Visual rating of the hippocampus in non‐demented elders: Does it measure hippocampal atrophy or other indices of brain atrophy? The SMART‐MR study

Visual rating of hippocampal atrophy is often used to differentiate between normal aging and Alzheimer's disease. We investigated whether two visual rating scales of hippocampal atrophy were related to hippocampal volumes, and if visual rating was related to global, cortical and subcortical brain atrophy in persons without dementia. Within the SMART‐MR study, a prospective cohort study among patients with manifest arterial disease, medial temporal lobe atrophy was qualitatively rated in 95 participants without dementia (mean age 62 ± 10 years) using two visual rating scales: the medial temporal lobe (MTA) score was rated on coronal oriented images and the perihippocampal cerebrospinal fluid (HCSF) score was rated on axial oriented images. Hippocampal volume assessed by manual segmentation on a 3‐dimensional FFE T1‐weighted MR image. Automated segmentation was used to quantify volumes of brain tissue and cerebrospinal fluid. Total brain volume, gray matter volume, and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), gray matter fraction (GMF) and ventricular fraction (VF). Using ANOVA, crude hippocampal volumes were smaller with increasing MTA and HSCF scores as were hippocampal volumes normalized for intracranial volume (P < 0.05). However, hippocampal volumes normalized for total brain size were not smaller with increasing MTA or HSCF scores (P = 0.33 and P = 0.49). Also, with increasing visual rating scores, BPF was smaller and VF was larger (P < 0.001), and the GMF decreased with increasing HCSF score (P = 0.008). In this nondemented population, visual rating of the medial temporal lobe reflects hippocampal atrophy as well as global and subcortical atrophy. © 2009 Wiley‐Liss, Inc.     

Correlation between cortical theta activity and hippocampal volumes in health, mild cognitive impairment, and mild dementia.

Cognitive decline is known to be associated with both increased theta power over frontal regions and hippocampal atrophy. The aim of this study was to reveal the relation between these parameters in groups with mild dementia, mild cognitive impairment, and healthy control subjects. The authors examined a preliminary randomly selected sample of 39 right-handed subjects joining the Leipzig Longitudinal Study of the Aged, consisting of 17 normal elderly subjects, 12 patients with mild cognitive impairment, and 10 patients with mild dementia assessed by Clinical Dementia Rating. All subjects were between 75 and 85 years old (mean age, 78 years; standard deviation, 2.78 years) and underwent EEG and brain MRI. Mean spectral power densities were calculated, and hippocampal body volume was measured. Significant negative linear correlations between theta power over frontal regions and hippocampal volumes were found. The results support the assumption about a relationship between hippocampal atrophy and theta power, and may be helpful for a better understanding of the course of Alzheimer's disease.     

Brain structure and cognition in a community sample of elderly Latinos

BACKGROUND: Previous studies have found that hippocampal atrophy and white matter hyperintensities (WMH) on MRI are linked to cognitive impairment and dementia. The authors measured these variables in a population-based cohort of older Mexican Americans with a wide spectrum of cognitive ability, ranging from normal cognition to dementia. OBJECTIVE: To investigate whether these structural brain changes were seen in individuals prior to the development of dementia and how these changes were related to the presence of dementia. METHODS: A sample of 122 subjects 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 (MI), cognitively impaired but not demented (CIND), and demented. Hippocampal volume was quantified using a region of interest approach. WMH was rated on a semiquantitative scale as the percent of total volume of white matter. RESULTS: Hippocampal volume was significantly reduced in CIND and demented individuals, and WMH were significantly increased in demented subjects. MI subjects did not have any significant changes in hippocampal volume or WMH. The risk for developing dementia was significantly and comparably increased in subjects with either hippocampal atrophy or high WMH. However, the risk for dementia increased dramatically in subjects with both hippocampal atrophy and a high degree of WMH. CONCLUSION: Reductions in hippocampal volume may be present before dementia but not until cognitive impairment is relatively severe. Because there is a synergistic effect between high WMH and hippocampal atrophy, interactions between vascular and degenerative processes may be important determinants of dementia.     

Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study

Cerebral blood flow (CBF) velocity is decreased in patients with Alzheimer's disease. It is being debated whether this reflects diminished demand because of advanced neurodegeneration or that cerebral hypoperfusion contributes to dementia. We examined the relation of CBF velocity as measured with transcranial Doppler with dementia and markers of incipient dementia (ie, cognitive decline and hippocampal and amygdalar atrophy on magnetic resonance imaging) in 1,730 participants of the Rotterdam Study aged 55 years and older. Cognitive decline in the 6.5 years preceding CBF velocity measurement was assessed with repeated Mini-Mental State Examinations in nondemented subjects (n = 1,716). Hippocampal and amygdalar volumes were assessed in a subset of 170 nondemented subjects. Subjects with greater CBF velocity were less likely to have dementia. Furthermore, in nondemented subjects, greater CBF velocity was related to significantly less cognitive decline over the preceding period (odds ratio per standard deviation increase in mean CBF 0.74 [95% confidence interval, 0.58-0.98]) and larger hippocampal and amygdalar volumes. A low CBF is associated with dementia, but also with markers of incipient dementia. Although we cannot exclude that this is caused by preclinical neurodegeneration leading to hypoperfusion, it does suggest that cerebral hypoperfusion precedes and possibly contributes to onset of clinical dementia.     

遗忘型轻度认知损害患者海马三维磁共振影像特点

目的 运用基于海马表面的形态分析技术,探讨遗忘型轻度认知损害(aMCI)患者的海马三维MRI特点.方法 对15例aMCI患者和16名年龄及教育程度相匹配的对照,行头颅三维MRI扫描,数据采集后采用InsightSNAP 1.4.1软件在可视三维窗口下选取冠状位逐层勾勒海马轮廓,计算机自动计算海马体积后,进行两组间海马体积的统计学分析;将海马磁共振影像经过三维网格重建,其曲面网格参数化为400×200的点,将各点到中轴线的径向距离进行两组间比较,获得左右海马径向距离t值图;再经多重比较校正后,获得aMCI组与健康对照组问的三维海马形态差异图.结果 左侧海马标化平均体积aMCI组(3247.5±600.2)mm3、健康对照组(3467.9±451.3)mm3,两者差异无统计学意义(t=1.161,P=0.255).右侧海马标化平均体积aMCI组(3416.8±699.1)mm3、健康对照组(3469.1±358.9)mm3,两者差异亦无统计学意义(U=0.178,P=0.859).运用基于海马表面的形态分析技术得到两组间三维海马形态差异图,结果显示aMCI组与健康对照组相比双侧海马的外侧及下表面(组织学上的CA1区和下托)明显萎缩.结论 aMCI患者海马体积未见显著性减小,但通过基于海马表面的形态分析,发现aMCI患者的海马部分区域形态有一定程度的萎缩,以双侧海马外侧及下表面的区域性萎缩为主.这一结果可能反映了aMCI的早期影像学标志.     

Differing patterns of temporal atrophy in Alzheimer's disease and semantic dementia

OBJECTIVE: To characterize and quantify the patterns of temporal lobe atrophy in AD vs semantic dementia and to relate the findings to the cognitive profiles. Medial temporal lobe atrophy is well described in AD. In temporal variant frontotemporal dementia (semantic dementia), clinical studies suggest polar and inferolateral temporal atrophy with hippocampal sparing, but quantification is largely lacking. METHODS: A volumetric method for quantifying multiple temporal structures was applied to 26 patients with probable AD, 18 patients with semantic dementia, and 21 matched control subjects. RESULTS: The authors confirmed the expected bilateral hippocampal atrophy in AD relative to controls, with involvement of the amygdala bilaterally and the right parahippocampal gyrus. Contrary to expectations, patients with semantic dementia had asymmetric hippocampal atrophy, more extensive than AD on the left. As predicted, the semantic dementia group showed more severe involvement of the temporal pole bilaterally and the left amygdala, parahippocampal gyrus (including the entorhinal cortex), fusiform gyrus, and the inferior and middle temporal gyri. Performance on semantic association tasks correlated with the size of the left fusiform gyrus, whereas naming appeared to depend upon a wider left temporal network. Episodic memory measures, with the exception of recognition memory for faces, did not correlate with temporal measures. CONCLUSIONS: Hippocampal atrophy is not specific for AD but is also seen in semantic dementia. Distinguishing the patients with semantic dementia was the severe global but asymmetric (left > right) atrophy of the amygdala, temporal pole, and fusiform and inferolateral temporal gyri. These findings have implications for diagnosis and understanding of the cognitive deficits in AD and semantic dementia.     

ORIGINAL ARTICLE: Computerized visuo‐spatial memory test as a supplementary screening test for dementia

Background: To prepare for a super‐aging society, effective dementia screening tests are required. The most salient deficit appearing from the early stages of dementia/Alzheimer's disease (AD) is a deterioration in memory. The Hasegawa Dementia Scale‐revised (HDS‐R) and the Mini‐Mental State Examination (MMSE) are widely used in Japan to screen for dementia. Both place an emphasis on memory function, but neither examines visuo‐spatial memory (VSM) function, even though VSM deficits are a sensitive marker for the detection of conversion to dementia. Furthermore, brief tests of VSM that are appropriate for screening have not been standardized. Thus, in the present study, we devised a brief, computer‐aided short‐term VSM test. Methods: Sixty‐six aged people were evaluated. Using the Clinical Dementia Rating (CDR), it was found that 29 could be considered normal controls (NC; CDR 0), 10 had mild cognitive impairment (MCI; CDR 0.5), 15 had mild dementia (CDR 1), and 12 had moderate to severe dementia (CDR 2–3). The VSM test estimated how many locations each subject could memorize. Several numbered circles were shown on a monitor and subjects were required to memorize the location of these circles sequentially. After the numbers on the circles on the screen had disappeared, the subjects were required to indicate the circles in ascending order. A touch panel screen was used for this test to make it easier. The HDS‐R was applied to subjects with MCI and dementia. Results: The mean (±SD) VSM score in subjects with MCI (5.70 ± 0.96) was significantly lower than that in NC subjects (6.69 ± 0.82), but significantly higher than that in subjects classified as CDR 1 (4.67 ± 0.87). There was no significant difference in VSM scores between subjects classified as CDR 1 and CDR 2–3 (3.80 ± 0.80). There was a moderate significant correlation between VSM and HDS‐R scores. Conclusion: In the present study, the VSM test detected differences in VSM function among NC subjects and subjects with MCI and mild dementia. The software program for the VSM test is distributed for free so that it can be widely used.     

Association between global brain volume and the rate of cognitive change in elderly humans without dementia

Patients with mild cognitive deficits experience different types of evolution. They are at increased risk of developing dementia, but they have also a chance of remaining stable in cognition or of improving. We investigated whether global brain volume, callosal size and hippocampal size are associated with the rate of cognitive change in elderly without dementia. Volumetric MR images were recorded from 39 controls and 35 patients with questionable dementia who were followed up longitudinally for a mean of 2.3 years. The outcome measure was the annual change in the test score in the Structured Interview for the Diagnosis of Alzheimer's Dementia and Multi-Infarct Dementia, which includes all items of the Mini-Mental State Examination. Global brain volume, grey matter volume and white matter volume were the only significant independent predictors of the rate of cognitive change.     

Longitudinal trajectory of Amyloid‐related hippocampal subfield atrophy in nondemented elderly

Hippocampal atrophy and abnormal β‐Amyloid (Aβ) deposition are established markers of Alzheimer's disease (AD). Nonetheless, longitudinal trajectory of Aβ‐associated hippocampal subfield atrophy prior to dementia remains unclear. We hypothesized that elevated Aβ correlated with longitudinal subfield atrophy selectively in no cognitive impairment (NCI), spreading to other subfields in mild cognitive impairment (MCI). We analyzed data from two independent longitudinal cohorts of nondemented elderly, including global PET‐Aβ in AD‐vulnerable cortical regions and longitudinal subfield volumes quantified with a novel auto‐segmentation method (FreeSurfer v.6.0). Moreover, we investigated associations of Aβ‐related progressive subfield atrophy with memory decline. Across both datasets, we found a converging pattern that higher Aβ correlated with faster CA1 volume decline in NCI. This pattern spread to other hippocampal subfields in MCI group, correlating with memory decline. Our results for the first time suggest a longitudinal focal‐to‐widespread trajectory of Aβ‐associated hippocampal subfield atrophy over disease progression in nondemented elderly.     

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.     

Characteristics of exploratory eye movements in elderly people: possibility of early diagnosis of dementia

Background: Visual cognitive dysfunction is one of the most important signs indicating the early stage of dementia. Thus, visual testing could be used as an aid to the clinical diagnosis of dementia. In the present study, exploratory eye movement was measured to evaluate visual cognitive function in elderly subjects, including those with dementia. Methods: We analyzed responsive search scores (RSS) from exploratory eye movements of 300 subjects who were examined with an eye mark recorder while viewing S shaped figures. Subjects were divided into three groups (dementia, intermediate, healthy) from the values of the Revised Hasegawa Dementia Scale (HDS‐R), the Mini‐Mental State Examination (MMSE) and the Clinical Dementia Rating. We further divided the intermediate groups into two subgroups, the high score and low score groups, based on RSS. In 202 subjects, Z‐scores of voxel‐based specific regional analysis system for Alzheimer's disease (VSRAD) were obtained from magnetic resonance imaging (MRI). Results: RSS of the dementia group were significantly lower than those in the intermediate and healthy groups, in order: dementia < intermediate < healthy groups. RSS of the low score intermediate group was significantly lower than that of the high score intermediate group. There was no significant difference between the low score intermediate and dementia groups, or between the high score intermediate and healthy groups. No significant differences of either HSD‐R or MMSE were observed between the low score and the high score intermediate groups. The Z‐score of VSRAD using MRI in the low score intermediate group was significantly higher than that in the high score intermediate group. Conclusions: These findings suggest that RSS using an eye mark recorder is a useful psychophysiological marker to evaluate the early stage of dementia as well as at‐risk elderly people.     

Parkinson's disease is associated with hippocampal atrophy.

Patients with Parkinson's disease (PD) may have hippocampal atrophy compared with controls. We compared hippocampal, and extra-hippocampal volumes between PD, PDD (patients with PD who have mild cognitive impairment or dementia), Alzheimer's disease (AD) and controls using volumetric magnetic resonance imaging (MRI). Participants (10 patients with PD, 10 with PDD, 11 with AD, and 12 control subjects) had an informant interview, neurological examination, and psychometric testing. Established, reliable methods were used to measure the hippocampus, parahippocampal gyrus, temporal, frontal, and parieto-occipital lobes. Correction for intracranial volume was carried out before comparison. There was no age difference between groups (mean age, 74 years). On the Clinical Dementia Rating scale (CDR) cognitive impairment was mild (CDR = 0.5) in the majority of PDD and AD patients. Hippocampal (P < 0.0004) volumes were smaller in the patient groups. Effect sizes compared with the control group were: PD, 0.66; PDD, 1.22; and AD, 1.81. The other volumes did not differ significantly. Among PD and PDD patients, recognition memory (r = 0.54, P = 0.015) and Mini-Mental State Examination scores (r = 0.56, P = 0.01) correlated with left, but not right hippocampal volume. In conclusion, hippocampal volume showed a pattern (Control > PD > PDD > AD) suggesting progressive hippocampal volume loss in PD. Volumetric MRI imaging might provide an early marker for dementia in PD.     

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 atrophy on MRI in frontotemporal lobar degeneration and Alzheimer's disease

BACKGROUND: Hippocampal atrophy on magnetic resonance imaging (MRI) is an early characteristic of Alzheimer's disease. However, hippocampal atrophy may also occur in other dementias, such as frontotemporal lobar degeneration (FTLD). OBJECTIVE: To investigate hippocampal atrophy on MRI in FTLD and its three clinical subtypes, in comparison with Alzheimer's disease, using volumetry and a visual rating scale. METHODS: 42 patients with FTLD (17 frontotemporal dementia, 13 semantic dementia, and 12 progressive non-fluent aphasia), 103 patients with Alzheimer's disease, and 73 controls were included. Hippocampal volumetry and the easily applicable medial temporal lobe atrophy (MTA) rating scale were applied to assess hippocampal atrophy. RESULTS: Multivariate analysis of variance for repeated measures showed an effect of diagnostic group on hippocampal volume. There was a significant diagnosis by side (left v right) interaction. Both FTLD and Alzheimer's disease showed hippocampal atrophy compared with controls. Results of the visual MTA rating scale confirmed these findings. Within the FTLD subtypes there were marked differences in hippocampal atrophy. Frontotemporal dementia and semantic dementia showed bilateral hippocampal atrophy, and in semantic dementia the left hippocampus was smaller than in Alzheimer's disease. No significant hippocampal atrophy was detected in non-fluent progressive aphasia. CONCLUSIONS: Hippocampal atrophy is not only a characteristic of Alzheimer's disease but also occurs in FTLD. The three clinical subtypes of FTLD show different patterns of hippocampal atrophy.     

A comparison of medial and lateral temporal lobe atrophy in dementia with Lewy bodies and Alzheimer's disease: magnetic resonance imaging volumetric study

OBJECTIVES: To compare medial and lateral temporal lobe atrophy on magnetic resonance imaging (MRI) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), and to examine the relationship between volumetric indices and cognitive and non-cognitive symptoms. METHODS: T(1)-weighted 1.0-tesla MRI scans were acquired in elderly subjects with DLB (n = 26; mean age = 75.8 years) and AD (n = 22; 77.3 years) and normal controls (n = 26; 76.2 years). MRI-based volume measurements of the hippocampus, parahippocampus, fusiform gyrus, combined inferior and middle temporal gyri, and superior temporal gyrus were acquired. RESULTS: Hippocampal and parahippocampal volumes were significantly larger in subjects with DLB compared to AD. Differences in hippocampal volumes between DLB and AD were observed across the entire length, and in all subjects with dementia there was a loss of hippocampal asymmetry compared to normal controls. Atrophy of temporal lobe structures correlated with memory impairment in both groups, and with age in DLB. There was no association between atrophy and psychotic symptoms in either group. CONCLUSIONS: Subjects with DLB and AD have a different pattern of temporal lobe atrophy with the most striking differences relating to medial rather than lateral temporal lobe structures. These structural differences could explain the relative preservation of memory function in DLB compared to AD.     

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.     

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.     

Use of hippocampal and amygdalar volumes on magnetic resonance imaging to predict dementia in cognitively intact elderly people

CONTEXT: The recent focus on the development of preventive interventions for Alzheimer disease has fueled the search for biomarkers of presymptomatic disease. Patients with Alzheimer disease and mild cognitive impairment have marked atrophy of the hippocampus and amygdala compared with healthy elderly people. Whether atrophy of these structures is also present in persons without cognitive impairment who later develop dementia is unknown. OBJECTIVE: To assess whether volumetric assessment of the hippocampus and amygdala using magnetic resonance imaging (MRI) predicts dementia in elderly people without cognitive impairment. DESIGN: Longitudinal cohort study. SETTING: A general community in the Netherlands. PARTICIPANTS: Five hundred eleven persons, aged 60 to 90 years, free of dementia at baseline were followed up during 3043 person-years (mean per person, 6.0 years). We performed volumetric assessment of the hippocampus and amygdala, obtained information about daily memory problems, and performed extensive neuropsychological testing in all study participants. MAIN OUTCOME MEASURE: Dementia, as assessed by repeated neuropsychological screening and monitoring of medical records. RESULTS: Thirty-five persons developed dementia (26 with Alzheimer disease). Hippocampal and amygdalar volumes were strongly associated with the risk of dementia; the age-, sex-, and education-adjusted hazard ratio per 1-SD decrease in volume was 3.0 (95% confidence interval, 2.0-4.6) for the hippocampus and 2.1 (95% confidence interval, 1.5-2.9) for the amygdala. The hazard ratios associated with atrophy were similar in persons without memory complaints or low cognitive function at baseline. Compared with those remaining free of dementia, baseline brain volumes were 17% smaller in persons who received a clinical diagnosis of dementia within 2 to 3 years after MRI and still 5% smaller in those whose conditions were diagnosed 6 years after MRI. CONCLUSION: Atrophy of the hippocampus and amygdala on MRI in cognitively intact elderly people predicts dementia during a 6-year follow-up.     

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.     

Comparing Hippocampal Atrophy in Alzheimer's Dementia and Dementia with Lewy Bodies

Background/Aims: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common neurodegenerative dementias. During the early stages, clinical distinction between them is often challenging. Our objective is to compare hippocampal atrophy patterns in mild AD and mild DLB. We hypothesized that DLB subjects have milder hippocampal atrophy relative to AD subjects. Methods: We analyzed the T1-weighted magnetic resonance imaging data from 113 subjects: 55 AD, 16 DLB and 42 cognitively normal elderly (normal controls, NC). Using the hippocampal radial distance technique and multiple linear regression, we analyzed the effect of clinical diagnosis on hippocampal radial distance, while adjusting for gender and age. Three-dimensional statistical maps were adjusted for multiple comparisons using permutation-based statistics with a threshold of p < 0.01. Results: Compared to NC, AD exhibited significantly greater atrophy in the cornu ammonis (CA)1, CA2-3 and subicular regions bilaterally while DLB showed left-predominant atrophy in the CA1 region and subiculum. Compared directly, AD and DLB did not reveal statistically significant differences. Conclusion: Hippocampal atrophy, while present in mildly impaired DLB subjects, is less severe than atrophy seen in mildly impaired AD subjects, when compared to NC. Both groups show predominant atrophy of the CA1 subfield and subiculum.