Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease

OBJECTIVE: To examine volumetric MRI correlates of longitudinal cognitive decline in normal aging, AD, and subcortical cerebrovascular brain injury (SCVBI). BACKGROUND: Previous cross-sectional studies examining the relationship between cognitive impairment and dementia have shown that hippocampal and cortical gray matter atrophy are the most important predictors of cognitive impairment, even in cases with SCVBI. The authors hypothesized that hippocampal and cortical gray matter volume also would best predict rate of cognitive decline in cases with and without SCVBI. METHODS: Subjects were recruited for a multicenter study of contributions to dementia of AD and SCVBI. The sample (n = 120) included cognitively normal, cognitively impaired, and demented cases with and without lacunes identified by MRI. Cases with cortical strokes were excluded. Average length of follow-up was 3.0 years. Measures of hippocampal volume, volume of cortical gray matter, presence of subcortical lacunes, and volume of white matter hyperintensity were derived from MRI. Random effects modeling of longitudinal data was used to assess effects of baseline MRI variables on longitudinal change in a measure of global cognitive ability. RESULTS: Cortical gray matter atrophy predicted cognitive decline regardless of whether lacunes were present. Hippocampal atrophy predicted decline only in those without lacunes. Neither lacunes nor white matter hyperintensity independently predicted decline. CONCLUSIONS: Results suggest that cortical atrophy is an index of disease severity in both AD and subcortical cerebrovascular brain injury and consequently predicts faster progression. Hippocampal volume may index disease severity and predict progression in AD. The absence of this effect in cases with lacunes suggests that this group is etiologically heterogeneous and is not composed simply of cases of AD with incidental stroke.     

Hippocampal size and dementia in stroke patients: the Sydney stroke study

BACKGROUND: Hippocampal atrophy is an early feature of Alzheimer's disease (AD) but it has also been reported in vascular dementia (VaD). It is uncertain whether hippocampal size can help differentiate the two disorders. METHODS: We assessed 90 stroke/TIA patients 3-6 months after the event, and 75 control subjects, with neuropsychological tests, medical and psychiatric examination and brain MRI scans. A diagnosis of VaD, vascular mild cognitive impairment (VaMCI) or no cognitive impairment (NCI) was reached by consensus on agreed criteria. T1-weighted MRI was used to obtain total intracranial volume (TICV), gray and white matter volume, CSF volume, hippocampus and amygdala volumes, and T2-weighted scans for white matter hyperintensity (WMH) ratings. RESULTS: Stroke/TIA patients had more white matter hyperintensities (WMHs), larger ventricle-to-brain ratios and smaller amygdalae than controls, but hippocampus size and gray and white matter volumes were not different. WMHs and amygdala but not hippocampal volume distinguished stroke/TIA patients with VaD and VaMCI and without NCI and amygdala volumes. Right hippocampus volume significantly correlated with new visual learning. CONCLUSIONS: Stroke/TIA patients and patients with post-stroke VaMCI or mild VaD do not have hippocampal atrophy. The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment, and this may be accounted for by white matter lesions. The hippocampus volume relates to episodic memory, especially right hippocampus and new visual learning. A longitudinal study of these subjects will determine whether hippocampal atrophy is a late development in VaD.     

Brain function and cognition in a community sample of elderly Latinos

BACKGROUND: Previous studies using PET to measure cerebral glucose metabolism in AD have found metabolic reductions in the temporoparietal and posterior cingulate cortices in individuals with dementia and those at risk of developing it. This study was designed to extend this finding to individuals selected from a population-based cohort of Mexican Americans with a wide spectrum of cognitive ability. METHODS: A group of 93 individuals was selected from the Sacramento Area Latino Study on Aging, and subjects were categorized into four groups of increasing levels of cognitive impairment: normal, memory impaired, cognitively impaired but not demented (CIND), and demented. PET was performed with the tracer [(18)F]-fluorodeoxyglucose, and data were analyzed with both statistical parametric mapping and an atrophy-corrected volume of interest approach. RESULTS: Individuals with dementia had metabolic reductions that were most robust in the posterior cingulate cortex, whereas CIND subjects had less statistically robust reductions in the posterior cingulate cortex. Cingulate hypometabolism increased the risk of dementia and was a significant risk factor for dementia in logistic regression models that also incorporated MR measures of hippocampal volume and white matter hyperintensities. CONCLUSION: Posterior cingulate cortical hypometabolism is clearly detected in individuals with dementia who are selected from a population with lower education and a high prevalence of cerebrovascular risk factors, supporting the generalizability of this finding. These metabolic reductions occur prior to the onset of dementia but only in those persons with relatively advanced symptoms.     

Correlates of memory function in community-dwelling elderly: the importance of white matter hyperintensities.

We sought to identify magnetic resonance- (MR)-imaged structures associated with declarative memory in a community-dwelling sample of elderly Mexican-American individuals with a spectrum of cognitive decline. Measured structures were the hemispheric volumes of the hippocampus (HC), parahippocampal gyrus, and remaining temporal lobes, as well as severity of white matter signal hyperintensities (WMH). Participants were an imaged subsample from the Sacramento Area Latino Study of Aging (SALSA), N = 122. Individuals were categorized as normal, memory impaired (MI), cognitively impaired non-demented (CIND), or demented. We show that WMH was the strongest structural predictor for performance on a delayed free-recall task (episodic memory) in the entire sample. The association of WMH with delayed recall was most prominent in elderly normals and mildly cognitively impaired individuals with no dementia or impairment of daily function. However, the left HC was associated with verbal delayed recall only in people with dementia. The right HC volume predicted nonverbal semantic-memory performance. We conclude that WMH are an important pathological substrate that affects certain memory functions in normal individuals and those with mild memory loss and discuss how tasks associated with WMH may rely upon frontal lobe function.     

Hippocampal volume and white matter disease in the prediction of dementia in Parkinson's disease

BackgroundLongitudinal neuroimaging studies could provide insights into pathophysiology of cognitive impairment in PD. We examined the role of hippocampal atrophy and cerebral white matter disease as risk factors for mild cognitive impairment and dementia in PD.MethodsProspective longitudinal study of patients with mild PD in a tertiary neurology center. All subjects underwent baseline MRI brain and had baseline and 6 monthly cognitive evaluations. Cognitive impairment was diagnosed based on the Movement Disorder Society Criteria. The predictive role of hippocampal volume and white matter hyperintensity at baseline on progression of cognitive impairment was studied.Results97 subjects with mean age 65.3 years, mean education of 10.3 years and mean Hoehn & Yahr of 1.9 were studied. Over 2 years, 16 subjects developed mild cognitive impairment and 8 subjects with mild cognitive impairment progressed to dementia. After adjusting for age and vascular risk factors, hippocampal volume was a significant predictor for mild cognitive impairment (OR 7.05, CI 1.5–34.1; p = 0.015) and dementia (OR 7.03, CI 2.39–25.2; p = 0.001). With Cox regression, hippocampal volume was a significant predictor for “time to cognitive impairment” (HR 7.67; CI 3.47–16.95, p < 0.001). Difference between survival curves based on volume of white matter hyperintensity in predicting “time to mild cognitive impairment” was significant (p = 0.0295).ConclusionsHippocampal volume is a major factor predicting the development of mild cognitive impairment and dementia in PD. White matter hyperintensity also contributes to the longitudinal cognitive status in PD.     

脑白质高信号患者认知障碍与海马亚区萎缩的相关性研究

目的 探讨脑白质高信号（white matter hyperintensity,WMH）患者海马亚区的萎缩情况及其与认知 功能障碍的相关性。 方法 前瞻性连续纳入南京鼓楼医院2017年1月-2019年12月收治的WMH患者,将同期门诊招募的健 康志愿者作为正常对照。所有受试者接受头颅MRI检查及认知功能检查,根据MMSE和MoCA评分将 WMH患者分成无认知障碍组及认知障碍组。利用FreeSurfer 6.0软件进行海马亚区的分割,计算双侧 海马尾、下托、CA1、海马裂、前下托、旁下托、分子层、齿状回、CA3、CA4、海马伞及海马杏仁核过渡区 的亚区体积,同时计算脑室周围、深部及总WMH体积。比较对照组、WMH认知障碍组和WMH无认知障 碍组之间总海马体积及各海马亚区体积的差异。在WMH患者中分析萎缩的海马亚区与WMH体积的相 关性,在WMH伴认知障碍组中分析海马亚区体积与各个认知域功能障碍的相关性。 结果 共纳入对照组85例,WMH无认知障碍组79例及WMH认知障碍患者89例。与对照组相比,WMH 无认知障碍组患者右侧齿状回（P =0.006）、CA3（P =0.006）和CA4（P =0.020）海马亚区出现萎缩,而 WMH认知功能障碍组则表现为右侧下托（P =0.022）、分子层（P =0.003）、齿状回（P =0.001）、CA3 （P =0.039）、CA4（P =0.003）及双侧海马伞亚区（左侧P =0.004,右侧P =0.020）体积降低。在WMH患者 中,右侧齿状回体积与总WMH体积（r =-0.134,P =0.035）及室周WMH体积（r =-0.128,P =0.045）呈负 相关,右侧CA3体积同样与总WMH（r =-0.149,P =0.020）及室周WMH（r =-0.139,P =0.029）呈负相关。 此外,在WMH伴认知障碍组中,总体认知功能（r =0.315,P =0.004）及语言功能（r =0.318,P =0.006） 均与右侧下托体积呈正相关;执行功能则与右侧分子层（r =0.300,P =0.006）、齿状回（r =0.333, P =0.002）和CA4（r =0.323,P =0.003）的体积呈正相关。 结论 WMH患者表现为非对称性海马萎缩模式,以右侧海马萎缩为主。右侧分子层、齿状回及CA4区 亚区影响WMH患者执行功能而右侧下托的萎缩则影响总体认知和语言功能。     

MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer's disease.

BACKGROUND: Causes of cognitive impairment in subcortical ischemic vascular disease (SIVD) are less well understood than in AD, but have been thought to result from direct effects of subcortical lacunes and white matter lesions, perhaps related to disruption of important cortical-subcortical pathways. OBJECTIVE: To examine the relation between cognitive abilities and quantitative MRI measures of subcortical cerebrovascular disease and cortical and hippocampal atrophy. METHODS: Subjects were 157 participants in a multicenter study of SIVD and AD who included cognitively normal, cognitively impaired, and demented individuals with and without subcortical lacunar infarcts. Dependent variables were neuropsychological tests of global cognitive function, memory, language, and executive function. Independent variables were quantitative MRI measures of volume of lacunar infarcts in specific subcortical structures, volume of white matter lesion (WML), volume of cortical gray matter (cGM), and total hippocampal volume (HV). Multiple regression analyses were used to identify MRI predictors of cognition. RESULTS: Subcortical lacunes were not related to cognitive measures independent of effects of other MRI variables. WML was independently related to selected, timed measures. HV and cGM were strong and independent predictors of cognitive variables, with effects that did not differ in subjects with and without subcortical lacunes. CONCLUSIONS: Results suggest that cognitive impairment associated with subcortical ischemic vascular disease is primarily a result of associated hippocampal and cortical changes.     

Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease

BACKGROUND: The cause of dementia in subcortical ischemic vascular disease (SIVD) is controversial. OBJECTIVES: To determine whether cognitive impairment in SIVD 1) correlates with measures of ischemic brain injury or brain atrophy, and/or 2) is due to concomitant AD. METHODS: Volumetric MRI of the brain was performed in 1) elderly subjects with lacunes (L) and a spectrum of cognitive impairment-normal cognition (NC+L, n = 32), mild cognitive impairment (CI+L, n = 26), and dementia (D+L, n = 29); 2) a comparison group with probable AD (n = 28); and 3) a control group with normal cognition and no lacunes (NC). The authors examined the relationship between the severity of cognitive impairment and 1) volume, number, and location of lacunes; 2) volume of white matter signal hyperintensities (WMSH); and 3) measures of brain atrophy (i. e., hippocampal, cortical gray matter, and CSF volumes). RESULTS: Among the three lacune groups, severity of cognitive impairment correlated with atrophy of the hippocampus and cortical gray matter, but not with any lacune measure. Although hippocampal atrophy was the best predictor of severity of cognitive impairment, there was evidence for a second, partially independent, atrophic process associated with ventricular dilation, cortical gray matter atrophy, and increase in WMSH. Eight autopsied SIVD cases showed variable severity of ischemic and neurofibrillary degeneration in the hippocampus, but no significant AD pathology in neocortex. The probable AD group gave evidence of only one atrophic process, reflected in the severity of hippocampal atrophy. Comparison of regional neocortical gray matter volumes showed sparing of the primary motor and visual cortices in the probable AD group, but relatively uniform atrophy in the D+L group. CONCLUSIONS: Dementia in SIVD, as in AD, correlates best with hippocampal and cortical atrophy, rather than any measure of lacunes. In SIVD, unlike AD, there is evidence for partial independence between these two atrophic processes. Hippocampal atrophy may result from a mixture of ischemic and degenerative pathologies. The cause of diffuse cortical atrophy is not known, but may be partially indexed by the severity of WMSH.     

A Canadian cohort study of cognitive impairment and related dementias (ACCORD): study methods and baseline results

The overall objective of the Canadian Collaborative Cohort of Related Dementias (ACCORD) study is to describe the diagnostic distribution, natural history and treatment outcomes of individuals referred from the community to dementia clinics in Canada. Between 1997 and 1999, an inception cohort of 1,136 subjects entered into this longitudinal study. At the baseline assessment, 10.9% of the subjects were classified as "not cognitively impaired" (NCI), 30.1% as "cognitively impaired not demented" (CIND), and 59% as demented. A subclassification of CIND included amnestic 25.1%, vascular cognitive impairment 18.1%, psychiatric 17.2%, neurologic 7.3%, medical/toxic metabolic 3.5%, mixed 7.6% and not specified 19.0%. The percentage of the cohort referred with dementia increased progressively each decade, while the proportions of CIND and NCI decreased. Within the dementia group, Alzheimer's disease accounted for 47.2% of the subjects, mixed dementias 33.7%, vascular dementia 8.7%, frontotemporal degenerations 5.4%, dementia with Lewy bodies 2.5%, and unclassifiable 1.8%. The ACCORD cohort will allow a detailed study of the longitudinal course of CIND, and the longer-term outcomes of both treated and untreated dementia subjects.     

Intracranial volume in mild cognitive impairment,Alzheimer's disease and vascular dementia: evidence for brain reserve?

OBJECTIVE: The possibility of brain volume reserve effects was examined in a sample of geriatric outpatients with mild cognitive impairment (MCI), Alzheimer's disease (AD) and vascular dementia (VaD). The total intracranial volume (ICV) served as an estimate of the maximum attained brain volume in life. METHODS: Subjects (n = 181, mean age 60.7) were consecutive referrals to a geriatric outpatients clinic (n = 96) and a group of age-matched healthy control subjects (n = 85). ICV and brain volume were attained from T1-weighted magnetic resonance images using a stereological method. Hippocampal atrophy was assessed with a visual rating scale. RESULTS: ICV was significantly smaller in patients with AD and VaD than in control subjects, but effect size was small. After adjusting for age and gender, having ICV in the smallest quartile significantly increased the risk of cognitive impairment (either MCI or dementia). In patients with dementia, but not in MCI, severity of cognitive impairment and ICV were moderately correlated. The effect of ICV on cognition was not mediated by hippocampal atrophy. CONCLUSIONS: These findings are compatible with volume reserve effects that modify the clinical expression of symptoms in both AD and VaD. They may have implications for the design of neuroimaging studies that use ICV for normalization procedures.     

Progression of white matter hyperintensities in Alzheimer disease, dementia with lewy bodies, and Parkinson disease dementia: a comparison with normal aging.

OBJECTIVE: The objective of this study was to investigate cross-sectional and longitudinal white matter hyperintensity (WMH) changes in older subjects with clinically diagnosed dementia. METHODS: Fluid-attenuated inversion recovery images were acquired one year apart in subjects with dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), Alzheimer disease (AD), and also healthy elderly comparison subjects. WMH volume was quantified using an automated technique. RESULTS: Baseline WMH (as a percent of brain volume) was significantly greater compared with healthy subjects (N=33, geometric mean WMH: 0.4%) in subjects with AD (N=23 [1.3%], analysis of variance post hoc p <0.001) but not PDD (N=13 [0.6%]) or DLB (N=14 [0.4%]). Increase in WMH volume (as a percent of brain volume) was not significantly different (Kruskal-Wallis p=0.4) between groups (AD median change: 0.08%; DLB: 0.025%; PDD: 0.07%, healthy: 0.02%). Severity of baseline WMH, rather than diagnosis or severity of dementia, was a significant predictor of lesion progression. Rate of change of WMH had no association with change in global cognitive performance. CONCLUSIONS: Significant WMH progression occurs in degenerative dementias with rates influenced by severity of lesions at baseline rather than dementia type or cognitive decline.     

White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer's disease

BACKGROUND AND OBJECTIVE: Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method of brain MRI segmentation for quantifying both tissue and WMH volumes in Alzheimer's disease (AD) and examined the association between WMH and structural and cognitive variables. METHODS: A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for probable AD was studied. Nineteen healthy volunteers of comparable age served as the control group. Patients had a complete neurological and neuropsychological evaluation, and a three dimensional MRI was obtained. Images were segmented into grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented images, and lobar assignments were based on Talairach coordinates. RESULTS: Mild and moderate to severe AD patients had significantly more WMH than controls (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely correlated with grey matter cortical volume (R(2) = 0.23, p<0.001), and were significantly associated with vascular risk factors and with a worse performance on memory tasks. CONCLUSION: Objective measurements of tissue volumes in AD demonstrated that WMH are significantly related to cortical atrophy and neuropsychological impairment.     

Hippocampal size may contribute to prospective diagnosis of age-related dementia

Background: The hippocampus is a center of cognitive function and therefore hippocampal atrophy is the major factor in cognitive decline. Analysis of hippocampal size may make it possible to predict progression in cognitive impairment. To address this point, the present study investigated the relationship between hippocampal atrophy and dementia using magnetic resonance (MR) images and the Hasegawa Dementia Scale‐Revised (HDS‐R). Methods: The present study was performed on 274 subjects (14–97 years old; average, 66 years; 106 male and 168 female) who had no focal neurological deficit. Hippocampal area and whole brain area were measured in three series of coronal MR images taken from a 5‐mm slice rostrally along dorsal edge of the pons, and hippocampal size normalized by calculating summated hippocampal areas as percentages of summated whole brain areas. Dementia was screened for using HDS‐R. Results: Hippocampal size decreased and HDS‐R reduced with age. Hippocampal atrophy was highly correlated with cognitive deterioration; a critical normalized hippocampal size for HDS‐R of less than 20, which corresponds with mild cognitive impairment and dementia, was found in 65% of over 60‐years old subjects and 98% of subjects with HDS‐R of less than 20 were over 60 years old. Conclusion: There is a high probability that over 60‐year‐old people with a normalized hippocampal size of less than 1.0 would develop dementia in the future, even though their HDS‐R might presently be over 20. Measurement of hippocampal size with coronal MR imaging may therefore contribute to prospective diagnoses of age‐related dementia.     

Neurological abnormalities in cognitively impaired but not demented elderly

OBJECTIVE: We determined the prevalence and clinical characteristics of elderly people with cognitively impaired but not demented (CIND) in the community. MATERIAL AND METHODS: We examined 945 elderly residents (aged 65 years or more) in a cross-sectional study of a standardized clinical examination in 27 randomly selected communities in the town of Mifune, a standard farming town in Japan. RESULTS: The prevalence of CIND and dementia were 10.8% and 4.8%, respectively, with both rates increasing with age. The frequency of most neurological signs in CIND elderly was greater than that found in subjects with no cognitive impairment (NCI) and less than that in subjects with dementia. The mean ADL disability score in CIND subjects also lay between the mean values for those with NCI and those with dementia. There were no differences in lifestyles between the CIND group and the other groups. CONCLUSION: The results suggest that a majority of CIND elderly suffer from brain dysfunction due to chronic neurological disorders or aging itself.     

Prevalence and cognitive performances of vascular cognitive impairment no dementia in Japan: the Osaki–Tajiri Project

Abstract  Prevalence, magnetic resonance imaging (MRI) findings, cognitive function and depression are four major aspects of vascular cognitive impairment no dementia (vascular CIND). We performed a community-based study to examine these using 497 community-residents aged 65 years or older. Vascular CIND was defined as a clinical dementia rating (CDR) 0.5 with cerebrovascular disease. Several neuropsychological tests were performed, including MMSE, Geriatric Depression Scale (GDS), and Trail Making Test (TMT). Cerebrovascular disease and white matter lesions were visually assessed using MRI. Prevalence of vascular CIND, localization of cerebrovascular disease, and the relationships amongst MRI findings, white matter lesions, cognitive impairment and depression were analyzed. The prevalence of vascular CIND was 8.5% amongst the total population, corresponding to the rate being 37.2% amongst the CDR 0.5 participants. Compared with the CDR 0, the CDR 0.5 group had more subjects with strategic cerebrovascular disease in the thalamus, etc. No effects of cerebrovascular disease on MMSE and GDS scores were found, but the CDR 0.5/strategic cerebrovascular disease group showed impaired TMT-B scores. In the CDR 0 group, only anterior periventricular hyperintensity was associated with TMT-A score independent of cerebrovascular disease. A vascular CIND population was identified, and executive dysfunction in this population is probably based on an impaired fronto-subcortical circuit.     

Cognitive impairment in community-dwelling older Nigerians: clinical correlates and stability of diagnosis

To determine correlates and outcome of cognitive impairment without dementia in community-dwelling elderly Nigerians. A total of 2487 community residents aged 65 years and over were screened using the Community Screening Interview for Dementia. A subset of 423 individuals received diagnostic clinical evaluation. Participants were diagnosed normal, demented, or cognitive impairment no dementia (CIND). Follow-up clinical diagnostic evaluation was conducted on CIND subjects approximately 2 years later. One hundred and fifty-two persons were diagnosed CIND. Eighty-seven CIND subjects were seen at follow-up assessment, 14 (16.1%) had converted to dementia, 22 (25.3%) reverted to normal, and 51 (58.6%) remained CIND. No baseline factors predicted later development of dementia amongst the CIND subjects. CIND subjects who reverted to normal tended to be male and to have higher baseline cognitive scores. Apolipoprotein status was not related to diagnosis at follow-up. CIND is common in community-dwelling Nigerians. Although the outcome is variable, it does represent a high-risk group for subsequent dementia.     

Quantitative MRI findings and cognitive impairment among community dwelling elderly subjects

OBJECTIVES: To study the factors which influence cognitive impairment among elderly subjects living in a local community, based on both MRI and clinical findings, to further elucidate the causes of dementia, and also to help develop strategies for its prevention. METHODS: Cranial MRI and other medical examinations were performed on non-demented elderly subjects who resided in one rural community. A total of 254 subjects aged from 60 to 91 years of age, with a mean age of 73.9 (SD 6.8) were examined. The mini mental state examination (MMSE) was used to identify cognitive impairment. White matter lesions and cerebral atrophy on MR images were measured quantitatively. A multivariate analysis was also performed with the existence of cognitive impairment as the dependent variable, and the MRI findings and clinical observations were used as the independent variables. RESULTS: Cognitive impairment was present in 46 subjects (18.1%). They were older, had a lower educational level, and more frequent hypertension compared with those without cognitive impairment. The packed cell volume was lower in the impaired group. In addition, their MRI findings showed significantly larger quantities of white matter lesions and cerebral atrophy, as well as more infarcts. A logistic regression analysis demonstrated a significant relation among such factors as white matter lesions (odds ratio (OR) 1.575, 95% confidence interval (95% CI) 1.123-2.208), cerebral atrophy (OR 0.761, 95%CI 0.587-0.987), and lower education (OR 0.682, 95%CI 0.544-0.855) for subjects with a cognitive impairment. CONCLUSIONS: White matter lesions and cerebral atrophy are factors which induce a cognitive impairment in community dwelling elderly subjects without dementia. It is important to carefully watch for any abnormalities in these factors, and to perform cohort studies to check for the above risk factors, to both prevent and make an early diagnosis of dementia.     

Outcomes of cognitively impaired not demented at 2 years in the Canadian Cohort Study of Cognitive Impairment and Related Dementias

BACKGROUND: People who are cognitively impaired not demented (CIND) can be at an increased risk for developing dementia, but little is known about the natural history of CIND in clinical settings. METHOD: We examined the 2-year outcome of CIND subjects in the Canadian Cohort Study of Cognitive Impairment and Related Dementias.CIND was diagnosed when at least one positive item was endorsed on the DSM-III-R dementia criteria, but not all criteria were met. CIND was further subclassified as: pre-Alzheimer's disease (pre-AD), vascular cognitive impairment (VCI-ND), non-AD degenerative, psychiatric, other neurologic, other medical conditions, mixed disorders and no etiology identified (not otherwise specified [NOS]). RESULT: Of 146 CIND patients with 2-year follow-up data available, 49 (34%) progressed to dementia, while 20 (14%) recovered to not cognitively impaired (NCI). Progressors were significantly older than stable CIND and reverters (p < 0.0001; mean age = 71.1, 64.3, and 59.1, respectively), and there were significantly (p = 0.001) more ApoE epsilon4 carriers among progressors (67%) than stable CIND (29%) and reverters (12%). Pre-AD CIND and VCI-ND had the highest rate of conversion to dementia (41.0 and 40.0%, respectively), while psychiatric CIND and CIND NOS had highest rate of recovery to NCI (20.0 and 30.0%, respectively). All conversions in pre-AD CIND were to 'probable AD'. CONCLUSION: CIND consists of a heterogeneous group of disorders that can be classified syndromically. Many subclassess - not just those with pre-AD CIND - are at high risk of progression to dementia, usually to Alzheimer's disease.     

Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia

OBJECTIVE: To determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMH), whole-brain atrophy, and cardiovascular risk factors predict the development of cognitive decline and dementia. DESIGN: Subjects were recruited into this prospective cohort study and followed for incident cognitive decline for mean (SD) 6.0 (4.1) years. Magnetic resonance imaging dual-echo sequences, obtained at baseline, were used to determine the volume of WMH and the brain parenchymal fraction (BPF), the proportion of the intracranial cavity occupied by brain. White matter hyperintensity volume was analyzed as the percentage of intracranial volume (WMHr); "high WMH" was defined as a WMHr more than 1 SD above the mean. SETTING: General community. PATIENTS: Volunteer sample consisting of 67 subjects with normal cognition and 156 subjects with mild cognitive impairment (MCI). MAIN OUTCOME MEASURES: Time to diagnosis of MCI (among those with normal cognition at baseline) or time to diagnosis of dementia, either all-cause or probable Alzheimer disease (AD) (among those with MCI at baseline). Cox proportional hazards models were used for multivariable analysis. RESULTS: High WMH was a predictor of progression from normal to MCI (adjusted hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.33-8.17; P= .01) but not conversion from MCI to all-cause dementia. Conversely, BPF did not predict progression from normal to MCI but did predict conversion to dementia (adjusted HR, 1.10 for each 1% decrease in BPF; 95% CI, 1.02-1.19; P= .02). When conversion to AD dementia was considered as the outcome, BPF was likewise a predictor (adjusted HR, 1.16 for each 1% decrease in BPF; 95% CI, 1.08-1.24; P< .001), but high WMH was not. Past tobacco smoking was associated with both progression from normal to MCI (adjusted HR, 2.71; 95% CI, 1.12-6.55; P= .03) and conversion to all-cause dementia (adjusted HR, 2.08; 95% CI, 1.13-3.82; P= .02), but not AD dementia. CONCLUSIONS: These findings suggest that WMH are associated with the risk of progressing from normal to MCI. In persons whose cognitive abilities are already impaired, BPF predicts the conversion to dementia.     

Entorhinal cortex atrophy differentiates Parkinson's disease patients with and without dementia

Volumetric measures of mesial temporal lobe structures on MRI scans recently have been explored as potential biomarkers of dementia in patients with PD, with investigations primarily focused on hippocampal volume. Both in vivo MRI and postmortem tissue studies in Alzheimer's disease, however, demonstrate that the entorhinal cortex (ERC) is involved earlier in disease-related pathology than the hippocampus. The ERC, a region integral in declarative memory function, projects multimodal sensory information to the hippocampus through the perforant path. In PD, ERC atrophy, as measured on MRI, however, has received less attention, compared to hippocampal atrophy. We compared ERC and hippocampal atrophy in 12 subjects with PD dementia including memory impairment, 14 PD subjects with normal cognition, and 14 healthy controls with normal cognition using manual segmentation methods on MRI scans. Though hippocampal volumes were similar in the two PD cognitive groups, ERC volumes were substantially smaller in the demented PD subjects, compared to cognitively normal PD subjects (P < 0.05). In addition, normalized ERC and hippocampal volumes for right and left hemispheres were significantly lower in the demented PD group, compared to healthy controls. Our findings suggest that ERC atrophy differentiates demented and cognitively normal PD subjects, in contrast to hippocampal atrophy. Thus, ERC atrophy on MRI may be a potential biomarker for dementia in PD, particularly in the setting of memory impairment.