Cardiovascular Disease Risk Models and Longitudinal Changes in Cognition: A Systematic Review

Background

Cardiovascular disease and its risk factors have consistently been associated with poor cognitive function and incident dementia. Whether cardiovascular disease prediction models, developed to predict an individual''s risk of future cardiovascular disease or stroke, are also informative for predicting risk of cognitive decline and dementia is not known.

Objective

The objective of this systematic review was to compare cohort studies examining the association between cardiovascular disease risk models and longitudinal changes in cognitive function or risk of incident cognitive impairment or dementia.

Materials and Methods

Medline, PsychINFO, and Embase were searched from inception to March 28, 2014. From 3,413 records initially screened, 21 were included.

Results

The association between numerous different cardiovascular disease risk models and cognitive outcomes has been tested, including Framingham and non-Framingham risk models. Five studies examined dementia as an outcome; fourteen studies examined cognitive decline or incident cognitive impairment as an outcome; and two studies examined both dementia and cognitive changes as outcomes. In all studies, higher cardiovascular disease risk scores were associated with cognitive changes or risk of dementia. Only four studies reported model prognostic performance indices, such as Area Under the Curve (AUC), for predicting incident dementia or cognitive impairment and these studies all examined non-Framingham Risk models (AUC range: 0.74 to 0.78).

Conclusions

Cardiovascular risk prediction models are associated with cognitive changes over time and risk of dementia. Such models are easily obtainable in clinical and research settings and may be useful for identifying individuals at high risk of future cognitive decline and dementia.     

Poor Decision Making Is a Consequence of Cognitive Decline among Older Persons without Alzheimer's Disease or Mild Cognitive Impairment

Objective

Decision making is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential decisions are made just as cognitive function declines. Increasing evidence suggests that older adults, even those without dementia, often make poor decisions and are selectively vulnerable to scams. To date, however, the factors associated with poor decision making in old age are unknown. The objective of this study was to test the hypothesis that poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment.

Methods

Participants were 420 non-demented persons from the Memory and Aging Project, a longitudinal, clinical-pathologic cohort study of aging in the Chicago metropolitan area. All underwent repeated cognitive evaluations and subsequently completed assessments of decision making and susceptibility to scams. Decision making was measured using 12 items from a previously established performance-based measure and a self-report measure of susceptibility to scams.

Results

Cognitive function data were collected over an average of 5.5 years prior to the decision making assessment. Regression analyses were used to examine whether the prior rate of cognitive decline predicted the level of decision making and susceptibility to scams; analyses controlled for age, sex, education, and starting level of cognition. Among 420 persons without dementia, more rapid cognitive decline predicted poorer decision making and increased susceptibility to scams (p’s<0.001). Further, the relations between cognitive decline, decision making and scams persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or even mild cognitive impairment).

Conclusions

Poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment, those widely considered “cognitively healthy.” These findings suggest that even very subtle age-related changes in cognition have detrimental effects on judgment.     

Memory Concerns,Memory Performance and Risk of Dementia in Patients with Mild Cognitive Impairment

Background

Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer''s dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).

Methods

We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.

Results

Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.

Conclusions

Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients'' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.     

Multi factorial interactions in the pathogenesis pathway of Alzheimer’s disease: a new risk charts for prevention of dementia

Background

The population longitudinal study named “The Conselice Study” has been the focus of the present investigation. 65 years old or older participants of this population study on brain aging were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 46 genetic, phenotypic, clinical and nutritional factors on incident cognitive decline and incident dementia cases were investigated.

Results

A new statistical approach, called the Auto Contractive Map (AutoCM) was applied to find relationship between variables and a possible hierarchy in the relevance of each variable with incident dementia. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Moreover, few variables resulted to be aggregation points in the variable connectivity map related to cognitive decline and dementia. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. A risk map for age associated cognitive decline and dementia has been constructed and will be presented and discussed.

Conclusion

This map of variables may be use to identify subjects with increased risk of developing cognitive decline end/or dementia and provide pivotal information for early intervention protocols for prevention of dementia.

     

Factors Predicting Reversion from Mild Cognitive Impairment to Normal Cognitive Functioning: A Population-Based Study

Introduction

Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition.

Methods

Our analyses considered 223 participants (48.9% male) aged 71–89 years, drawn from the prospective, population-based Sydney Memory and Ageing Study. All were diagnosed with MCI at baseline and subsequently classified with either normal cognition or repeat diagnosis of MCI after two years (a further 11 participants who progressed from MCI to dementia were excluded). Associations with reversion were investigated for (1) baseline factors that included diagnostic features, personality, neuroimaging, sociodemographics, lifestyle, and physical and mental health; (2) longitudinal change in potentially modifiable factors.

Results

There were 66 reverters to normal cognition and 157 non-reverters (stable MCI). Regression analyses identified diagnostic features as most predictive of prognosis, with reversion less likely in participants with multiple-domain MCI (p = 0.011), a moderately or severely impaired cognitive domain (p = 0.002 and p = 0.006), or an informant-based memory complaint (p = 0.031). Reversion was also less likely for participants with arthritis (p = 0.037), but more likely for participants with higher complex mental activity (p = 0.003), greater openness to experience (p = 0.041), better vision (p = 0.014), better smelling ability (p = 0.040), or larger combined volume of the left hippocampus and left amygdala (p<0.040). Reversion was also associated with a larger drop in diastolic blood pressure between baseline and follow-up (p = 0.026).

Discussion

Numerous factors are associated with reversion from MCI to normal cognition. Assessing these factors could facilitate more accurate prognosis of individuals with MCI. Participation in cognitively enriching activities and efforts to lower blood pressure might promote reversion.     

The Influence of Multimorbidity on Clinical Progression of Dementia in a Population-Based Cohort

Introduction

Co-occurrence with other chronic diseases may influence the progression of dementia, especially in case of multiple chronic diseases. We aimed to verify whether multimorbidity influenced cognitive and daily functioning during nine years after dementia diagnosis compared with the influence in persons without dementia.

Methods

In the Kungsholmen Project, a population-based cohort study, we followed 310 persons with incident dementia longitudinally. We compared their trajectories with those of 679 persons without dementia. Progression was studied for cognition and activities of daily life (ADLs), measured by MMSE and Katz Index respectively. The effect of multimorbidity and its interaction with dementia status was studied using individual growth models.

Results

The mean (SD) follow-up time was 4.7 (2.3) years. As expected, dementia related to both the decline in cognitive and daily functioning. Irrespective of dementia status, persons with more diseases had significantly worse baseline daily functioning. In dementia patients having more diseases also related to a significantly faster decline in daily functioning. Due to the combination of lower functioning in ADLs at baseline and faster decline, dementia patients with multimorbidity were about one to two years ahead of the decline of dementia patients without any co-morbidity. In persons without dementia, no significant decline in ADLs over time was present, nor was multimorbidity related to the decline rate. Cognitive decline measured with MMSE remained unrelated to the number of diseases present at baseline.

Conclusion

Multimorbidity was related to baseline daily function in both persons with and without dementia, and with accelerated decline in people with dementia but not in non-demented individuals. No relationship of multimorbidity with cognitive functioning was established. These findings imply a strong interconnection between physical and mental health, where the greatest disablement occurs when both somatic and mental disorders are present.     

Neural Substrates of Cognitive Subtypes in Parkinson's Disease: A 3-Year Longitudinal Study

Background

The neuropsychological features and neuropathological progression patterns associated with rapidly evolving cognitive decline or dementia in Parkinson''s disease (PD) remain to be elucidated.

Methods

Fifty-three PD patients without dementia were recruited to participate in a 3-year longitudinal cohort study. The patients were grouped according to the Clinical Dementia Rating (CDR). Group-wise comparisons were made with regard to demographic characteristics, motor symptoms, neuropsychological performances and 18F-fluorodeoxyglucose positron emission tomography.

Results

Patients who had memory-plus cognitive impairment (patients whose CDR was 0 at baseline and 0.5 in memory and other domains at follow-up, and those whose baseline CDR was 0.5 in memory and other domains) exhibited higher age at onset, visuoperceptual impairment, non-tremor-dominant motor disturbance, rapid symptomatic progression and posterior neocortical hypometabolism. In patients who were cognitively unimpaired and those who had memory-dominant cognitive impairment (patients whose CDR was 0 at baseline and 0.5 only in memory domain at follow-up, and those whose baseline CDR was 0.5 only in memory domain), the posterior neocortex was relatively unaffected until a later stage of the disease.

Conclusions

These results suggest that visuoperceptual impairment and the early involvement of the posterior neocortex may be risk factors for rapid symptomatic progression and dementia in PD.     

Differentiating the Cognitive Profile of Schizophrenia from That of Alzheimer Disease and Depression in Late Life

Background

To compare the cognitive profile of older patients with schizophrenia to those with other neuropsychiatric disorders assessed in a hospital-based memory clinic.

Methods

Demographic, clinical, and cognitive data of all patients referred to the memory clinic at the Centre for Addiction and Mental Health between April 1, 2006 and August 15, 2008 were reviewed. We then identified four groups of older patients with: (1) late-life schizophrenia (LLS) and no dementia or depression (DEP); (2) Alzheimer''s disease (AD); (3) DEP and no dementia or LLS; (4) normal cognition (NC) and no DEP or LLS.

Results

The four groups did not differ in demographic data except that patients with AD were about 12 years older than those with LLS. However, they differed on cognitive tests even after controlling for age. Patients with LLS were impaired on most cognitive tests in comparison with patients with NC but not on recalling newly learned verbal information at a short delay. They experienced equivalent performance on learning new verbal information in comparison with patients with AD, but better performance on all other tests of memory, including the ability to recall newly learned verbal information. Finally, they were more impaired than patients with DEP in overall memory.

Conclusions

Patients with LLS have a different cognitive profile than patients with AD or DEP. Particularly, memory impairment in LLS seems to be more pronounced in learning than recall. These findings suggest that cognitive and psychosocial interventions designed to compensate for learning deficits may be beneficial in LLS.     

Changes in White Matter Integrity before Conversion from Mild Cognitive Impairment to Alzheimer’s Disease

Background

Mild cognitive impairment (MCI) may represent an early stage of dementia conferring a particularly high annual risk of 15–20% of conversion to Alzheimer’s disease (AD). Recent findings suggest that not only gray matter (GM) loss but also a decline in white matter (WM) integrity may be associated with imminent conversion from MCI to AD.

Objective

In this study we used Voxel-based morphometry (VBM) to examine if gray matter loss and/or an increase of the apparent diffusion coefficient (ADC) reflecting mean diffusivity (MD) are an early marker of conversion from MCI to AD in a high risk population.

Method

Retrospective neuropsychological and clinical data were collected for fifty-five subjects (MCI converters n = 13, MCI non-converters n = 14, healthy controls n = 28) at baseline and one follow-up visit. All participants underwent diffusion weighted imaging (DWI) and T1-weighted structural magnetic resonance imaging scans at baseline to analyse changes in GM density and WM integrity using VBM.

Results

At baseline MCI converters showed impaired performance in verbal memory and naming compared to MCI non-converters. Further, MCI converters showed decreased WM integrity in the frontal, parietal, occipital, as well as the temporal lobe prior to conversion to AD. Multiple regression analysis showed a positive correlation of gray matter atrophy with specific neuropsychological test results.

Conclusion

Our results suggest that additionally to morphological changes of GM a reduced integrity of WM indicates an imminent progression from MCI stage to AD. Therefore, we suggest that DWI is useful in the early diagnosis of AD.     

Homocysteine, grey matter and cognitive function in adults with cardiovascular disease

Background

Elevated total plasma homocysteine (tHcy) has been associated with cognitive impairment, vascular disease and brain atrophy.

Methods

We investigated 150 volunteers to determine if the association between high tHcy and cerebral grey matter volume and cognitive function is independent of cardiovascular disease.

Results

Participants with high tHcy (≥15 µmol/L) showed a widespread relative loss of grey matter compared with people with normal tHcy, although differences between the groups were minimal once the analyses were adjusted for age, gender, diabetes, hypertension, smoking and prevalent cardiovascular disease. Individuals with high tHcy had worse cognitive scores across a range of domains and less total grey matter volume, although these differences were not significant in the adjusted models.

Conclusions

Our results suggest that the association between high tHcy and loss of cerebral grey matter volume and decline in cognitive function is largely explained by increasing age and cardiovascular diseases and indicate that the relationship is not causal.     

Shorter telomeres may mark early risk of dementia: preliminary analysis of 62 participants from the nurses' health study

Background

Dementia takes decades to develop, and effective prevention will likely require early intervention. Thus, it is critical to identify biomarkers of preclinical disease, allowing targeting of high-risk subjects for preventive efforts. Since telomeres shorten with age and oxidative stress, both of which are important contributors to the onset of dementia, telomere length might be a valuable biomarker.

Methodology/Principal Findings

Among 62 participants of the Nurses'' Health Study, we conducted neurologic evaluations, including patient and caregiver interviews, physical exam, neurologic exam, and neuropsychologic testing. We also conducted magnetic resonance imaging (MRI) in a sample of 29 of these women. In these preliminary data, after adjustment for numerous health and lifestyle factors, we found that truncated telomeres in peripheral blood leukocytes segregate with preclinical dementia states, including mild cognitive impairment (MCI); the odds of MCI were 12-fold higher (odds ratio = 12.00, 95% confidence interval 1.24–116.5) for those with shorter telomere length compared to longer telomere length. In addition, decreasing telomere length was strongly related to decreasing hippocampal volume (p = 0.038).

Conclusions

These preliminary data suggest that telomere length may be a possible early marker of dementia risk, and merits further study in large, prospective investigations.     

Depression and Incident Dementia. An 8-Year Population-Based Prospective Study

Aims

The aim of the study was to investigate the impact of depression (categorical diagnosis; major depression, MD) and depressive symptoms (dimensional diagnosis and symptom patterns) on incident dementia in the German general population.

Methods

Within the Leipzig Longitudinal Study of the Aged (LEILA 75+), a representative sample of 1,265 individuals aged 75 years and older were interviewed every 1.5 years over 8 years (mean observation time 4.3 years; mean number of visits 4.2). Cox proportional hazards and binary logistic regressions were used to estimate the effect of baseline depression and depressive symptoms on incident dementia.

Results

The incidence of dementia was 48 per 1,000 person-years (95% confidence interval (CI) 45–51). Depressive symptoms (Hazard ratio HR 1.03, 95% CI 1.01–1.05), and in particular mood-related symptoms (HR 1.08, 95% CI 1.03–1.14), showed a significant impact on the incidence of dementia only in univariate analysis, but not after adjustment for cognitive and functional impairment. MD showed only a significant impact on incidence of dementia in Cox proportional hazards regression, but not in binary logistic regression models.

Discussion

The present study using different diagnostic measures of depression on future dementia found no clear significant associations of depression and incident dementia. Further in-depth investigation would help to understand the nature of depression in the context of incident dementia.     

Confounding by Indication Probably Distorts the Relationship between Steroid Use and Cardiovascular Disease in Rheumatoid Arthritis: Results from a Prospective Cohort Study

Objective

To evaluate the risk of cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids.

Methods

Retrospective analysis of exposure to glucocorticoids in a prospective cohort of 353 patients with rheumatoid arthritis followed from June 2001 up to November 2011 for incident cardiovascular disease in a hospital-based outpatient cohort in the Netherlands. Hazard ratios with 95%-confidence intervals were calculated for the association between different types of exposure to glucocorticoids and incident cardiovascular disease. Associations were adjusted for demographics, cardiovascular risk factors and disease related parameters.

Results

Recent and current exposure to glucocorticoids were associated with incident cardiovascular disease, as was a longer duration of exposure and cumulative exposure to glucocorticoids. Adjustment for disease activity and severity negated the association.

Conclusion

In observational studies the finding of incident cardiovascular disease in patients with rheumatoid arthritis exposed to glucocorticoids is strongly confounded by indication due to high disease activity. The adverse cardiovascular effects of glucocorticoids might be balanced by positive effects working through inflammation control.     

Aging Affects the Mental Rotation of Left and Right Hands

Background

Normal aging significantly influences motor and cognitive performance. Little is known about age-related changes in action simulation. Here, we investigated the influence of aging on implicit motor imagery.

Methodology/Principal Findings

Twenty young (mean age: 23.9±2.8 years) and nineteen elderly (mean age: 78.3±4.5 years) subjects, all right-handed, were required to determine the laterality of hands presented in various positions. To do so, they mentally rotated their hands to match them with the hand-stimuli. We showed that: (1) elderly subjects were affected in their ability to implicitly simulate movements of the upper limbs, especially those requiring the largest amplitude of displacement and/or with strong biomechanical constraints; (2) this decline was greater for movements of the non-dominant arm than of the dominant arm.

Conclusions/Significance

These results extend recent findings showing age-related alterations of the explicit side of motor imagery. They suggest that a general decline in action simulation occurs with normal aging, in particular for the non-dominant side of the body.     

Patterns of cognitive performance in healthy ageing in Northern Portugal: a cross-sectional analysis

Background

The Minho Integrative Neuroscience Database (MIND)-Ageing project aims to identify predictors of healthy cognitive ageing, including socio-demographic factors. In this exploratory analysis we sought to establish baseline cohorts for longitudinal assessment of age-related changes in cognition.

Methods

The population sample (472 individuals) was strictly a convenient one, but similar to the Portuguese population in the age profile. Participants older than 55 years of age were included if they did not present defined disabling pathologies or dementia. A standardized clinical interview was conducted to assess medical history and a battery of neuropsychological tests was administered to characterize global cognition (Mini Mental State Examination), memory and executive functions (Selective Reminding Test; Stroop Color and Word Test; and Block Design subtest of the Wechsler Adult Intelligence Scale). Cross-sectional analysis of the neuropsychological performance with individual characteristics such as age, gender, educational level and setting (retirement home, senior university, day care center or community), allowed the establishment of baseline clusters for subsequent longitudinal studies.

Results

Based on different socio-demographic characteristics, four main clusters that group distinctive patterns of cognitive performance were identified. The type of institution where the elders were sampled from, together with the level of formal education, were the major hierarchal factors for individual distribution in the four clusters. Of notice, education seems to delay the cognitive decline that is associated with age in all clusters.

Conclusions

Social-inclusion/engagement and education seem to have a protective effect on mental ageing, although this effect may not be effective in the eldest elders.     

Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study

Background

Rapid demographic ageing is a growing public health issue in many low- and middle-income countries (LAMICs). Mild cognitive impairment (MCI) is a construct frequently used to define groups of people who may be at risk of developing dementia, crucial for targeting preventative interventions. However, little is known about the prevalence or impact of MCI in LAMIC settings.

Methods and Findings

Data were analysed from cross-sectional surveys established by the 10/66 Dementia Research Group and carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India on 15,376 individuals aged 65+ without dementia. Standardised assessments of mental and physical health, and cognitive function were carried out including informant interviews. An algorithm was developed to define Mayo Clinic amnestic MCI (aMCI). Disability (12-item World Health Organization disability assessment schedule [WHODAS]) and informant-reported neuropsychiatric symptoms (neuropsychiatric inventory [NPI-Q]) were measured. After adjustment, aMCI was associated with disability, anxiety, apathy, and irritability (but not depression); between-country heterogeneity in these associations was only significant for disability. The crude prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Country differences changed little (range 0.6%–4.6%) after standardization for age, gender, and education level. In pooled estimates, aMCI was modestly associated with male gender and fewer assets but was not associated with age or education. There was no significant between-country variation in these demographic associations.

Conclusions

An algorithm-derived diagnosis of aMCI showed few sociodemographic associations but was consistently associated with higher disability and neuropsychiatric symptoms in addition to showing substantial variation in prevalence across LAMIC populations. Longitudinal data are needed to confirm findings—in particular, to investigate the predictive validity of aMCI in these settings and risk/protective factors for progression to dementia; however, the large number affected has important implications in these rapidly ageing settings. Please see later in the article for the Editors'' Summary     

Resting Brain Perfusion and Selected Vascular Risk Factors in Healthy Elderly Subjects

Background and Purpose

Both cerebral hypoperfusion and vascular risk factors have been implicated in early aging of the brain and the development of neurodegenerative disease. However, the current knowledge of the importance of cardiovascular health on resting brain perfusion is limited. The aim of the present study was to elucidate the relation between brain perfusion variability and risk factors of endothelial dysfunction and atherosclerosis in healthy aged subjects.

Methods

Thirty-eight healthy subjects aged 50–75 years old were included. Mean global brain perfusion was measured using magnetic resonance phase contrast mapping and regional brain perfusion by use of arterial spin labeling.

Results

Mean global brain perfusion was inversely correlated with caffeine and hematocrit, and positively with end-tidal P_CO2. Furthermore, the mean global brain perfusion was inversely correlated with circulating homocysteine, but not with asymmetric dimethylarginine, dyslipidemia or the carotid intima-media thickness. The relative regional brain perfusion was associated with circulating homocysteine, with a relative parietal hypoperfusion and a frontal hyperperfusion. No effect on regional brain perfusion was observed for any of the other risk factors. A multiple regression model including homocysteine, caffeine, hematocrit and end-tidal P_CO2, explained nearly half of the observed variability.

Conclusion

Both intrinsic and extrinsic factors influenced global cerebral perfusion variation between subjects. Further, the results suggest that the inverse relation between homocysteine and brain perfusion is owing to other mechanisms, than reflected by asymmetric dimethylarginine, and that homocysteine may be a marker of cerebral perfusion in aging brains.     

Age and Vascular Burden Determinants of Cortical Hemodynamics Underlying Verbal Fluency

Background

Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer''s disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands.

Methods

Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated.

Results

Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics.

Conclusion

Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.     

Cognitive Decline in Patients with Alzheimer’s Disease and Its Related Factors in a Memory Clinic Setting,Shanghai, China

Objectives

Progressive cognitive decline is a characteristic hallmark of AD. It is important to identify prognostic markers to improve patient care and long-term planning. We aimed to identify the characteristics of disease progression in AD patients, focusing on cognitive decline and its related factors.

Methods

Clinically diagnosed AD patients in a memory clinic were followed. The mini–mental state examination (MMSE) and a battery of other neuropsychological tests were performed to assess the rate of cognitive decline and to analyze the related factors.

Results

A total of 165 AD patients were analyzed for cognitive changes. The MMSE scores declined at a rate of 1.52 points per year. Most neuropsychological test scores deteriorated significantly over time. Younger and early-onset AD patients deteriorated more rapidly than older and late-onset patients in global cognition and executive function. Men declined faster in memory but slower in attention than women. Higher education was associated with more rapid deterioration in visuo-spatial ability. Family history, hypertension and cerebral vascular disease were also associated with disease progression.

Conclusion

Attention, executive and visuo-spatial functions deteriorate at faster rates than other cognitive functions in AD patients. Age and age at onset were the main factors that associated with deterioration.