Early Stages Of Cognitive Impairment Research Articles

The Role of Suboptimal Home-Measured Blood Pressure Control for Cognitive Decline

Aim: We aim to analyze if there is any correlation between suboptimal home-/self-measured blood pressure values and the results from neuropsychological screening tests for early cognitive impairment. Methods: We studied 325 patients with treated hypertension. Mean age was 66.12 (±10.1) years. There were 119 (36.6%) male and 206 (63.4%) female patients, among them 52 (16%) with atrial fibrillation. Neuropsychological tests performed were the Mini-Mental State Examination, Montreal Cognitive Assessment, and Hachinski Ischemic Score; additionally, home-measured blood pressure was used. Results: There is a nonlinear age- and risk factor-dependent correlation between early stages of cognitive impairment and suboptimal home-measured blood pressure. Conclusion: The use of specific and sensitive neuropsychological tests for early cognitive impairment in patients with suboptimal home-measured blood pressure is effective in the everyday practice.

Frailty and Quality of Life for People With Alzheimer’s Dementia and Mild Cognitive Impairment

Our aim was to investigate the relationship between frailty and health-related quality of life (HR-QOL) in cognitively impaired elderly individuals. A cross-sectional observational study of a convenience sample of 115 patients with a diagnosis of Alzheimer's dementia or mild cognitive impairment. Frailty was measured using the biological syndrome model and HR-QOL was measured using the DEMQOL-Proxy. Regression models were constructed to establish the factors associated with HR-QOL. Frailty and neuropsychiatric symptoms were associated with HR-QOL, with Mini-Mental State Examination (MMSE) scores ≥21 (P = .037, P ≤ .001, and R (2) = .362). Functional limitation was associated with HR-QOL, with MMSE scores ≤20 (P = .017 and R (2) = .377). Frailty and neuropsychiatric symptoms were the determinants of HR-QOL in the earlier stages of cognitive impairment. Functional limitation predicted HR-QOL in the later stages of cognitive impairment. Frailty may represent a novel modifiable target in early dementia to improve HR-QOL for patients.

Atrial fibrillation (AF) and cognitive impairment in the elderly: A case–control study

AF is able not only to increase the risk of cognitive decline due to acute cerebrovascular events, but also to reduce cardiac output, with the consequence of impaired cerebral perfusion. The aim of this study was to evaluate the association between AF, dementia and depression in patients with negative anamnesis for past strokes. Our sample included 26 patients with a diagnosis of AF (paroxystic, persistent, permanent) and 31 patients with sinus rhythm, enrolled as controls. All selected patients underwent a Multidimensional Geriatric Assessment in order to investigate cognitive and behavioral functions. Statistical analysis of results showed a greater frequency of latent cognitive impairment in patients with AF, even in the absence of memory disorders. As a matter of facts, AF patients showed Mini Mental State Examination (MMSE) scores significantly lower than those with sinus rhythm (p<0.05) and Geriatric Depression Scale (GDS) scores higher than those without AF, evidencing a greater risk of depression too (p<0.02). Results showed a statistically significant association between AF, depression and cognitive impairment in early stage. In conclusion, AF is not only associated with the risk of developing cognitive impairment, but it can also be considered as a risk factor for dementia and depression, even in the absence of medical history of past stroke.

Atrophy of the Cholinergic Basal Forebrain Over the Adult Age Range and in Early Stages of Alzheimer's Disease

The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative changes during normal aging as well as severe atrophy in Alzheimer's disease (AD). However, there is a controversy regarding how the cholinergic lesion in AD relates to early and incipient stages of the disease. In vivo imaging studies on the structural integrity of the BFCS in normal and pathologic aging are rare. We applied automated morphometry techniques in combination with high-dimensional image warping and a cytoarchitectonic map of basal forebrain cholinergic nuclei to a large cross-sectional data set of high-resolution magnetic resonance imaging scans, covering the whole adult age range (20-94 years; n = 211) as well as patients with very mild AD (Clinical Dementia Rating = .5; n = 69) and clinically manifest AD (AD; Clinical Dementia Rating = 1; n = 28). For comparison, we investigated hippocampus volume using automated volumetry. Volume of the BFCS declined from early adulthood on, and atrophy aggravated in advanced age. Volume reductions in very mild AD were most pronounced in posterior parts of the nucleus basalis of Meynert, whereas in AD, atrophy was more extensive and included the whole BFCS. In clinically manifest AD, the diagnostic accuracy of BFCS volume reached the diagnostic accuracy of hippocampus volume. Our findings indicate that cholinergic degeneration in AD occurs against a background of age-related atrophy and that exacerbated atrophy in AD can be detected at earliest stages of cognitive impairment. Automated in vivo morphometry of the BFCS may become a useful tool to assess BF cholinergic degeneration in normal and pathologic aging.

Cognitive impairment in early stages of multiple sclerosis

Cognitive dysfunction involves 40-65% of multiple sclerosis patients and can have a great functional impact. It can be detected in all the disease phenotypes since the early stages of the disease, and tends to progress over time. Memory, complex attention, information-processing speed and executive functions are most commonly involved. The relationship between cognitive changes and magnetic resonance imaging (MRI) findings may involve changes in different areas, including white matter lesions, cortical and deep grey matter and normal appearing brain tissue on conventional MRI. The search for effective therapeutic strategies is a major undertaking, involving the use of both pharmacologic and rehabilitative approaches. Early treatment with disease-modifying drugs that can contain the disease burden in the brain seems to be highly advisable in order to prevent or delay the development of cognitive impairment.

Vascular cognitive impairment: Current concepts and Indian perspective

Cognitive impairment due to cerebrovascular disease is termed “Vascular Cognitive Impairment” (VCI) and forms a spectrum that includes Vascular Dementia (VaD) and milder forms of cognitive impairment referred to as Vascular Mild Cognitive Impairment (VaMCI). VCI represents a complex neurological disorder that occurs as a result of interaction between vascular risk factors such as hypertension, diabetes, obesity, dyslipidemia, and brain parenchymal changes such as macro and micro infarcts, haemorrhages, white matter changes, and brain atrophy occurring in an ageing brain. Mixed degenerative and vascular pathologies are increasingly being recognised and an interaction between the AD pathology, vascular risk factors, and strokes is now proposed. The high cardiovascular disease burden in India, increasing stroke incidence, and ageing population have contributed to large numbers of patients with VCI in India. Inadequate resources coupled with low awareness make it a problem that needs urgent attention, it is important identify patients at early stages of cognitive impairment, to treat appropriately and prevent progression to frank dementia.

Cognitive impairment and dementia in Parkinson's disease

Over the last decade, the importance of cognitive impairment and dementia in Parkinson's disease (PDD) has been increasingly recognized. Investigators have proposed criteria for PD dementia, and mild cognitive impairment. Risk profiles associated with the development of dementia based on demographic, neurological, neuropsychological, imaging, and genetic investigations have been delineated. The FDA has approved a treatment for PDD, and efforts now are directed toward intervention at earlier stages of cognitive impairment.

Overgenerality of Autobiographical Memory in People with Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease

Episodic autobiographical memory (ABM) is important for social functioning. Loss of specificity in ABM retrieval has been observed in people with mild to moderate Alzheimer's disease (AD). Our aim was to extend these findings to subjects with amnestic mild cognitive impairment (aMCI) and very early AD. We performed a cued ABM task with both subject groups and healthy elderly controls. Although aMCI participants performed better than early AD subjects both showed reduced specificity of ABM retrieval when compared with controls. We conclude that qualitative memory retrieval deficits could contribute to social functioning impairment in people with aMCI and early AD, and highlight the complexity of symptoms already present in early stages of cognitive impairment.

Structural and functional biomarkers of prodromal Alzheimer's disease: A high-dimensional pattern classification study

This work builds upon previous studies that reported high sensitivity and specificity in classifying individuals with mild cognitive impairment (MCI), which is often a prodromal phase of Alzheimer's disease (AD), via pattern classification of MRI scans. The current study integrates MRI and PET 15O water scans from 30 participants in the Baltimore Longitudinal Study of Aging, and tests the hypothesis that joint evaluation of structure and function can yield higher classification accuracy than either alone. Classification rates of up to 100% accuracy were achieved via leave-one-out cross-validation, whereas conservative estimates of generalization performance in new scans, evaluated via bagging cross-validation, yielded an area under the receiver operating characteristic (ROC) curve equal to 0.978 (97.8%), indicating excellent diagnostic accuracy. Spatial maps of regions determined to contribute the most to the classification implicated many temporal, prefrontal, orbitofrontal, and parietal regions. Detecting complex patterns of brain abnormality in early stages of cognitive impairment has pivotal importance for the detection and management of AD.

Neurocognitive Impairment and Dementia in Mood Disorders

Neurocognitive Impairment and Dementia in Mood Disorders

Subcortical Hyperintensities Are Associated With Cognitive Decline in Patients With Mild Cognitive Impairment

It has been suggested that subcortical lesions may influence cognitive performances at early stages of cognitive impairment but not in late stages of dementia. We aimed to test whether cognitive decline is associated with subcortical hyperintensities in patients with mild cognitive impairment (MCI). We included 170 consecutive MCI patients (mean follow-up, 3.8+/-1.6 years). We assessed subcortical hyperintensities on a baseline magnetic resonance imaging scan with a semiquantitative rating scale. The mean annual cognitive decline was calculated with the Mini-Mental State Examination and the Dementia Rating Scale at baseline and the end of follow-up. Compared with patients whose cognitive performances remained stable or improved during follow-up, patients whose cognitive performances declined often had a larger amount (greater than the median of the distribution) of periventricular (PVH) (P=0.0005) and white-matter (P=0.02) hyperintensities. The rate of cognitive decline was higher with increasing PVH: mean change in the Mini-Mental State Examination score=0.16 vs -0.66 points/year in patients with PVH in the first versus third tertile (P=0.0002). The rate of decline in executive functioning was also higher with increasing PVH: mean change in the Dementia Rating Scale initiation subscore=-0.05 vs -1.42 points/year in patients with PVH in the first versus third tertile (P=0.04). These associations were independent of vascular risk factors, temporal lobe atrophy, and MCI subtype and were stronger in patients with baseline executive dysfunction. White-matter hyperintensities and especially PVH were significantly associated with cognitive decline in MCI patients. This result was independent of the MCI subtype but stronger in cases of executive dysfunction at baseline.

Detection of prodromal Alzheimer's disease via pattern classification of magnetic resonance imaging

We report evidence that computer-based high-dimensional pattern classification of magnetic resonance imaging (MRI) detects patterns of brain structure characterizing mild cognitive impairment (MCI), often a prodromal phase of Alzheimer's disease (AD). Ninety percent diagnostic accuracy was achieved, using cross-validation, for 30 participants in the Baltimore Longitudinal Study of Aging. Retrospective evaluation of serial scans obtained during prior years revealed gradual increases in structural abnormality for the MCI group, often before clinical symptoms, but slower increase for individuals remaining cognitively normal. Detecting complex patterns of brain abnormality in very early stages of cognitive impairment has pivotal importance for the detection and management of AD.

Early-Stage Cognitive Impairment: A Social Work Practice and Research Agenda

With the current emphasis on early diagnosis of mild cognitive impairment or dementia such as Alzheimer's disease, it is increasingly common to receive the diagnosis of impairment before functioning is seriously compromised. People in the early stages of cognitive loss experience distress related to their current and future functioning and yet are capable of participating in psychosocial treatment or support. Although most published studies deal with services for caregivers rather than direct practice with the cognitively impaired person, there is a growing body of clinical and research reports on psychosocial interventions offered directly to people with early cognitive loss. These interventions are aimed at alleviating the stress, depression, and anxiety while promoting a positive outlook. Gerontological social work practitioners and researchers are well positioned to further develop, implement, and evaluate these promising intervention approaches with early-stage cognitive loss.

Welcome Harmonizations

Welcome Harmonizations

National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards

One in 3 individuals will experience a stroke, dementia or both. Moreover, twice as many individuals will have cognitive impairment short of dementia as either stroke or dementia. The commonly used stroke scales do not measure cognition, while dementia criteria focus on the late stages of cognitive impairment, and are heavily biased toward the diagnosis of Alzheimer disease. No commonly agreed standards exist for identifying and describing individuals with cognitive impairment, particularly in the early stages, and especially with cognitive impairment related to vascular factors, or vascular cognitive impairment. The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) convened researchers in clinical diagnosis, epidemiology, neuropsychology, brain imaging, neuropathology, experimental models, biomarkers, genetics, and clinical trials to recommend minimum, common, clinical and research standards for the description and study of vascular cognitive impairment. The results of these discussions are reported herein. The development of common standards represents a first step in a process of use, validation and refinement. Using the same standards will help identify individuals in the early stages of cognitive impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress.

Amyloid-β at sublethal level impairs BDNF-induced arc expression in cortical neurons

Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive dysfunction that probably due to a deficit in synaptic plasticity. One member of neurotrophins, brain-derived neurotrophic factor (BDNF), is known to be involved in the hippocampal long-term potentiation (LTP), a cellular model for learning and memory. Moreover, activity-regulated cytoskeleton-associated gene ( Arc), an immediate early gene, is found to be a downstream effector of the BDNF signaling cascade. Inhibition of Arc protein synthesis impairs both the maintenance of LTP and the consolidation of long-term memory. In addition, the formation of senile plaques is a pathological feature in AD and mainly consists of the deposition of amyloid-β (Aβ), a proteolytic product of amyloid precursor protein. Several studies concerning neurobehavioral performance have suggested that Aβ at sublethal levels interfere with the signaling cascades critical for synaptic plasticity and thus lead to the cognitive impairment in early stage of AD. Whether the BDNF-mediated Arc synthesis is impaired by sublethal Aβ in early AD is still unclear. Therefore, in the present study, primary cultures of neonatal rat cortical neurons were used to evaluate the effect of sublethal Aβ on the BDNF-induced Arc protein expression. Consistent with the literature, Arc, an indicator of synaptic plasticity, was induced by BDNF (25 ng/ml) in both dose- and time-dependent manners. After treating cultures with sublethal Aβ (5 μM), a significant suppression was observed on the level of BDNF-induced Arc protein expression. This result indicates that Aβ at sublethal level impairs the BDNF-mediated signaling in cortical neurons and thus underlies the deficits of synaptic plasticity occurred at the early stage of AD before significant neuronal loss.

Blood Cells Cholinesterase Activity in Early Stage Alzheimer’s Disease and Vascular Dementia

Blood acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities have been studied as markers for Alzheimer’s disease (AD), but their usefulness as a disease marker is controversial. To determine cholinesterase (ChE) activity during AD progression and whether ChE changes associate to other dementias, ChE activity was measured in lymphocytes, erythrocytes and platelets. Subjects underwent extensive medical and neuropsychological examination. Both early-AD and AD patients had lower AChE activity in lymphocytes compared to control subjects (p < 0.0001). In contrast, erythrocyte AChE activity was higher in patients with vascular dementia (p = 0.004). Low ChE activity in lymphocytes was the best discriminator for AD. Because it was already low at very early stages of AD, ChE could be helpful as an early biomarker of differential diagnosis for the follow-up of patients during their early stages of cognitive impairment before a clinical dementia is established.

Assessment of Coping in Cognitively Impaired Older Adults

This pilot study examined dispositional coping styles and distress among cognitively impaired older adults (n =28), anxious/depressed older adults (n =42) and non-distressed older adults (n =25). Participants completed the Coping Orientations to Problems Experienced Scale (COPE) and the Brief Symptom Inventory. Internal consistency analyses showed that the COPE was reliably completed by the cognitively impaired participants, with one internally poor subscale. Regarding coping clusters (problem focused, emotional focused, dysfunctional), cognitively impaired older adults reported lower levels of problem focused coping and emotional focused coping techniques than anxious/depressed and control participants. Regarding specific coping scales, cognitively impaired participants were lower on positive reinterpretation and higher on behavioral disengagement than the other groups. Among cognitively impaired persons, the coping strategy of venting emotions was positively correlated with distress, whereas the strategy of accepting the situation was negatively related to distress. An implication of the study is that an assessment of coping may be useful in the early Stages of cognitive impairment.

Current concepts in mild cognitive impairment.

The field of aging and dementia is focusing on the characterization of the earliest stages of cognitive impairment. Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). Mild cognitive impairment refers to the clinical condition between normal aging and AD in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. When these persons are observed longitudinally, they progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals. Consequently, this condition has been recognized as suitable for possible therapeutic intervention, and several multicenter international treatment trials are under way. Because this is a topic of intense interest, a group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials, and ethics was convened to summarize the current state of the field of MCI. Participants reviewed the world scientific literature on aging and MCI and summarized the various topics with respect to available evidence on MCI. Diagnostic criteria and clinical outcomes of these subjects are available in the literature. Mild cognitive impairment is believed to be a high-risk condition for the development of clinically probable AD. Heterogeneity in the use of the term was recognized, and subclassifications were suggested. While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made.

Estrogen replacement therapy and cognitive decline in memory-impaired post-menopausal women

Background: Estrogen replacement therapy (ERT) may delay dementia-related cognitive decline in post-menopausal women, but few studies have longitudinally examined this relationship and none has controlled for baseline functioning or concurrent medication. Methods: We report the results of a 1-year retrospective longitudinal study examining cognitive functioning in female estrogen and nonestrogen users ( n = 3128) who presented to the state of California memory disorder clinics in a naturalistic multisite study of senile dementia, Alzheimer’s type (SDAT), and other cognitive impairments. Results: At baseline, estrogen users had significantly lower rates of SDAT diagnoses (possible and probable) than nonestrogen users, and significantly higher rates of the lesser diagnoses of “cognitive impairment” and “no dementia.” ERT was significantly associated with higher cognitive functioning at baseline and at 1 year follow-up ( n = 358). Nonestrogen users deteriorated significantly from baseline to follow-up; estrogen users did not. Results were similar in groups matched on baseline Blessed-Roth Dementia Rating Scale (BRDRS) ratings ( n = 32) and in a variety of subpopulations. Conclusions: These findings are consistent with estrogen acting as a protective factor against cognitive deterioration in post-menopausal women with SDAT and other cognitive impairments, and may suggest an increased effect in earlier stages of cognitive impairment.