters haptic perception and the underlying mechanisms of somatosensory and sensorimotor integration. Changes in haptic sensitivity and acuity (the abilities to detect and to discriminate between haptic stimuli) due to Parkinson's disease were systematically quantified and contrasted to the performance of healthy older and young adults. Using a robotic force environment, virtual contours of various curvatures were presented. Participants explored these contours with their hands and indicated verbally whether they could detect or discriminate between two contours. To understand what aspects of sensory or sensorimotor integration are altered by ageing and disease, we manipulated the sensorimotor aspect of the task: the robot either guided the hand along the contour or the participant actively moved the hand. Active exploration relies on multimodal sensory and sensorimotor integration, while passive guidance only requires sensory integration of proprioceptive and tactile information. The main findings of the study are as follows: first, a decline in haptic precision can already be observed in adults before the age of 70 years. Parkinson's disease may lead to an additional decrease in haptic sensitivity well beyond the levels typically seen in middle-aged and older adults. Second, the haptic deficit in Parkinson's disease is general in nature. It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller perceivable range and a diminished ability to discriminate between two perceivable haptic stimuli). Third, thresholds during both active and passive exploration are elevated, but not significantly different from each other. That is, active exploration did not enhance the haptic deficit when compared to passive hand motion. This implies that Parkinson's disease affects early stages of somatosensory integration that ultimately have an impact on processes of sensorimotor integration. Our results suggest that

  12. The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer’s Disease

    PubMed Central

    De Vos, Ann; Struyfs, Hanne; Jacobs, Dirk; Fransen, Erik; Klewansky, Tom; De Roeck, Ellen; Robberecht, Caroline; Van Broeckhoven, Christine; Duyckaerts, Charles; Engelborghs, Sebastiaan; Vanmechelen, Eugeen

    2016-01-01

    Background: In diagnosing Alzheimer’s disease (AD), ratios of cerebrospinal fluid (CSF) biomarkers, such as CSF Aβ1-42/tau, have an improved diagnostic performance compared to the single analytes, yet, still a limited value to predict cognitive decline. Since synaptic dysfunction/loss is closely linked to cognitive impairment, synaptic proteins are investigated as candidate CSF AD progression markers. Objective: We studied CSF levels of the postsynaptic protein neurogranin and protein BACE1, predominantly localized presynaptically, and their relation to CSF total-tau, Aβ1-42, Aβ1-40, and Aβ1-38. All six analytes were considered as single parameters as well as ratios. Methods: Every ELISA involved was based on monoclonal antibodies, including the BACE1 and neurogranin immunoassay. The latter specifically targets neurogranin C-terminally truncated at P75, a more abundant species of the protein in CSF. We studied patients with MCI due to AD (n = 38) and 50 dementia due to AD patients, as well as age-matched cognitively healthy elderly (n = 20). A significant subset of the patients was followed up by clinical and neuropsychologically (MMSE) examinations for at least one year. Results: The single analytes showed statistically significant differences between the clinical groups, but the ratios of analytes indeed had a higher diagnostic performance. Furthermore, only the ratio of CSF neurogranin trunc P75/BACE1 was significantly correlated with the yearly decline in MMSE scores in patients with MCI and dementia due to AD, pointing toward the prognostic value of the ratio. Conclusion: This is the first study demonstrating that the CSF neurogranin trunc P75/BACE1 ratio, reflecting postsynaptic/presynaptic integrity, is related to cognitive decline. PMID:27392859

  13. Poor Aerobic Fitness May Contribute to Cognitive Decline in HIV-infected Older Adults

    PubMed Central

    Mapstone, Mark; Hilton, Tiffany N.; Yang, Hongmei; Guido, Joseph J.; Luque, Amneris E.; Hall, William J.; Dewhurst, Stephen; Shah, Krupa

    2013-01-01

    The HIV-infected older adult (HOA) community is particularly vulnerable to cognitive impairment. Previous studies in the general older adult population have reported that lower scores on tests of cognitive function often correlate negatively with aerobic fitness [5–7]. HIV-infected individuals have significantly reduced aerobic fitness and physical function compared to HIV-uninfected individuals. Determining important correlates of cognitive ability may be beneficial in not only detecting precursors to future cognitive impairments, but also target areas for interventions. The purpose of this study was to investigate the relationship between cognitive ability and aerobic fitness in HIV-infected older adults. We conducted a cross-sectional study of HOA on antiretroviral therapy (ART) >50 years of age. Domain specific cognitive function was assessed by means of a neuropsychological battery. Aerobic fitness (VO2peak) was assessed using a graded, progressive treadmill test. Thirty-seven HOA on ART (mean±SD: age 59±6 years, BMI 28±5, CD4 663±337 cells/ml, duration since HIV diagnosis 17±7 years; 81% males) completed the cognitive tests. Several domains of cognition were significantly associated with VO2peak by Spearman correlation analysis (p<0.05). By step-wise adjusted regression VO2peak was most frequently and significantly related to many cognitive domains such as verbal and visual memory, visual perception, and language (p<0.05). We found that participants with higher Vo2peak were less likely to have more severe forms of HIV-associated neurocognitive disorders (HAND) such as mild neurocognitive disorder (OR=0.65; p=0.01) and HIV-associated dementia (OR=0.64; p=0.0006). In HOA and in conclusion, aerobic fitness is related to cognitive performance on various tasks. The likelihood of cognitive impairment increased with lower fitness levels. Therefore, increased fitness may serve an important factor in maintenance of cognition and neural integrity for aging HIV

  14. Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline.

    PubMed

    Noguchi-Shinohara, Moeko; Yuki, Sohshi; Dohmoto, Chiaki; Ikeda, Yoshihisa; Samuraki, Miharu; Iwasa, Kazuo; Yokogawa, Masami; Asai, Kimiko; Komai, Kiyonobu; Nakamura, Hiroyuki; Yamada, Masahito

    2014-01-01

    Our objective was to determine whether the consumption of green tea, coffee, or black tea influences the incidence of dementia and mild cognitive impairment (MCI) in older people. We conducted a population-based prospective study with Japanese residents aged >60 years from Nakajima, Japan (the Nakajima Project). Participants received an evaluation of cognitive function and blood tests. The consumption of green tea, coffee, and black tea was also evaluated at baseline. Of 723 participants with normal cognitive function at a baseline survey (2007-2008), 490 completed the follow up survey in 2011-2013. The incidence of dementia during the follow-up period (mean ± SD: 4.9 ± 0.9 years) was 5.3%, and that of MCI was 13.1%. The multiple-adjusted odds ratio for the incidence of overall cognitive decline (dementia or MCI) was 0.32 (95% CI: 0.16-0.64) among individuals who consumed green tea every day and 0.47 (95% CI: 0.25-0.86) among those who consumed green tea 1-6 days per week compared with individuals who did not consume green tea at all. The multiple-adjusted odds ratio for the incidence of dementia was 0.26 (95% CI: 0.06-1.06) among individuals who consumed green tea every day compared with those who did not consume green tea at all. No association was found between coffee or black tea consumption and the incidence of dementia or MCI. Our results indicate that green tea consumption is significantly associated with reduced risk of cognitive decline, even after adjustment for possible confounding factors.

  15. Consumption of Green Tea, but Not Black Tea or Coffee, Is Associated with Reduced Risk of Cognitive Decline

    PubMed Central

    Noguchi-Shinohara, Moeko; Yuki, Sohshi; Dohmoto, Chiaki; Ikeda, Yoshihisa; Samuraki, Miharu; Iwasa, Kazuo; Yokogawa, Masami; Asai, Kimiko; Komai, Kiyonobu; Nakamura, Hiroyuki; Yamada, Masahito

    2014-01-01

    Our objective was to determine whether the consumption of green tea, coffee, or black tea influences the incidence of dementia and mild cognitive impairment (MCI) in older people. We conducted a population-based prospective study with Japanese residents aged >60 years from Nakajima, Japan (the Nakajima Project). Participants received an evaluation of cognitive function and blood tests. The consumption of green tea, coffee, and black tea was also evaluated at baseline. Of 723 participants with normal cognitive function at a baseline survey (2007–2008), 490 completed the follow up survey in 2011–2013. The incidence of dementia during the follow-up period (mean ± SD: 4.9±0.9 years) was 5.3%, and that of MCI was 13.1%. The multiple-adjusted odds ratio for the incidence of overall cognitive decline (dementia or MCI) was 0.32 (95% CI: 0.16–0.64) among individuals who consumed green tea every day and 0.47 (95% CI: 0.25–0.86) among those who consumed green tea 1–6 days per week compared with individuals who did not consume green tea at all. The multiple-adjusted odds ratio for the incidence of dementia was 0.26 (95% CI: 0.06–1.06) among individuals who consumed green tea every day compared with those who did not consume green tea at all. No association was found between coffee or black tea consumption and the incidence of dementia or MCI. Our results indicate that green tea consumption is significantly associated with reduced risk of cognitive decline, even after adjustment for possible confounding factors. PMID:24828424

  16. Neuroticism Combined With Slower and More Variable Reaction Time: Synergistic Risk Factors for 7-Year Cognitive Decline in Females

    PubMed Central

    Shickle, Darren A.; Roberts, Beverly A.; Deary, Ian J.

    2012-01-01

    Objective. Among adults, slower and more variable reaction times are associated with worse cognitive function and increased mortality risk. Therefore, it is important to elucidate risk factors for reaction time change over the life course. Method. Data from the Health and Lifestyle Survey (HALS) were used to examine predictors of 7-year decline in reaction time (N = 4,260). Regression-derived factor scores were used to summarize general change across 4 reaction time variables: simple mean, 4-choice mean, simple variability, and 4-choice variability (53.52% of variance). Results. Age (B = .02, p < .001) and HALS1 baseline reaction time (B = −.10, p = .001) were significant risk factors for males (N = 1,899). In addition to these variables, in females (N = 2,361), neuroticism was significant and interacted synergistically with baseline reaction time (B = .06, p = .04). Adjustment for physiological variables explained the interaction with neuroticism, suggesting that candidate mechanisms had been identified. Discussion. A priority for future research is to replicate interactions between personality and reaction time in other samples and find specific mechanisms. Stratification of population data on cognitive health by personality and reaction time could improve strategies for identifying those at greater risk of cognitive decline. PMID:22367712

  17. Disruptions in Brain Networks of Older Fallers Are Associated with Subsequent Cognitive Decline: A 12-Month Prospective Exploratory Study

    PubMed Central

    Hsu, Chun Liang; Voss, Michelle W.; Handy, Todd C.; Davis, Jennifer C.; Nagamatsu, Lindsay S.; Chan, Alison; Bolandzadeh, Niousha; Liu-Ambrose, Teresa

    2014-01-01

    Cognitive impairment and impaired mobility are major public health concerns. There is growing recognition that impaired mobility is an early biomarker of cognitive impairment and dementia. The neural basis for this association is currently unclear. We propose disrupted functional connectivity as a potential mechanism. In this 12-month prospective exploratory study, we compared functional connectivity of four brain networks– the default mode network (DMN), fronto-executive network (FEN), fronto-parietal network (FPN), and the primary motor sensory network (SMN) – between community-dwelling older adults with ≥ two falls in the last 12 months and their non-falling counterparts (≤ one fall in the last 12 months). Functional connectivity was examined both at rest and during a simple motor tapping task. Compared with non-fallers, fallers showed more connectivity between the DMN and FPN during right finger tapping (p = 0.04), and significantly less functional connectivity between the SMN and FPN during rest (p≤0.05). Less connectivity between the SMN and FPN during rest was significantly associated with greater decline in both cognitive function and mobility over the12-month period (r = −0.32 and 0.33 respectively; p≤0.04). Thus, a recent history of multiple falls among older adults without a diagnosis of dementia may indicate sub-clinical changes in brain function and increased risk for subsequent decline. PMID:24699668

  18. Accelerating Leadership Development via Immersive Learning and Cognitive Apprenticeship

    ERIC Educational Resources Information Center

    Backus, Clark; Keegan, Kevin; Gluck, Charles; Gulick, Lisa M. V.

    2010-01-01

    The authors put forward an approach to leadership development that builds on the principle of accelerated learning. They argue that leadership development, particularly in a period of recession or slow economic growth, needs to deliver results more quickly and with fewer resources. Indeed, they raise the question of whether or not this is what is…

  19. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances

    PubMed Central

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging. PMID:27616991

  20. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances.

    PubMed

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging.

  1. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

    PubMed Central

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  2. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions.

    PubMed

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons.

  3. Angiotensin Converting Enzyme Inhibitors and Cognitive Decline in Older Adults with Hypertension: Results from the Cardiovascular Health Study

    PubMed Central

    Sink, Kaycee M.; Leng, Xiaoyan; Williamson, Jeff; Kritchevsky, Stephen B.; Yaffe, Kristine; Kuller, Lewis; Yasar, Sevil; Atkinson, Hal; Robbins, Mike; Psaty, Bruce; Goff, David C.

    2010-01-01

    Background Hypertension (HTN) is a risk factor for dementia and animal studies suggest that centrally active (cross the blood brain barrier) angiotensin converting enzyme (ACE) inhibitors may protect against dementia beyond HTN control. Methods Participants in the Cardiovascular Health Study cognition substudy (mean age 75 yrs) with treated HTN and no diagnosis of heart failure (n= 1054) were followed for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared to other antihypertensive agents, was associated with lower risk of incident dementia, cognitive decline (by the modified mini mental state exam, 3MSE), or incident disability in instrumental activities of daily living (IADL). Results Among 414 participants exposed to ACE inhibitors and 640 not, there were 158 cases of incident dementia. Compared to other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (HR 1.01, 95% CI 0.88–1.15), difference in 3MSE scores (−0.32 points/yr, p=0.15), or odds of IADL disability (OR (95% CI) 1.06 (0.99–1.14). Adjusted results were similar. However, centrally active ACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (p= 0.01) and non-centrally active ACE inhibitors were associated with greater risk of incident dementia (adjusted HR 1.20 (1.00–1.43) per year of exposure) and greater odds of IADL disability (adjusted OR 1.16 (1.03–1.30) per year of exposure) compared to other anti-HTN drugs. Conclusions While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within class differences in regards to these outcomes. These results should be confirmed with an RCT of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia. PMID:19597068

  4. Memory factors in Rey AVLT: Implications for early staging of cognitive decline.

    PubMed

    Fernaeus, Sven-Erik; Ostberg, Per; Wahlund, Lars-Olof; Hellström, Ake

    2014-12-01

    Supraspan verbal list learning is widely used to assess dementia and related cognitive disorders where declarative memory deficits are a major clinical sign. While the overall learning rate is important for diagnosis, serial position patterns may give insight into more specific memory processes in patients with cognitive impairment. This study explored these patterns in a memory clinic clientele. One hundred eighty three participants took the Rey Auditory-Verbal Learning Test (RAVLT). The major groups were patients with Alzheimer's disease (AD), Vascular Dementia (VD), Mild Cognitive Impairment (MCI), and Subjective Cognitive Impairment (SCI) as well as healthy controls (HC). Raw scores for the five trials and five serial partitions were factor analysed. Three memory factors were found and interpreted as Primacy, Recency, and Resistance to Interference. AD and MCI patients had impaired scores in all factors. SCI patients were significantly impaired in the Resistance to Interference factor, and in the Recency factor at the first trial. The main conclusion is that serial position data from word list testing reflect specific memory capacities which vary with levels of cognitive impairment.

  5. The effect of Chinese Jinzhida recipe on the hippocampus in a rat model of diabetes-associated cognitive decline

    PubMed Central

    2013-01-01

    Background To investigate the effects of treatment with Multi component Chinese Medicine Jinzhida (JZD) on behavioral deficits in diabetes-associated cognitive decline (DACD) rats and verify our hypothesis that JZD treatment improves cognitive function by suppressing the endoplasmic reticulum stress (ERS) and improving insulin signaling transduction in the rats’ hippocampus. Methods A rat model of type 2 diabetes mellitus (T2DM) was established using high fat diet and streptozotocin (30 mg/kg, ip). Insulin sensitivity was evaluated by the oral glucose tolerance test and the insulin tolerance test. After 7 weeks, the T2DM rats were treated with JZD. The step-down test and Morris water maze were used to evaluate behavior in T2DM rats after 5 weeks of treatment with JZD. Levels of phosphorylated proteins involved in the ERS and in insulin signaling transduction pathways were assessed by Western blot for T2DM rats’ hippocampus. Results Compared to healthy control rats, T2DM rats initially showed insulin resistance and had declines in acquisition and retrieval processes in the step-down test and in spatial memory in the Morris water maze after 12 weeks. Performance on both the step-down test and Morris water maze tasks improved after JZD treatment. In T2DM rats, the ERS was activated, and then inhibited the insulin signal transduction pathways through the Jun NH2-terminal kinases (JNK) mediated. JZD treatment suppressed the ERS, increased insulin signal transduction, and improved insulin resistance in the rats’ hippocampus. Conclusions Treatment with JZD improved cognitive function in the T2DM rat model. The possible mechanism for DACD was related with ERS inducing the insulin signal transduction dysfunction in T2DM rats’ hippocampus. The JZD could reduce ERS and improve insulin signal transduction and insulin resistance in T2DM rats’ hippocampus and as a result improved the cognitive function. PMID:23829668

  6. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy.

    PubMed

    Francis, George J; Martinez, Jose A; Liu, Wei Q; Xu, Kevin; Ayer, Amit; Fine, Jared; Tuor, Ursula I; Glazner, Gordon; Hanson, Leah R; Frey, William H; Toth, Cory

    2008-12-01

    Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential adverse systemic effects. Daily I-I, subcutaneous insulin (S-I) or placebo in separate cohorts of diabetic and non-diabetic CD1 mice were delivered over 8 months of life. Radio-labelled insulin delivery revealed that I-I delivered more rapid and substantial insulin levels within the cerebrum with less systemic insulin detection when compared with S-I. I-I delivery slowed development of cognitive decline within weekly cognitive/behavioural testing, ameliorated monthly magnetic resonance imaging abnormalities, prevented quantitative morphological abnormalities in cerebrum, improved mouse mortality and reversed diabetes-mediated declines in mRNA and protein for phosphoinositide 3-kinase (PI3K)/Akt and for protein levels of the transcription factors cyclic AMP response element binding protein (CREB) and glycogen synthase kinase 3beta (GSK-3beta) within different cerebral regions. Although the murine diabetic brain was not subject to cellular loss, a diabetes-mediated loss of protein and mRNA for the synaptic elements synaptophysin and choline acetyltransferase was prevented with I-I delivery. As a mechanism of delivery, I-I accesses the brain readily and slows the development of diabetes-induced brain changes as compared to S-I delivery. This therapy and delivery mode, available in humans, may be of clinical utility for the prevention of pathological changes in the diabetic human brain.

  7. Cognitive decline in Alzheimer’s disease is associated with selective changes in calcineurin/NFAT signaling

    PubMed Central

    Abdul, Hafiz Mohmmad; Sama, Michelle A.; Furman, Jennifer L.; Mathis, Diana M.; Beckett, Tina L.; Weidner, Adam M.; Patel, Ela S.; Baig, Irfan; Murphy, M. Paul; 3rd, Harry LeVine; Kraner, Susan D.; Norris, Christopher M.

    2009-01-01

    Upon activation by calcineurin, the nuclear factor of activated T cells (NFAT) translocates to the nucleus and guides the transcription of numerous molecules involved in inflammation and Ca2+ dysregulation, both of which are prominent features of Alzheimer’s disease (AD). However, NFAT signaling in AD remains relatively uninvestigated. Using isolated cytosolic and nuclear fractions prepared from rapid-autopsy postmortem human brain tissue, we show that NFATs 1 and 3 shifted to nuclear compartments in the hippocampus at different stages of neuropathology and cognitive decline, while NFAT2 remained unchanged. NFAT1 exhibited greater association with isolated nuclear fractions in subjects with mild cognitive impairment (MCI), while NFAT3 showed a strong nuclear bias in subjects with severe dementia and AD. Similar to NFAT1, calcineurin-Aα also exhibited a nuclear bias in the early stages of cognitive decline. But, unlike NFAT1 and similar to NFAT3, the nuclear bias for calcineurin became more pronounced as cognition worsened. Changes in calcineurin/NFAT3 were directly correlated to soluble Aβ(1-42) levels in postmortem hippocampus, and oligomeric Aβ, in particular, robustly stimulated NFAT activation in primary rat astrocyte cultures. Oligomeric Aβ also caused a significant reduction in excitatory amino acid transporter 2 (EAAT2) protein levels in astrocyte cultures, which was blocked by NFAT inhibition. Moreover, inhibition of astrocytic NFAT activity in mixed cultures ameliorated Aβ-dependent elevations in glutamate and neuronal death. The results suggest that NFAT signaling is selectively altered in AD and may play an important role in driving Aβ-mediated neurodegeneration. PMID:19828810

  8. Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession.

    PubMed

    Liu, Dong; Pitta, Michael; Jiang, Haiyang; Lee, Jong-Hwan; Zhang, Guofeng; Chen, Xinzhi; Kawamoto, Elisa M; Mattson, Mark P

    2013-06-01

    Impaired brain energy metabolism and oxidative stress are implicated in cognitive decline and the pathologic accumulations of amyloid β-peptide (Aβ) and hyperphosphorylated tau in Alzheimer's disease (AD). To determine whether improving brain energy metabolism will forestall disease progress in AD, the impact of the β-nicotinamide adenine dinucleotide precursor nicotinamide on brain cell mitochondrial function and macroautophagy, bioenergetics-related signaling, and cognitive performance were studied in cultured neurons and in a mouse model of AD. Oxidative stress resulted in decreased mitochondrial mass, mitochondrial degeneration, and autophagosome accumulation in neurons. Nicotinamide preserved mitochondrial integrity and autophagy function, and reduced neuronal vulnerability to oxidative/metabolic insults and Aβ toxicity. β-Nicotinamide adenine dinucleotide biosynthesis, autophagy, and phosphatidylinositol-3-kinase signaling were required for the neuroprotective action of nicotinamide. Treatment of 3xTgAD mice with nicotinamide for 8 months resulted in improved cognitive performance, and reduced Aβ and hyperphosphorylated tau pathologies in hippocampus and cerebral cortex. Nicotinamide treatment preserved mitochondrial integrity, and improved autophagy-lysosome procession by enhancing lysosome/autolysosome acidification to reduce autophagosome accumulation. Treatment of 3xTgAD mice with nicotinamide resulted in elevated levels of activated neuroplasticity-related kinases (protein kinase B [Akt] and extracellular signal-regulated kinases) and the transcription factor cyclic adenosine monophosphate (AMP) response element-binding protein in the hippocampus and cerebral cortex. Thus, nicotinamide suppresses AD pathology and cognitive decline in a mouse model of AD by a mechanism involving improved brain bioenergetics with preserved functionality of mitochondria and the autophagy system.

  9. Trajectory of Declines in Physical Activity in Community-Dwelling Older Women: Social Cognitive Influences

    PubMed Central

    Hall, Katherine S.; Motl, Robert W.; White, Siobhan M.; Wójcicki, Thomas R.; Hu, Liang; Doerksen, Shawna E.

    2009-01-01

    Studies examining physical activity behavior suggest that activity levels decline with age. Such declines are particularly problematic among older adults in light of the research suggesting a protective effect of physical activity on numerous physical health outcomes associated with independent living. Despite a growing recognition of the importance of a physically active lifestyle, little is known about the role of demographic and psychosocial variables on this trajectory of change. In this study, the roles played by outcome expectations, self-efficacy, and functional limitations on changes in physical activity levels over a 2-year period in older women were assessed using latent growth curve modeling. Data were obtained from 249 community-dwelling older women (M age = 68.12, n = 81 Black, and n = 168 White). Demographic, health status, and psychosocial data were collected via self-report upon entry into the study. Self-reported physical activity was assessed at baseline and again at 12 and 24 months. As expected, physical activity declined over the 2-year period. Self-efficacy demonstrated an indirect association with the trajectory of decline in physical activity through functional limitations. Importantly, the pattern of relationships appears independent of demographic factors and chronic health conditions. PMID:19528360

  10. Trajectory of declines in physical activity in community-dwelling older women: social cognitive influences.

    PubMed

    McAuley, Edward; Hall, Katherine S; Motl, Robert W; White, Siobhan M; Wójcicki, Thomas R; Hu, Liang; Doerksen, Shawna E

    2009-09-01

    Studies examining physical activity behavior suggest that activity levels decline with age. Such declines are particularly problematic among older adults in light of the research suggesting a protective effect of physical activity on numerous physical health outcomes associated with independent living. Despite a growing recognition of the importance of a physically active lifestyle, little is known about the role of demographic and psychosocial variables on this trajectory of change. In this study, the roles played by outcome expectations, self-efficacy, and functional limitations on changes in physical activity levels over a 2-year period in older women were assessed using latent growth curve modeling. Data were obtained from 249 community-dwelling older women (M age = 68.12, n = 81 Black, and n = 168 White). Demographic, health status, and psychosocial data were collected via self-report upon entry into the study. Self-reported physical activity was assessed at baseline and again at 12 and 24 months. As expected, physical activity declined over the 2-year period. Self-efficacy demonstrated an indirect association with the trajectory of decline in physical activity through functional limitations. Importantly, the pattern of relationships appears independent of demographic factors and chronic health conditions.

  11. A 'Disease Severity Index' to identify individuals with Subjective Memory Decline who will progress to mild cognitive impairment or dementia.

    PubMed

    Ferreira, Daniel; Falahati, Farshad; Linden, Cecilia; Buckley, Rachel F; Ellis, Kathryn A; Savage, Greg; Villemagne, Victor L; Rowe, Christopher C; Ames, David; Simmons, Andrew; Westman, Eric

    2017-03-13

    Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer's disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions. Identifying those with higher risk to develop dementia is thus a major challenge. We tested a novel disease severity index generated by multivariate data analysis with numerous structural MRI measures as input. The index was used to identify SMD individuals with high risk of progression to mild cognitive impairment (MCI) or AD. A total of 69 healthy controls, 86 SMD, 45 MCI, and 38 AD patients were included. Subjects were followed up for 7.5 years. Clinical, cognitive, PET amyloid imaging and APOE ε4 data were used as outcome variables. The results showed that SMD evidenced cognitive performance intermediate between healthy controls and MCI. The disease severity index identified eleven (13%) SMD individuals with an AD-like pattern of brain atrophy. These individuals showed lower cognitive performance, increased CDR-SOB, higher amyloid burden and worse clinical progression (6.2 times higher likelihood to develop MCI, dementia or die than healthy controls). The current disease severity index may have relevance for clinical practice, as well as for selecting appropriate individuals for clinical trials.

  12. Estimating the Co-Development of Cognitive Decline and Physical Mobility Limitations in Older U.S. Adults.

    PubMed

    Bishop, Nicholas J; Eggum-Wilkens, Natalie D; Haas, Steven A; Kronenfeld, Jennie J

    2016-04-01

    This study examines the co-development of cognitive and physical function in older Americans using an age-heterogeneous sample drawn from the Health and Retirement Study (1998-2008). We used multiple-group parallel process latent growth models to estimate the association between trajectories of cognitive function as measured by immediate word recall scores, and limitations in physical function as measured as an index of functional mobility limitations. Nested model fit testing was used to assess model fit for the separate trajectories followed by estimation of an unconditional parallel process model. Controls for demographic characteristics, socioeconomic status, and chronic health conditions were added to the best-fitting parallel process model. Pattern mixture models were used to assess the sensitivity of the parameter estimates to the effect of selective attrition. Results indicated that favorable cognitive health and mobility at initial measurement were associated with faster decline in the alternate functional domain. The cross-process associations remained significant when we adjusted estimates for the influence of covariates and selective attrition. Demographic and socioeconomic characteristics were consistently associated with initial cognitive and physical health but had few relations with change in these measures.

  13. Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats.

    PubMed

    Kishi, Takuya; Hirooka, Yoshitaka; Nagayama, Tomomi; Isegawa, Kengo; Katsuki, Masato; Takesue, Ko; Sunagawa, Kenji

    2015-01-01

    In metabolic syndrome (MetS), previous studies have suggested that cognitive decline is worsened. Among the factors associated with cognition, decreased brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. We previously reported that exercise training with calorie restriction yielded protection against cognitive decline via BDNF in the hippocampus of hypertensive rats. The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). After treatment for 28 days, body weight, insulin, fasting blood glucose, adiponectin, systolic blood pressure, and oxidative stress in the hippocampus were significantly lower, and BDNF expression in the hippocampus was significantly higher in CR and CR+A than in HF. Cognitive performance determined by the Morris water maze test was significantly higher in CR than in HF, whereas the benefit was attenuated in CR+A. In conclusion, calorie restriction protects against cognitive decline via up-regulation of BDNF/TrkB through an antioxidant effect in the hippocampus of dietary-induced obesity rats.

  14. Is Metformin-Induced Vitamin B12 Deficiency Responsible for Cognitive Decline in Type 2 Diabetes?

    PubMed Central

    Khattar, Deepti; Khaliq, Farah; Vaney, Neelam; Madhu, S. V.

    2016-01-01

    Introduction: Diabetes mellitus has its deleterious effects on various aspects of cognition such as memory function, executive function, and information-processing speed. The present study aims to assess cognition in diabetes patients and also tries to find its association with Vitamin B12 deficiency induced by metformin. Materials and Methods: Thirty diabetics taking metformin and thirty nondiabetic controls were enrolled. Event-related potentials (ERPs) and serum Vitamin B12 levels were evaluated in them. Results: Vitamin B12 levels were found to be deficient, and latencies of waves P200 and P300 were prolonged in the diabetics as compared to the controls. The dose and duration of metformin had no association with the ERPs. Conclusions: Although the Vitamin B12 levels were deficient in diabetics on metformin, this is not the reason behind the cognitive impairment found in them. PMID:27570337

  15. Respiratory training as strategy to prevent cognitive decline in aging: a randomized controlled trial

    PubMed Central

    Ferreira, Leandro; Tanaka, Kátia; Santos-Galduróz, Ruth Ferreira; Galduróz, José Carlos Fernandes

    2015-01-01

    Background Inadequate oxygenation may cause lesions and brain atrophy during aging. Studies show a positive association between pulmonary function and the cognitive performance of individuals from middle age on. Objective To investigate the effect of aerobic physical exercises and respiratory training on the blood oxygenation, pulmonary functions, and cognition of the elderly. Design This was a randomized and controlled trial with three parallel groups. A total of 195 community-dwelling elderly were assessed for eligibility; only n=102 were included and allocated into the three groups, but after 6 months, n=68 were analyzed in the final sample. Participants were randomized into a social interaction group (the control group), an aerobic exercise group (the “walking” group), or a respiratory training group (the “breathing” group). The main outcome measures were the Wechsler Adult Intelligence Scale, Wechsler Memory Scale, Wisconsin Card Sorting Test, respiratory muscular strength, cirtometry (thoracic–abdominal circumference); oxygen saturation in arterial blood (SpO2), and hemogram. Results No differences were observed for any of the blood parameters. Aerobic exercise and respiratory training were effective in improving the pulmonary parameters. Better cognitive performance was observed for the breathing group as regards abstraction and mental flexibility. The walking group remained stable in the cognitive performance of most of the tests, except attention. The control group presented worst performance in mental manipulation of information, abstraction, mental flexibility, and attention. Conclusion Our results showed that both the walking and breathing groups presented improvement of pulmonary function. However, only the breathing group showed improved cognitive function (abstraction, mental flexibility). The improvement in cognitive functions cannot be explained by blood parameters, such as SpO2, erythrocytes, hemoglobin, and hematocrit. PMID:25848235

  16. White matter tract covariance patterns predict age-declining cognitive abilities

    PubMed Central

    Gazes, Yunglin; Bowman, F. DuBois; Razlighi, Qolamreza R.; O’Shea, Deirdre; Stern, Yaakov; Habeck, Christian

    2015-01-01

    Previous studies investigating the relationship of white matter (WM) integrity to cognitive abilities and aging and have either focused on a global measure or a few selected WM tracts. Ideally, contribution from all of the WM tracts should be evaluated at the same time. However, the high collinearity among WM tracts precludes systematic examination of WM tracts simultaneously without sacrificing statistical power due to stringent multiple-comparison corrections. Multivariate covariance techniques enable comprehensive simultaneous examination of all WM tracts without being penalized for high collinearity among observations. Method In this study, Scaled Subprofile Modeling (SSM) was applied to the mean integrity of 18 major WM tracts to extract covariance patterns that optimally predicted four cognitive abilities (perceptual speed, episodic memory, fluid reasoning, and vocabulary) in 346 participants across ages 20 to 79 years old. Using expression of the covariance patterns, age-independent effects of white matter integrity on cognition and the indirect effect of WM integrity on age-related differences in cognition were tested separately, but inferences from the indirect analyses were cautiously made given cross-sectional data set was used in the analysis. Results A separate covariance pattern was identified that significantly predicted each cognitive ability after controlling for age except for vocabulary, but Age by WM covariance pattern interactions were not significant for any of the three abilities. Furthermore, each of the patterns mediated the effect of age on the respective cognitive ability. A distinct set of WM tracts was most influential in each of the three patterns. The WM covariance pattern accounting for fluid reasoning showed the most number of influential WM tracts whereas the episodic memory pattern showed the least number. Conclusion Specific patterns of WM tracts make significant contributions to the age-related differences in perceptual speed

  17. IQ as moderator of terminal decline in perceptual and motor speed, spatial, and verbal ability: Testing the cognitive reserve hypothesis in a population-based sample followed from age 70 until death.

    PubMed

    Thorvaldsson, Valgeir; Skoog, Ingmar; Johansson, Boo

    2017-03-01

    Terminal decline (TD) refers to acceleration in within-person cognitive decline prior to death. The cognitive reserve hypothesis postulates that individuals with higher IQ are able to better tolerate age-related increase in brain pathologies. On average, they will exhibit a later onset of TD, but once they start to decline, their trajectory is steeper relative to those with lower IQ. We tested these predictions using data from initially nondemented individuals (n = 179) in the H70-study repeatedly measured at ages 70, 75, 79, 81, 85, 88, 90, 92, 95, 97, 99, and 100, or until death, on cognitive tests of perceptual-and-motor-speed and spatial and verbal ability. We quantified IQ using the Raven's Coloured Progressive Matrices (RCPM) test administrated at age 70. We fitted random change point TD models to the data, within a Bayesian framework, conditioned on IQ, age of death, education, and sex. In line with predictions, we found that 1 additional standard deviation on the IQ scale was associated with a delay in onset of TD by 1.87 (95% highest density interval [HDI; 0.20, 4.08]) years on speed, 1.96 (95% HDI [0.15, 3.54]) years on verbal ability, but only 0.88 (95% HDI [-0.93, 3.49]) year on spatial ability. Higher IQ was associated with steeper rate of decline within the TD phase on measures of speed and verbal ability, whereas results on spatial ability were nonconclusive. Our findings provide partial support for the cognitive reserve hypothesis and demonstrate that IQ can be a significant moderator of cognitive change trajectories in old age. (PsycINFO Database Record

  18. Is there a role for physical activity in preventing cognitive decline in people with mild cognitive impairment?

    PubMed

    Barber, Sally E; Clegg, Andrew P; Young, John B

    2012-01-01

    Mild cognitive impairment (MCI) is a common clinical syndrome that identifies people at high risk of developing dementia. Although treatments for MCI are currently unavailable, preliminary evidence has identified potential neuro-protective effects of physical activity, which may lead to improved outcomes. However, there is uncertainty regarding the effectiveness, feasibility and acceptability of this treatment strategy. These uncertainties require further investigation before physical activity interventions can be recommended for routine care.

  19. Age-Related Declines in General Cognitive Abilities of Balb/C Mice and General Activity Are Associated with Disparities in Working Memory, Body Weight, and General Activity

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan

    2008-01-01

    A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…

  20. Fatty acid status and its relationship to cognitive decline and homocysteine levels in the elderly.

    PubMed

    Baierle, Marília; Vencato, Patrícia H; Oldenburg, Luiza; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Duarte, Marta M M F; Veit, Juliana C; Somacal, Sabrina; Emanuelli, Tatiana; Grune, Tilman; Breusing, Nicolle; Garcia, Solange C

    2014-09-12

    Polyunsaturated fatty acids (PUFAs), especially the n-3 series, are known for their protective effects. Considering that cardiovascular diseases are risk factors for dementia, which is common at aging, the aim of this study was to evaluate whether fatty acid status in the elderly was associated with cognitive function and cardiovascular risk. Forty-five elderly persons (age ≥ 60 years) were included and divided into two groups based on their Mini-Mental Status Examination score adjusted for educational level: the case group (n = 12) and the control group (n = 33). Serum fatty acid composition, homocysteine (Hcy), hs-CRP, lipid profile and different cognitive domains were evaluated. The case group, characterized by reduced cognitive performance, showed higher levels of 14:0, 16:0, 16:1n-7 fatty acids and lower levels of 22:0, 24:1n-9, 22:6n-3 (DHA) and total PUFAs compared to the control group (p < 0.05). The n-6/n-3 ratio was elevated in both study groups, whereas alterations in Hcy, hs-CRP and lipid profile were observed in the case group. Cognitive function was positively associated with the 24:1n-9, DHA and total n-3 PUFAs, while 14:0, 16:0 and 16:1n-7 fatty acids, the n-6/n-3 ratio and Hcy were inversely associated. In addition, n-3 PUFAs, particularly DHA, were inversely associated with cardiovascular risk, assessed by Hcy levels in the elderly.

  1. Linking the developmental and degenerative theories of schizophrenia: association between infant development and adult cognitive decline.

    PubMed

    Kobayashi, Hiroyuki; Isohanni, Matti; Jääskeläinen, Erika; Miettunen, Jouko; Veijola, Juha; Haapea, Marianne; Järvelin, Marjo-Riitta; Jones, Peter B; Murray, Graham K

    2014-11-01

    Neurodevelopmental and neurodegenerative theories may be viewed as incompatible accounts that compete to explain the pathogenesis of schizophrenia. However, it is possible that neurodevelopmental and neurodegenerative processes could both reflect common underlying causal mechanisms. We hypothesized that cognitive dysfunction would gradually deteriorate over time in schizophrenia and the degree of this deterioration in adulthood would be predicted by an infant measure of neurodevelopment. We aimed to examine the association between age of learning to stand in infancy and deterioration of cognitive function in adulthood. Participants were nonpsychotic control subjects (n = 76) and participants with schizophrenia (n = 36) drawn from the Northern Finland 1966 Birth Cohort study. The schizophrenia group showed greater deterioration in abstraction with memory than controls, but there were no differences between schizophrenia and controls in rate of change of other cognitive measures. Age of learning to stand in infancy significantly inversely predicted later deterioration of abstraction with memory in adult schizophrenia (later infant development linked to greater subsequent cognitive deterioration during adulthood), possibly suggesting a link between abnormal neurodevelopmental and neurodegenerative processes in schizophrenia.

  2. Cohort Differences in Cognitive Aging and Terminal Decline in the Seattle Longitudinal Study

    ERIC Educational Resources Information Center

    Gerstorf, Denis; Ram, Nilam; Hoppmann, Christiane; Willis, Sherry L.; Schaie, K. Warner

    2011-01-01

    Life span researchers have long been interested in how and why fundamental aspects of human ontogeny differ between cohorts of people who have lived through different historical epochs. When examined at the same age, later born cohorts are often cognitively and physically fitter than earlier born cohorts. Less is known, however, about cohort…

  3. Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review.

    PubMed

    Panza, F; Solfrizzi, V; Barulli, M R; Bonfiglio, C; Guerra, V; Osella, A; Seripa, D; Sabbà, C; Pilotto, A; Logroscino, G

    2015-03-01

    A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer's disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although

  4. The omega-6/omega-3 ratio and dementia or cognitive decline: a systematic review on human studies and biological evidence.

    PubMed

    Loef, Martin; Walach, Harald

    2013-01-01

    It has been suggested that the intake of certain fatty acids may influence the risk of dementia. However, current reviews have focused only on the therapeutic effects of omega-3 fatty acids, mostly as supplements. To date, the evidence for the relevance of the omega-6/omega-3 ratio has been neglected. Therefore, we searched the databases Alois, Medline, Biosis, Embase, Cochrane Central Register of Controlled Trials, and The Cochrane Database of Systematic Reviews for "essential fatty acids" and "dementia" and aimed to conduct a comprehensive review across study types. All studies that reported on the association between the n-6/n-3 ratio and dementia or cognitive decline were selected. In the 13 animal studies we examined, the dietary n-6/n-3 ratio was shown to affect brain composition, Alzheimer's disease pathology, and behavior. Our review of the 14 studies in humans that fulfilled the selection criteria (7 prospective studies, 3 cross-sectional studies, 1 controlled trial, 3 case-control studies) provided evidence, albeit limited, supporting an association between the n-6/n-3 ratio, cognitive decline, and incidence of dementia. This review supports growing evidence of a positive association between the dietary n-6/n-3 ratio and the risk of Alzheimer's disease.

  5. Correcting Bias Caused by Missing Data in the Estimate of the Effect of Apolipoprotein ε4 on Cognitive Decline.

    PubMed

    Hall, Charles B; Lipton, Richard B; Katz, Mindy J; Wang, Cuiling

    2015-01-01

    Longitudinal administration of neuropsychological instruments are often used to assess age-related changes in cognition. Informative loss to follow-up may bias the results of these studies. Herein, we use auxiliary data to adjust for informative loss to follow-up. In the Einstein Aging Study, memory was assessed annually in a community sample of adults age 70+, free of dementia at baseline, using the free recall from the Free and Cued Selective Reminding Test, and via telephone using the Memory Impairment Screen for Telephone (the auxiliary data). Joint linear mixed models were used to assess how the effect of the APOE ε4 genotype may be affected by informative missingness in the in-person data. A total of 620 EAS participants contributed 2085 person years of follow-up to the analyses. Memory decline rates estimated in joint models were 19% greater in ε4 negative participants and 27% greater in ε4 positive participants compared to traditional approaches; the effect of APOE ε4 on memory decline was 37% greater. Joint modeling methods can help address bias caused by informative missing data in the estimation of the effect of risk factors on cognitive change, and may be applicable to a broader range of outcomes in longitudinal aging studies.

  6. Fish oil promotes survival and protects against cognitive decline in severely undernourished mice by normalizing satiety signals

    PubMed Central

    Avraham, Yosefa; Saidian, Mayer; Burston, James J.; Mevorach, Raphael; Vorobiev, Lia; Magen, Iddo; Kunkes, Eithan; Borges, Beatriz; Lichtman, Aron H.; Berry, Elliot M.

    2010-01-01

    Severe malnutrition resulting from anorexia nervosa or involuntary starvation leads to low weight, cognitive deficits, and increased mortality rates. In the present study, we examined whether fish oil supplementation, compared with canola oil, would ameliorate the morbidity and mortality associated with these conditions by normalizing endocannabinoid and monoaminergeric systems as well as other systems involved in satiety and cognitive function within the hypothalamus and hippocampus. Female Sabra mice restricted to 40% of their daily food intake exhibited decreased body weight, were sickly in appearance, displayed cognitive deficits, and had increased mortality rates. Strikingly, fish oil supplementation that contains high omega-3 fatty acids levels decreased mortality and morbidity, and normalized the expression of genes and neurotransmitters in the hippocampus and hypothalamus. Fish oil supplementation, but not canola oil, increased survival rates, improved general appearance, and prevented cognitive decline, despite the facts that both diets contained an equivalent number of calories and that there were no differences in weight between mice maintained on the two diets in 100% but decrease in the 40%. In the hypothalamus, the beneficial effects of fish oil supplementation were related to normalization of the endocannabinoid 2-arachidonylglycerol (2-AG), serotonin (5-HT) (p<0.056), dopamine (DA), neuropeptide Y (NPY), and Ca2+/calmodulin (CaM)-dependent protein kinase (Camkk2). In the hippocampus, fish oil supplementation normalized 5-HT, Camkk2, silent mating type information regulation 1 (SIRT-1), and brain-derived neurotrophic factor (BDNF). In conclusion, dietary supplements of fish oil, as source of omega-3 fatty acids, may alleviate cognitive impairments associated with severe diet restriction and prolong survival independently of weight gain by normalizing neurochemical systems. PMID:21109417

  7. Diffusion Tensor Imaging of Normal-Appearing White Matter as Biomarker for Radiation-Induced Late Delayed Cognitive Decline

    SciTech Connect

    Chapman, Christopher H.; Nagesh, Vijaya; Sundgren, Pia C.; Buchtel, Henry; Chenevert, Thomas L.; Junck, Larry; Lawrence, Theodore S.; Tsien, Christina I.; Cao, Yue

    2012-04-01

    Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results: In both structures, longitudinal diffusivity ({lambda}{sub Double-Vertical-Line }) decreased and perpendicular diffusivity ({lambda}{sub Up-Tack }) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum {lambda}{sub Up-Tack} at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in {lambda}{sub Up-Tack} at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum {lambda}{sub Double-Vertical-Line} (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum {lambda}{sub Double-Vertical-Line} changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.

  8. What physical performance measures predict incident cognitive decline among intact older adults? A 4.4year follow up study.

    PubMed

    Veronese, Nicola; Stubbs, Brendon; Trevisan, Caterina; Bolzetta, Francesco; De Rui, Marina; Solmi, Marco; Sartori, Leonardo; Musacchio, Estella; Zambon, Sabina; Perissinotto, Egle; Crepaldi, Gaetano; Manzato, Enzo; Sergi, Giuseppe

    2016-08-01

    Reductions in physical performance, cognitive impairment (CI) and decline (CD), are common in older age, but few prospective cohort studies have considered the relationship between these domains. In this study we investigated whether reduced physical performance and low handgrip/lower limbs strength, could predict a higher incidence of CI/CD during a 4-year follow-up among a cohort of elderly individuals. From 3099 older community-dwelling individuals initially enrolled in the Progetto Veneto Anziani (PRO.V.A.) study, 1249 participants without CI at the baseline were included (mean age 72.2years, 59.5% females). Physical performance measures included the Short Physical Performance Battery (SPPB), 4m gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), categorized in gender-specific tertiles. CI was defined as a Mini-Mental State Examination (MMSE) score below 24; CD a decline of 3 or more points in the MMSE without CI. At baseline, participants developing CI during follow-up scored significantly worse across all physical performance measures compared to those that retained normal cognitive status. After adjusting for potential confounders, a significant trend for MMSE changes was noted for all physical performance tests, except for the SPPB and chair stands time. Multinomial logistic regression revealed that slow gait speed at baseline significantly predicted CD at follow up. Poor SPPB performance and slower gait speed predicted the onset of CI at the follow-up. In conclusion, slow walking speed appears to be the best independent predictor of poor cognitive status over a 4.4-year follow-up, while other items of SPPB were also significantly associated with CI.

  9. Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy

    PubMed Central

    Laurent, Cyril; Dorothée, Guillaume; Hunot, Stéphane; Martin, Elodie; Monnet, Yann; Duchamp, Marie; Dong, Yuan; Légeron, François-Pierre; Leboucher, Antoine; Burnouf, Sylvie; Faivre, Emilie; Carvalho, Kévin; Caillierez, Raphaëlle; Zommer, Nadège; Demeyer, Dominique; Jouy, Nathalie; Sazdovitch, Veronique; Schraen-Maschke, Susanna; Delarasse, Cécile; Buée, Luc

    2017-01-01

    Abstract Alzheimer’s disease is characterized by the combined presence of amyloid plaques and tau pathology, the latter being correlated with the progression of clinical symptoms. Neuroinflammatory changes are thought to be major contributors to Alzheimer’s disease pathophysiology, even if their precise role still remains largely debated. Notably, to what extent immune responses contribute to cognitive impairments promoted by tau pathology remains poorly understood. To address this question, we took advantage of the THY-Tau22 mouse model that progressively develops hippocampal tau pathology paralleling cognitive deficits and reappraised the interrelationship between tau pathology and brain immune responses. In addition to conventional astroglial and microglial responses, we identified a CD8-positive T cell infiltration in the hippocampus of tau transgenic mice associated with an early chemokine response, notably involving CCL3. Interestingly, CD8-positive lymphocyte infiltration was also observed in the cortex of patients exhibiting frontemporal dementia with P301L tau mutation. To gain insights into the functional involvement of T cell infiltration in the pathophysiological development of tauopathy in THY-Tau22 mice, we chronically depleted T cells using anti-CD3 antibody. Such anti-CD3 treatment prevented hippocampal T cell infiltration in tau transgenic animals and reverted spatial memory deficits, in absence of tau pathology modulation. Altogether, these data support an instrumental role of hippocampal T cell infiltration in tau-driven pathophysiology and cognitive impairments in Alzheimer’s disease and other tauopathies. PMID:27818384

  10. Hippocampal Volume Is Related to Cognitive Decline and Fornicial Diffusion Measures in Multiple Sclerosis

    PubMed Central

    Koenig, Katherine A.; Sakaie, Ken E.; Lowe, Mark J.; Lin, Jian; Stone, Lael; Bermel, Robert A.; Beall, Erik B.; Rao, Stephen M.; Trapp, Bruce D.; Phillips, Micheal D.

    2014-01-01

    Purpose To assess for associations between hippocampal atrophy and measures of cognitive function, hippocampal magnetization transfer ratio (MTR), and diffusion measures of the fornix, the largest efferent white matter tract from the hippocampus, in patients with multiple sclerosis (MS) and controls. Materials and Methods A total of 53 patients with MS and 20 age- and sex-matched healthy controls participated in cognitive testing and scanning including high spatial-resolution diffusion imaging and a T1-MPRAGE scan. Hippocampal volume and fornicial thickness measures were calculated and compared to mean values of fornicial transverse diffusivity, mean diffusivity, longitudinal diffusivity, fractional anisotropy, mean hippocampal MTR, and scores on measures of episodic memory, processing speed, and working memory tasks. Results In patients with MS, hippocampal volume was significantly related to fornicial diffusion measures (P < 7 × 10−4) and to measures of verbal (P = 0.030) and visual spatial (P = 0.004) episodic memory and a measure of information processing speed (P < 0.037). Discussion These results highlight the role of the hippocampus in cognitive dysfunction in patients with MS and suggest that measures of hippocampal atrophy could be used to capture aspects of disease progression. PMID:24512796

  11. Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment.

    PubMed

    Xie, Chunming; Bai, Feng; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Chen, Gang; Li, Wenjun; Chen, Guangyu; Zhang, Zhijun; Li, Shi-Jiang

    2012-10-15

    Abnormalities of functional connectivity in the default mode network (DMN) recently have been reported in patients with amnestic mild cognitive impairment (aMCI), Alzheimer's disease (AD) or other psychiatric diseases. As such, these abnormalities may be epiphenomena instead of playing a causal role in AD progression. To date, few studies have investigated specific brain networks, which extend beyond the DMN involved in the early AD stages, especially in aMCI. The insula is one site affected by early pathological changes in AD and is a crucial hub of the human brain networks. Currently, we explored the contribution of the insula networks to cognitive performance in aMCI patients. Thirty aMCI and 26 cognitively normal (CN) subjects participated in this study. Intrinsic connectivity of the insula networks was measured, using the resting-state functional connectivity fMRI approach. We examined the differential connectivity of insula networks between groups, and the neural correlation between the altered insula networks connectivity and the cognitive performance in aMCI patients and CN subjects, respectively. Insula subregional volumes were also investigated. AMCI subjects, when compared to CN subjects, showed significantly reduced right posterior insula volumes, cognitive deficits and disrupted intrinsic connectivity of the insula networks. Specifically, decreased intrinsic connectivity was primarily located in the frontal-parietal network and the cingulo-opercular network, including the anterior prefrontal cortex (aPFC), anterior cingulate cortex, operculum, inferior parietal cortex and precuneus. Increased intrinsic connectivity was primarily situated in the visual-auditory pathway, which included the posterior superior temporal gyrus and middle occipital gyrus. Conjunction analysis was performed; and significantly decreased intrinsic connectivity in the overlapping regions of the anterior and posterior insula networks, including the bilateral aPFC, left

  12. Current evidence for the use of coffee and caffeine to prevent age-related cognitive decline and Alzheimer's disease.

    PubMed

    Carman, A J; Dacks, P A; Lane, R F; Shineman, D W; Fillit, H M

    2014-04-01

    Although nothing has been proven conclusively to protect against cognitive aging, Alzheimer's disease or related dementias, decades of research suggest that specific approaches including the consumption of coffee may be effective. While coffee and caffeine are known to enhance short-term memory and cognition, some limited research also suggests that long-term use may protect against cognitive decline or dementia. In vitro and pre-clinical animal models have identified plausible neuroprotective mechanisms of action of both caffeine and other bioactive components of coffee, though epidemiology has produced mixed results. Some studies suggest a protective association while others report no benefit. To our knowledge, no evidence has been gathered from randomized controlled trials. Although moderate consumption of caffeinated coffee is generally safe for healthy people, it may not be for everyone, since comorbidities and personal genetics influence potential benefits and risks. Future studies could include short-term clinical trials with biomarker outcomes to validate findings from pre-clinical models and improved epidemiological studies that incorporate more standardized methods of data collection and analysis. Given the enormous economic and emotional toll threatened by the current epidemic of Alzheimer's disease and other dementias, it is critically important to validate potential prevention strategies such as coffee and caffeine.

  13. A conceptualization of the utility of subjective cognitive decline in clinical trials of preclinical Alzheimer’s disease

    PubMed Central

    Buckley, Rachel F.; Villemagne, Victor L.; Masters, Colin L.; Ellis, Kathryn A.; Rowe, Christopher C.; Johnson, Keith; Sperling, Reisa; Amariglio, Rebecca

    2017-01-01

    Introduction This commentary outlines a conceptual model for subjective cognitive decline (SCD) in relation to Alzheimer’s disease (AD) biomarkers in the preclinical stages of disease, and a framework for effectively utilizing SCD in secondary prevention clinical trials. Objective Mounting evidence supports the notion that SCD is sensitive to encroaching Aβ-amyloid and neurodegeneration. SCD has also been shown to provide additive information of AD-dementia risk beyond what is known about the biomarker status of the individual. Thus, we provide recommendations for the implementing SCD measurement in clinical trials. Results We argue that SCD can be measured at three catch points within the course of the clinical trial; firstly, at the initial recruitment and screening phase, secondly, to create more robust estimates of rates of AD-dementia progression, and finally, to measure subjective experiences of cognitive change and quality of life over the course of the trial as a proxy of clinically meaningful functional improvement. We provide recommendations of how SCD can be approached at each of these points Conclusion SCD is an important component of the preclinical AD-dementia trajectory. Future studies need to elucidate the interactive influence of Aβ-amyloid and tau on SCD from a spatiotemporal perspective. Even as this evidence accrues, it is clear that SCD can provide unique and additive information about rates of progression and subjectively experienced cognitive change within clinical trials. PMID:27514526

  14. Alpha band disruption in the AD-continuum starts in the Subjective Cognitive Decline stage: a MEG study

    PubMed Central

    López-Sanz, D.; Bruña, R.; Garcés, P.; Camara, C.; Serrano, N.; Rodríguez-Rojo, I. C.; Delgado, M. L.; Montenegro, M.; López-Higes, R.; Yus, M.; Maestú, F.

    2016-01-01

    The consideration of Subjective Cognitive Decline (SCD) as a preclinical stage of AD remains still a matter of debate. Alpha band alterations represent one of the most significant changes in the electrophysiological profile of AD. In particular, AD patients exhibit reduced alpha relative power and frequency. We used alpha band activity measured with MEG to study whether SCD and MCI elders present these electrophysiological changes characteristic of AD, and to determine the evolution of the observed alterations across AD spectrum. The total sample consisted of 131 participants: 39 elders without SCD, 41 elders with SCD and 51 MCI patients. All of them underwent MEG and MRI scans and neuropsychological assessment. SCD and MCI patients exhibited a similar reduction in alpha band activity compared with the no SCD group. However, only MCI patients showed a slowing in their alpha peak frequency compared with both SCD and no SCD. These changes in alpha band were related to worse cognition. Our results suggest that AD-related alterations may start in the SCD stage, with a reduction in alpha relative power. It is later, in the MCI stage, where the slowing of the spectral profile takes place, giving rise to objective deficits in cognitive functioning. PMID:27883082

  15. Fast but fleeting: adaptive motor learning processes associated with aging and cognitive decline.

    PubMed

    Trewartha, Kevin M; Garcia, Angeles; Wolpert, Daniel M; Flanagan, J Randall

    2014-10-01

    Motor learning has been shown to depend on multiple interacting learning processes. For example, learning to adapt when moving grasped objects with novel dynamics involves a fast process that adapts and decays quickly-and that has been linked to explicit memory-and a slower process that adapts and decays more gradually. Each process is characterized by a learning rate that controls how strongly motor memory is updated based on experienced errors and a retention factor determining the movement-to-movement decay in motor memory. Here we examined whether fast and slow motor learning processes involved in learning novel dynamics differ between younger and older adults. In addition, we investigated how age-related decline in explicit memory performance influences learning and retention parameters. Although the groups adapted equally well, they did so with markedly different underlying processes. Whereas the groups had similar fast processes, they had different slow processes. Specifically, the older adults exhibited decreased retention in their slow process compared with younger adults. Within the older group, who exhibited considerable variation in explicit memory performance, we found that poor explicit memory was associated with reduced retention in the fast process, as well as the slow process. These findings suggest that explicit memory resources are a determining factor in impairments in the both the fast and slow processes for motor learning but that aging effects on the slow process are independent of explicit memory declines.

  16. Schisantherin A recovers Aβ-induced neurodegeneration with cognitive decline in mice.

    PubMed

    Li, Xiaolong; Zhao, Xu; Xu, Xuan; Mao, Xin; Liu, Zhi; Li, Huan; Guo, Lin; Bi, Kaishun; Jia, Ying

    2014-06-10

    Schisantherin A (STA) is a main bioactive lignan isolated from Schisandra chinensis (Turcz.) Baill., which has been widely used as a tonic in traditional Chinese medicine for many years. Lots of studies have reported that STA exhibited anti-inflammatory and antioxidant effects. This paper was designed to investigate the effects of STA on cognitive function and neurodegeneration in the mouse control of Alzheimer's disease (AD) induced by Aβ1-42. It was found that successive intracerebroventricular (ICV) administration of STA (0.01 and 0.1mg/kg) for 5days significantly attenuated Aβ1-42-induced learning and memory impairment as measured by the Y-maze test, shuttle-box test and Morris water maze test. Furthermore, STA at a dose of 0.1mg/kg restored the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as the levels of Aβ1-42, malondialdehyde (MDA) and glutathione (GSH) to some extent in the hippocampus and cerebral cortex. It also noticeably improved the histopathological changes in the hippocampus. The results suggested that STA might protect against cognitive deficits, oxidative stress and neurodegeneration induced by Aβ1-42, and serve as a potential agent in treatment of AD.

  17. Progressive neuropathology and cognitive decline in a single Arctic APP transgenic mouse model.

    PubMed

    Rönnbäck, Annica; Zhu, Shunwei; Dillner, Karin; Aoki, Mikio; Lilius, Lena; Näslund, Jan; Winblad, Bengt; Graff, Caroline

    2011-02-01

    The Arctic APP mutation (E693G) leads to dementia with clinical features similar to Alzheimer disease (AD), but little is known about the pathogenic mechanism of this mutation. To address this question, we have generated a transgenic mouse model, TgAPParc, with neuron-specific expression of human APP with the Arctic mutation (hAPParc). Heterozygous mice from two separate founder lines with different levels of expression of hAPParc were analyzed with respect to brain morphology and behavior every 3 months until the age of 18 months. Standard histological stainings and immunohistochemistry using a panel of Aβ antibodies showed an age- and dose-dependant progression of amyloid deposition in the brain, starting in the subiculum and spreading to the thalamus. Cognitive behavioral testing revealed deficits in hippocampus-dependent spatial learning and memory in the Barnes maze test. This study demonstrates that the Arctic APP mutation is sufficient to cause amyloid deposition and cognitive dysfunction, and thus the TgAPParc mouse model provides a valuable tool to study the effect of the Arctic mutation in vivo without possible confounding effect of other APP mutations.

  18. CANTAB object recognition and language tests to detect aging cognitive decline: an exploratory comparative study

    PubMed Central

    Cabral Soares, Fernanda; de Oliveira, Thaís Cristina Galdino; de Macedo, Liliane Dias e Dias; Tomás, Alessandra Mendonça; Picanço-Diniz, Domingos Luiz Wanderley; Bento-Torres, João; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2015-01-01

    Objective The recognition of the limits between normal and pathological aging is essential to start preventive actions. The aim of this paper is to compare the Cambridge Neuropsychological Test Automated Battery (CANTAB) and language tests to distinguish subtle differences in cognitive performances in two different age groups, namely young adults and elderly cognitively normal subjects. Method We selected 29 young adults (29.9±1.06 years) and 31 older adults (74.1±1.15 years) matched by educational level (years of schooling). All subjects underwent a general assessment and a battery of neuropsychological tests, including the Mini Mental State Examination, visuospatial learning, and memory tasks from CANTAB and language tests. Cluster and discriminant analysis were applied to all neuropsychological test results to distinguish possible subgroups inside each age group. Results Significant differences in the performance of aged and young adults were detected in both language and visuospatial memory tests. Intragroup cluster and discriminant analysis revealed that CANTAB, as compared to language tests, was able to detect subtle but significant differences between the subjects. Conclusion Based on these findings, we concluded that, as compared to language tests, large-scale application of automated visuospatial tests to assess learning and memory might increase our ability to discern the limits between normal and pathological aging. PMID:25565785

  19. Human brain networks in cognitive decline: a graph theoretical analysis of cortical connectivity from EEG data.

    PubMed

    Vecchio, Fabrizio; Miraglia, Francesca; Marra, Camillo; Quaranta, Davide; Vita, Maria Gabriella; Bramanti, Placido; Rossini, Paolo Maria

    2014-01-01

    The aim of this study was to investigate the neuronal network characteristics in physiological and pathological brain aging. A database of 378 participants divided in three groups was analyzed: Alzheimer's disease (AD), mild cognitive impairment (MCI), and normal elderly (Nold) subjects. Through EEG recordings, cortical sources were evaluated by sLORETA software, while graph theory parameters (Characteristic Path Length λ, Clustering coefficient γ, and small-world network σ) were computed to the undirected and weighted networks, obtained by the lagged linear coherence evaluated by eLORETA software. EEG cortical sources from spectral analysis showed significant differences in delta, theta, and alpha 1 bands. Furthermore, the analysis of eLORETA cortical connectivity suggested that for the normalized Characteristic Path Length (λ) the pattern differences between normal cognition and dementia were observed in the theta band (MCI subjects are find similar to healthy subjects), while for the normalized Clustering coefficient (γ) a significant increment was found for AD group in delta, theta, and alpha 1 bands; finally, the small world (σ) parameter presented a significant interaction between AD and MCI groups showing a theta increase in MCI. The fact that AD patients respect the MCI subjects were significantly impaired in theta but not in alpha bands connectivity are in line with the hypothesis of an intermediate status of MCI between normal condition and overt dementia.

  20. Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

    PubMed Central

    Gómez Ravetti, Martín; Rosso, Osvaldo A.; Berretta, Regina; Moscato, Pablo

    2010-01-01

    Background Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation

  1. Exploratory Decision-Making as a Function of Lifelong Experience, Not Cognitive Decline

    PubMed Central

    2016-01-01

    Older adults perform worse than younger adults in some complex decision-making scenarios, which is commonly attributed to age-related declines in striatal and frontostriatal processing. Recently, this popular account has been challenged by work that considered how older adults’ performance may differ as a function of greater knowledge and experience, and by work showing that, in some cases, older adults outperform younger adults in complex decision-making tasks. In light of this controversy, we examined the performance of older and younger adults in an exploratory choice task that is amenable to model-based analyses and ostensibly not reliant on prior knowledge. Exploration is a critical aspect of decision-making poorly understood across the life span. Across 2 experiments, we addressed (a) how older and younger adults differ in exploratory choice and (b) to what extent observed differences reflect processing capacity declines. Model-based analyses suggested that the strategies used by the 2 groups were qualitatively different, resulting in relatively worse performance for older adults in 1 decision-making environment but equal performance in another. Little evidence was found that differences in processing capacity drove performance differences. Rather the results suggested that older adults’ performance might result from applying a strategy that may have been shaped by their wealth of real-word decision-making experience. While this strategy is likely to be effective in the real world, it is ill suited to some decision environments. These results underscore the importance of taking into account effects of experience in aging studies, even for tasks that do not obviously tap past experiences. PMID:26726916

  2. Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women.

    PubMed

    Vercambre, Marie-Noël; Boutron-Ruault, Marie-Christine; Ritchie, Karen; Clavel-Chapelon, Françoise; Berr, Claudine

    2009-08-01

    The objective of the present study was to determine the potential long-term impact of dietary habits on age-related decline among 4809 elderly women (born between 1925 and 1930) in the 'Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale' (E3N) study, a French epidemiological cohort. In 1993, an extensive diet history self-administered questionnaire was sent to all participants, and in 2006 another questionnaire on instrumental activities of daily living (IADL) and recent cognitive change was sent to a close relative or friend of each woman. Logistic models adjusted for socio-demographic, lifestyle and health factors were performed to evaluate associations between habitual dietary intakes and two outcomes of interest based on the informant response: recent cognitive decline and IADL impairment. Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy desserts and ice-cream. IADL impairment was associated with a lower intake of vegetables. The odds of recent cognitive decline increased significantly with decreasing intake of soluble dietary fibre and n-3 fatty acids but with increasing intake of retinol. The odds of IADL impairment increased significantly with decreasing intakes of vitamins B2, B6 and B12. These results are consistent with a possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats and B-group vitamins, and support dietary intervention to prevent cognitive decline.

  3. Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women

    PubMed Central

    Vercambre, Marie-Noël; Boutron-Ruault, Marie-Christine; Ritchie, Karen; Clavel-Chapelon, Françoise; Berr, Claudine

    2009-01-01

    The objective of this study was to determine the potential long-term impact of dietary habits on age-related decline among 4,809 elderly women (born between 1925 and 1930) in the E3N study, a French longitudinal cohort. In 1993, an extensive diet history self-administered questionnaire was sent to all participants, and in 2006 another questionnaire on instrumental activities of daily living (IADL) and recent cognitive change was sent to a close relative/friend of each woman. Logistic models adjusted for sociodemographic, lifestyle and health factors were performed to evaluate associations between habitual dietary intakes and two outcomes of interest based on the informant response: recent cognitive decline and IADL impairment. Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy dessert and ice-cream. IADL impairment was associated with lower intake of vegetables. The odds of recent cognitive decline increased significantly with decreasing intake of soluble dietary fibre and n-3 fatty acids but with increasing intake of retinol. The odds of IADL impairment increased significantly with decreasing intake of vitamins B2, B6, and B12. These results are consistent with a possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats, and B-group vitamins, and support dietary intervention to prevent cognitive decline. PMID:19203415

  4. Prevalence of Cognitive Impairment in Recently Diagnosed Type 2 Diabetes Patients: Are Chronic Inflammatory Diseases Responsible for Cognitive Decline?

    PubMed Central

    Lavielle, Pilar; Talavera, Juan O.; Reynoso, Nancy; González, Marissa; Gómez-Díaz, Rita A.; Cruz, Miguel; Vázquez, Felipe; Wacher, Niels H.

    2015-01-01

    Objective To estimate the prevalence of cognitive impairment (CI) among patients recently diagnosed with type 2 diabetes (RDD) and to identify any relationships between CI and RDD comorbidities. Methods: One thousand seven hundred twelve patients with RDD participated in a cross-sectional study. The patients’ sociodemographic and clinical data were registered. Results The sample population had an average age of 51 ± 11 years, and 63.26% of the patients were female. CI was diagnosed in 38 patients (2.2%) and was more common among both females (2.8% vs. 1.3%, p = 0.063) and the elderly (0% at an age ≤ 30 years vs. 10.4% at an age > 70 years, p = 0.0001). Rheumatoid arthritis (present in 15.8% vs. absent in 2.1%) and asthma (13% vs. 2.1%) correlated significantly with CI based on the results of our logistic regression analysis. Conclusion Age, female gender, rheumatoid arthritis and asthma are risk factors for CI in the setting of RDD. PMID:26517541

  5. High Dose B Vitamin Supplementation and Cognitive Decline in Alzheimer’s Disease: A Randomized Controlled Trial

    PubMed Central

    Aisen, Paul S.; Schneider, Lon S.; Sano, Mary; Diaz-Arrastia, Ramon; van Dyck, Christopher H.; Weiner, Myron F.; Bottiglieri, Teodoro; Jin, Shelia; Stokes, Karen T.; Thomas, Ronald G.; Thal, Leon J.

    2009-01-01

    Context Blood levels of homocysteine may be elevated in Alzheimer’s disease (AD), and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B6 and B12. Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess impact on cognitive decline. Objective To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. Design We conducted a multicenter, randomized, double-blind controlled clinical trial of high-dose folate/B6/B12 supplementation in individuals with AD. Setting The study was conducted between March, 2003 and February, 2007 at clinical research sites of the Alzheimer’s Disease Cooperative Study located throughout the US. Patients A total of 409 participants (out of 601 screened) with mild to moderate AD (Mini-Mental Status Scores between 14 and 26, inclusive) and normal folic acid, B12 and homocysteine levels were enrolled in this trial; 340 completed the trial on study medication. Intervention Participants were randomly assigned to two groups of unequal size: 60% were treated with daily high-dose supplements (folate 5mg, vitamin B6 25mg, vitamin B12 1 mg), and 40% were treated with identical placebo; the duration of treatment was 18 months. Main Outcome Measure The primary outcome measure was the change in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAScog). Results Although the vitamin supplement regimen was effective in reducing homocysteine levels (active −2.42±3.35; placebo -0.86±2.59; p<0.001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-Cog over 18 months (placebo: 0.372 point/month vs active: 0.401 point/month, p-value=0.522, CI of rate difference: (−0.06, 0.12), based on the Generalized Estimating

  6. Yuzu extract prevents cognitive decline and impaired glucose homeostasis in β-amyloid-infused rats.

    PubMed

    Yang, Hye Jeong; Hwang, Jin Taek; Kwon, Dae Young; Kim, Min Jung; Kang, Suna; Moon, Na Rang; Park, Sunmin

    2013-07-01

    Our preliminary study revealed that dementia induced by β-amyloid accumulation impairs peripheral glucose homeostasis (unpublished). We therefore evaluated whether long-term oral consumption of yuzu (Citrus junos Tanaka) extract improves cognitive dysfunction and glucose homeostasis in β-amyloid-induced rats. Male rats received hippocampal CA1 infusions of β-amyloid (25-35) [plaque forming β-amyloid; Alzheimer disease (AD)] or β-amyloid (35-25) [non-plaque forming β-amyloid; C (non-Alzheimer disease control)] at a rate of 3.6 nmol/d for 14 d. AD rats were divided into 2 dietary groups that received either 3% lyophilized 70% ethanol extracts of yuzu (AD-Y) or 3% dextrin (AD-C) in high-fat diets (43% energy as fat). The AD-C group exhibited greater hippocampal β-amyloid deposition, which was not detected in the C group, and attenuated hippocampal insulin signaling. Yuzu treatment prevented β-amyloid accumulation, increased tau phosphorylation, and attenuated hippocampal insulin signaling observed in AD-C rats. Consistent with β-amyloid accumulation, the AD-C rats experienced cognitive dysfunction, which was prevented by yuzu. AD-C rats gained less weight than did C rats due to decreased feed consumption, and yuzu treatment prevented the decrease in feed consumption. Serum glucose concentrations were higher in AD-C than in C rats at 40-120 min after glucose loading during an oral-glucose-tolerance test, but not at 0-40 min. Serum insulin concentrations were highly elevated in AD-C rats but not enough to lower serum glucose to normal concentrations, indicating that rats in the AD-C group had insulin resistance and a borderline diabetic state. Although AD-C rats were profoundly insulin resistant, AD-Y rats exhibited normal first and second phases of glucose tolerance and insulin sensitivity and secretion. In conclusion, yuzu treatment prevented the cognitive dysfunction and impaired energy and glucose homeostasis induced by β-amyloid infusion.

  7. APPLYING SPARSE CODING TO SURFACE MULTIVARIATE TENSOR-BASED MORPHOMETRY TO PREDICT FUTURE COGNITIVE DECLINE

    PubMed Central

    Zhang, Jie; Stonnington, Cynthia; Li, Qingyang; Shi, Jie; Bauer, Robert J.; Gutman, Boris A.; Chen, Kewei; Reiman, Eric M.; Thompson, Paul M.; Ye, Jieping; Wang, Yalin

    2016-01-01

    Alzheimer’s disease (AD) is a progressive brain disease. Accurate diagnosis of AD and its prodromal stage, mild cognitive impairment, is crucial for clinical trial design. There is also growing interests in identifying brain imaging biomarkers that help evaluate AD risk presymptomatically. Here, we applied a recently developed multivariate tensor-based morphometry (mTBM) method to extract features from hippocampal surfaces, derived from anatomical brain MRI. For such surface-based features, the feature dimension is usually much larger than the number of subjects. We used dictionary learning and sparse coding to effectively reduce the feature dimensions. With the new features, an Adaboost classifier was employed for binary group classification. In tests on publicly available data from the Alzheimers Disease Neuroimaging Initiative, the new framework outperformed several standard imaging measures in classifying different stages of AD. The new approach combines the efficiency of sparse coding with the sensitivity of surface mTBM, and boosts classification performance. PMID:27499829

  8. An Unusual Presentation of Neurocysticercosis: A Space-Occupying Lesion in the Fourth Ventricle Associated with Progressive Cognitive Decline

    PubMed Central

    Kurz, Carolin; Schmidt, Veronika; Poppert, Holger; Wilkins, Patricia; Noh, John; Poppert, Sven; Schlegel, Jürgen; Ertelt-Delbridge, Claire; da Costa, Clarissa Prazeres; Winkler, Andrea S.

    2016-01-01

    We communicate a case of a middle-aged Brazilian patient with an unusual presentation of fourth ventricular neurocysticercosis: occurrence of two intraventricular cysts at different locations in the brain within 2 years and cognitive decline as the only neurological symptom. Neurocysticercosis was confirmed by magnetic resonance imaging, serology, histology, and genetic analysis. Neurocysticercosis should be considered as a differential diagnosis in cases with atypical neurologic or psychiatric symptoms, atypical neuroimaging, and travel history. Especially, fourth ventricular cysts carry the risk of obstructive hydrocephalus and brainstem compression and therefore should be extirpated completely. If complete removal of the cystic structures cannot be proven in cases with surgically treated neurocysticercosis, anthelminthic therapy and thorough follow-up examinations should be conducted. PMID:26621562

  9. Shared Neuropathological Characteristics of Obesity, Type 2 Diabetes and Alzheimer’s Disease: Impacts on Cognitive Decline

    PubMed Central

    Walker, Jennifer M.; Harrison, Fiona E.

    2015-01-01

    In the past few decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM), as well as older individuals at risk for Alzheimer’s disease (AD), has increased. While the consumption of diets high in fat (total and saturated) have been linked to increased risk of AD, diets rich in antioxidants, polyunsaturated fats, and omega-3 fatty acids are associated with decreased risk. Additionally, AD patients are at increased risk for developing T2DM. Recent research suggests that there are stronger similarities between AD and T2DM than have previously been considered. Here we review the neurocognitive and inflammatory effects of high-fat diet consumption, its relationship to AD, and the treatment potential of dietary interventions that may decrease risk of cognitive decline and other associated neuropathological changes, such as insulin resistance, oxidative stress, and chronic inflammatory processes. PMID:26340637

  10. Higher serum cholesterol is associated with intensified age-related neural network decoupling and cognitive decline in early- to mid-life.

    PubMed

    Spielberg, Jeffrey M; Sadeh, Naomi; Leritz, Elizabeth C; McGlinchey, Regina E; Milberg, William P; Hayes, Jasmeet P; Salat, David H

    2017-03-31

    Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Meanage  = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  11. Association between Cerebrospinal Fluid Biomarkers for Alzheimer's Disease, APOE Genotypes and Auditory Verbal Learning Task in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

    PubMed

    Mandecka, Monika; Budziszewska, Magdalena; Barczak, Anna; Pepłońska, Beata; Chodakowska-Żebrowska, Małgorzata; Filipek-Gliszczyńska, Anna; Nesteruk, Marta; Styczyńska, Maria; Barcikowska, Maria; Gabryelewicz, Tomasz

    2016-07-29

    In the course of Alzheimer's disease (AD), early pathological changes in the brain start decades before any clinical manifestation. The concentration levels of AD cerebrospinal fluid (CSF) biomarkers, such as amyloid-β1-42 (Aβ1-42), total tau (T-tau), and phosphorylated tau (P-tau), may reflect a cerebral pathology facilitating an early diagnosis of the disease and predicting a cognitive deterioration. The aim of this study was to estimate the prevalence of AD CSF biomarkers in those individuals with a subjective cognitive decline (SCD), a mild cognitive impairment (MCI), and Alzheimer's dementia (AD-D), together with the relationships between the biomarkers, an APOE ɛ4 presence, and a verbal episodic memory performance. We included 252 patients from the memory clinic with a diagnosis of SCD (n = 85), MCI (n = 87), and AD-D (n = 80). A verbal episodic memory performance level was assessed and was based on a delayed recall trial from the 10-word list of an auditory verbal learning task (AVLT). We found that the patients with more severe cognitive impairments had significantly lower levels of Aβ1-42 and higher levels of T-tau and P-tau. This pattern was also typical for the APOE ɛ4 carriers, who had lower levels of Aβ1-42 than the noncarriers in the AD-D and MCI groups. The levels of T-tau and P-tau were significantly higher in the APOE ɛ4 carriers than in the noncarriers, but only in the MCI patients. The AVLT performance in the whole study samples was predicted by age, Aβ1-42, and the T-tau CSF biomarkers, but not by the APOE genotyping.

  12. The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline.

    PubMed

    Pickart, Loren; Vasquez-Soltero, Jessica Michelle; Margolina, Anna

    2017-02-15

    Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions. GHK, which declines with age, has health promoting effects on many tissues such as chondrocytes, liver cells and human fibroblasts, improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, boney tissue), increases collagen, decorin, angiogenesis, and nerve outgrowth, possesses anti-oxidant, anti-inflammatory, anti-pain and anti-anxiety effects, increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells. Studies using the Broad Institute Connectivity Map show that GHK peptide modulates expression of multiple genes, resetting pathological gene expression patterns back to health. GHK has been recommended as a treatment for metastatic cancer, Chronic Obstructive Lung Disease, inflammation, acute lung injury, activating stem cells, pain, and anxiety. Here, we present GHK's effects on gene expression relevant to the nervous system health and function.

  13. The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline

    PubMed Central

    Pickart, Loren; Vasquez-Soltero, Jessica Michelle; Margolina, Anna

    2017-01-01

    Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions. GHK, which declines with age, has health promoting effects on many tissues such as chondrocytes, liver cells and human fibroblasts, improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, boney tissue), increases collagen, decorin, angiogenesis, and nerve outgrowth, possesses anti-oxidant, anti-inflammatory, anti-pain and anti-anxiety effects, increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells. Studies using the Broad Institute Connectivity Map show that GHK peptide modulates expression of multiple genes, resetting pathological gene expression patterns back to health. GHK has been recommended as a treatment for metastatic cancer, Chronic Obstructive Lung Disease, inflammation, acute lung injury, activating stem cells, pain, and anxiety. Here, we present GHK’s effects on gene expression relevant to the nervous system health and function. PMID:28212278

  14. Severe Decline of Estimated Glomerular Filtration Rate Associates with Progressive Cognitive Deterioration in the Elderly: A Community-Based Cohort Study

    PubMed Central

    Chen, Yi-Chi; Weng, Shuo-Chun; Liu, Jia-Sin; Chuang, Han-Lin; Hsu, Chih-Cheng; Tarng, Der-Cherng

    2017-01-01

    Cognitive dysfunction is closely related to aging and chronic kidney disease (CKD). However, the association between renal function changes and the risk of developing cognitive impairment has not been elucidated. This longitudinal cohort study was to determine the influence of annual percentage change in estimated glomerular filtration rate (eGFR) on subsequent cognitive deterioration or death of the elderly within the community. A total of 33,654 elders with eGFR measurements were extracted from the Taipei City Elderly Health Examination Database. The Short Portable Mental Status Questionnaire was used to assess their cognitive progression at least twice during follow-up visits. Multivariable Cox regression models were used to estimate the hazard ratio (HR) for cognitive deterioration or all-cause mortality with the percentage change in eGFR. During a median follow-up of 5.4 years, the participants with severe decline in eGFR (>20% per year) had an increased risk of cognitive deterioration (HR, 1.33; 95% confidence interval [CI], 1.08–1.72) and the composite outcome (HR, 1.17; 95% CI, 1.03–1.35) when compared with those who had stable eGFR. Severe eGFR decline could be a possible predictor for cognitive deterioration or death among the elderly. Early detection of severe eGFR decline is a critical issue and needs clinical attentions. PMID:28209982

  15. Cognitive decline and cardiometabolic risk among Hispanic and non-Hispanic white adults in the San Luis Valley Health and Aging Study.

    PubMed

    Hildreth, Kerry L; Grigsby, Jim; Bryant, Lucinda L; Wolfe, Pamela; Baxter, Judith

    2014-04-01

    Cardiometabolic risk factors, including hypertension, dyslipidemia, central obesity, insulin resistance and diabetes are linked to cognitive impairment. The Hispanic population appears to be differentially affected by both cardiometabolic risk factors and cognitive impairment. We sought to determine whether ethnic differences in cognitive impairment in long-resident southwestern US elders was explained by the presence of cardiometabolic risk factors, and to explore patterns of cognitive decline over time. We performed a secondary analysis of data collected on 378 Hispanic and 409 non-Hispanic white adult participants in a longitudinal study of community-dwelling elderly in southern Colorado. Measures of cardiometabolic risk included waist circumference, blood pressure, diagnosis of diabetes, and random blood glucose. Cognitive measures included the Mini-Mental State Exam (MMSE) and the behavioral dyscontrol scale (a measure of executive cognitive function), at baseline and after an average of 22 months. Subjects were also administered the Center for Epidemiologic Studies Depression Scale, and the Coronary Artery Risk Development in Young Adults 1-Year Activity Recall. At baseline, Hispanic elders had a greater number of cardiometabolic risk factors and lower MMSE and behavioral dyscontrol scale scores than non-Hispanic whites. Hispanic ethnicity was associated with a greater likelihood of decline in general cognitive function, but not executive cognitive function, after adjusting for age and education. This differential decline was not explained by either individual or total number of baseline cardiometabolic risk factors, depression, or physical activity. A borderline increased risk of decline in general cognitive function was seen in sedentary individuals (P = 0.05).

  16. Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer's disease.

    PubMed

    Zumkehr, Joannee; Rodriguez-Ortiz, Carlos J; Cheng, David; Kieu, Zanett; Wai, Thin; Hawkins, Charlesice; Kilian, Jason; Lim, Siok Lam; Medeiros, Rodrigo; Kitazawa, Masashi

    2015-07-01

    Glial glutamate transporter, GLT-1, is the major Na(+)-driven glutamate transporter to control glutamate levels in synapses and prevent glutamate-induced excitotoxicity implicated in neurodegenerative disorders including Alzheimer's disease (AD). Significant functional loss of GLT-1 has been reported to correlate well with synaptic degeneration and severity of cognitive impairment among AD patients, yet the underlying molecular mechanism and its pathological consequence in AD are not well understood. Here, we find the temporal decrease in GLT-1 levels in the hippocampus of the 3xTg-AD mouse model and that the pharmacological upregulation of GLT-1 significantly ameliorates the age-dependent pathological tau accumulation, restores synaptic proteins, and rescues cognitive decline with minimal effects on Aβ pathology. In primary neuron and astrocyte coculture, naturally secreted Aβ species significantly downregulate GLT-1 steady-state and expression levels. Taken together, our data strongly suggest that GLT-1 restoration is neuroprotective and Aβ-induced astrocyte dysfunction represented by a functional loss of GLT-1 may serve as one of the major pathological links between Aβ and tau pathology.

  17. Vascular risk factors and Alzheimer's disease pathogenesis: are conventional pharmacological approaches protective for cognitive decline progression?

    PubMed

    Safouris, Apostolos; Psaltopoulou, Theodora; Sergentanis, Theodoros N; Boutati, Eleni; Kapaki, Elisabeth; Tsivgoulis, Georgios

    2015-01-01

    Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than half of cases with cognitive impairment. With numbers of patients expected to rise sharply over the following years in parallel with the ageing of population, there is intense clinical interest in discovering modifiable risk factors that may contribute to the increasing prevalence of AD. Accumulating data from in vitro and epidemiological studies have highlighted the vascular component of AD and raised hope that treatment of vascular risk factors could eventually lead to primary prevention of AD. Among all the possible pathologic processes that have been tested for an association with AD, diabetes, hypertension and dyslipidemia are the most prominent. Here, we will briefly review the data highlighting a potential correlation of these diseases with AD. Then, we will present observational studies and clinical trials that assessed the impact of their respective approved medical therapies on AD incidence. We conclude by providing clinical information for the physician on potentially effective and non-effective medical treatments. Further research is ongoing and time will show whether AD will cease to be considered a pure, non-preventable neurodegenerative process or whether vascular risk factor management may also result in primary AD prevention.

  18. Decline of human tactile angle discrimination in patients with mild cognitive impairment and Alzheimer's disease.

    PubMed

    Yang, Jiajia; Ogasa, Takashi; Ohta, Yasuyuki; Abe, Koji; Wu, Jinglong

    2010-01-01

    There is a need to differentiate between patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from normal-aged controls (NC) in the field of clinical drug discovery. In this study, we developed a tactile angle discrimination system and examined whether the ability to discriminate tactile angle differed between patients with MCI and AD and the NC group. Thirty-seven subjects were divided into three groups: NC individuals (n=14); MCI patients (n=10); and probable AD patients (n=13). All subjects were asked to differentiate the relative sizes of the reference angle (60°) and one of eight comparison angles by passive touch. The accuracy of angle discrimination was measured and the discrimination threshold was calculated. We discovered that there were significant differences in the angle discrimination thresholds of AD patients compared to the NC group. Interestingly, we also found that ability to discriminate tactile angle of MCI patients were significantly lower than that of the NC group. This is the first study to report that patients with MCI and AD have substantial performance deficits in tactile angle discrimination compared to the NC individuals. This finding may provide a monitor and therapeutic approach in AD diagnosis and treatment.

  19. IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

    PubMed Central

    Fu, Amy K. Y.; Hung, Kwok-Wang; Yuen, Michael Y. F.; Zhou, Xiaopu; Mak, Deejay S. Y.; Chan, Ivy C. W.; Cheung, Tom H.; Zhang, Baorong; Fu, Wing-Yu; Liew, Foo Y.; Ip, Nancy Y.

    2016-01-01

    Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD. PMID:27091974

  20. [Cognitive decline in Alzheimer's disease. A follow three or more years of a sample of patients].

    PubMed

    Conde-Sala, Josep Lluís; Garre-Olmo, Josep; Vilalta-Franch, Joan; Llinàs-Reglà, Jordi; Turró-Garriga, Oriol; Lozano-Gallego, Manuela; Hernández-Ferràndiz, Marta; Pericot-Nierga, Imma; López-Pousa, Secundino

    2013-06-16

    Introduccion. Las tasas de declive cognitivo en los pacientes con enfermedad de Alzheimer presentan variaciones debido a diversos factores. Objetivo. Determinar la influencia de la edad, escolaridad, genero, actividades de la vida diaria (AVD) e inhibidores de la acetilcolinesterasa (IAChE) y memantina en el ritmo y tasas de declive cognitivo. Pacientes y metodos. Estudio retrospectivo de una muestra de 383 pacientes con enfermedad de Alzheimer, con evaluaciones neuropsicologicas durante un periodo superior a tres años. Se utilizo como medida cognitiva el Cambridge Cognitive Examination (CAMCOG). Se agruparon los pacientes segun su tasa de declive anual (TDA) y se realizaron analisis bivariante y de regresion lineal multivariante utilizando como variable dependiente la diferencia de puntuaciones en el CAMCOG (basal-final). Resultados. La menor edad (beta = –0,23; p < 0,001), la mayor escolaridad (beta = 0,26; p < 0,001) y el mayor deterioro de las AVD (beta = 0,24; p < 0,001) estuvieron asociados a un mayor declive en todos los pacientes. Los farmacos tuvieron un efecto benefico (beta = –0,18; p = 0,011) en el grupo con menor y mas lento declive (TDA < 5%). Conclusiones. La menor edad, la mayor escolaridad y el deterioro de las AVD se relacionan con un mayor declive cognitivo. Los IAChE y la memantina tuvieron un efecto benefico, enlenteciendo el declive en el grupo de pacientes con menor TDA.

  1. Cortical connectivity and memory performance in cognitive decline: A study via graph theory from EEG data.

    PubMed

    Vecchio, F; Miraglia, F; Quaranta, D; Granata, G; Romanello, R; Marra, C; Bramanti, P; Rossini, P M

    2016-03-01

    Functional brain abnormalities including memory loss are found to be associated with pathological changes in connectivity and network neural structures. Alzheimer's disease (AD) interferes with memory formation from the molecular level, to synaptic functions and neural networks organization. Here, we determined whether brain connectivity of resting-state networks correlate with memory in patients affected by AD and in subjects with mild cognitive impairment (MCI). One hundred and forty-four subjects were recruited: 70 AD (MMSE Mini Mental State Evaluation 21.4), 50 MCI (MMSE 25.2) and 24 healthy subjects (MMSE 29.8). Undirected and weighted cortical brain network was built to evaluate graph core measures to obtain Small World parameters. eLORETA lagged linear connectivity as extracted by electroencephalogram (EEG) signals was used to weight the network. A high statistical correlation between Small World and memory performance was found. Namely, higher Small World characteristic in EEG gamma frequency band during the resting state, better performance in short-term memory as evaluated by the digit span tests. Such Small World pattern might represent a biomarker of working memory impairment in older people both in physiological and pathological conditions.

  2. Over the Hill at 24: Persistent Age-Related Cognitive-Motor Decline in Reaction Times in an Ecologically Valid Video Game Task Begins in Early Adulthood

    PubMed Central

    Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  3. Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

    PubMed

    Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load.

  4. Cognitive and Functional Decline among Individuals 50 Years of Age or Older in Cambé, Paraná, Brazil: A Population-Based Study

    PubMed Central

    Cabrera, Marcos Aparecido Sarria; Bortoletto, Maira Aira Sayuri Sakay; de Souza, Regina Kazue Tanno; Prina, Douglas Manuel Carrapeiro; Vieira, Maria Cristina Umpierrez; Silva, Ana Maria Rigo

    2016-01-01

    Aims To identify the frequency of cognitive and functional decline (CFD) among adults 50 years of age and older by a population-based study. Methods Cognitive function was analyzed by the Mini-Mental State Examination, and the functional conditions were based on instrumental activities of daily living (IADL). Cases of CFD included individuals with cognitive decline and 2 or more compromised IADL. Results A total of 693 individuals were studied. The frequency of CFD was 16.3%. A low socioeconomic profile was associated with greater CFD independent of gender, age, education, and presence of depression (OR = 2.46; 95% CI: 1.53-3.97). Conclusions These data show a high frequency of CFD among adults 50 years and older. Individuals with less education and a lower socioeconomic level exhibited poorer cognitive and functional conditions. PMID:27350779

  5. Predictors of placebo group decline in the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) in 24 week clinical trials of Alzheimer's disease.

    PubMed

    Irizarry, Michael C; Webb, David J; Bains, Chanchal; Barrett, Steven J; Lai, Robert Y; Laroche, Janette P; Hosford, David; Maher-Edwards, Gareth; Weil, John G

    2008-07-01

    One limitation of several recent 24 week Alzheimer's disease (AD) clinical trials was the lack of cognitive decline detected by the AD Assessment Scale-cognitive subscale (ADAS-cog) in the placebo groups, possibly obscuring true medication effects. Data from 733 individuals in the placebo arms of six AD clinical trials performed 1996-1997 were pooled to examine the relationship of clinical, demographic, and genetic characteristics with the 24 week change in ADAS-cog. Baseline cognitive and functional status and the screening-to-baseline change in ADAS-cog were the strongest independent predictors of the 24 week change in ADAS-cog. The ADAS-cog did not detect progression in patients with mild dementia (screening Mini-Mental State Exam, MMSE, >or=20). The change in ADAS-cog from screening to baseline was inversely correlated with the 24 week change score; it was more difficult to detect cognitive decline at 24 weeks if individuals markedly worsened from screening to baseline. The effects of baseline MMSE and screening-to-baseline change in ADAS-cog generalized to the placebo group (N=106) of another AD study performed in 2004-2005. Overcoming lack of placebo decline in AD clinical trials will require scales more sensitive to cognitive decline in mild AD and strategies to reduce within-person variability in outcome measures.

  6. Classification of Symptomatic and Asymptomatic Patients with and without Cognitive Decline Using Non-invasive Carotid Plaque Strain Indices as Biomarkers.

    PubMed

    Wang, Xiao; Jackson, Daren C; Mitchell, Carol C; Varghese, Tomy; Wilbrand, Stephanie M; Rocque, Brandon G; Hermann, Bruce P; Dempsey, Robert J

    2016-04-01

    Vascular cognitive decline may be caused by micro-emboli generated by carotid plaque instability. We previously found that maximum strain indices in carotid plaque were significantly correlated with cognitive function. In the work described here, we examined these associations with a larger sample size, as well as evaluated the performance of these maximum strain indices in predicting cognitive impairment. Ultrasound-based strain imaging and cognition assessment were conducted on 75 human patients. Patients underwent one of two standardized cognitive test batteries, either the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or the National Institute of Neurologic Disorder and Stroke-Canadian Stroke Network (NINDS-CSN) Vascular Cognitive Impairment Harmonization Standards (60 min). Scores were standardized within each battery to allow these data to be combined across all participants. Radiofrequency signals for ultrasound strain imaging were acquired on the carotid arteries using either a Siemens Antares with a VFX 13-5 linear array transducer or a Siemens S2000 with an 18 L6 linear array transducer. The same hierarchical block-matching motion tracking algorithm developed in our laboratory was used to estimate accumulated axial, lateral, and shear strain indices in carotid plaque, with inclusion of adventitia regardless of the ultrasound system and transducer used. Associations between cognitive z-scores and maximum strain indices were examined using Pearson's correlation coefficients. Maximum strain indices were also employed to predict cognitive impairment using receiver operating characteristic analysis. All correlations between maximum strain indices and total cognition were statistically significant (p < 0.05), indicating that these indices have good utility in predicting cognitive impairment. Maximum lateral strain indices provided an area under the curve of 0.85 for symptomatic patients and 0.68 for asymptomatic patients. Our

  7. Associations of Objectively and Subjectively Measured Sleep Quality with Subsequent Cognitive Decline in Older Community-Dwelling Men: The MrOS Sleep Study

    PubMed Central

    Blackwell, Terri; Yaffe, Kristine; Laffan, Alison; Ancoli-Israel, Sonia; Redline, Susan; Ensrud, Kristine E.; Song, Yeonsu; Stone, Katie L.

    2014-01-01

    Study Objectives: To examine associations of objectively and subjectively measured sleep with subsequent cognitive decline. Design: A population-based longitudinal study. Setting: Six centers in the United States. Participants: Participants were 2,822 cognitively intact community-dwelling older men (mean age 76.0 ± 5.3 y) followed over 3.4 ± 0.5 y. Interventions: None. Measurements and Results: Objectively measured sleep predictors from wrist actigraphy: total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), number of long wake episodes (LWEP). Self-reported sleep predictors: sleep quality (Pittsburgh Sleep Quality Index [PSQI]), daytime sleepiness (Epworth Sleepiness Scale [ESS]), TST. Clinically significant cognitive decline: five-point decline on the Modified Mini-Mental State examination (3MS), change score for the Trails B test time in the worse decile. Associations of sleep predictors and cognitive decline were examined with logistic regression and linear mixed models. After multivariable adjustment, higher levels of WASO and LWEP and lower SE were associated with an 1.4 to 1.5-fold increase in odds of clinically significant decline (odds ratio 95% confidence interval) Trails B test: SE < 70% versus SE ≥ 70%: 1.53 (1.07, 2.18); WASO ≥ 90 min versus WASO < 90 min: 1.47 (1.09, 1.98); eight or more LWEP versus fewer than eight: 1.38 (1.02, 1.86). 3MS: eight or more LWEP versus fewer than eight: 1.36 (1.09, 1.71), with modest relationships to linear change in cognition over time. PSQI was related to decline in Trails B performance (3 sec/y per standard deviation increase). Conclusions: Among older community-dwelling men, reduced sleep efficiency, greater nighttime wakefulness, greater number of long wake episodes, and poor self-reported sleep quality were associated with subsequent cognitive decline. Citation: Blackwell T; Yaffe K; Laffan A; Ancoli-Israel S; Redline S; Ensrud KE; Song Y; Stone KL. Associations of objectively and

  8. Cohorts based on Decade of Death: No Evidence for Secular Trends Favoring Later Cohorts in Cognitive Aging and Terminal Decline in the AHEAD Study

    PubMed Central

    Hülür, Gizem; Infurna, Frank J.; Ram, Nilam; Gerstorf, Denis

    2012-01-01

    Studies of birth-year cohorts examined over the same age range often report secular trends favoring later-born cohorts, who are cognitively fitter and show less steep cognitive declines than earlier-born cohorts. However, there is initial evidence that those advantages of later-born cohorts do not carry into the last years of life, suggesting that pervasive mortality-related processes minimize differences that were apparent earlier in life. Elaborating this work from an alternative perspective on cohort differences, we compared rates of cognitive aging and terminal decline in episodic memory between cohorts based on the year participants had died, earlier (between 1993 and 1999) or later in historical time (between 2000 and 2010). Specifically, we compared trajectories of cognitive decline in two death-year cohorts of participants in the Asset and Health Dynamics among the Oldest Old (AHEAD) Study that were matched on age at death and education and controlled for a variety of additional covariates. Results revealed little evidence of secular trends favoring later cohorts. To the contrary, the cohort that died in the 2000s showed a less favorable trajectory of age-related memory decline than the cohort who died in the 1990s. In examinations of change in relation to time-to-death, the cohort dying in the 2000s experienced even steeper terminal declines than the cohort dying in the 1990s. We suggest that secular increases in “manufacturing” survival may exacerbate age- and mortality-related cognitive declines among the oldest old. PMID:23046001

  9. Enhancing Cognitive Functioning in Healthly Older Adults: a Systematic Review of the Clinical Significance of Commercially Available Computerized Cognitive Training in Preventing Cognitive Decline.

    PubMed

    Shah, Tejal M; Weinborn, Michael; Verdile, Giuseppe; Sohrabi, Hamid R; Martins, Ralph N

    2017-03-01

    Successfully assisting older adults to maintain or improve cognitive function, particularly when they are dealing with neurodegenerative disorders such as Alzheimer's disease (AD), remains a major challenge. Cognitive training may stimulate neuroplasticity thereby increasing cognitive and brain reserve. Commercial brain training programs are computerized, readily-available, easy-to-administer and adaptive but often lack supportive data and their clinical validation literature has not been previously reviewed. Therefore, in this review, we report the characteristics of commercially available brain training programs, critically assess the number and quality of studies evaluating the empirical evidence of these programs for promoting brain health in healthy older adults, and discuss underlying causal mechanisms. We searched PubMed, Google Scholar and each program's website for relevant studies reporting the effects of computerized cognitive training on cognitively healthy older adults. The evidence for each program was assessed via the number and quality (PEDro score) of studies, including Randomized Control Trials (RCTs). Programs with clinical studies were subsequently classified as possessing Level I, II or III evidence. Out of 18 identified programs, 7 programs were investigated in 26 studies including follow-ups. Two programs were identified as possessing Level I evidence, three programs demonstrated Level II evidence and an additional two programs demonstrated Level III evidence. Overall, studies showed generally high methodological quality (average PEDro score = 7.05). Although caution must be taken regarding any potential bias due to selective reporting, current evidence supports that at least some commercially available computerized brain training products can assist in promoting healthy brain aging.

  10. Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice

    PubMed Central

    Qiu, Li-Li; Luo, Dan; Zhang, Hui; Shi, Yun S.; Li, Yan-Jun; Wu, Dan; Chen, Jiang; Ji, Mu-Huo; Yang, Jian-Jun

    2016-01-01

    Postoperative cognitive decline (POCD) is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediated-abnormalities in parvalbumin (PV) interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in 16-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO). Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide (LPS) in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1β (IL-1β), markers of oxidative stress and NADPH oxidase 2 (Nox2) in the hippocampus. In addition, LPS exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived reactive oxygen species (ROS) production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice. PMID:27790135

  11. Fifteen-Year Follow-Up of 92 Hospitalized Adults with Down's Syndrome: Incidence of Cognitive Decline, Its Relationship to Age and Neuropathology

    ERIC Educational Resources Information Center

    Margallo-Lana, M. L.; Moore, P. B.; Kay, D. W. K.; Perry, R. H.; Reid, B. E.; Berney, T. P.; Tyrer, S. P.

    2007-01-01

    Background: The clinical and neuropathological features associated with dementia in Down's syndrome (DS) are not well established. Aims: To examine clinico-pathological correlations and the incidence of cognitive decline in a cohort of adults with DS. Method: A total of 92 hospitalized persons with DS were followed up from 1985 to December 2000.…

  12. Antiphospholipid antibodies, brain infarcts, and cognitive and motor decline in aging (ABICMA): design of a community-based, longitudinal, clinical-pathological study.

    PubMed

    Arvanitakis, Zoe; Brey, Robin L; Rand, Jacob H; Schneider, Julie A; Leurgans, Sue E; Yu, Lei; Buchman, Aron S; Arfanakis, Konstantinos; Fleischman, Debra A; Boyle, Patricia A; Bennett, David A; Levine, Steven R

    2013-01-01

    The overall goal of the Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging study is to test the hypothesis that antiphospholipid antibodies (aPL) are associated with an increased risk of pathologically proven brain infarcts and are related to cognitive and motor decline in aging. Putative biologic mechanisms underlying the association of aPL with infarcts and the relation of aPL with clinical outcomes of cognitive and motor impairment, including vascular and other processes, will be examined. The design of this longitudinal, clinical-pathologic study involves quantifying four aPL assays, and relating these to brain infarcts, and to cognitive and motor decline. Vascular mechanisms assessed using antemortem magnetic resonance neuroimaging and postmortem neuropathology, as well as nonvascular mechanisms of inflammation and blood-brain barrier permeability alterations will be examined as plausible mediators of the relation of aPL to cognitive and motor impairment. We will take advantage of antemortem biological specimens (longitudinally collected sera and plasma from which aPL, annexins, C-reactive protein, and matrix metalloproteinases will be quantified), and clinical, neuroimaging, and postmortem neuropathologic data from about 800 elderly, community-dwelling women and men who have agreed to brain autopsy at the time of death, participating in one of two ongoing studies of aging: the Religious Orders Study and the Memory and Aging Project.

  13. Is there a decline in cognitive functions after combined electroconvulsive therapy and antipsychotic therapy in treatment-refractory schizophrenia?

    PubMed

    Pawełczyk, Agnieszka; Kołodziej-Kowalska, Emilia; Pawełczyk, Tomasz; Rabe-Jabłońska, Jolanta

    2015-03-01

    An analysis of literature shows that there is still little evidence concerning the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic therapy in a group of treatment-resistant schizophrenia patients. More precisely, its influence on cognitive functions is still equivocal. The aim of this study was to assess the influence of ECT combined with antipsychotic therapy on working memory, attention, and executive functions in a group of treatment-refractory schizophrenia patients. Twenty-seven patients completed the study: 14 men and 13 women, aged 21 to 55 years (mean age, 32.8 years), diagnosed with treatment-resistant schizophrenia. Each patient underwent a course of ECT sessions and was treated with antipsychotic medications. Before the ECT and within 3 days after the last ECT session, the participants were assessed with the following neuropsychological tests: Trail Making Test (TMT) and Wisconsin Cart Sorting Test (WCST). There were no significant differences in the TMT and WCST results after combined ECT and antipsychotic therapy in treatment-refractory schizophrenia patients. According to the results of the neuropsychological tests, there was no decline in attention, executive functions, or working memory. The current study shows no significant difference in attention, working memory, or executive functions after treatment with a combination of electroconvulsive and antipsychotic therapy. This suggests that combined electroconvulsive therapy may not have a negative influence on the neuropsychological functioning of patients with treatment resistant schizophrenia.

  14. Neurological Soft Signs in Aging, Mild Cognitive Impairment, and Alzheimer’s Disease – The Impact of Cognitive Decline and Cognitive Reserve

    PubMed Central

    Urbanowitsch, Nadja; Degen, Christina; Toro, Pablo; Schröder, Johannes

    2015-01-01

    Objectives: Neurological soft signs (NSS), i.e., minor motor and sensory changes, are a common feature in severe psychiatric disorders. We sought to establish the frequency of NSS in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) on basis of a large population-based sample and to identify their neuropsychological correlates including cognitive reserve. Methods: Neurological soft signs were examined using an abbreviated version of the Heidelberg NSS Scale in 221 “old” participants born between 1930 and 1932 (63 with MCI, 15 with AD, 143 healthy old controls) and 256 healthy “young” participants (born between 1950 and 1952) of the population-based interdisciplinary longitudinal study of aging. Subjects received thorough neuropsychological testing; years of school education were used as a proxy for cognitive reserve. Results: Neurological soft signs scores were significantly (p < 0.001) higher in the AD patients (5.6 ± 3.11) than in the healthy old controls (2.8 ± 1.90) and in the MCI patients (3.0 ± 1.96). This result was confirmed after years of school education, which were inversely correlated (r = −0.25; p < 0.001) with NSS were entered as a covariate. In the patients, but not in the controls, NSS were significantly correlated with deficits in executive functioning and visuospatial functioning. Comparison of NSS scores between “old” (2.84 ± 1.9) and “young” (2.46 ± 1.97) controls yielded only minor, non-significant differences after education (13.86 ± 3.0 vs. 14.61 ± 2.48 years, respectively) was controlled for. Conclusion: Our results demonstrate that NSS are frequently found in mild AD, but not in MCI. NSS refer to frontal-executive deficits and visuospatial dysfunction rather than age per se and can be partly compensated for by cognitive reserve. PMID:25717306

  15. The Faces Symbol Test, a newly developed screening instrument to assess cognitive decline related to multiple sclerosis: first results of the Berlin Multi-Centre FST Validation Study.

    PubMed

    Scherer, P; Penner, I K; Rohr, A; Boldt, H; Ringel, I; Wilke-Burger, H; Burger-Deinerth, E; Isakowitsch, K; Zimmermann, M; Zahrnt, S; Hauser, R; Hilbert, K; Tiel-Wilck, K; Anvari, K; Behringer, A; Peglau, I; Friedrich, H; Plenio, A; Benesch, G; Ehret, R; Nippert, I; Finke, G; Schulz, I; Bergtholdt, B; Breitkopf, S; Kaskel, P; Reischies, F; Kugler, J

    2007-04-01

    Reliable, language-independent, short screening instruments to test for cognitive function in patients with multiple sclerosis (MS) remain rare, despite the high number of patients affected by cognitive decline. We developed a new, short screening instrument, the Faces Symbol Test (FST), and compared its diagnostic test characteristics with a composite of the Digit Symbol Substitution Test (DSST) and the Paced Auditory Serial Addition Test (PASAT), in 108 MS patients and 33 healthy controls. An Informant-Report Questionnaire, a Self-Report Questionnaire, and a neurologist's estimation of the Every Day Life Cognitive Status were also applied to the MS patients. The statistical analyses comprised of a receiver operating characteristic analysis for test accuracy and for confounding variables. The PASAT and DSST composite score estimated that 36.5% of the MS patients had cognitive impairment. The FST estimated that 40.7% of the MS patients were cognitively impaired (sensitivity 84%; specificity 85%). The FST, DSST and PASAT results were significantly correlated with the patients' physical impairment, as measured by the Expanded Disability Status Scale (EDSS). The results suggest that the FST might be a culture-free, sensitive, and practical short screening instrument for the detection of cognitive decline in patients with MS, including those in the early stages.

  16. The Decline of Academic Motivation during Adolescence: An Accelerated Longitudinal Cohort Analysis on the Effect of Psychological Need Satisfaction

    ERIC Educational Resources Information Center

    Gnambs, Timo; Hanfstingl, Barbara

    2016-01-01

    Adolescents typically exhibit a marked decline in academic intrinsic motivation throughout their school careers. Following self-determination theory, it is hypothesised that traditional school environments insufficiently satisfy three basic psychological needs of youths during maturation, namely the needs for autonomy, competence and relatedness.…

  17. Can cognitive activities during breaks in repetitive manual work accelerate recovery from fatigue? A controlled experiment.

    PubMed

    Mathiassen, Svend Erik; Hallman, David M; Lyskov, Eugene; Hygge, Staffan

    2014-01-01

    Neurophysiologic theory and some empirical evidence suggest that fatigue caused by physical work may be more effectively recovered during "diverting" periods of cognitive activity than during passive rest; a phenomenon of great interest in working life. We investigated the extent to which development and recovery of fatigue during repeated bouts of an occupationally relevant reaching task was influenced by the difficulty of a cognitive activity between these bouts. Eighteen male volunteers performed three experimental sessions, consisting of six 7-min bouts of reaching alternating with 3 minutes of a memory test differing in difficulty between sessions. Throughout each session, recordings were made of upper trapezius muscle activity using electromyography (EMG), heart rate and heart rate variability (HRV) using electrocardiography, arterial blood pressure, and perceived fatigue (Borg CR10 scale and SOFI). A test battery before, immediately after and 1 hour after the work period included measurements of maximal shoulder elevation strength (MVC), pressure pain threshold (PPT) over the trapezius muscles, and a submaximal isometric contraction. As expected, perceived fatigue and EMG amplitude increased during the physical work bouts. Recovery did occur between the bouts, but fatigue accumulated throughout the work period. Neither EMG changes nor recovery of perceived fatigue during breaks were influenced by cognitive task difficulty, while heart rate and HRV recovered the most during breaks with the most difficult task. Recovery of perceived fatigue after the 1 hour work period was also most pronounced for the most difficult cognitive condition, while MVC and PPT showed ambiguous patterns, and EMG recovered similarly after all three cognitive protocols. Thus, we could confirm that cognitive tasks between bouts of fatiguing physical work can, indeed, accelerate recovery of some factors associated with fatigue, even if benefits may be moderate and some responses may be

  18. Can Cognitive Activities during Breaks in Repetitive Manual Work Accelerate Recovery from Fatigue? A Controlled Experiment

    PubMed Central

    Mathiassen, Svend Erik; Hallman, David M.; Lyskov, Eugene; Hygge, Staffan

    2014-01-01

    Neurophysiologic theory and some empirical evidence suggest that fatigue caused by physical work may be more effectively recovered during “diverting” periods of cognitive activity than during passive rest; a phenomenon of great interest in working life. We investigated the extent to which development and recovery of fatigue during repeated bouts of an occupationally relevant reaching task was influenced by the difficulty of a cognitive activity between these bouts. Eighteen male volunteers performed three experimental sessions, consisting of six 7-min bouts of reaching alternating with 3 minutes of a memory test differing in difficulty between sessions. Throughout each session, recordings were made of upper trapezius muscle activity using electromyography (EMG), heart rate and heart rate variability (HRV) using electrocardiography, arterial blood pressure, and perceived fatigue (Borg CR10 scale and SOFI). A test battery before, immediately after and 1 hour after the work period included measurements of maximal shoulder elevation strength (MVC), pressure pain threshold (PPT) over the trapezius muscles, and a submaximal isometric contraction. As expected, perceived fatigue and EMG amplitude increased during the physical work bouts. Recovery did occur between the bouts, but fatigue accumulated throughout the work period. Neither EMG changes nor recovery of perceived fatigue during breaks were influenced by cognitive task difficulty, while heart rate and HRV recovered the most during breaks with the most difficult task. Recovery of perceived fatigue after the 1 hour work period was also most pronounced for the most difficult cognitive condition, while MVC and PPT showed ambiguous patterns, and EMG recovered similarly after all three cognitive protocols. Thus, we could confirm that cognitive tasks between bouts of fatiguing physical work can, indeed, accelerate recovery of some factors associated with fatigue, even if benefits may be moderate and some responses may

  19. Greater Age-Related Decline in Markers of Physical, Mental and Cognitive Health among Israeli Older Adults Exposed to Lifetime Cumulative Adversity

    PubMed Central

    Shrira, Amit

    2013-01-01

    Objectives This longitudinal investigation addressed whether and how lifetime cumulative adversity and depressive symptoms moderated age-related decline in markers of physical, mental and cognitive health. Method 1,248 older adults (mean age = 62 at Wave 1) who completed the first two waves of the Israeli component of the Survey of Health, Ageing and Retirement in Europe (SHARE-Israel) reported on exposure to potentially traumatic life events, depressive symptoms, and three outcomes – disability, quality of life and cognitive markers. Results Age was related to greater functional decline in outcome measures across the two waves (i.e., increase in disability and decrease in quality of life and cognitive functioning). This age-related decline became stronger as lifetime adversity increased. A three-way interaction showed that the greatest age-related functional decline in outcome measures was especially salient among those with high level of lifetime adversity and high level of depressive symptoms. Conclusion Lifetime cumulative adversity is associated with a more noticeable process of age-related dysfunction across various markers of health. Although the majority of older adults are resilient to lifetime adversity, prevention and intervention programs should be aimed at mitigating the pronounced senescence observed when adversity accumulated to a large degree, and especially when it is accompanied with high level of distress. PMID:24328416

  20. Resting-State Functional Connectivity of the Striatum in Early-Stage Parkinson’s Disease: Cognitive Decline and Motor Symptomatology

    PubMed Central

    Manza, Peter; Zhang, Sheng; Li, Chiang-Shan R.; Leung, Hoi-Chung

    2016-01-01

    Parkinson’s disease is a neurodegenerative disorder characterized by changes to dopaminergic function in the striatum and a range of cognitive and motor deficits. Neuroimaging studies have repeatedly shown differences in activation and functional connectivity patterns of the striatum between symptomatic individuals with Parkinson’s disease and healthy controls. However, the presence and severity of cognitive and motor symptoms seem to differ dramatically among individuals with Parkinson’s disease at the early-stages. To investigate the neural basis of such heterogeneity, we examined the resting state functional connectivity patterns of caudate and putamen subdivisions in relation to cognitive and motor impairments among 62 early-stage individuals with Parkinson’s disease (21 females, 23 drug naive, ages 39–77 years, average UPDRS motor scores off medication = 18.56, average H&Y stage = 1.66). We also explored how changes in striatal connectivity relate to changes in symptomatology over a year. There are two main findings. First, higher motor deficit rating was associated with weaker coupling between anterior putamen and midbrain including substantia nigra. Intriguingly, steeper declines in functional connectivity between these regions were associated with greater declines in motor function over the course of 1 year. Second, decline in cognitive function, particularly in the memory and visuospatial domains, was associated with stronger coupling between the dorsal caudate and the rostral anterior cingulate cortex. These findings remained significant after controlling for age, medication, gender, and education. In sum, our findings suggest that cognitive decline and motor deficit are each associated with a differentiable pattern of functional connectivity of striatal subregions. PMID:26566885

  1. Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

    PubMed

    Daulatzai, Mak Adam

    2016-10-01

    Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

  2. Long-term moderate alcohol consumption does not exacerbate age-related cognitive decline in healthy, community-dwelling older adults

    PubMed Central

    Moussa, Malaak N.; Simpson, Sean L.; Mayhugh, Rhiannon E.; Grata, Michelle E.; Burdette, Jonathan H.; Porrino, Linda J.; Laurienti, Paul J.

    2015-01-01

    Recent census data has found that roughly 40% of adults 65 years and older not only consume alcohol but also drink more of it than previous generations. Older drinkers are more vulnerable than younger counterparts to the psychoactive effects of alcohol due to natural biological changes that occur with aging. This study was specifically designed to measure the effect of long-term moderate alcohol consumption on cognitive health in older adult drinkers. An extensive battery of validated tests commonly used in aging and substance use literature was used to measure performance in specific cognitive domains, including working memory and attention. An age (young, old) * alcohol consumption (light, moderate) factorial study design was used to evaluate the main effects of age and alcohol consumption on cognitive performance. The focus of the study was then limited to light and moderate older drinkers, and whether or not long-term moderate alcohol consumption exacerbated age-related cognitive decline. No evidence was found to support the idea that long-term moderate alcohol consumption in older adults exacerbates age-related cognitive decline. Findings were specific to healthy community dwelling social drinkers in older age and they should not be generalized to individuals with other consumption patterns, like heavy drinkers, binge drinkers or ex-drinkers. PMID:25601835

  3. Suppression of the aging-associated decline in physical performance by a combination of resveratrol intake and habitual exercise in senescence-accelerated mice.

    PubMed

    Murase, Takatoshi; Haramizu, Satoshi; Ota, Noriyasu; Hase, Tadashi

    2009-08-01

    The decline in physical performance with increasing age is a crucial problem in our aging society. We examined the effects of resveratrol, a natural polyphenolic compound present in grapes, in combination with habitual exercise on the aging-associated decline in physical performance in senescence-accelerated prone mice (SAMP1). The endurance capacity of SAMP1 mice undergoing an exercise regimen (SAMP1-Ex) decreased over 12 weeks whereas that of SAMP1 mice fed 0.2% (w/w) resveratrol along with exercise (SAMP1-ExRes) remained significantly higher. In the SAMP1-ExRes group, there was a significant increase in oxygen consumption and skeletal muscle mRNA levels of mitochondrial function-related enzymes. These results suggest that the intake of resveratrol, together with habitual exercise, is beneficial for suppressing the aging-related decline in physical performance and that these effects are attributable, at least in part, to improved mitochondrial function in skeletal muscle.

  4. One-trial 10-item free-recall performance in Taiwanese elderly and near-elderly: A potential screen for cognitive decline.

    PubMed

    Tractenberg, Rochelle E; Aisen, Paul S; Chuang, Yi-Li

    2005-01-01

    To explore a one-trial 10-item free-recall test as a potential dementia screening tool, we analyzed recall scores and individualized serial position effects in near-elderly (N = 2,336) and elderly (N = 2,371) participants in a population-based survey in Taiwan. Age and sex were significantly associated with recall score [younger > older (p < 0.001); men > women (p < 0.001)]; after controlling for gender and age group, weak association between recall and education was still observed. By contrast, serial position effects (SPEs), defined for each participant and analyzed aggregated over each age group, were not associated with education and tended not to be associated with sex. Primacy effects were observed in 67 to 80 percent, and recency effects were observed in 41 to 54 percent of respondents. Because SPEs were defined for each respondent, we could determine that loss of the primacy effect was associated with significantly larger losses in total recall score in elderly persons who had exhibited both SPEs at the first survey, as compared to those who maintained both SPEs at successive surveys (p < 0.01). Elderly subjects showed slight longitudinal decline in free recall. A one-trial 10-item free-recall test demonstrated age-related cognitive decline in this Taiwanese population survey cohort; SPEs at the individual level may be useful markers for important cognitive change and warrant further study and benchmarking against valid and reliable tests of memory and cognitive decline.

  5. Long-term ginsenoside Rg1 supplementation improves age-related cognitive decline by promoting synaptic plasticity associated protein expression in C57BL/6J mice.

    PubMed

    Yang, Lumeng; Zhang, Jing; Zheng, Kunmu; Shen, Hui; Chen, Xiaochun

    2014-03-01

    In aging individuals, age-related cognitive decline is the most common cause of memory impairment. Among the remedies, ginsenoside Rg1, a major active component of ginseng, is often recommended for its antiaging effects. However, its role in improving cognitive decline during normal aging remains unknown and its molecular mechanism partially understood. This study employed a scheme of Rg1 supplementation for female C57BL/6J mice, which started at the age of 12 months and ended at 24 months, to investigate the effects of Rg1 supplementation on the cognitive performance. We found that Rg1 supplementation improved the performance of aged mice in behavior test and significantly upregulated the expression of synaptic plasticity-associated proteins in hippocampus, including synaptophysin, N-methyl-D-aspartate receptor subunit 1, postsynaptic density-95, and calcium/calmodulin-dependent protein kinase II alpha, via promoting mammalian target of rapamycin pathway activation. These data provide further support for Rg1 treatment of cognitive degeneration during aging.

  6. Antihypertensive treatment with cerebral hemodynamics monitoring by ultrasonography in elderly hypertensives without a history of stroke may prevent or slow down cognitive decline. A pending issue.

    PubMed

    Hadjiev, Dimiter I; Mineva, Petya P

    2011-03-01

    The role of the antihypertensive therapy in preventing cognitive disorders in elderly persons without a history of stroke is still a matter of debate. This article focuses on the pathogenesis of vascular cognitive disorders in hypertension and on the impact of antihypertensive treatment in their prevention. Cerebral white matter lesions, caused by small vessel disease and cerebral hypoperfusion, have been found in the majority of elderly hypertensives. They correlate with cognitive disorders, particularly impairments of attention and executive functions. Excessive blood pressure lowering in elderly patients with long-standing hypertension below a certain critical level, may increase the risk of further cerebral hypoperfusion because of disrupted cerebral blood flow autoregulation. As a result, worsening of the cognitive functions could occur, especially in cases with additional vascular risk factors. Five randomized, placebo-controlled trials have focused on the efficacy of antihypertensive treatments in preventing cognitive impairments in elderly patients without a prior cerebrovascular disease. Four of them have not found positive effects. We suggest that repeated neuropsychological assessments and ultrasonography for evaluation of carotid atherosclerosis, as well as cerebral hemodynamics monitoring could adjust the antihypertensive therapy with the aim to decrease the risk of cerebral hypoperfusion and prevent or slow down cognitive decline in elderly hypertensives. Prospective studies are needed to confirm such a treatment strategy.

  7. Reduced quality and accelerated follicle loss with female reproductive aging - does decline in theca dehydroepiandrosterone (DHEA) underlie the problem?

    PubMed

    Ford, Judith H

    2013-12-13

    Infertility, spontaneous abortion and conception of trisomic offspring increase exponentially with age in mammals but in women there is an apparent acceleration in the rate from about age 37. The problems mostly commonly occur when the ovarian pool of follicles is depleted to a critical level with age but are also found in low follicular reserve of other etiologies. Since recent clinical studies have indicated that dehydroepiandrosterone (DHEA) supplementation may reverse the problem of oocyte quality, this review of the literature was undertaken in an attempt to find an explanation of why this is effective? In affected ovaries, oxygenation of follicular fluid is low, ultrastructural disturbances especially of mitochondria, occur in granulosa cells and oocytes, and considerable disturbances of meiosis occur. There is, however, no evidence to date that primordial follicles are compromised. In females with normal fertility, pre-antral ovarian theca cells respond to stimulation by inhibin B to provide androgen-based support for the developing follicle. With depletion of follicle numbers, inhibin B is reduced with consequent reduction in theca DHEA. Theca cells are the sole ovarian site of synthesis of DHEA, which is both a precursor of androstenedione and an essential ligand for peroxisome proliferator-activated receptor alpha (PPARα), the key promoter of genes affecting fatty acid metabolism and fat transport and genes critical to mitochondrial function. As well as inducing a plethora of deleterious changes in follicular cytoplasmic structure and function, the omega 9 palmitate/oleate ratio is increased by lowered activity of PPARα. This provides conditions for increased ceramide synthesis and follicular loss through ceramide-induced apoptosis is accelerated. In humans critical theca DHEA synthesis occurs at about 70 days prior to ovulation thus effective supplementation needs to be undertaken about four months prior to intended conception; timing which is also

  8. Demographic Features and Neuropsychological Correlates in a Cohort of 200 Patients with Vascular Cognitive Decline Due to Cerebral Small Vessel Disease

    PubMed Central

    Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Rajeswaran, Jamuna; Christopher, Rita; Philip, Mariamma

    2016-01-01

    Introduction: Vascular dementia is the second most common form of dementia and is potentially reversible. Small vessel disease (SVD) closely mimics degenerative dementia in view of its sub-acute onset and progressive course. Therefore, unlike large vessel disease, Hachinski Ischemic scale score may not always reflect vascular cognitive decline resulting in diagnostic and therapeutic confusions. Therefore, there is a need for detailed neuropsychological assessment for various cognitive domains for early identification of vascular cognitive decline as it carries a very good long term prognosis for cognitive morbidity, unlike degenerative dementias. Patients and Methods: This prospective study involves thorough domain based neuropsychological assessment of patients with a radiological diagnosis of SVD involving the following parameters-digit forward and backward, category fluency, color trails, stick test, logical memory test, and bender gestalt test. Magnetic resonance imaging scans done using 3-tesla machines and SVD graded using Fazekas visual scale. Results: The mean Hachinskis score was less sensitive for differentiating vascular dementia from degenerative dementia. However, the domain based neuropsychological scores were highly sensitive showing statistically significant impairment in all 6 domains tested and compared with Fazekas 1-3 grades in imaging. Discussion and Conclusion: This study aimed at establishing an early diagnosis of vascular mild cognitive impairment using domain wise neuropsychological testing and correlating it with radiological scores. Hachinskis score is more sensitive for large vessel disease in view of acute onset and step-like progression as against steady progression in SVD. However, domain-wise testing was highly sensitive in identifying early cognitive impairment in patients with SVD, and early therapeutic interventions are highly rewarding. PMID:27114624

  9. The Cognitive Reserve Hypothesis: A Longitudinal Examination of Age-Associated Declines in Reasoning and Processing Speed

    ERIC Educational Resources Information Center

    Tucker-Drob, Elliot M.; Johnson, Kathy E.; Jones, Richard N.

    2009-01-01

    The term cognitive reserve is frequently used to refer to the ubiquitous finding that, during later life, those higher in experiential resources (e.g., education, knowledge) exhibit higher levels of cognitive function. This observation may be the result of either experiential resources playing protective roles with respect to the cognitive…

  10. Intranasal Insulin Prevents Cognitive Decline, Cerebral Atrophy and White Matter Changes in Murine Type I Diabetic Encephalopathy

    ERIC Educational Resources Information Center

    Francis, George J.; Martinez, Jose A.; Liu, Wei Q.; Xu, Kevin; Ayer, Amit; Fine, Jared; Tuor, Ursula I.; Glazner, Gordon; Hanson, Leah R.; Frey, William H., II; Toth, Cory

    2008-01-01

    Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential…

  11. Reduction of Synaptojanin 1 Accelerates Aβ Clearance and Attenuates Cognitive Deterioration in an Alzheimer Mouse Model*

    PubMed Central

    Zhu, Li; Zhong, Minghao; Zhao, Jiaying; Rhee, Hannah; Caesar, Ina; Knight, Elysse M.; Volpicelli-Daley, Laura; Bustos, Victor; Netzer, William; Liu, Lijuan; Lucast, Louise; Ehrlich, Michelle E.; Robakis, Nikolaos K.; Gandy, Samuel E.; Cai, Dongming

    2013-01-01

    Recent studies link synaptojanin 1 (synj1), the main phosphoinositol (4,5)-biphosphate phosphatase (PI(4,5)P2-degrading enzyme) in the brain and synapses, to Alzheimer disease. Here we report a novel mechanism by which synj1 reversely regulates cellular clearance of amyloid-β (Aβ). Genetic down-regulation of synj1 reduces both extracellular and intracellular Aβ levels in N2a cells stably expressing the Swedish mutant of amyloid precursor protein (APP). Moreover, synj1 haploinsufficiency in an Alzheimer disease transgenic mouse model expressing the Swedish mutant APP and the presenilin-1 mutant ΔE9 reduces amyloid plaque load, as well as Aβ40 and Aβ42 levels in hippocampus of 9-month-old animals. Reduced expression of synj1 attenuates cognitive deficits in these transgenic mice. However, reduction of synj1 does not affect levels of full-length APP and the C-terminal fragment, suggesting that Aβ generation by β- and γ-secretase cleavage is not affected. Instead, synj1 knockdown increases Aβ uptake and cellular degradation through accelerated delivery to lysosomes. These effects are partially dependent upon elevated PI(4,5)P2 with synj1 down-regulation. In summary, our data suggest a novel mechanism by which reduction of a PI(4,5)P2-degrading enzyme, synj1, improves amyloid-induced neuropathology and behavior deficits through accelerating cellular Aβ clearance. PMID:24052255

  12. A Meta-Analysis of Cognitive Impairment and Decline Associated with Adjuvant Chemotherapy in Women with Breast Cancer

    PubMed Central

    Ono, Miyuki; Ogilvie, James M.; Wilson, Jennifer S.; Green, Heather J.; Chambers, Suzanne K.; Ownsworth, Tamara; Shum, David H. K.

    2015-01-01

    A meta-analysis was performed to quantify the magnitude and nature of the association between adjuvant chemotherapy and performance on a range of cognitive domains among breast cancer patients. A total of 27 studies (14 cross-sectional, 8 both cross-sectional and prospective, and 5 prospective) were included in the analyses, involving 1562 breast cancer patients who had undergone adjuvant chemotherapy and 2799 controls that included breast cancer patients who did not receive adjuvant chemotherapy. A total of 737 effect sizes (Cohen’s d) were calculated for cross-sectional and prospective longitudinal studies separately and classified into eight cognitive domains. The mean effect sizes varied across cross-sectional and prospective longitudinal studies (ranging from −1.12 to 0.62 and −0.29 to 1.12, respectively). Each cognitive domain produced small effect sizes for cross-sectional and prospective longitudinal studies (ranging from −0.25 to 0.41). Results from cross-sectional studies indicated a significant association between adjuvant chemotherapy and cognitive impairment that held across studies with varied methodological approaches. For prospective studies, results generally indicated that cognitive functioning improved over time after receiving adjuvant chemotherapy. Greater cognitive impairment was reported in cross-sectional studies comparing chemotherapy groups with healthy control groups. Results suggested that cognitive impairment is present among breast cancer patients irrespective of a history of chemotherapy. Prospective longitudinal research is warranted to examine the degree and persisting nature of cognitive impairment present both before and after chemotherapy, with comparisons made to participants’ cognitive function prior to diagnosis. Accurate understanding of the effects of chemotherapy is essential to enable informed decisions regarding treatment and to improve quality of life among breast cancer patients. PMID:25806355

  13. Association of Muscle Strength with the Risk of Alzheimer’s Disease and the Rate of Cognitive Decline in Community-Dwelling Older Persons

    PubMed Central

    Boyle, Patricia A.; Buchman, Aron S.; Wilson, Robert S.; Leurgans, Sue E.; Bennett, David A.

    2010-01-01

    Objective Loss of muscle strength is common and associated with a variety of adverse health outcomes in old age, but few studies have examined the association of muscle strength with the risk of Alzheimer’s disease (AD) or mild cognitive impairment (MCI). We tested the hypothesis that muscle strength is associated with incident AD and MCI. Design Prospective, observational cohort study. Setting Retirement communities across the Chicago metropolitan area. Participants More than 900 community-based older persons without dementia at the baseline evaluation and in whom strength was measured in nine muscle groups in both arms and legs as well as in the axial muscles and summarized into a composite measure of muscle strength. Main Outcome Measures Incident AD, MCI and rate of change in global cognitive function. Results During a mean follow-up of 3.6 years, 138 persons developed AD. In a proportional hazards model adjusted for age, sex, and education, each 1 unit increase in muscle strength at baseline was associated with about a 43% decrease in the risk of AD (HR, 0.57; 95% CI, 0.41,0.79). The association of muscle strength with AD persisted even after adjustment for several covariates, including body mass index, physical activity, pulmonary function, vascular risk factors, vascular diseases and apolipoprotein E4 status. Further, in a mixed-effects model adjusted for age, sex, education, and baseline level of global cognition, increased muscle strength was associated with a slower rate of decline in global cognitive function (p<0.001). Finally, muscle strength was associated with a decreased risk of MCI, the precursor to AD (HR, 0.67; 95% CI, 0.54, 0.84). Conclusion These findings suggest a link between muscle strength, AD and cognitive decline in older persons. PMID:19901164

  14. Level of Cognitive Performance as a Correlate and Predictor of Health Behaviors that Protect against Cognitive Decline in Late Life: The Path through Life Study

    ERIC Educational Resources Information Center

    Anstey, Kaarin J.; Low, Lee-Fay; Christensen, Helen; Sachdev, Perminder

    2009-01-01

    There is a lack of information on how cognitive ability relates to both health behaviors and change in health behaviors over time. This study examined verbal ability and processing speed as predictors of health behaviors in the PATH Through Life Study that includes cohorts aged in their 20s, 40s and 60s. Higher cognitive scores were associated…

  15. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    PubMed

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.

  16. Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study1.

    PubMed

    Sanders, Chelsea; Behrens, Stephanie; Schwartz, Sarah; Wengreen, Heidi; Corcoran, Chris D; Lyketsos, Constantine G; Tschanz, JoAnn T

    2016-02-27

    Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer's disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time β= 0.22, p = 0.017; mMNA by time2 β= -0.04, p = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (β= 0.35, p <  0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention.

  17. The functional-cognitive framework as a tool for accelerating progress in cognitive neuroscience: On the benefits of bridging rather than reducing levels of analyses.

    PubMed

    Vahey, Nigel; Whelan, Robert

    2016-02-01

    The subject matter of neuroscience research is complex, and synthesising the wealth of data from this research to better understand mental processes is challenging. A useful strategy, therefore, may be to distinguish explicitly between the causal effects of the environment on behaviour (i.e. functional analyses) and the mental processes that mediate these effects (i.e. cognitive analyses). In this article, we describe how the functional-cognitive (F-C) framework can accelerate cognitive neuroscience and also advance a functional treatment of brain activity. We first highlight that cognitive neuroscience can particularly benefit from the F-C approach by providing an alternative to the problematic practice of reducing cognitive constructs to behavioural and/or neural proxies. Next, we outline how functional (behaviour-environment) relations can serve as a bridge between cognitive and neural processes by restoring mental constructs to their original role as heuristic tools. Finally, we give some examples of how both cognitive neuroscience and traditional functional approaches can mutually benefit from the F-C framework.

  18. Parallel declines in cognition, motivation, and locomotion in aging mice: association with immune gene upregulation in the medial prefrontal cortex

    PubMed Central

    Bordner, Kelly A.; Kitchen, Robert R.; Carlyle, Becky; George, Elizabeth D.; Mahajan, Milind C.; Mane, Shrikant M.; Taylor, Jane R.; Simen, Arthur A.

    2013-01-01

    Aging in humans is associated with parallel changes in cognition, motivation, and motoric performance. Based on the human aging literature, we hypothesized that this constellation of age-related changes is mediated by the medial prefrontal cortex and that it would be observed in aging mice. Toward this end, we performed detailed assessments of cognition, motivation, and motoric behavior in aging mice. We assessed behavioral and cognitive performance in C57Bl/6 mice aged 6, 18, and 24 months, and followed this with microarray analysis of tissue from the medial prefrontal cortex and analysis of serum cytokine levels. Multivariate modeling of these data suggested that the age-related changes in cognition, motivation, motor performance, and prefrontal immune gene expression were highly correlated. Peripheral cytokine levels were also correlated with these variables, but less strongly than measures of prefrontal immune gene upregulation. To determine whether the observed immune gene expression changes were due to prefrontal microglial cells, we isolated CD11b-positive cells from the prefrontal cortex and subject them to next-generation RNA sequencing. Many of the immune changes present in whole medial prefrontal cortex were enriched in this cell population. These data suggest that, as in humans, cognition, motivation, and motoric performance in the mouse change together with age and are strongly associated with CNS immune gene upregulation. PMID:21453768

  19. A role for HLA-DRB1*1101 and DRB1*0801 in cognitive ability and its decline with age.

    PubMed

    Payton, Antony; Dawes, Piers; Platt, Hazel; Morton, Cynthia C; Moore, David R; Massey, Jonathan; Horan, Michael; Ollier, William; Munro, Kevin J; Pendleton, Neil

    2016-03-01

    Cognitive abilities (memory, processing speed, vocabulary, and fluid intelligence) are correlated with educational attainment and occupational status, as well as physical and mental health. The variation in cognitive abilities observed within a population has a substantial genetic contribution (heritability ∼50%) and yet the identification of genetic polymorphisms from both genome-wide association and candidate studies have to date only uncovered a limited number of genetic variants that exert small genetic effects. Here we impute human leukocyte antigens (HLA) using existing genome-wide association data from 1,559 non-pathological elderly volunteers who have been followed for changes in cognitive functioning between a 12- and 18-year period. Specifically, we investigate DRB1*05 (*11/*12) and DRB1*01, which have previously been associated with cognitive ability. We also analyze DRB1*0801, which shares close sequence homology with DRB1*1101. Together with DRB1*1101, DRB1*0801 has been associated with several diseases including multiple sclerosis and primary biliary cirrhosis, which themselves are associated with cognitive impairment. We observed that both DRB1*0801 and DRB1*1101 were significantly associated with vocabulary ability (cross-sectional and longitudinal scores) and that the effects were in opposite directions with DRB1*0801 associated with lower score and faster decline. This opposing affect is similar to that reported by other groups in systemic lupus erythematosus, type 1 diabetes, and primary biliary cirrhosis. DRB1*0801 was also significantly associated with reduced memory ability. We observed no associations between cognitive abilities and DRB1*01 or DRB1*12.

  20. Aspirin for the prevention of cognitive decline in the elderly: rationale and design of a neuro-vascular imaging study (ENVIS-ion)

    PubMed Central

    2012-01-01

    Background This paper describes the rationale and design of the ENVIS-ion Study, which aims to determine whether low-dose aspirin reduces the development of white matter hyper-intense (WMH) lesions and silent brain infarction (SBI). Additional aims include determining whether a) changes in retinal vascular imaging (RVI) parameters parallel changes in brain magnetic resonance imaging (MRI); b) changes in RVI parameters are observed with aspirin therapy; c) baseline cognitive function correlates with MRI and RVI parameters; d) changes in cognitive function correlate with changes in brain MRI and RVI and e) whether factors such as age, gender or blood pressure influence the above associations. Methods/Design Double-blind, placebo-controlled trial of three years duration set in two Australian academic medical centre outpatient clinics. This study will enrol 600 adults aged 70 years and over with normal cognitive function and without overt cardiovascular disease. Subjects will undergo cognitive testing, brain MRI and RVI at baseline and after 3 years of study treatment. All subjects will be recruited from a 19,000-patient clinical outcome trial conducted in Australia and the United States that will evaluate the effects of aspirin in maintaining disability-free longevity over 5 years. The intervention will be aspirin 100 mg daily versus matching placebo, randomized on a 1:1 basis. Discussion This study will improve understanding of the mechanisms at the level of brain and vascular structure that underlie the effects of aspirin on cognitive function. Given the limited access and high cost of MRI, RVI may prove useful as a tool for the identification of individuals at high risk for the development of cerebrovascular disease and cognitive decline. Trial Registration clinicaltrials.gov Identifier: NCT01038583 PMID:22315948

  1. Long-term post-operative cognitive decline in the elderly: the effects of anesthesia type, apolipoprotein E genotype, and clinical antecedents

    PubMed Central

    Ancelin, Marie-Laure; De Roquefeuil, Guilhem; Scali, Jacqueline; Bonnel, François; Adam, Jean-François; Cheminal, Jean-Claude; Cristol, Jean-Paul; Dupuy, Anne-Marie; Carrière, Isabelle; Ritchie, Karen

    2010-01-01

    Cognitive dysfunction in the elderly commonly observed following anesthesia has been attributed to age-related neuronal changes exacerbated by pharmacotoxic effects. However, the extent to which these changes may persist following recovery from surgery is still largely unknown. This study investigates the long-term effects of anesthesia on cognitive functioning after orthopedic surgery in 270 elderly patients over the age of 65 who completed a computerized cognitive battery before and 8 days, 4 and 13 months after surgery. Their performance was compared to that of 310 elderly controls who completed the same neuro-psychiatric evaluation at baseline and one-year interval. Multivariate analyses adjusted for socio-demographic variables, depressive symptomatology, vascular pathology as well as baseline cognitive performance. We found early and transient post-operative decline in reaction time and constructional praxis. With regard to long-term changes we observed improvement compared to controls in most verbal tasks (probably due to learning effects). On the other hand, a clear dissociation effect was observed for several areas of visuospatial functioning which persisted up to the 13-month follow-up. This specific pattern of visuospatial deficit was found to be independent of apolipoprotein E genotype and closely resembles what has recently been termed vascular mild cognitive impairment, in turn associated with subtle sub-cortical vascular changes. The observation of only minor differences between persons operated by general and regional anesthesia makes it difficult to attribute these changes directly to the anesthetic agents themselves, suggesting that cognitive dysfunction may be attributable at least in part to peri-operative conditions, notably stress and glucocorticoid exposure. PMID:20858969

  2. A ‘Disease Severity Index’ to identify individuals with Subjective Memory Decline who will progress to mild cognitive impairment or dementia

    PubMed Central

    Ferreira, Daniel; Falahati, Farshad; Linden, Cecilia; Buckley, Rachel F.; Ellis, Kathryn A.; Savage, Greg; Villemagne, Victor L.; Rowe, Christopher C.; Ames, David; Simmons, Andrew; Westman, Eric

    2017-01-01

    Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer’s disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions. Identifying those with higher risk to develop dementia is thus a major challenge. We tested a novel disease severity index generated by multivariate data analysis with numerous structural MRI measures as input. The index was used to identify SMD individuals with high risk of progression to mild cognitive impairment (MCI) or AD. A total of 69 healthy controls, 86 SMD, 45 MCI, and 38 AD patients were included. Subjects were followed up for 7.5 years. Clinical, cognitive, PET amyloid imaging and APOE ε4 data were used as outcome variables. The results showed that SMD evidenced cognitive performance intermediate between healthy controls and MCI. The disease severity index identified eleven (13%) SMD individuals with an AD-like pattern of brain atrophy. These individuals showed lower cognitive performance, increased CDR-SOB, higher amyloid burden and worse clinical progression (6.2 times higher likelihood to develop MCI, dementia or die than healthy controls). The current disease severity index may have relevance for clinical practice, as well as for selecting appropriate individuals for clinical trials. PMID:28287184

  3. Supplementation with Lactobacillus plantarum WCFS1 Prevents Decline of Mucus Barrier in Colon of Accelerated Aging Ercc1−/Δ7 Mice

    PubMed Central

    van Beek, Adriaan A.; Sovran, Bruno; Hugenholtz, Floor; Meijer, Ben; Hoogerland, Joanne A.; Mihailova, Violeta; van der Ploeg, Corine; Belzer, Clara; Boekschoten, Mark V.; Hoeijmakers, Jan H. J.; Vermeij, Wilbert P.; de Vos, Paul; Wells, Jerry M.; Leenen, Pieter J. M.; Nicoletti, Claudio; Hendriks, Rudi W.; Savelkoul, Huub F. J.

    2016-01-01

    Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1−/Δ7 mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in Ercc1−/Δ7 mice was characterized by a thin (< 10 μm) mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1−/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1−/Δ7 mice. L. plantarum- and L. casei-treated Ercc1−/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum – but not with L. casei and B. breve – prevented the decline in the mucus barrier in Ercc1−/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly. PMID:27774093

  4. Cognitive performance during sustained wakefulness: A low dose of caffeine is equally effective as modafinil in alleviating the nocturnal decline.

    PubMed

    Dagan, Yaron; Doljansky, Julia T

    2006-01-01

    Cognitive performance at night exhibits a substantial drop, typically before dawn. One of the means of dealing with this phenomenon, as well as with the accompanying sleepiness during sustained wakefulness, is the administration of stimulants. The most widely used and well-documented stimulants are caffeine, amphetamines, and modafinil. Of these, amphetamines are the least recommended, as they may severely affect behavior. Caffeine and modafinil seem to produce relatively milder side effects and usually only at high doses. Previous comparison studies have revealed equal efficacy of both the stimulants in maintaining alertness and performance during sustained wakefulness. However, these studies used relatively high, and thus not completely safe, doses of these drugs (600 mg caffeine and 400 mg modafinil). Therefore, the aim of the present study was to assess the efficacy of a low and medically safe dose of caffeine (200 mg) and modafinil (200 mg) in maintaining cognitive performance during sustained wakefulness. A flight simulation task was chosen for the assessment of the stimulants in a counter-balanced, within-subject design under four different conditions: baseline (no drugs), placebo, caffeine (200 mg), and modafinil (200 mg). The equal effectiveness of both drugs in abolishing the nocturnal drop in cognitive performance, as well as of oral temperature and blood pressure, supported the use of low doses of caffeine and modafinil for the maintenance of alertness in healthy subjects during sustained wakefulness.

  5. The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease.

    PubMed

    Brewer, George J

    2009-06-01

    It is a pleasure and an honor to contribute a paper to a special issue of the Journal of the American College of Nutrition honoring Stanley Wallach and Pearl Small. In this brief review I advance the hypothesis that copper toxicity is the major cause of the epidemic of mild cognitive impairment and Alzheimer's disease engulfing our aging population. This epidemic is recent, exploding in the last 50-60 years. The disease was virtually unknown 100 years ago. And it involves only developed countries that use copper plumbing. Something in our environment associated with development is poisoning the minds of our aged. The epidemic is associated with the use of copper plumbing, and the taking of copper in multi-mineral supplements. Food copper (organic copper) is processed by the liver and is transported and sequestered in a safe manner. Inorganic copper, such as that in drinking water and copper supplements, largely bypasses the liver and enters the free copper pool of the blood directly. This copper is potentially toxic because it may penetrate the blood/brain barrier. I review a web of animal and human data that tightens the noose around the hypothesis that copper toxicity is causing the epidemic of Alzeimer's disease and loss of cognition in our aging population.

  6. Decline of Cosmetic Outcomes Following Accelerated Partial Breast Irradiation Using Intensity Modulated Radiation Therapy: Results of a Single-Institution Prospective Clinical Trial

    SciTech Connect

    Liss, Adam L.; Ben-David, Merav A.; Jagsi, Reshma; Hayman, James A.; Griffith, Kent A.; Moran, Jean M.; Marsh, Robin B.; Pierce, Lori J.

    2014-05-01

    Purpose: To report the final cosmetic results from a single-arm prospective clinical trial evaluating accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) with active-breathing control (ABC). Methods and Materials: Women older than 40 with breast cancer stages 0-I who received breast-conserving surgery were enrolled in an institutional review board-approved prospective study evaluating APBI using IMRT administered with deep inspiration breath-hold. Patients received 38.5 Gy in 3.85-Gy fractions given twice daily over 5 consecutive days. The planning target volume was defined as the lumpectomy cavity with a 1.5-cm margin. Cosmesis was scored on a 4-category scale by the treating physician. Toxicity was scored according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0). We report the cosmetic and toxicity results at a median follow-up of 5 years. Results: A total of 34 patients were enrolled. Two patients were excluded because of fair baseline cosmesis. The trial was terminated early because fair/poor cosmesis developed in 7 of 32 women at a median follow-up of 2.5 years. At a median follow-up of 5 years, further decline in the cosmetic outcome was observed in 5 women. Cosmesis at the time of last assessment was 43.3% excellent, 30% good, 20% fair, and 6.7% poor. Fibrosis according to CTCAE at last assessment was 3.3% grade 2 toxicity and 0% grade 3 toxicity. There was no correlation of CTCAE grade 2 or greater fibrosis with cosmesis. The 5-year rate of local control was 97% for all 34 patients initially enrolled. Conclusions: In this prospective trial with 5-year median follow-up, we observed an excellent rate of tumor control using IMRT-planned APBI. Cosmetic outcomes, however, continued to decline, with 26.7% of women having a fair to poor cosmetic result. These results underscore the need for continued cosmetic assessment for patients treated with APBI by technique.

  7. B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline.

    PubMed

    Mitchell, E Siobhan; Conus, Nelly; Kaput, Jim

    2014-11-01

    The B vitamins folic acid, vitamin B12 and B6 are essential for neuronal function, and severe deficiencies have been linked to increased risk of neurodevelopmental disorders, psychiatric disease and dementia. Polymorphisms of genes involved in B vitamin absorption, metabolism and function, such as methylene tetrahydrofolate reductase (MTHFR), cystathionine β synthase (CβS), transcobalamin 2 receptor (TCN2) and methionine synthase reductase (MTRR), have also been linked to increased incidence of psychiatric and cognitive disorders. However, the effects of these polymorphisms are often quite small and many studies failed to show any meaningful or consistent associations. This review discusses previous findings from clinical studies and highlights gaps in knowledge. Future studies assessing B vitamin-associated polymorphisms must take into account not just traditional demographics, but subjects' overall diet, relevant biomarkers of nutritional status and also analyze related genetic factors that may exacerbate behavioral effects or nutritional status.

  8. Extrinsic and Intrinsic Brain Network Connectivity Maintains Cognition across the Lifespan Despite Accelerated Decay of Regional Brain Activation

    PubMed Central

    Henson, Richard N.A.; Tyler, Lorraine K.; Razi, Adeel; Geerligs, Linda; Ham, Timothy E.; Rowe, James B.

    2016-01-01

    The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors. SIGNIFICANCE STATEMENT Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a

  9. Sex-dependent modulation of age-related cognitive decline by the L-type calcium channel gene Cacna1c (Cav 1.2).

    PubMed

    Zanos, Panos; Bhat, Shambhu; Terrillion, Chantelle E; Smith, Robert J; Tonelli, Leonardo H; Gould, Todd D

    2015-10-01

    Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age-related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex-dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age-related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age-related contextual memory declines.

  10. Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline.

    PubMed

    Thal, Dietmar Rudolf; Ghebremedhin, Estifanos; Orantes, Mario; Wiestler, Otmar D

    2003-12-01

    Sporadic, late-onset Alzheimer disease (AD) constitutes the most frequent cause of dementia in the elderly population. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis/lipohyalinosis (AS/LH). The present study was carried out to examine the coincidence of these small vessel pathologies during the development of cognitive deficits, amyloid beta-protein (A beta) deposition, and neurofibrillary tangle (NFT) formation in sporadic late-onset AD. We correlated the clinical dementia rating (CDR) score, the sequential extension of AD-related A beta deposition into different parts of the brain, and the extension of NFTs to involve more brain regions with the distribution of CAA and AS/LH in 52 human autopsy brains. The extension of CAA and AS/LH to involve different areas of the brain was associated with a rise of CDR scores and an increase in the extension of A beta deposition and NFT generation. AD cases showed a higher number of regions with CAA and AS/LH compared to nondemented patients with AD-related pathology and controls. Moreover, we demonstrated a hierarchical sequence in which the different regions of the brain exhibited CAA and AS/LH-affected vessels, allowing the distinction of 3 stages in the development of CAA and AS/LH. The first stage of CAA involved leptomeningeal and neocortical vessels. The second stage was characterized by additional A beta deposition in allocortical and midbrain vessels. Finally, in a third stage, CAA was observed in the basal ganglia, the thalamus, and in the lower brainstem. In contrast, AS/LH initially affected the basal ganglia in stage A. In stage B this pathology made inroads into the deep white matter, the leptomeningeal arteries of the cortex, the cerebellum, and into the thalamus. Stage C was characterized by AS/LH in brainstem vessels. Our results demonstrate widespread CAA and AS/LH to be associated with the

  11. Slowing of Hippocampal Activity Correlates with Cognitive Decline in Early Onset Alzheimer's Disease. An MEG Study with Virtual Electrodes.

    PubMed

    Engels, Marjolein M A; Hillebrand, Arjan; van der Flier, Wiesje M; Stam, Cornelis J; Scheltens, Philip; van Straaten, Elisabeth C W

    2016-01-01

    Pathology in Alzheimer's disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using "virtual MEG electrodes". We used resting-state MEG recordings from 27 early onset AD patients [age 60.6 ± 5.4, 12 females, mini-mental state examination (MMSE) range: 19-28] and 26 cognitively healthy age- and gender-matched controls (age 61.8 ± 5.5, 14 females). Activity was reconstructed using beamformer-based virtual electrodes for 78 cortical regions and 6 hippocampal regions. Group differences in peak frequency and relative power in six frequency bands were identified using permutation testing. For the patients, spearman correlations between the MMSE scores and peak frequency or relative power were calculated. Moreover, receiver operator characteristic curves were plotted to estimate the diagnostic accuracy. We found a lower hippocampal peak frequency in AD compared to controls, which, in the patients, correlated positively with MMSE [r(25) = 0.61; p < 0.01] whereas hippocampal relative theta power correlated negatively with MMSE [r(25) = -0.54; p < 0.01]. Cortical peak frequency was also lower in AD in association areas. Furthermore, cortical peak frequency correlated positively with MMSE [r(25) = 0.43; p < 0.05]. In line with this finding, relative theta power was higher in AD across the cortex, and relative alpha and beta power was lower in more circumscribed areas. The average cortical relative theta power was the best discriminator between AD and controls (sensitivity 82%; specificity 81%). Using beamformer-based virtual electrodes, we were able to detect hippocampal activity in AD. In AD, this hippocampal activity is slowed, and correlates better with cognition than the (slowed) activity in cortical areas. On the other

  12. Cognitive control adjustments in healthy older and younger adults: Conflict adaptation, the error-related negativity (ERN), and evidence of generalized decline with age.

    PubMed

    Larson, Michael J; Clayson, Peter E; Keith, Cierra M; Hunt, Isaac J; Hedges, Dawson W; Nielsen, Brent L; Call, Vaughn R A

    2016-03-01

    Older adults display alterations in neural reflections of conflict-related processing. We examined response times (RTs), error rates, and event-related potential (ERP; N2 and P3 components) indices of conflict adaptation (i.e., congruency sequence effects) a cognitive control process wherein previous-trial congruency influences current-trial performance, along with post-error slowing, correct-related negativity (CRN), error-related negativity (ERN) and error positivity (Pe) amplitudes in 65 healthy older adults and 94 healthy younger adults. Older adults showed generalized slowing, had decreased post-error slowing, and committed more errors than younger adults. Both older and younger adults showed conflict adaptation effects; magnitude of conflict adaptation did not differ by age. N2 amplitudes were similar between groups; younger, but not older, adults showed conflict adaptation effects for P3 component amplitudes. CRN and Pe, but not ERN, amplitudes differed between groups. Data support generalized declines in cognitive control processes in older adults without specific deficits in conflict adaptation.

  13. Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival.

    PubMed

    Lopes, M H; Santos, T G; Rodrigues, B R; Queiroz-Hazarbassanov, N; Cunha, I W; Wasilewska-Sampaio, A P; Costa-Silva, B; Marchi, F A; Bleggi-Torres, L F; Sanematsu, P I; Suzuki, S H; Oba-Shinjo, S M; Marie, S K N; Toulmin, E; Hill, A F; Martins, V R

    2015-06-01

    Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrP(C)) triggers a large number of trophic effects in the nervous system. We found that both PrP(C) and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrP(C) and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrP(C) binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrP(C) binding site (HOP230-245) abrogates this effect. PrP(C) knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrP(C)-HOP engagement is a promising approach for GBM therapy.

  14. Using an eHealth Intervention to Stimulate Health Behavior for the Prevention of Cognitive Decline in Dutch Adults: A Study Protocol for the Brain Aging Monitor

    PubMed Central

    2015-01-01

    Background Internet-delivered intervention programs are an effective way of changing health behavior in an aging population. The same population has an increasing number of people with cognitive decline or cognitive impairments. Modifiable lifestyle risk factors such as physical activity, nutrition, smoking, alcohol consumption, sleep, and stress all influence the probability of developing neurodegenerative diseases such as Alzheimer’s disease. Objective This study aims to answer two questions: (1) Is the use of a self-motivated, complex eHealth intervention effective in changing multiple health behaviors related to cognitive aging in Dutch adults in the work force, especially those aged 40 and over? and (2) Does this health behavior change result in healthier cognitive aging patterns and contribute to preventing or delaying future onset of neurodegenerative syndromes? Methods The Brain Aging Monitor study uses a quasi-experimental 2-year pre-posttest design. The Brain Aging Monitor is an online, self-motivated lifestyle intervention program. Recruitment is done both in medium to large organizations and in the Dutch general population over the age of 40. The main outco