A E George

Specific Hippocampal Volume Reductions in Individuals at Risk for Alzheimer’s Disease

Our goal was to ascertain the involvement of the temporal lobe in the preclinical (not yet diagnosable) stages of dementia of the Alzheimers type (DAT) by using MRI-derived volumes. We assessed anatomical subdivisions of the temporal lobe on three groups of carefully screened age- and education-matched elderly individuals: 27 normal elderly (NL), 22 individuals with minimal cognitive impairment (MCI), who did not fulfill DAT criteria but were regarded at high risk for future DAT, and 27 DAT individuals. We found hippocampal volume reductions of 14% for the MCI and 22% for the DAT group compared to the NL group. Utilizing regression analyses and after accounting for gender head size-age, generalized atrophy (CSF), and other temporal lobe subvolumes, the hippocampal volume separated NL from MCI individuals, correctly classifying 74%. For NL and MCI groups combined the hippocampal volume was the only temporal lobe subvolume related to delayed recall memory performance. When contrasting MCI and DAT individuals, the fusiform gyrus volume uniquely improved the ability of the hippocampal volume to separate MCI from DAT individuals from 74 to 80%. Our cross-sectional data suggest that, within the temporal lobe, specific hippocampal volume reductions separated the group at risk for DAT from the normal group. By the time impairments are sufficient to allow a diagnosis of DAT to be made, in addition to the medial temporal lobe volume reductions, the lateral temporal lobe is also showing volume reductions, most saliently involving the fusiform gyrus.

Frequency of hippocampal formation atrophy in normal aging and Alzheimer's disease

We used CT and MR to examine the frequency of occurrence of hippocampal formation atrophy (HA) in a research clinic population of 130 normal elderly, 72 nondemented patients with very mild memory and cognitive impairments (MCI), 73 mild Alzheimers disease (AD) patients, and 130 patients with moderate to severe AD. HA was found in 29% of the normal elderly group and its frequency of occurrence was strongly related to increasing age. For normal elderly 60-75 years of age, 15% had HA: the proportion rose to 48% in subjects 76-90 years of age. Among the three groups of impaired patients, the frequencies of HA ranged from 78% in the MCI patients to 96% in the advanced AD group. Unlike the normal elderly group, the percentages were not related to age. In both the normal elderly group and MCI group disproportionately more males than females had HA. After controlling for learning and the effects of generalized brain changes as reflected in ventricular size, only in the normal group was HA associated with reduced delayed verbal recall performance. Follow-up examinations for 15 individuals with baseline HA. 4 who at entry were MCI and 11 probable AD, yielded clinical and neuropathologic diagnoses of AD in all cases. The results of the present study indicate that hippocampal formation atrophy is associated with memory and cognitive impairments. Further longitudinal and neuropathologic work is required to validate the relationship between hippocampal formation atrophy and AD.

Hippocampal formation size predicts declining memory performance in normal aging

Hippocampal formation (HF) atrophy, although common in normal aging, has unknown clinical consequences.We used MRI to derive HF size measurements at baseline on 44 cognitively normal older adults entering a longitudinal study of memory function (mean age = 68.4 years, mean follow-up = 3.8 years). Only one subject became demented at follow-up. Multiple regression analyses controlling for age, gender, education, and diffuse cerebral atrophy revealed that HF size significantly predicted longitudinal change on memory tests previously found sensitive to decline in normal aging. These results indicate HF atrophy may be a risk factor for accelerated memory dysfunction in normal aging. NEUROLOGY 1996;47: 810-813

HIPPOCAMPAL ATROPHY IN EARLY ALZHEIMER'S DISEASE: ANATOMIC SPECIFICITY AND VALIDATION

We evaluated three groups of elderly individuals who were carefully screened to rule out clinically significant diseases that could affect cognition. They were matched for age and education. The groups included normals (N=18), Alzheimers Disease (AD) patients (N=15), and minimally impaired individuals with memory complaints and impairments but who did not fulfill criteria for AD (N=17). Volumetric measurements of different regions of the temporal lobe on the coronal scan as well as ratings of the perihippocampal cerebrospinal fluid (CSF) accumulation (HCSF) on the negative angle axial MR were carried out. Volume reductions were found in AD relative to the normals for both medial and lateral temporal lobe volumes. Only hippocampal volume reductions were found in the minimal group. The minimally impaired individuals had equivalent hippocampal volume reductions and significantly larger parahippocampal and lateral temporal lobe gyri than the AD group. The axial HCSF was validated using the coronal volumes. The combination of coronal hippocampal and perihippocampal CSF was the best predictor of the axial HCSF rating. The parahippocampal volume did not add to the predictive ability of the hippocampal-perihippocampal CSF combination. Future work should validate these findings with longitudinal designs as well as assess the issue of normal aging of these structures and their relationship to cognitive function.

In Vivo Structural Studies of the Hippocampus in Normal Aging and in Incipient Alzheimer's Diseasea

Population trends indicate that in the near future the size of the elderly population will increase. This will result in a large increment in the numbers of persons suffering mild to severe levels of cognitive impairment. While considerable efforts continue to be made to explain brain changes associated with Alzheimer disease (AD), little is known of the brain changes in aging without dementia or so‐called normal aging. Pathologic studies suggest that the medial temporal lobe is informative in the examination of the early brain changes related to AD. However, pathologic studies only offer a single observation and considerable uncertainty exists regarding the likelihood of progression of disease and the development of dementia. Several structural neuroimaging studies have recently investigated this anatomy and recent reports are encouraging for a medial temporal lobe based diagnosis for age‐related cognitive impairments. We will present our findings on the MRI anatomy of the hippocampal formation as well as data bearing on the use of hippocampal formation imaging in the diagnosis of AD and as a predictive marker for future dementia. Our findings suggest an anatomically specific relationship between hippocampal volume and secondary memory performance. Because these observations apply to nondemented and normal elderly subjects, we are encouraged that the anatomy of age‐related cognitive impairments can be reliably recognized and possibly put to use in therapeutic studies.

Hippocampal atrophy correlates with severe cognitive impairment in elderly patients with suspected normal pressure hydrocephalus.

Measurements of hippocampal formation atrophy using MRI have been useful in distinguishing demented patients with a diagnosis of probable Alzheimers disease from cognitively normal controls. To determine whether there is a similar relationship between hippocampal size and dementia in elderly patients suspected of normal pressure hydrocephalus (NPH), the authors obtained mini-mental status examination (MMSE) scores and MRI measurements of hippocampal size and CSF volume on 16 elderly patients whose severe ventriculomegaly and unexplained gait impairment made NPH a probable diagnosis. Hippocampal size correlated strongly with MMSE score (r = 0.75, p < 0.001); no significant MMSE correlation was found for ventricular CSF volume or extra-ventricular/ventricular CSF ratio. It was concluded that hippocampal atrophy is associated with severe cognitive dysfunction in many elderly patients with a diagnosis of NPH. As a hypothesis for further investigation, the detection of such atrophy may help identify cases where the presence of a pathology of Alzheimers disease complicates the diagnosis of NPH.

Abnormal Temporal Lobe Response in Alzheimer's Disease during Cognitive Processing as Measured by 11C-2-Deoxy-D-Glucose and PET

Elderly controls and probable Alzheimers disease patients underwent serial positron emission tomography (PET) studies during a baseline condition and while performing a verbal memory task. for the temporal lobes, all 7 Alzheimer patients demonstrated a relative shift in glucose metabolic rates to the right hemisphere during the memory condition relative to baseline, and 5 of 7 controls showed a shift to the left hemisphere. Baseline absolute regional metabolic rates replicate previous findings and were somewhat less useful than the memory challenge in differentiating patients from controls. These results indicate that a temporal lobe abnormality in Alzheimers disease is related to memory performance.

The Early Detection of Brain Pathology in Alzheimer’s Disease

Studies of aged animals and aging humans have revealed numerous age — associated decrements in brain functioning. Foremost among behavioral changes are the declines in memory functioning. While animal studies have linked many of these aging changes to brain alterations, very little direct evidence is available for the human. By and large, our current understandings suggest that damage to the hippocampus is at least in part related to these age-related memory changes. In Alzheimer’s disease (AD) many of these age-related behavioral changes are markedly exacerbated and there is clear evidence for extensive neuropathological involvement of the hippocampus and associated regions.

Elevated Cerebellar Glucose Metabolism in Microvascular White Matter Disease: Normal Aging and Alzheimer's Disease

Young normal, elderly, and clinically diagnosed Alzheimer disease subjects who had undergone positron emission tomography (PET) and computed tomography (CT) examinations were studied to determine the effect of periventricular white matter lesions on cerebellar glucose metabolic rates. PET-determined cerebellar metabolic rates were elevated in subjects with periventricular white matter lesions. These results suggest the cautious use of cortical-to-cerebellar ratios in future PET or single-photonemission CT (SPECT) studies.

Positron emission tomography with the deoxyglucose technique and the diagnosis of Alzheimer's disease

Riege and Metter provide a useful review of the application of PET in the evaluation of Alzheimers disease (AD). We share their enthusiasm for continued support and development of tools to image metabolic processes. Our commentary focuses on neuroimaging and the diagnosis of AD and introduces some new data that directly impacts on the interpretation of PET-2-deoxyglucose (2DG) data.