Hachinski Score Research Articles

Association Between VISTA and Vascular Cognitive Impairment in Older Chinese Adults: A Cross-Sectional Study.

Vascular cognitive impairment(VCI) ranks as the second most prevalent type of dementia.Increasing evidence has shown that inflammation and multi-faceted neuro-immune interactions integrate systemic and central inflammatory pathways, thereby inducing vascular tissue injury and contributing to the development of vascular cognitive impairment (VCI).V-type immunoglobulin-like suppressor of T cell activation (VISTA) is an Negative checkpoint regulators(NCR) that is associated with CNS homeostasis, interactions with peripheral immunity and CNS inflammation.The primary objective of this study was to seek the correlation between VISTA and VCI in patients with cardiovascular risk factors.Our secondary objective was to explore the potential of VISTA as a biomarker for VCI. We enrolled individuals with cardiovascular risk factors in this cross-sectional study research and categorized them into two groups: without cognitive impairment (control) and with cognitive impairment (VCI). VISTA expression in peripheral blood mononuclear cells (PBMCs) was analyzed using relative quantitative polymerase chain reaction. VISTA expression was identified in monocyte subsets using flow cytometry. We use Enzyme linked immunosorbent assay to detect inflammatory factors in serum. In PBMC in patients with VCI, the expression of VSIR was significantly reduced. In contrast to controls, fasting glucose, fibrosis, and the levels of interleukin 6 (IL-6) in VCI patients were noticeably higher, and uric acid levels were significantly lower. Vsir mRNA expression in PBMCs correlated negatively with IL-6 levels, Trail Making Test B scores, and Hachinski scores and positively with Boston Naming Test scores. In intermediate monocytes, flow cytometry showed reduced Vsir expression, which was connected with VCI. The percentage of intermediate monocytes, uric acid, and the VISTA mean fluorescence intensity on intermediate monocytes were shown to be independent factors to VCI by multivariate logistic regression analysis. Decreased VISTA promotes the occurrence of VCI in patients with cardiovascular risk factors by promoting monocytes toward the proinflammatory intermediate monocyte subset. VISTA may serve as a potential biomarker for distinguishing VCI in individuals with cardiovascular risk factors.

A comparative study of Amyloid positive and negative individuals with “Alzheimer Syndrome”

AbstractBackgroundOutside academic centres, the diagnosis of probable Alzheimer’s Disease remains a clinical diagnosis supported by basic blood work and structural brain imaging. It has already been documented, approximately 1/3rd of individuals meeting clinical criteria for probable AD, do not show underlying amyloidopathy on PET or cerebrospinal fluid. Thus, the clinical “Alzheimer Syndrome” encompasses individuals with abnormal amyloid (Amyloid positive: A+), as well as “amyloid negative” individuals lacking amyloidopathy. Finding ways to distinguish these subgroups clinically will become increasingly important as anti‐amyloid therapies become more available. It is not yet clear if these two groups have any clinical or imaging features that might distinguish them. Our objective was to find out if there are any clinical or imaging pointers towards amyloid biomarker status.MethodsA retrospective chart review of 23 patients screened for anti‐amyloid clinical trials was performed, of whom 13 were (A+) and 10 were (A‐). The following information was collected from the chart review‐ demography, medical history, clinical presentation, course of disease and rate of progression, neuropsychological test scores, blood work, brain scans, and any other relevant investigations. Relevant data were subjected to appropriate statistical analysis.ResultsThis is an ongoing study and the results are derived from interim analysis. Comparison of the (A+) and (A‐) groups revealed no statistically significant difference in terms of age, sex, amnestic presentation and cognitive decline rate. We did not find evidence (in this small group) that (A‐) subjects had a greater vascular load ‐ no difference in Hachinski score or Fazekas score. The only statistically significant difference between the groups was found in their NPI scores, with the A+ group showing a higher score (2.92 versus 0.80, p = 0.008).ConclusionAmyloid positive individuals are more likely to have neuropsychiatric manifestations during the course of their cognitive decline than their Amyloid negative counterpart. Work is ongoing to delineate biological and biomarker differences that account for the cortical dementia (Alzheimer Syndrome) in Amyloid negative subjects. Delineating differences in clinical presentation may prove useful in specifying which of these individuals are actually Amyloid positive. Confirmation in a larger group of subjects will be necessary.

Executive function performance depends on hypertension in individuals with sub‐threshold total Hachinski score

AbstractBackgroundThe Hachinski Ischemia Scale (HIS) differentiates AD and vascular dementia and is used to include individuals with minimal vascular risk factors in ADNI i.e., HIS ≤ 4. HIS score includes history of hypertension (HMHYPERT), a known risk for mild cognitive impairment (MCI) and vascular dementia. Cerebrovascular disease affects performance on tasks involving executive function, such as, planning and processing speed more than memory. Here, we determined if HMHYPERT scores influences executive functioning in all ADNI3 participants with normal cognition (CN) and MCI even with minimal vascular risks.MethodWe included a total of 272 participants (102 MCI, age = 74± 8 [42F, 50 HMHYPERT>0], MoCA = 23 ±3 and 170 CN, age = 73 ±6, [109F, 62 HMHYPERT>0], MoCA = 26 ±3), who underwent HIS, Trails Making Test B, Clock Drawing and Copy scores for executive function, and The Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LOGMEM) scores for memory performance within 12 months. We converted both memory tests into z‐scores and created a composite memory score. Similarly, we created a composite executive function score. To determine if HMHYPERT was associated particularly with executive function, we ran the linear regression analyses twice for the two composite cognitive scores. The following model was used: Composite score ∼ Normalized Age + Sex + Cognitive status * HMHYPERT.Result Executive function: Fig. 1 A shows scores for Trails B, Clock Draw and Clock Copy. The regression analysis showed that executive function was associated with only sex and HYMHYPERT (p<0.05).Memory function Fig. 1 B shows scores for Logical Memory and RAVLT tests in CN and MCI. As expected, MCI groups demonstrate the lowest averages compared to CN groups. As expected, regression analysis showed that memory performance was strongly determined by diagnostic status (p<0.001). Age was significantly associated with memory performance (p<0.05). HMHYPERT was only marginally significantly associated with memory performance (p = 0.08).ConclusionUsing HMHYPERT score as a measure of vascular risk, we observed notable differences in executive function. Although HIS scores ≤ 4 minimize vascular pathology in ADNI3, cognitive performance is still associated with these scores.

Low-Dose Whole Brain Radiation Therapy for Alzheimer's Dementia: Results From a Pilot Trial in Humans

We report neurocognitive, imaging, ophthalmologic, and safety outcomes following low-dose whole brain radiation therapy (LD-WBRT) for patients with early Alzheimer dementia (eAD) treated in a pilot trial. Trial-enrolled patients were at least 55 years of age, had eAD meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) Alzheimer's Criteria with confirmatory fluorodeoxyglucose and florbetapir positron emission tomography findings; had the capacity to complete neurocognitive function, psychological function, and quality-of-life assessments; had a Rosen modified Hachinski score ≤4; and had estimated survival >12 months. Five patients were treated with LD-WBRT (2 Gy × 5 over 1 week; 3 female; mean age, 73.2 years [range, 69-77]). Four of 5 patients had improved (n = 3) or stable (n = 1) Mini-Mental State Examination (second edition) T-scores at 1 year. The posttreatment scores of all 3 patients who improved increased to the average range. There were additional findings of stability of naming and other cognitive skills as well as stability to possible improvement in imaging findings. No safety issues were encountered. The only side effect was temporary epilation with satisfactory hair regrowth. Our results from 5 patients with eAD treated with LD-WBRT (10 Gy in 5 fractions) demonstrate a positive safety profile and provide preliminary, hypothesis-generating data to suggest that this treatment stabilizes or improves cognition. These findings will require further evaluation in larger, definitive, randomized trials.

Machine Learning Model-Based Applications for Food Management in Alzheimer’s Using Regression Analysis Approach

Alzheimer’s disease (AD) has become a public health concern due to its misinterpretation with vascular dementia (VD) and mixed dementia Alzheimer’s disease (MXD). Therefore, an accurate differentiation of these diseases is essential for improving the treatment procedure. It has been seen that nutrition along with several other factors plays a role in the disease progression. Scientists are trying to find a solution using some machine learning (ML) techniques. The ML algorithms used for this purpose are neural networks, support vector machines, regression and many more. The current research is focused on understanding the extent of the application of machine learning tools in enhancing food management for patients with Alzheimer’s since there is no cure known for the same. A total of 100 patient data have been collected where the patients had AD, VD, and MXD. Their demographic data, dietary intake, Fazekas scores, and Hachinski scores were collected (independent variables) and analysed in IBM SPSS by considering the risk of development of AD, VD, and MXD as dependent variables. The findings showed that age is highly related ( p < 0.001 ) to the development of these three diseases and other demographics are not prioritized. Discussion of other available journal articles showed that nutritional intake, Fazekas scores, Hachinski scores, and gender are also indicators for predicting these diseases ( p < 0.001 ). Thus, this study concluded that age, gender, diet consumption, and Fazekas and Hachinski scores are important indicators for differentiating AD from other diseases, and ML can be used to create a custom nutrition plan based on the patient’s diet and stage of disease progression. Lastly, future scopes of ML have been explained in this paper.

A Modified CAIDE Risk Score as a Screening Tool for Cognitive Impairment in Older Adults.

Although an efficacious dementia-risk score system, Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) was derived using midlife risk factors in a population with low educational attainment that does not reflect today's US population, and requires laboratory biomarkers, which are not always available. Develop and validate a modified CAIDE (mCAIDE) system and test its ability to predict presence, severity, and etiology of cognitive impairment in older adults. Population consisted of 449 participants in dementia research (N = 230; community sample; 67.9±10.0 years old, 29.6%male, 13.7±4.1 years education) or receiving dementia clinical services (N = 219; clinical sample; 74.3±9.8 years old, 50.2%male, 15.5±2.6 years education). The mCAIDE, which includes self-reported and performance-based rather than blood-derived measures, was developed in the community sample and tested in the independent clinical sample. Validity against Framingham, Hachinski, and CAIDE risk scores was assessed. Higher mCAIDE quartiles were associated with lower performance on global and domain-specific cognitive tests. Each one-point increase in mCAIDE increased the odds of mild cognitive impairment (MCI) by up to 65%, those of AD by 69%, and those for non-AD dementia by > 85%, with highest scores in cases with vascular etiologies. Being in the highest mCAIDE risk group improved ability to discriminate dementia from MCI and controls and MCI from controls, with a cut-off of ≥7 points offering the highest sensitivity, specificity, and positive and negative predictive values. mCAIDE is a robust indicator of cognitive impairment in community-dwelling seniors, which can discriminate well between dementia severity including MCI versus controls. The mCAIDE may be a valuable tool for case ascertainment in research studies, helping flag primary care patients for cognitive testing, and identify those in need of lifestyle interventions for symptomatic control.

Vascular Parkinsonism (VP) score: A simple clinical scale to differentiate vascular from degenerative parkinsonism

Background: Vascular parkinsonism(VP) constitutes (5-8) % of all parkinsonian disorders. Despite several existing diagnostic criteria for VP, there is no standard clinical grading scale for VP analogous to those for vascular dementia, like the Hachinski score.

Prevalence of Dementia among Well-Educated Old-Age Pensioners in Parakou (Benin) in 2014

Introduction: The number of people living with dementia is growing worldwide and most rapidly in low- and middle-income countries. Little is known about dementia in Benin. We estimated the prevalence of dementia among retired people in Parakou, a northern city in Benin, and then assessed associated factors. Methods: A cross-sectional study was performed in Parakou from July to August 2014. Participants were recruited at 2 centers, the National Center of Social Security and the Public Treasury of Benin. Participants with cognitive impairment were defined as having a low cognitive score (<7) for the brief version of the Community Screening Interview for Dementia and were invited to neurological examination. DSM-IV-TR criteria were used to diagnose dementia and the HACHINSKI score was used to differentiate dementia subtypes. A logistic regression model was performed to identify factors associated with dementia. Results: Overall, 440 retired people were included in the study. They were mainly male (92.3%) and their mean age was 64.9 ± 6.0 years. The prevalence of cognitive impairment was 7.7% (95% CI 5.2–10.2). Fourteen participants were diagnosed with dementia, representing a prevalence of 3.2% (95% CI 1.5–4.8). Alzheimer disease was the most frequent subtype (64.3%), followed by vascular dementia (21.4%). Retired people diagnosed with dementia were all men and were aged between 61 and 71 years. Most of them were living alone. The main factors associated with dementia were older age, low fruit and vegetables consumption, and living alone. Discussion: This study showed a low prevalence of dementia among retired older people in Benin. Despite this, greater attention must be given to the potential burden dementia places on families for better care, before the expected aging of the population becomes more significant.

Alzheimer's disease patients institutionalized in group homes run by long-term care insurance exhibit fewer symptoms of behavioural problems as evaluated by the Behavioural Pathology in Alzheimer's Disease Rating Scale.

The behavioural and psychological symptoms of dementia (BPSD) caused by Alzheimer's disease (AD) can burden caregivers. Group homes (GH), small nursing homes, for the elderly with dementia are institutions commonly run by the public long-term care insurance system in Japan. The purpose of this study was to compare the prevalence of BPSD of AD, as evaluated by the Behavioural Pathology in Alzheimer's Disease Rating Scale, between GH patients and community residents. A total of 74 patients with AD were enrolled: 37 were patients institutionalized in GH (Hachinski score < 5) and 37 were demographic-matched community residents undergoing treatment at the Osaki-Tajiri SKIP Center. There were no significant differences in mean age (81.4 vs 81.1 years, P = 0.816), mean educational level (7.7 vs 8.0 years, P = 0.497), sex (women/men: 30/7 vs 30/7, P = 1.000) and mean Mini-Mental State Examination scores (14.1 vs 14.1, P = 0.950) between the two groups. Care level (range: 0.5-5.0, slight to bedridden), activities of daily living care level (range: 1-7, almost normal to severe), and the presence or absence BPSD based on the domains of the Behavioural Pathology in Alzheimer's Disease Rating Scale were compared. GH patients had a significantly higher care level (P < 0.05) and activities of daily living care level (P < 0.05) but had fewer symptoms of BPSD (P < 0.05) than community residents. When the activities of daily living care level was controlled, GH patients had significantly fewer symptoms than community residents in Aggressiveness (21% vs 50%; χ2 = 4.5, P = 0.035), Affective disturbances (13% vs 42%; χ2 = 5.1, P = 0.023), and Anxieties and phobias (4% vs 46%; χ2 = 11.1, P = 0.001). GH run by the long-term care insurance system appear to be effective in improving environmental factors for moderate AD patients and reducing Aggressiveness, Affective disturbances, and Anxieties and phobias.

Genetic architecture of resilience of executive functioning

The genetic basis of resilience, defined as better cognitive functioning than predicted based on neuroimaging or neuropathology, is not well understood. Our objective was to identify genetic variation associated with executive functioning resilience. We computed residuals from regression models of executive functioning, adjusting for age, sex, education, Hachinski score, and MRI findings (lacunes, cortical thickness, volumes of white matter hyperintensities and hippocampus). We estimated heritability and analyzed these residuals in models for each SNP. We further evaluated our most promising SNP result by evaluating cis-associations with brain levels of nearby (±100 kb) genes from a companion data set, and comparing expression levels in cortex and cerebellum from decedents with AD with those from other non-AD diseases. Complete data were available for 750 ADNI participants of European descent. Executive functioning resilience was highly heritable (H² = 0.76; S.E. = 0.44). rs3748348 on chromosome 14 in the region of RNASE13 was associated with executive functioning resilience (p-value = 4.31 × 10⁻⁷). rs3748348 is in strong linkage disequilibrium (D' of 1.00 and 0.96) with SNPs that map to TPPP2, a member of the α-synuclein family of proteins. We identified nominally significant associations between rs3748348 and expression levels of three genes (FLJ10357, RNASE2, and NDRG2). The strongest association was for FLJ10357 in cortex, which also had the most significant difference in expression between AD and non-AD brains, with greater expression in cortex of decedents with AD (p-value = 7 × 10⁻⁷). Further research is warranted to determine whether this signal can be replicated and whether other loci may be associated with cognitive resilience.

Antipsychotic Use Is Not Associated with an Increased Burden of Cerebrovascular Pathology at Autopsy (S04.004)

Objective: Assess the correlations between antipsychotic medication use in elderly dementia persons with neuropathological outcomes data, including cerebrovascular disease (CVD) pathology. Background A 2006 FDA-issued black box indicated that elderly patients with dementia treated with antipsychotics are at an increased risk of death, primarily from vascular complications (myocardial infarction and stroke) and infections (pneumonia). Despite the profound impact this warning has had on the field, the cerebrovascular consequences of antipsychotic use in dementia remain poorly understood. Design/Methods: We identified all subjects with a history of dementia related psychosis treated with antipsychotic agents (DPAP; n=32) in the University of Kentucky Alzheimer9s Disease Center Brain Bank. Control subjects were placed in two cohorts matched for age, gender, apoe, education and MMSE including subjects with dementia but no psychosis or antipsychotic medication (DNPNAP group; n=32), and subjects with dementia and psychosis but no antipsychotic medication (DPNAP group; n=32). Demographic, clinical, genetic, and neuropathological features were compared between groups. Results: Comparative analysis of vascular risk factors (hypertension, hyperlipidemia, myocardial infarction, smoking, diabetes mellitus, cardiac arrhythmia, and Hachinski scores) revealed no significant between group differences. Clinical diagnoses including Alzheimer9s, Lewy-Body, frontotemporal, and vascular dementia did not differ between groups. Cause of death including myocardial infarction, stroke, and pneumonia did not differ between groups (p=0.73, χ2 test). Braak, CERAD, amyloid angiopathy, and Lewy body scores supported the diagnoses of moderate to severe dementia in the majority of cases (86%), but did not differ between groups. No statistically significant differences were found between the 3 groups for degree of atherosclerosis (p=0.25) or lacunar (p=0.34), micro- (p= 0.67), hemorrhagic (p= 0.81), or macro (p= 0.90) infarcts. Conclusions: Antipsychotic medication use is not associated with increased burden of cerebrovascular disease on neuropathological examination. Future studies investigating causal relationship between antipsychotic use and increased risk of death in dementia patients is warranted. Disclosure: Dr. Singhal has nothing to disclose. Dr. Abner has nothing to disclose. Dr. Schmitt has nothing to disclose. Dr. Nelson has nothing to disclose. Dr. Jicha has received personal compensation for activities with Pfizer Inc, Janssen Immunotherapy, and Eli Lilly & Company. Dr. Jicha has received research support from Baxter, Janssen, Pfizer Inc, Medivation, and Danone.

Clinical correlates of cerebral white matter hyperintensities in cognitively normal older adults

Many research studies have demonstrated asymptomatic white matter hyperintensities (WMHs) in older adults, which are postulated to be ischemic in origin. We hypothesized that certain clinical predictors, measured in a population of healthy older adults, would have a positive relationship with WMH scoring on magnetic resonance imaging (MRI). As part of a longitudinal study of cognitive aging we have performed MRI on healthy older adults. In a group of 46 volunteers (25 females; median age 73, range 63–84 years), we have calculated of the Hachinski score and Framingham Stroke Risk Profile (FSRP). Volunteers also provided self-reported health information using the Cornell Medical Index (CMI). These were compared against the total Age Related White Matter Changes (ARWMC) score. The mean total ARWMC score was 7.4 ± 5.27 (±S.D.) and only 3 (6.5%) individuals had no evidence of WMH. Regression analysis of individual variables identified self-report of cardiovascular disease from the CMI, section C as the only significant predictor of ARWMC. A multivariate linear regression model also identified FSRP at 1 year as a second independently significant predictor. The multivariate model accounted for 19% of the variance in total ARWMC score. The only 6.5% of individuals who had no WMH is in keeping with previous studies. The important finding was the positive relationship with self-reported cardiovascular disease, which is a possible biomarker of sub-clinical cerebrovascular disease (CVD).

Alzheimer disease versus mixed dementias: An EEG perspective

Objective To examine differences between patients with AD ( n = 54) and mixed (vascular Alzheimer) dementia ( n = 24), and controls ( n = 66), with respect to clinic, neuropsychology, neuroradiology and quantitative EEG (QEEG). Methods We used CAMDEX, CT and QEEG. Results Patients with mixed dementia had more subcortical lesions. Increased slow frequency EEG power was observed in mixed dementia compared to AD, whereas the level of high frequency power was nearly normal in mixed dementia, but decreased in pure AD. Topography of slow band power was unaltered in both groups, but was changed for fast bands. The Hachinski score and neuropsychological tests showed small differences between mixed dementia and pure AD. Conclusion Neuroimaging and QEEG made a greater differential diagnostic contribution than clinical symptoms and neuropsychology. An alteration of slow frequency power with nearly normal high frequency power in mixed dementia may reflect subcortical pathology, whereas cortical pathology in pure AD may relate to decreased fast frequency power. With vascular pathology, less AD pathology is needed for a similar severity of dementia. Significance In dementia of the Alzheimer type a vascular component is often found – especially at an older age. The quantitative EEG can contribute to a better understanding of the interaction of the two components.

Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial

PBT2 is a metal-protein attenuating compound (MPAC) that affects the Cu2(+)-mediated and Zn2(+)-mediated toxic oligomerisation of Abeta seen in Alzheimer's disease (AD). Strong preclinical efficacy data and the completion of early, clinical safety studies have preceded this phase IIa study, the aim of which was to assess the effects of PBT2 on safety, efficacy, and biomarkers of AD. Between December 6, 2006, and September 21, 2007, community-dwelling patients over age 55 years were recruited to this 12-week, double-blind, randomised trial of PBT2. Patients were randomly allocated to receive 50 mg PBT2, 250 mg PBT2, or placebo. Inclusion criteria were early AD (mini-mental state examination [MMSE] score between 20 and 26 points or Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) score between 10 and 25 points), taking a stable dose of acetylcholinesterase inhibitor (donepezil, galantamine, or rivastigmine) for at least 4 months, a modified Hachinski score of 4 points or less, and CT or MRI results that were consistent with AD. The principal outcomes were safety and tolerability. Secondary outcomes were plasma and CSF biomarkers and cognition. Analysis was intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00471211. 78 patients were randomly assigned (29 to placebo, 20 to PBT2 50 mg, and 29 to PBT2 250 mg) and 74 (95%) completed the study. 42 (54%) patients had at least one treatment emergent adverse event (10 [50%] on PBT2 50 mg, 18 [62%] on PBT2 250 mg, and 14 [48%] on placebo). No serious adverse events were reported by patients on PBT2. Patients treated with PBT2 250 mg had a dose-dependent (p=0.023) and significant reduction in CSF Abeta(42) concentration compared with those treated with placebo (difference in least squares mean change from baseline was -56.0 pg/mL, 95% CI -101.5 to -11.0; p=0.006). PBT2 had no effect on plasma biomarkers of AD or serum Zn(2+) and Cu(2+) concentrations. Cognition testing included ADAS-cog, MMSE, and a neuropsychological test battery (NTB). Of these tests, two executive function component tests of the NTB showed significant improvement over placebo in the PBT2 250 mg group: category fluency test (2.8 words, 0.1 to 5.4; p=0.041) and trail making part B (-48.0 s, -83.0 to -13.0; p=0.009). The safety profile is favourable for the ongoing development of PBT2. The effect on putative biomarkers for AD in CSF but not in plasma is suggestive of a central effect of the drug on Abeta metabolism. Cognitive efficacy was restricted to two measures of executive function. Future trials that are larger and longer will establish if the effects of PBT2 on biomarkers and cognition that are reported here translate into clinical effectiveness.

Hypoalbuminemia and Not Hyperhomocysteinemia as a Risk Factor for Dementia in Hemodialysis Patients

The most common causes of morbidity and mortality in uremic patients are cardiovascular disease and central nervous system dysfunction. However, the exact causes of dementia in uremic patients remain unclear. This study attempted to determine which risk factors are associated with dementia in hemodialysis patients. In total, 147 chronic uremic patients receiving regular hemodialysis treatment were recruited. Data for risk factors regarding cardiovascular disease and dementia, such as hypertension, diabetes mellitus, smoking, age, illiteracy, serum levels of albumin, cholesterol, triglycerides, and homocysteine, and liver function, were recorded. The Mini-Mental Status examination was used to assess mental function, and the Hachinski ischemic scale was applied to differentiate among dementia types. The diagnosis of dementia was based on criteria from the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. Twenty-six patients were diagnosed as manifesting dementia. Of all patients with dementia, 21 had a Hachinski score of 0 to 4, and 5 had a score of 7 to 10. In a multiple logistic regression analysis, low serum albumin and illiteracy were significantly associated with dementia. However, no difference existed between the two groups in terms of homocysteine levels. This study demonstrated that uremic patients were prone to nonvascular dementia. We conclude that hypoalbuminemia and not hyperhomocysteinemia is a risk factor for dementia in hemodialysis patients.

The pathophysiology of the aqueduct stroke volume in normal pressure hydrocephalus: can co-morbidity with other forms of dementia be excluded?

Variable results are obtained from the treatment of normal pressure hydrocephalus (NPH) by shunt insertion. There is a high correlation between NPH and the pathology of Alzheimer's disease (AD) on brain biopsy. There is an overlap between AD and vascular dementia (VaD), suggesting that a correlation exists between NPH and other forms of dementia. This study seeks to (1) understand the physiological factors behind, and (2) define the ability of, the aqueduct stroke volume to exclude dementia co-morbidity. Twenty-four patients from a dementia clinic were classified as having either early AD or VaD on the basis of clinical features, Hachinski score and neuropsychological testing. They were compared with 16 subjects with classical clinical findings of NPH and 12 aged-matched non-cognitively impaired subjects. MRI flow quantification was used to measure aqueduct stroke volume and arterial pulse volume. An arterio-cerebral compliance ratio was calculated from the two volumes in each patient. The aqueduct stroke volume was elevated in all three forms of dementia, with no significant difference noted between the groups. The arterial pulse volume was elevated by 24% in VaD and reduced by 35% in NPH, compared to normal (P = 0.05 and P = 0.002, respectively), and was normal in AD. There was a spectrum of relative compliance with normal compliance in VaD and reduced compliance in AD and NPH. The aqueduct stroke volume depends on the arterial pulse volume and the relative compliance between the arterial tree and brain. The aqueduct stroke volume cannot exclude significant co-morbidity in NPH.

Clinical significance of subcortical vascular disease in patients with mild cognitive impairment

Patients with mild cognitive impairment (MCI) typically present with memory complaints. Some of these patients have subcortical vascular disease on computed tomography (CT) scan, namely white matter changes and lacunar infarcts, however it is not known whether these findings are associated with more pronounced cognitive deficits. In the present study we compare demographic, clinical and neuropsychological characteristics of MCI patients according to the presence or the absence of subcortical vascular disease. Forty consecutive patients with memory complaints, at least one neuropsychological memory test below 1 SD the normal for age and education, and maintained activities of daily living, were included. Patients with dementia, history of stroke or transient ischemic attack, or other brain disorders, were excluded. Twenty-five (62.5%) patients with MCI had no ischemic lesions on CT scan, and 15 (37.5%) were found to have subcortical vascular changes. MCI patients with subcortical vascular changes were older (77.1 +/- 6.8 vs. 70.8 +/- 7.5 years old), and more often males. The number of vascular risk factors, the frequency of neurological signs, the Hachinski score and the neuropsychological tests scores were not significantly different. The presence of subcortical vascular disease on CT scan is frequent in older patients with MCI, but does not appear to be associated with the severity of cognitive deficits.

Exploring sex differences in the relationship between depressive symptoms and dementia incidence: prospective results from the PAQUID Study.

To estimate the predictive relationship between depressive symptoms and 8-year dementia incidence in a large prospective community sample of French older adults and to compare the effect magnitude for men and women. Prospective population-based cohort with four interview waves and complete vital status ascertainment. Urban and rural communities in the Aquitaine Region (Gironde and Dordogne), southwest France. Three thousand seven hundred seventy-seven adults aged 65 and older residing in noninstitutional settings at study baseline. Each participant was interviewed by a neuropsychologist and screened for dementia with the Mini-Mental State Examination, a cognitive test battery, and a standardized questionnaire designed to ascertain the presence of the criteria for dementia according to the Diagnostic and Statistical Manual for Mental Disorders, Third Edition, Revised (DSM-III-R). Dementia status and subtype were confirmed using neurological examination and categorized according to DSM-III-R criteria for dementia and the National Institute of Neurological Disorders and Stroke/Alzheimer's and Related Disorders Association criteria. The Hachinski score was calculated to specify the etiology: possible or probable Alzheimer's disease, vascular dementia, and other types of dementia. Depressive symptomatology was evaluated using the Center for Epidemiologic Studies-Depression scale. Statistical analyses were weighted to correct for attrition not due to mortality. Ninety-seven men (incidence rate: 14.4/1,000) and 183 women (Incidence rate: 19.0/1,000) developed dementia during 8 years of follow-up. Baseline prevalence of depressive symptomatology was 12.9% for men and 14.7% for women. Depressive symptoms increased risk of dementia at subsequent interview wave, but only for men (odds ratio (OR) (men) = 3.5, 95% confidence interval (CI) = 1.9-6.5; OR (women) = 1.2, 95% CI = 0.7-2.0, P-value for sex difference = 0.03). The hypothesis that vascular depression might explain the observed sex difference was studied, and it was found that risk was 50% higher for men with hypertension who were depressed than for normotensive men. For women, hypertension status did not modify the absence of an association. This study supports the hypothesis of a relationship between proximal depressive symptomatology and dementia in men, but distant depression did not increase dementia risk in this sample. The results suggest that depression in older men might reflect a form of vascular depression associated with cerebral vascular pathology or multiinfarct disease that may amplify the dementing or declining process, hence accelerating the onset of manifest symptoms of dementia.

Patient Populations in Clinical Studies of Donepezil in Vascular Dementia

There are difficulties in accurately defining patients with vascular dementia (VaD) and, therefore, little is known about the characteristics of this population. To examine the population characteristics in patients with VaD enrolled in two randomized, double-blind, placebo-controlled, 24-week clinical trials of the efficacy and tolerability of the acetylcholinesterase inhibitor donepezil. Enrolled patients had probable or possible VaD, classified according to NINDS-AIREN criteria. Patients were excluded if they had a diagnosis of Alzheimer's disease or dementia caused by other conditions not associated with the cardiovascular system. A total of 1,219 patients, 73% with probable VaD and 27% with possible VaD, were enrolled. Patients had a mean Hachinski score of 9.7, with memory impairment the most prominent feature of their dementia. Sixty-eight percent of patients had a history of at least one stroke and 28% of patients had a history of transient ischemic attack before dementia. In the 99% of patients who had abnormal computer-assisted tomography or magnetic resonance imaging scans, cortical and subcortical infarcts were among the lesions observed, with significant white-matter lesions also present in some patients. Seventy-three percent of patients had experienced an abrupt onset of cognitive symptoms. Vascular risk factors were prominent and included hypertension (70%), smoking (62%), and hypercholesterolemia (39%). The patients enrolled in these trials had probable or possible VaD; these patients exhibited a history of cerebrovascular disease and a broad range of comorbid cardiovascular conditions. The large number of patients enrolled will permit a thorough examination of the efficacy and tolerability of donepezil in VaD.

Alzheimer's disease and brain infarcts in the elderly. Agreement with neuropathology.

Clarifying the etiology of dementia is one of the most difficult diagnostic challenges, especially in the elderly. We examined the accuracy of clinical criteria to distinguish Alzheimer's disease (AD) and dementia associated with infarcts of the brain, either isolated (vascular dementia) or associated with degenerative lesions (mixed dementia). We carried out a prospective clinico-neuropathological study in a selected series of hospitalized patients. We evaluated the clinical aspects of 33 patients aged over 75 years by use of the criteria and scores of DSMIII, NINCDS-ADRDA, Loeb and Gandolfo, ADDTC and NINDS-AIREN and the Hachinski Ischemic Score. The neuropathological diagnosis was considered to be the gold standard. When comparing clinical criteria and neuropathology, the agreement was moderate for Hachinski's score (0.50) and Loeb's score (0.43) and substantial for the ADDTC (0.63) and the NINDS-AIREN (0.67). When mixed dementias were excluded, the agreement between all clinical criteria and scores and the pathological diagnosis rose to 0.88. Hachinski's score was the most sensitive (0.89) and the NINDS-AIREN the most specific (0.86) for the diagnosis of vascular dementia. In conclusion, all sets of clinical criteria distinguished pure AD from vascular dementia with a high accuracy whereas mixed dementia was clinically under-recognized. The NINDS-AIREN criteria were the most discriminating for the accurate identification of patients with mixed dementia.