Apolipoprotein E in Taiwan Chinese patients with dementia

To clarify whether Alzheimer's disease (AD) and vascular dementia (VaD) share the same risk factors in Taiwan Chinese patients. Using the criteria of the NINCDS- ADRDA and NINDS-AIREN, 154 AD patients, 30 VaD patients, and 112 controls were enrolled. Their apolipoprotein E (ApoE) genes, extracted from peripheral blood leukocytes, were analyzed. The epsilon4 allele frequency was significantly higher in AD patients than in the control group. The odds ratio of carrying at least one copy of the epsilon4 allele in AD patients is 2.7 compared with control subjects. There was no significant difference between the VaD patients and the control subjects in their ApoE epsilon4 or epsilon2 allele frequency. The present study demonstrates a strong association between the ApoE epsilon4 allele and AD, but not between the ApoE epsilon4 allele and VaD. This suggests that AD and VaD do not share the same pathogenesis and deserve further investigation.     

Apolipoprotein E gene polymorphism in Indian patients with Alzheimer's disease and vascular dementia

The association of apolipoprotein E (ApoE) gene polymorphism with Alzheimer's disease (AD) has been reported in several populations including one from a rural community in North India. However, the association of ApoE polymorphism with vascular dementia (VaD) is yet to be established in this population. In a case-control study involving 54 cases of dementia (29 AD and 25 VaD) and 76 age-matched healthy controls, the frequency of epsilon4 allele was significantly higher among cases of AD and VaD compared with controls (p < 0.001). The epsilon3epsilon3 (p < 0.05) and epsilon2epsilon3 (p < 0.001) genotypes were found to be protective. The odds of developing AD or VaD were 4.4 and 3.7 times higher, respectively, in the presence of even a single epsilon4 allele. Our results suggest that the increased risk of developing AD or VaD is similar among Asian Indians with ApoE epsilon4 compared with the Caucasian population.     

Presenilin gene predisposes to late-onset degenerative but not vascular dementia: a comparative study of PS1 and ApoE genes in a North Indian Cohort

BACKGROUND: Variation in the presenilin gene shifts the cleavage site of amyloid precursor protein producing an insoluble peptide Abeta(42) (instead of Abeta(40), which is soluble when produced in restricted amount), which is prone to aggregation in the brain in the form of amyloid plaques not only in Alzheimer's disease (AD) but also in other degenerative dementias. The role of presenilin 1 (PS1) and apolipoprotein E (ApoE) genes has not been explored in degenerative dementias other than AD. OBJECTIVE: To study the association of PS1 intron 8 and ApoE epsilon4 gene polymorphism in degenerative and vascular dementia patients in the North Indian population. DESIGN: A hospital-based association study on degenerative and vascular dementia patients proven on the basis of clinical profile and MRI. Participants: A group of 107 dementia patients and 162 age- and sex-matched controls from a North Indian cohort participated in the study. All patients had Mini Mental State Examination scores less than 24 and met the DSM-IV criteria for dementia. RESULTS: The frequency of genotype 1/1 and allele 1 in degenerative dementias (73.12 and 83.70%, respectively) was higher than what had been reported so far in AD. A significant association of PS1 intron 8 polymorphism was found with degenerative dementias but not with vascular dementias (OR 2.50, 95% CI 1.27-5.00). On the other hand, ApoE epsilon4 allele was found to significantly increase the risk for both vascular and degenerative dementias (p = 0.0001, OR 3.45, 95% CI 1.74-6.86). CONCLUSION: While ApoE epsilon4 allele increases the susceptibility to both degenerative and vascular dementia, PS1 allele 1 increases the susceptibility to degenerative dementias only.     

Apolipoprotein E epsilon4 allele frequency in elderly depressed patients with and without cerebrovascular disease

Late-onset depression (LOD) could be a very early manifestation of Alzheimer's disease (AD), although contradictory results have been reported. Cerebrovascular disease (CVD) may favor the development of LOD, and that the particular forms of vascular depression should be individualized. The Apolipoprotein E (ApoE) epsilon4 allele was shown to be a risk factor for AD. Its role in LOD is controversial, while it is still unknown in vascular depression. Our objective was to clarify the relationship between ApoE epsilon4 allele and LOD in patients with and without CVD. We examined the ApoE phenotypes in a sample of 311 subjects: 50 with vascular LOD, 24 with LOD without CVD, 115 with AD and 122 normal controls (NC). The study of the ApoE epsilon4 allele frequency showed significant differences between: AD group and the vascular LOD and NC groups; LOD group without CVD compared with NC group (p<0.05 to 0.001). The frequency of the epsilon4 allele in the LOD group without CVD did not differ significantly from the AD group, similarly the frequency of the epsilon4 allele in the vascular LOD group was not different from that in NC. The study suggests an association between the ApoE epsilon4 allele and the LOD without CVD. These patients could be at risk of developing AD by an epsilon4-dependent pathway. In contrast, the results show no association between the presence of ApoE epsilon4 allele and vascular depression and provide further evidence in support of the concept that ApoE epsilon4 allele is not associated with clinical CVD.     

Defining dementia: clinical criteria for the diagnosis of vascular dementia

The recognition of cerebrovascular disease (CVD) as a contributing factor and a cause of dementia has led to the development of clinical criteria for vascular dementia (VaD). Due to high specificity, the consensus criteria developed by the National Institute for Neurological and Communicative Disorders and Stroke (NINDS)–Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) have been used in controlled clinical trials to select patients with pure VaD. VaD is predominantly a subcortical frontal form of dementia with prominent executive dysfunction. In contrast, the criteria of the NINCDS–Alzheimer's Disease and Related Disorders Association (ADRDA) emphasize memory loss as the main feature to distinguish Alzheimer's disease (AD) from VaD and from other forms of dementia. Moreover, CVD may precipitate the clinical expression of AD. Although no criteria have been created specifically for patients having AD with CVD, the ischemic score, the Informant Questionnaire on Cognitive Decline in the Elderly and a history of prestroke mild cognitive impairment (MCI) may be useful for identifying patients with this mixed form of dementia.     

Incidence and risk factors for mild cognitive impairment: a population-based three-year follow-up study of cognitively healthy elderly subjects

BACKGROUND: Mild cognitive impairment (MCI) has attracted considerable interest as a potential predictor of Alzheimer's disease (AD). Both the apolipoprotein E (ApoE) epsilon4 allele and vascular factors have been associated with a higher risk for AD, recently they have also been linked to the risk of MCI. OBJECTIVES: To estimate the incidence of MCI among cognitively healthy elderly subjects during a 3-year follow-up, and to evaluate the impact of demographic and vascular factors as well as the ApoE epsilon4 allele on the conversion to MCI. METHODS: At baseline, the cognitive abilities of 806 out of 1,150 eligible subjects (aged 60-76 years) from a population-based sample were examined. Cognitively intact subjects (n = 747) were followed for an average of 3 years. RESULTS: 66 subjects (8.8%) had converted to MCI. The global incidence rate of MCI was 25.94/1,000 person-years. Persons with higher age (OR 1.08, 95% CI 1.01-1.16), ApoE epsilon4 allele carriers (OR 2.04, 95% CI 1.15-3.64) and persons with medicated hypertension (OR 1.86, 95% CI 1.05-3.29) were more likely to convert to MCI than those individuals of lower age and without an ApoE epsilon4 allele or medicated hypertension. Persons with high education (OR 0.79, 95% CI 0.70-0.89) were less likely to convert to MCI than persons with low or no education. In subjects with both the ApoE epsilon4 allele and medicated hypertension, the crude OR for conversion was 3.92 (95% CI 1.81-8.49). In subjects with cardiovascular disease, the crude OR for conversion was 2.13 (95% CI 1.26-3.60). Gender, elevated blood pressure, diabetes or cerebrovascular disease had no significant effect on the conversion to MCI. CONCLUSION: Higher age, the presence of at least one ApoE epsilon4 allele and medicated hypertension are independent risk factors, but high education is a protective factor for MCI. The results suggest that vascular factors may have an important role in the pathogenesis of MCI.     

Inheritance of the ApoE epsilon4 allele increases the rate of brain atrophy in dementia patients.

We investigated the influence of the apolipoprotein (ApoE) epsilon4 allele on the rate of brain atrophy in patients with clinical dementia and in subjects at risk for dementia. Eighty-one subjects, consecutively referred to a memory clinic due to symptoms of dementia, went through a comprehensive examination, including cerebral magnetic resonance imaging. After an initial investigation these subjects were divided into one of six diagnostic groups; Alzheimer's disease (AD, n = 23), objective cognitive impairment (OCI, n = 27), subjective cognitive impairment (SCI, n = 17), vascular dementia (VaD), frontotemporal dementia (FTD) and unspecified dementia (USD). The last three groups were joined into one diagnostic group designated 'other dementia' (OD, altogether n = 14). In order to study the progression of cognitive impairment as well as the rate of atrophy in different brain regions all subjects were reinvestigated after an average period of 16 months. Interest was focused on investigating if those subjects with one or two epsilon4 alleles differed in either dementia progression or rate of brain atrophy compared to those without the epsilon4 allele. We found that the ApoE epsilon4 carriers had a statistically significantly larger increase in ventricular volume as compared with the ApoE epsilon4 noncarriers. In all diagnostic groups the ApoE epsilon4 carriers showed a greater rate of ventricular volume increase, as compared to the noncarriers. However, this difference was statistically significant only for the OD subjects. No statistical significant changes over time were seen for whole brain volume or volume of the temporal lobes and the medial temporal lobes. The diagnostic groups differed in dementia progression with the AD subjects having the most pronounced reduction in MMSE scores as compared to subjects at risk for AD (OCI and SCI subjects). The presence of ApoE epsilon4 allele did not influence the change in MMSE in any of the diagnostic groups.     

Association of the apolipoprotein E epsilon4 allele with late-onset depression.

Apolipoprotein E (ApoE) phenotyping was determined in 42 subjects with Alzheimer's disease (AD), 49 with depression, including 26 with early-onset depression (EOD) and 23 with late-onset depression (LOD), and 49 controls. In the EOD group, the frequency of the ApoE epsilon4 allele was not different from the control frequency (p = 0.532) but was significantly lower than in AD (p < 0.001). In the LOD group, the ApoE epsilon4 frequency was significantly higher than in the controls (p = 0.034) but was not different from that in the AD group (p = 0.229). Individuals with ApoE epsilon4 were at greater risk of getting AD (odds ratio, OR = 5.5, 95% confidence interval, CI, 2.0-14.0) or LOD (OR = 6.1, 95% CI, 1.9-19.0) than of EOD (OR = 0.7, 95% CI, 0.2-2.5). These results suggest an association between the ApoE epsilon4 allele frequency and LOD. Patients with LOD could be at risk of developing AD by an epsilon4-dependent pathway.     

Prevention and early intervention for vascular dementia in community dwelling elderly: Findings from the Nakayama study

Cerebrovascular disease (CVD) may be the single most common risk factor for age‐associated dementia (in particular for vascular dementia (VaD)), and there is definite potential for prevention and treatment of CVD. After one of the most comprehensive and precise type‐specific prevalence surveys of dementia (first Nakayama study), we have continued the preventive and early interventional approaches to CVD and VaD, including treatment of cardiovascular risk factors. In this cohort study, 88% of patients with ‘vascular cognitive impairment without dementia’, who were alive at 3‐years follow up, were still diagnosed with ‘vascular cognitive impairment without dementia’ and only 12% progressed to dementia. Compared with the results of previous studies, active control of risk factors and prevention of recurrent stroke may reduce the incidence of dementia and slow the progression of cognitive impairment in patients with ‘vascular cognitive impairment without dementia’.     

Long-term safety and cognitive effects of galantamine in the treatment of probable vascular dementia or Alzheimer's disease with cerebrovascular disease.

The relationship between cholinergic dysfunction and cognitive and functional impairment in patients with vascular dementia (VaD) and Alzheimer's disease (AD) with cerebrovascular disease (CVD) suggests a potential role for cholinomimetic therapy. Initial studies of galantamine demonstrated cognitive, behavioral, and functional benefits in these populations. 326 patients with VaD or AD with CVD who completed an initial 12-month trial were treated with galantamine 24 mg/day in a 24-month, open-label extension. This interim analysis was performed at month 12 of the open-label extension (248 completed the trial). Galantamine (up to 24 months total) was well tolerated in both groups. The most frequently reported adverse events, characteristic of older dementia patients, included depression, agitation, and insomnia. Gastrointestinal adverse events were less common than initially, indicating declining incidence with long-term therapy. Patients taking galantamine for the entire study demonstrated the least cognitive decline on AD Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of galantamine were evident in both groups; cognitive baseline levels were maintained for approximately 21 months in VaD patients and for 12 months in patients with AD with CVD. Long-term (up to 24 months) galantamine therapy in patients with VaD and AD with CVD is well tolerated and associated with prolonged maintenance of cognitive function.     

Metabolic Syndrome,Mild Cognitive Impairment,and Dementia: A Meta-Analysis of Longitudinal Studies

ObjectiveA systematic review and a meta-analysis of both clinical and population-based studies was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to clarify whether Metabolic Syndrome (MetS) is a risk or a protective factor for incident dementia, Alzheimer disease (AD), and vascular dementia (VaD), and whether it's involved in progression to dementia in patients affected by mild cognitive impairment (MCI).MethodsSearch terms included (“metabolic syndrome” OR “syndrome x” OR “plurimetabolic syndrome”) AND (“dementia” OR “Alzheimer disease” OR “vascular dementia” OR “mild cognitive impairment” OR “MCI”). Research was restricted to articles published in English between January 1, 2000 and August 31, 2018. No age limit was set.ResultsAt the end of the selection procedure, nine longitudinal studies were selected for the meta-analysis: six studies enrolled cognitively well-functioning participants and three studies involved MCI patients. A total of 18,313 participants aged older than 40 years with mean MetS prevalence of 22.7% were followed on average for 9.41years. A fixed model was used to estimate pooled hazard ratios and 95% confidence intervals.ConclusionNo statistically significant pooled association emerged between MetS and incident dementia and AD. MetS increased the incidence of pure VaD. MetS increased the risk of progression from MCI to dementia. Follow-up length might be a key factor in investigating these associations further. Because MetS is constituted by a set of potentially modifiable factors, further studies with longer follow-up and repeated assessment of both MetS and cognitive status are desirable to draw definite conclusions.     

ApoE epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy

PURPOSE: To clarify the possible role of other factors including the ApoE epsilon4 allele for memory decline in temporal lobe epilepsy (TLE). METHODS: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD +/- 17.9; range, 14 to 87 years) with mild nonlesional TLE, who rarely or never had seizures at long-term follow-up. The mean age at seizure onset was 33.0 years (SD, +/-21.7), and the mean duration of epilepsy was 17.1 years (SD, +/-15.7). RESULTS: Thirty-four (25%) of 138 patients had test scores indicating verbal learning deficit (VLD). The presence of an ApoE epsilon4 allele was associated with an increased risk of VLD (OR, 4.18; 95% CI, 1.66-10.55). The effect of the ApoE genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with VLD (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration > or =25.5 years (OR, 7.06; 95% CI, 1.67-29.85), especially if they carried the epsilon4 allele (OR, 32.29; 95% CI, 5.23-195.72). CONCLUSIONS: These results provide evidence for an alteration in cognitive performance as a function of the presence of the ApoE epsilon4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE.     

Association between apolipoprotein E epsilon4 allele and apathy in probable Alzheimer's disease

OBJECTIVE: There have been inconclusive results to date on the association between the Apolipoprotein E (ApoE) genotype and neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD). We investigated whether ApoE epsilon4 allele is associated with NPS in probable AD. METHOD: Data for 197 subjects with probable AD were analysed. The Neuropsychiatric Inventory was used to evaluate the frequency and severity of NPS. Multiple logistic regression models were used to test the association between ApoE genotype and NPS in AD. RESULTS: The ApoE epsilon3/3 genotype was present in 52.3%, epsilon3/4 in 44.1%, and epsilon4/4 in 3.6% of patients. ApoE epsilon4 carriers showed a higher frequency of apathy than non-carriers. After multiple adjustments, the ApoE epsilon4 allele was significantly associated with apathy. CONCLUSION: Our results suggest a relationship between the ApoE epsilon4 allele and apathy in patients with AD.     

Apolipoprotein E genotypes in hospitalized elderly patients with vascular dementia

BACKGROUND: Polymorphism in the apolipoprotein E (APOE) gene is the major genetic risk factor associated with late-onset Alzheimer's Disease (AD). However, it is still unclear if a relationship exists between the APOE epsilon4 allele and vascular dementia (VaD) in elderly subjects. OBJECTIVES: To evaluate the prevalence of APOE alleles in elderly patients with VaD compared to AD patients and to control subjects with no cognitive impairment (NoCI). PATIENTS AND METHODS: We evaluated 396 consecutive patients aged > or =65 years with definite or suspected cognitive impairment with a clinical (Mini-Mental State Examination, Clinical Dementia Rating, Geriatric Depression Scale), functional (Activities of Daily Living, Instrumental Activities of Daily Living), comorbidity (Cumulative Illness Rating Scale) and instrumental (CT scan, NMR) assessment. Diagnosis of dementia was made according to NINCDS-ADRDA and NINDS-AIREN Work Group and the DSM-IV. APOE genotypes were analyzed by a recently described method resulting in positive/negative chain reaction products for each APOE genotype. Statistical analysis was carried out using the Pearson chi(2), the Kruskal-Wallis test and the ANOVA post hoc comparisons. RESULTS: A total of 287 elderly patients (males = 138, females = 149, mean age = 77.8 +/- 6.9 years, range = 65-98) with diagnoses of VaD (n = 97), AD (n = 82) or NoCI (n = 108) were included in the study. A significantly higher APOE epsilon4 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects, while no differences were found between VaD patients and subjects with NoCI (AD = 24.3%, VaD = 10.3, NoCI = 8.7, p < 0.05). Furthermore, a significantly lower APOE epsilon3 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects but not between VaD and NoCI patients (AD = 71.3%, VaD = 80.9, NoCI = 83.4, p < 0.05). No significant differences were observed in the APOE epsilon2 allele (VaD = 8.8%, AD = 4.4, NoCI = 7.9, p = n.s.) among the 3 groups. CONCLUSIONS: In this population, the frequency of the APOE epsilon4 allele is lower in VaD than in AD.     

Apolipoprotein E and intronic polymorphism of presenilin 1 and alpha-1-antichymotrypsin in Alzheimer's disease and vascular dementia

Apolipoprotein E (ApoE) genotypes, presenilin 1 (PS-1) and alpha(1)-antichymotrypsin (ACT) polymorphism and the association of the genotypes were examined in patients with Alzheimer's disease (AD, n = 121) or vascular dementia (VD, n = 68) in comparison with elderly controls (n = 125). The frequency of the ApoE epsilon 4 allele was significantly increased both in late-onset AD (0.35) and in VD (0.17); the frequency of ApoE epsilon 2 was significantly reduced in AD, but it was similar in VD and controls. The presence of the allele 1 of PS-1 intronic polymorphism was not associated with AD or VD and was not influenced by the ApoE genotypes. Also, the frequency of allele A of the intronic polymorphism of ACT was similar in AD, VD and controls and it was not altered by ApoE or PS-1 genotypes. The results confirm the association between ApoE epsilon 4 and AD and indicate an increase in ApoE epsilon 4 in Vd, too. A potential protective role of ApoE epsilon 2 is also suggested for late-onset AD but not for VD. No association was shown between ACT allele A and PS-1 allele 1 in AD or VD.     

Prospective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects

OBJECTIVE: The authors conducted a prospective study of neurodegenerative and vascular dementia in Belgium. Strict diagnostic inclusion criteria were used to include well defined patients and controls. The results of apolipoprotein E (APOE) genotype effect on risk and clinical characteristics are presented. METHODS: APOE genotyping was performed in patients with probable Alzheimer's disease (AD) (n=504), frontotemporal dementia (FTD) (n=47), vascular dementia (VaD) (n=152), mixed dementia (n=132), mild cognitive impairment (MCI) (n=44), Parkinson's disease (PD) (n=30), dementia with Lewy bodies (DLB) (n=17), and multisystem atrophy (MSA)/progressive supranuclear palsy (PSP) (n=12). RESULTS: The APOE allele frequencies of this Belgian control population (epsilon 2: 6.9%; epsilon 3: 76.2%; epsilon 4: 16.9%) did not differ from those reported for other white populations. AD, MCI, and mixed dementia patients had higher APOE epsilon 4 (32.9%, 38.6%, and 28.4% respectively) and lower APOE epsilon 3 (62.2%, 53.4%, and 66.3%) frequencies compared with controls, whereas only AD and mixed dementia patients had lower APOE epsilon 2 frequencies (4.9% and 5.3%). Apart from a borderline significant different distribution of APOE allele frequencies in VaD patients compared with controls, no other differences were detected. The influence of APOE epsilon 4 on clinical features of dementia was limited to lower age at onset in AD patients and a less pronounced negative correlation between age at onset and number of epsilon 4 alleles in MCI and mixed dementia patients. CONCLUSIONS: This study confirmed the risk association between APOE epsilon 4 and AD. The observation that APOE epsilon 4 is associated with mixed dementia reflected the role of AD in the aetiopathogenesis of this condition. Although MCI is an aetiologically heterogeneous syndrome, the increased APOE epsilon 4 frequencies indicated that a large proportion of the MCI patients included in the study might be predisposed to develop AD.     

Association between apolipoprotein CI HpaI polymorphism and sporadic Alzheimer's disease in Chinese

OBJECTIVE: To investigate into the relationship of apolipoprotein CI (ApoCI) polymorphism with sporadic Alzheimer's disease (AD) in Chinese. SUBJECTS AND METHODS: A total of 257 AD patients and 242 age-matched elderly individuals were genotyped for the ApoCI HpaI and apolipoprotein E (ApoE) HhaI polymorphisms. RESULTS: The ApoCI A allele was associated with AD of moderate to severe dementia when patients were divided into two subgroups according to Clinical Dementia Rating scale, and the AA genotype was strongly associated with moderate to severe AD in ApoE epsilon4 allele carriers [odds ratio (OR) = 8.19, 95% confidential interval: 1.28-52.30, after adjusting for age and gender by logistic regression analysis], although in total no significant differences of allele or genotype frequency between patients and controls were found. CONCLUSION: The present study partially confirmed the previous findings, suggesting that the ApoCI A allele might contribute to the susceptibility to moderate to severe sporadic AD in Chinese.     

Neuropsychiatric symptoms and functional status in Alzheimer's disease and vascular dementia patients

Neuropsychiatric symptoms (NPS) are increasingly recognized as common in patients with dementia, both of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). In this study, 302 demented patients, 166 with AD and 136 with VaD, were evaluated for NPS according to the Neuropsychiatric Inventory (NPI) score at the Alzheimer's Evaluation Unit of Casa Sollievo della Sofferenza Hospital-IRCCS, San Giovanni Rotondo, Italy. A comprehensive geriatric assessment was also performed in all demented patients. The means of NPI scores did not differ in two groups. The overall prevalence of NPS was similar in both groups of patients (69.7% vs. 69.4%). Patients with AD had higher frequency in agitation/aggression and irritability/lability than VaD patients. Logistic analysis demonstrated a significant association between severity of the cognitive impairment and depression and eating disorders in both AD and VaD patients. The association with agitation/aggression, irritability/lability, and aberrant motor activity was found in AD only, and with apathy in VaD patients only. In both AD and VaD patients, there was a significant association between the impairment in activities of daily living (ADL) and the majority of NPI domains. A significant association was also found between the impairment of the instrumental activities of daily living (IADL) and agitation/aggression, anxiety, aberrant motor activity in AD and depression, apathy, irritability/lability, sleep disturbance and eating disorders in both AD and VaD patients. In particular, a causal mediation analysis was performed to better understand whether the relationship of NPS to functional impairment was direct or mediated by severity of cognitive dysfunction, i.e., Clinical dementia rating scale (CDR) score. Only agitation/aggression was mediated by the CDR score in affecting ADL status in VaD patients (OR: 1.12, 95% CI: 1.01-1.27). The NPI-Distress scores showed a significantly higher levels of distress in caregivers of AD than VaD. There were significant differences between AD and VaD patients with NPS, and these symptoms varied according to dementia subtype and severity and induced marked disability in ADL and IADL, increasing, prevalently, the distress of the caregivers of AD patients.     

Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia

Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions.Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.