Hippocampal atrophy in normal aging. An association with recent memory impairment.

OBJECTIVE To estimate the prevalence of radiographically detectable hippocampal atrophy (HA) in a normal aging sample and to test whether such atrophy is associated with memory dysfunction. DESIGN One hundred fifty-four medically healthy and cognitively normal elderly persons (aged 55 to 88 years) received magnetic resonance imaging and/or computed tomographic scans designed to identify HA. One hundred forty-five of these subjects also underwent psychometric tests of memory function. Multivariate analyses of variance were used to evaluate differences in memory performance between subjects with and without HA. SETTING This study was conducted at a research clinic for the investigation of age-associated neuropsychological and neuroradiologic changes. PARTICIPANTS Based on the following criteria, 154 subjects were consecutively selected from a larger group of elderly research volunteers participating in a study of normal aging: age of 55 years or greater; Global Deterioration Scale score of 2 or less; and Mini-Mental State examination score of 28 or greater. Subjects with evidence for significant medical, psychiatric, or neurologic disease were excluded. MAIN OUTCOME MEASURES Outcome measurements included individual psychometric test scores and computed tomographic-magnetic resonance imaging hippocampal atrophy ratings. RESULTS Nearly 33% of the subjects had radiographic evidence for HA. The prevalence of HA increased significantly with age and was more common in male than female subjects. After controlling for age, level of education, and vocabulary, subjects with HA were found to perform more poorly on tests of recent (secondary) verbal memory when compared with subjects without HA (P < .01). No significant differences were found for tests of immediate (primary) memory. CONCLUSION We conclude that HA is a common accompaniment of normal aging and is associated with mild memory impairment. Additional research is needed to determine whether HA constitutes a significant risk for future dementia.

[1]  W. Scoville,et al.  LOSS OF RECENT MEMORY AFTER BILATERAL HIPPOCAMPAL LESIONS , 1957, Journal of neurology, neurosurgery, and psychiatry.

[2]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[3]  V. A. Kral,et al.  Senescent forgetfulness: benign and malignant. , 1962, Canadian Medical Association journal.

[4]  B. Milner Amnesia following operation on the temporal lobes , 1996 .

[5]  Alistair Burns,et al.  Observations on the brains of demented old people. B.E. Tomlinson, G. Blessed and M. Roth, Journal of the Neurological Sciences (1970) 11, 205–242; (1968) 7, 331–356 , 1997 .

[6]  J. G. Gilbert,et al.  Patterns of declining memory. , 1971, Journal of gerontology.

[7]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[8]  A. M. Dam,et al.  THE DENSITY OF NEURONS IN THE HUMAN HIPPOCAMPUS , 1979 .

[9]  S. Ferris,et al.  Operationalizing Memory Impairment for Elderly Persons: The Guild Memory Test , 1980, Psychological reports.

[10]  B. Reisberg,et al.  The Global Deterioration Scale for assessment of primary degenerative dementia. , 1982, The American journal of psychiatry.

[11]  L. Squire,et al.  Preserved learning in monkeys with medial temporal lesions: sparing of motor and cognitive skills , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  A. K. Miller,et al.  AUTOMATED DIFFERENTIAL CELL COUNTING ON A SECTOR OF THE NORMAL HUMAN HIPPOCAMPUS: THE INFLUENCE OF AGE , 1984, Neuropathology and applied neurobiology.

[13]  J. Fitzgerald,et al.  Autobiographical memory across the life-span. , 1984, Journal of gerontology.

[14]  V. Hachinski,et al.  A NEW DEFINITION OF ALZHEIMER'S DISEASE: A HIPPOCAMPAL DEMENTIA , 1985, The Lancet.

[15]  J. Ulrich,et al.  Alzheimer changes in nondemented patients younger than sixty‐five: Possible early stages of Alzheimer's disease and senile dementia of Alzheimer type , 1985, Annals of neurology.

[16]  B. Reisberg,et al.  Cognitive Function in Normal Aging and Early Dementia , 1985 .

[17]  L. Squire,et al.  Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  B. Reisberg,et al.  Assessing cognitive impairment and evaluating treatment effects: Psychometric performance tests. , 1986 .

[19]  L. Wolfson,et al.  Clinico‐pathologic studies in dementia , 1988, Neurology.

[20]  M. Folstein,et al.  Mini-Mental State Examination (MMSE) , 2019, Encyclopedia of Gerontology and Population Aging.

[21]  B. Reisberg,et al.  Stage‐specific behavioral, cognitive, and in vivo changes in community residing subjects with age‐associated memory impairment and primary degenerative dementia of the Alzheimer type , 1988 .

[22]  Esiri Mm,et al.  The site of the earliest lesions of Alzheimer's disease. , 1988 .

[23]  R. Katzman.,et al.  Clinical, pathological, and neurochemical changes in dementia: A subgroup with preserved mental status and numerous neocortical plaques , 1988, Annals of neurology.

[24]  B. Reisberg,et al.  Global Deterioration Scale (GDS). , 1988, Psychopharmacology bulletin.

[25]  W. Jagust,et al.  Quantitative NMR measurements of hippocampal atrophy in Alzheimer's disease , 1988, Magnetic resonance in medicine.

[26]  R D Hill,et al.  Very mild senile dementia of the Alzheimer type. II. Psychometric test performance. , 1989, Archives of neurology.

[27]  D. Amaral,et al.  Hippocampal abnormalities in amnesic patients revealed by high-resolution magnetic resonance imaging , 1989, Nature.

[28]  M J de Leon,et al.  Alzheimer's disease: longitudinal CT studies of ventricular change. , 1989, AJR. American journal of roentgenology.

[29]  B. Reisberg,et al.  Stage specific incidence of potentially remediable behavioral symptoms in aging and Alzheimer's disease:A study of 120 patients using BEHAVE-AD , 1989 .

[30]  M. Albert,et al.  Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. , 1989, JAMA.

[31]  Gwenn S. Smith,et al.  EARLY MARKER FOR ALZHEIMER'S DISEASE: THE ATROPHIC HIPPOCAMPUS , 1989, The Lancet.

[32]  S. M. de la Monte,et al.  Quantitation of cerebral atrophy in preclinical and end‐stage alzheimer's disease , 1989, Annals of neurology.

[33]  E. Masliah,et al.  Diffuse plaques do not accentuate synapse loss in Alzheimer's disease. , 1990, The American journal of pathology.

[34]  A. R. Damasio,et al.  Memory‐related neural systems in Alzheimer's disease , 1990, Neurology.

[35]  J. Price,et al.  Very mild Alzheimer's disease , 1991, Neurology.

[36]  O Nalcioglu,et al.  Quantification of magnetic resonance scans for hippocampal and parahippocampal atrophy in Alzheimer's disease , 1991, Neurology.

[37]  B. Reisberg,et al.  Cognition-independent neurologic symptoms in normal aging and probable Alzheimer's disease. , 1991, Archives of neurology.

[38]  R. Gur,et al.  Gender differences in age effect on brain atrophy measured by magnetic resonance imaging. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[39]  L. Squire,et al.  The medial temporal lobe memory system , 1991, Science.

[40]  B. Reisberg,et al.  Mild cognitive impairment in the elderly , 1991, Neurology.

[41]  Morris Moscovitch,et al.  The neuropsychology of memory and aging. , 1992 .

[42]  C. Jack,et al.  MR‐based hippocampal volumetry in the diagnosis of Alzheimer's disease , 1992, Neurology.

[43]  R. D'Agostino,et al.  Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study , 1992, Neurology.

[44]  Gwenn S. Smith,et al.  The Early Detection of Brain Pathology in Alzheimer’s Disease , 1992 .

[45]  Gwenn S. Smith,et al.  The radiologic prediction of Alzheimer disease: the atrophic hippocampal formation. , 1993, AJNR. American journal of neuroradiology.