Cognitive Decline In Elderly Individuals Research Articles

Cognitive Patterns of Normal Elderly Subjects Are Consistent With Frontal Cortico-Subcortical and Fronto-Parietal Neuropsychological Models of Brain Aging

Three neuropsychological theories have been developed according to a possible existence of a similar pattern of cognitive decline in elderly individuals and patients with brain damage. The respective neuropsychological theories attribute age-related deficits to: (a) dysfunction of the frontal lobes, (b) temporo-parietal dysfunction, or (c) decline of right-hemisphere functions. In the present study, we examined which of these theories best explains the cognitive patterns of normal elderly subjects older than 80 years of age (old elderly). Thirty normal old elderly subjects, 14 patients with subcortical vascular dementia, 14 with mild Alzheimer's disease, 15 with damage of the right hemisphere of the brain, and 20 young elderly controls participated. A test battery covering the main cognitive domains was administered to all participants. A hierarchical cluster analysis revealed five groups of individuals with different cognitive patterns across the whole sample. Old elderly subjects were assigned to four groups according to: (a) preserved overall cognitive performance, (b) processing speed decline, (c) attention decline, or (d) executive impairment. The results of the study are most congruent with models emphasizing frontal-lobe cortical–subcortical and fronto-parietal changes in old age. The results also indicate considerable heterogeneity in the cognitive patterns of normal old elderly adults.

Vascular risk factors: a ticking time bomb to Alzheimer's disease.

Evidence is growing that vascular risk factors (VRFs) for Alzheimer's disease (AD) affect cerebral hemodynamics to launch a cascade of cellular and molecular changes that initiate cognitive deficits and eventual progression of AD. Neuroimaging studies have reported VRFs for AD to be accurate predictors of cognitive decline and dementia. In regions that participate in higher cognitive function, middle temporal, posterior cingulate, inferior parietal and precuneus regions, and neuroimaging studies indicate an association involving VRFs, cerebral hypoperfusion, and cognitive decline in elderly individuals who develop AD. The VRF can be present in cognitively intact individuals for decades before mild cognitive deficits or neuropathological signs are manifested. In that sense, they may be "ticking time bombs" before cognitive function is demolished. Preventive intervention of modifiable VRF may delay or block progression of AD. Intervention could target cerebral blood flow (CBF), since most VRFs act to lower CBF in aging individuals by promoting cerebrovascular dysfunction.

Chronoscopic reading in whole body reaction times in detecting cognitive dysfunction in metabolic syndrome: A case control study

The metabolic syndrome, a clustering of several commonly occurring disorders that include abdominal obesity, hypertriglyceridemia, low high-density lipoprotein level, hypertension, and hyperglycemia, has been specifically investigated as a risk factor for cognitive decline in elderly individuals. The metabolic syndrome may be a risk factor for cognitive decline because it summarizes the joint effects of these risk factors. It is known that difference between simple and choice reaction time (RT) implies time required for cognition. Though delayed choice RTs indicate involvement of cognition, they cannot quantify how much time is required for cognition. In whole body simple reaction time (WBSRT), RT is split into two chronoscopic readings: C1 and C2. C1 measures time required for central processing which requires cognition and C2 measures total RT. C2-C1 measures time required for peripheral motor response. We hypothesized that whole body choice RT chronoscopic reading 1 (WBCRTC1) will be delayed in metabolic syndrome and WBCRTC1 will have predictive value in detecting cognitive dysfunction. Hospital-based cross-sectional case-control study. Study was conducted on 120 subjects using visual and WBSRT having criteria of age (40-60 years) and metabolic syndrome, compared with equal number of age- and sex-matched controls. Statistical analysis was done by independent t-test and duration of metabolic syndrome was correlated with cognition times (WBCRTC1) using Pearson's correlation. Predictive value of WBCRTC1 was calculated using receiver operating characteristic curve. Delayed visual simple RT, visual choice RT, WBSRT, and whole body choice RT (WBCRT) observed among subjects metabolic syndrome when compared with controls. Choice RTs were more delayed compared to simple RTs. WBCRTC1 (608.8 ± 132 ms) was more delayed than WBSRTC1 (424.05 ± 89.9 ms) among metabolic syndrome indicating cognitive dysfunction. Unfortunately, there was no significant correlation between duration of metabolic syndrome with cognition. The best cut-off value for WBCRTC1, when predicting cognitive dysfunction in metabolic syndrome was 542.5 ms (sensitivity 36.7% and specificity 31.6%). WBCRTC1 can be used as a tool to detect cognitive dysfunction.

Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals

BackgroundAdvanced glycations end products increase oxidant stress, inflammation, and neurotoxicity. Serum levels are increased in diabetes and aging. We examined the relationship between serum methylglyoxal derivatives (sMG), and cognitive decline, in 267 non-demented elderly. MethodsTobit mixed regression models assessed the association of baseline sMG with cognitive decline in the Mini Mental State Exam (MMSE) over time, controlling for sociodemographic factors (age, sex, and years of education), cardiovascular risk factors (diabetes and presence of an ApoE4 allele), and kidney function. sMG was assessed by ELISA. ResultsThe fully adjusted model showed an annual decline of 0.26 MMSE points per unit increase in baseline sMG (p=0.03). Significance was unchanged as additional risk factors were added to the model. The interactions of sMG with diabetes, sex, age, kidney function, and ApoE4 genotype were not significant. ConclusionsHigher levels of baseline sMG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, ApoE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated sMG may be indicative of brain cell injury initiated before clinically evident cognitive compromise.

The Association of Age With Rate of Cognitive Decline in Elderly Individuals Residing in Supporting Care Facilities

This study examines the effect of age on rate of cognitive decline in different stages of dementia, of nursing home and assisted-living residents. In this longitudinal study, the Mini Mental State Examination (MMSE) was used to measure rate of cognitive decline in subjects who were nondemented [Clinical Dementia Rating (CDR)=0; n=353], questionably demented (CDR=0.5; n=121), or frankly demented (CDR≥1; n=213) at baseline. A generalized estimating equation was used to model the MMSE scores over time (mean follow-up 2.9±2.0 y). The generalized estimating equation model had the MMSE scores at successive follow-up time points as dependent variables and had linear and quadratic age, follow-up time from baseline, CDR at baseline, and all the interactions among them as independent variables, controlling for MMSE at baseline, sex, race, and education. The mean age of the entire sample was 85.2±7.4 years at baseline. There were no significant interactions of linear age effects with rate of cognitive decline. The analysis of interaction of quadratic age with rate of cognitive decline showed complex relationships: in the nondemented group, there was no substantial quadratic association of age with the rate of cognitive decline (P=0.13); in the questionable demented group, the oldest subjects declined relatively faster (P=0.02); and in the demented group, the youngest and oldest subjects tended to decline relatively less than subjects in the intermediate ages (P=0.07). This study adds an additional aspect to the complexity of the association between age and rate of cognitive decline, showing that the direction and amplitude of this effect differs according to the stage along the course of cognitive decline.

Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals

Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals

Prevention of psychiatric illness in the elderly, I: Path to prevention of dementia

Prevention of psychiatric illness in the elderly, I: Path to prevention of dementia

Age-associated leukoaraiosis and cortical cholinergic deafferentation

To investigate the relationship between age-associated MRI leukoaraiosis or white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity. One possible mechanism of cognitive decline in elderly individuals with leukoaraiosis is disruption of cholinergic fibers by strategically located white matter lesions. Periventricular lesions may have a higher chance of disrupting cholinergic projections compared with more superficial nonperiventricular white matter lesions because of anatomic proximity to the major cholinergic axonal projection bundles that originate from the basal forebrain. Community-dwelling, middle-aged and elderly subjects without dementia (mean age 71.0 +/- 9.2 years; 55-84 years; n = 18) underwent brain MRI and AChE PET imaging. The severity of periventricular and nonperiventricular WMH on fluid-attenuated inversion recovery MRI images was scored using the semiquantitative rating scale of Scheltens et al. [11C]methyl-4-piperidinyl propionate AChE PET imaging was used to assess cortical AChE activity. Age-corrected Spearman partial rank correlation coefficients were calculated. The severity of periventricular (R = -0.52, p = 0.04) but not nonperiventricular (R = -0.20, not significant) WMH was inversely related to global cortical AChE activity. Regional cortical cholinergic effects of periventricular WMH were most significant for the occipital lobe (R = -0.58, p = 0.02). The presence of periventricular but not nonperiventricular white matter hyperintensities (WMH) is significantly associated with lower cortical cholinergic activity. These findings support a regionally specific disruption of cholinergic projection fibers by WMH.

Fish consumption, long-chain omega-3 fatty acids and risk of cognitive decline or Alzheimer disease: a complex association

Long-chain omega-3 fatty acids could have neuroprotective properties against dementia, which is becoming a major global public health issue. We conducted a systematic review of the literature to establish the association between eating fish (a source of long-chain omega-3 fatty acids) or taking long-chain omega-3 fatty acid supplements and the risk of cognitive decline or Alzheimer disease (AD). We identified eleven observational studies and four clinical trials. All three observational studies that used cognitive decline as an outcome reported significant benefits, whereas only four of eight observational studies that used incidence of AD or dementia as an outcome reported positive findings. None of four small clinical trials provided convincing evidence for the use of this approach in the prevention or treatment of any form of dementia. In summary, the existing data favor a role for long-chain omega-3 fatty acids in slowing cognitive decline in elderly individuals without dementia, but not for the prevention or treatment of dementia (including AD). This apparent dichotomy might reflect differences in study designs with regard to participants, dosages, the ratio of long-chain omega-3 to omega-6 fatty acids, or the choice of outcome measurements. Large clinical trials of extended duration should help to provide definitive answers.

O1-05-05: Predicting cognitive decline in non-demented elderly with MRI, DTI, and longitudinal single-voxel spectroscopic imaging

Background: It is important to predict cognitive decline in elderly individuals who may be at risk for Alzheimer’s disease (AD). Objective: To determine the regional patterns of gray and white matter change and metabolic changes in the brain that best predict cognitive decline. Methods: Sixty-two non-demented subjects (74.0 8.5 years old) were assessed with the Mini-mental status exam (MMSE) and the California Verbal Learning Test (CVLT) at baseline and follow-up 1.1 0.2 years later. Of the 62 subjects, 48 scored below (impaired) and 14 scored at or above (controls) the ageand education-adjusted norms on the CVLT. Predictors were structural and diffusion-tensor imaging (DTI) and single voxel H MRS imaging at baseline and 6 months later. The outcome measure was the 1-year change in a memory composite score derived from immediate recall trials 1-4 of the CVLT. Results: Stepwise linear regression models were used to determine the relationship between baseline MMSE scores and demographic information with subsequent cognitive decline. These models revealed group status (i.e., control vs. impaired; r 0.11, p 0.008) and educational level (r 0.11, p 0.02) to be significant predictors of decline. Imaging variables were then added to the models to determine the predictive “added value” of volumetric MRI, DTI and MRS imaging to cognitive testing. In one model, left temporal white matter (WM) volume (r 0.13, p 0.007), group status (r 0.22, p 0.002), and baseline MMSE (r 0.27, p 0.049) were significant predictors of cognitive decline. Another model revealed fractional anisotopry (FA) of the right posterior cingulum (r 0.21, p 0.007) and sex (r 0.39, p 0.02) to be significant predictors decline. A third model showed change in N-acetylaspartate (NAA)/creatine (Cr) ratio (r 0.27, p 0.0001) and educational level (r 0.40, p 0. 02) to be significant predictors of decline. Conclusions: Together these results suggest that temporal WM volume, posterior cingulum FA, and change in the posterior cingulate NAA/Cr ratio may add predictive value to neuropsychological testing for predicting cognitive decline.

Cognitive impact of microvascular lesions and lacunes in the aging brain

Most previous studies addressed the cognitive impact of microvascular pathology and lacunar infarcts using radiologic correlations which are known to correlate poorly with neuropathological data. Moreover, the absence of systematic bilateral assessment of vascular lesions as well as the masking effect of Alzheimer's disease related pathology and macrovascular lesions may explain discrepancies among previous reports. In order to define the relative contribution of silent lacunes and microvascular lesions in cognitive decline, we performed a detailed neuropathological analysis in both cortical and subcortical areas of 72 elderly individuals without significant neurofibrillary tangle pathology or macrovascular lesions. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included As-protein deposition staging and bilateral assessment of microvascular ischemic pathology and lacunes; statistical analysis included multivariate models controlling for age, amyloid deposits and significant microvascular pathology. Thalamic and basal ganglia lacunes were negatively associated with CDR scores; cortical microinfarcts, periventricular and deep white matter demyelination also significantly affected cognition. In a multivariate model, cortical microinfarcts and thalamic and basal ganglia lacunes explained 22% of CDR variability; amyloid deposits and microvascular pathology explained 12% and the assessment of thalamic and basal ganglia lacunes added an extra 17%. Deep white matter lacunes were not related to cognitive status both in univariate and multivariate models. Our autopsy series provides important evidence that gray matter lacunes and cortical miroinfarcts are independent predictors of cognitive decline in elderly individuals without concomitant dementing processes such as Alzheimer's disease. from International Society on Brain and Behaviour: 2nd International Congress on Brain and Behaviour Thessaloniki, Greece. 17–20 November 2005

Indices of low-grade chronic inflammation correlate with early cognitive deterioration in an elderly Greek population

Elevated serum levels of adhesion molecules (AM) reflect low-grade chronic inflammation and have been associated with several conditions of neuronal damage. The aim of the present study was the investigation of possible correlation between early cognitive decline and inflammatory processes in the elderly as indicated by plasma C-reactive protein (CRP) and AM levels. Thirty-seven subjects with dementia were selected from a community-dwelling, genetically isolated, geriatric population (above 60 years of age) based on the Mini Mental State Examination scale (MMSE) and the Diagnostic and Statistical Manual (DSM-IV) criteria. In parallel, a group of 33 age-matched healthy controls were selected from the same population. The levels of CRP (mg/l), sICAM-1 (ng/ml) and sVCAM-1 (ng/ml) were measured in the serum samples of both groups. Serum concentrations of all three molecules sICAM-1, sVCAM-1 and CRP were significantly higher in the dementia group when compared to controls (656.78 ± 161.51 versus 467.05 ± 231.26, p < 0.01; 631.64 ± 149.76 versus 449.04 ± 285.27, p < 0.01; 1.53 ± 0.97 versus 0.7221 ± 0.61, p < 0.01, respectively). Furthermore, a positive correlation was observed between the three molecules studied and the degree of severity of cognitive impairment. The findings of this study enhance the hypothesis of the presence of an underlying inflammatory process leading to cognitive deterioration and predisposing dementia in the elderly. The present work supports the evaluation of inflammatory molecules as early indicators of cognitive decline in elderly individuals.

Cognitive Consequences of Thalamic, Basal Ganglia, and Deep White Matter Lacunes in Brain Aging and Dementia

Most previous studies addressed the cognitive impact of lacunar infarcts using radiologic correlations that are known to correlate poorly with neuropathological data. Moreover, absence of systematic bilateral assessment of vascular lesions and masking effects of Alzheimer disease pathology and macrovascular lesions may explain discrepancies among previous reports. To define the relative contribution of silent lacunes to cognitive decline, we performed a detailed analysis of lacunar and microvascular pathology in both cortical and subcortical areas of 72 elderly individuals without significant neurofibrillary tangle pathology or macrovascular lesions. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Abeta-protein deposition staging and bilateral assessment of microvascular ischemic pathology and lacunes; statistical analysis included multivariate models controlling for age, amyloid deposits, and microvascular pathology. Thalamic and basal ganglia lacunes were negatively associated with CDR scores; cortical microinfarcts, periventricular and diffuse white matter demyelination also significantly affected cognition. In a multivariate model, cortical microinfarcts and thalamic and basal ganglia lacunes explained 22% of CDR variability; amyloid deposits and microvascular pathology explained 12%, and the assessment of thalamic and basal ganglia lacunes added an extra 17%. Deep white matter lacunes were not related to cognitive status in univariate and multivariate models. In agreement with the recently proposed concept of subcortical ischemic vascular dementia, our autopsy series provides important evidence that gray matter lacunes are independent predictors of cognitive decline in elderly individuals without concomitant dementing processes such as Alzheimer disease.

Increase in epinephrine excretion is associated with cognitive decline in elderly men: MacArthur studies of successful aging

High stress hormone levels are associated with increased risk of cognitive decline in elderly individuals. However, the effect of late-life changes in stress hormone levels on cognitive decline risk has not been examined. Our objective was to investigate whether increase over time in urinary epinephrine excretion in older adults was associated with subsequent cognitive decline. Measurements were made on 154 high-functioning men and women, 70-79 years of age, in 1988, 1991, and 1995. Twelve-hour overnight urinary excretion of epinephrine (normalized by creatinine excretion to adjust for body size) was recorded in 1988 and 1991. Cognitive functioning was assessed in 1991 and 1995 by summary scores based on standard tests of language, memory, abstraction, spatial recognition, and spatial construction. Compared to individuals whose epinephrine excretion decreased between 1988 and 1991, the individuals whose epinephrine excretion increased over the same period had greater subsequent declines in summary cognitive scores between 1991 and 1995. After adjusting for baseline epinephrine, baseline cognitive function, and relevant covariates, and stratifying by gender, increases in urine epinephrine were positively associated with cognitive decline only in men. We conclude that increase in urinary excretion of epinephrine predicts subsequent cognitive decline in older men.

In reply to the letter to the editor

While the growing interest in the role of oxidative stress and ischemia in the pathogenesis of dementia provides a welcome reprieve from the stale arguments and deafening mantras chanted by the BAPtists and Tauists, I believe we are at a critical phase in which we still have the opportunity to utilize objective scientific methods to further unravel the mechanisms of Alzheimertype neurodegeneration. First and foremost, in contrast to Dr. Rafael’s suggestion, Alzheimer’s disease is a genuine entity. Anyone who has seriously studied the disease at both clinical and pathological levels can recognize the classical features and distinguish them from pure cerebrovascular or hypoxic-ischemic injury. Although the clinical manifestations of AD and vascular dementia overlap extensively in the early stages, this does not indicate that the two disease processes are one and the same. Another important concept that deserves intense investigation is that cerebrovascular injury can contribute to and exacerbate AD-type dementia. By now, there is ample evidence that both disease processes can co-exist in the brain, and therefore are likely to contribute to the cell loss and associated clinical manifestations of dementia. By way of analogy, cirrhosis of the liver can be caused by chronic Hepatits B virus infection. However, acute or chronic ethanol abuse can also cause liver injury, and each type of exposure can exacerbate liver injury and progression to cirrhosis that is mediated by chronic Hepatitis B virus infection. These are A plus B scenarios. In our manuscript, we made deliberate efforts to objectively evaluate the consequences of transient hypoxia in relation to AD-type neurodegeneration by evaluating the effects of hypoxic injury on known molecular markers of AD. The study was inspired by recent reports showing cognitive decline in elderly individuals who had undergone cardio-thoracic surgery. The results of our experiments showed that transient hypoxia was sufficient to trigger a neurodegeneration cascade that is reminiscent of the changes that occur in AD. Although we produced substantial neuronal dysfunction, we did not produce AD. We concluded that transient hypoxia (A) can contribute to the progression of AD (B) in much the same way that acute ethanol toxicity (A) can exacerbate the clinical course of chronic Hepatitis B infection (B) in the liver. However, what we found of particular interest was that the AD-type abnormalities developed after a delay and they were not produced immediately with the insult. Therefore, an acute insult can result in delayed onset of neurodegeneration. While we share the interest in determining the potential role of chronic hypoxic-ischemic injury in relation to AD-type dementia, the fact is that acute injury is probably sufficient to do the job, and therefore, it is not necessary to invoke a chronic hypoxic-ischemic hypothesis. The challenge awaiting is to generate an experimental model of chronic hypoperfusion that truly mimics the human condition, i.e. not chronic bilateral ligation of the carotid arteries, and determine the extent to which AD-type molecular abnormalities develop in that setting. The third message, which is of paramount importance is that, recognizing the potential impact of acute hypoxic or ischemic injury as a co-factor in the pathogenesis of AD-type dementia opens the door for the implementation of prophylactic neuroprotective agents in risky clinical circumstances. Ignoring this principle will likely aid and abet in the projected disastrous growth in the population of demented individuals as is projected for the next several decades. On the other hand, the liberal use of safe and effective neuroprotec-

Social networks, social integration, and social engagement determine cognitive decline in community-dwelling Spanish older adults.

To examine the influence of social networks and social engagement on cognitive decline in a population-based cohort of elderly people, and to assess gender differences in the effect of social relations on cognition. A longitudinal study of community-dwelling people over 65 was carried out. Cognitive function (orientation and memory) in 1997 and cognitive decline (absent, mild, and severe) over 4 years (1993-1997) were assessed using an instrument previously validated for populations with a low level of education. The effect of social networks, social integration, and social engagement with friends, children, and relatives on cognitive function and cognitive decline was estimated by multiple linear and logistic regressions after adjusting for age, sex, education, depressive symptoms, systolic and diastolic blood pressure, and functional status. Poor social connections, infrequent participation in social activities, and social disengagement predict the risk of cognitive decline in elderly individuals. The probability of cognitive decline was lower for both men and women with a high frequency of visual contact with relatives and community social integration. Engagement with friends seemed to be protective for cognitive decline in women but not in men. This longitudinal study indicates that few social ties, poor integration, and social disengagement are risk factors for cognitive decline among community-dwelling elderly persons. The nature of the ties that influence cognition may vary in men and women.

Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of Vascular Aging.

To examine whether baseline high blood pressure and antihypertensive treatment predicts cognitive decline in elderly individuals. A longitudinal population-based study of elderly individuals (n = 1,373) in Nantes (western France) was undertaken. Individuals 59 to 71 years of age were selected from electoral rolls. High blood pressure at baseline was defined as systolic blood pressure > or =160 mm Hg or diastolic blood pressure > or =95 mm Hg. Cognitive decline was defined as a drop of 4 points or more on the Mini-Mental State Examination between baseline and the 4-year assessment. There is an association between high blood pressure at baseline and cognitive decline at the 4-year assessment (odds ratio, 2.8; 95% CI, 1.6 to 5.0). In participants with high blood pressure, the risk of cognitive decline was 4.3 (95% CI, 2.1 to 8.8) in those without antihypertensive therapy and 1.9 (95% CI, 0.8 to 4.4) in those being treated. In participants with high blood pressure both at baseline and at the 2-year assessment, the risk for untreated participants was 6.0 (95% CI, 2.4 to 15.0) compared with 1.3 (95% CI, 0.3 to 4.9) in treated participants. High blood pressure was associated with cognitive decline. In individuals with high blood pressure, cognitive decline occurred in a relatively short time period and the risk was highest in untreated hypertensive patients.