MRI Volumetric Studies in Alzheimer's Disease: Relationship to Clinical and Neuropsychological Variables
1994; Elsevier BV; Volume: 2; Issue: 1 Linguagem: Inglês
10.1097/00019442-199400210-00005
ISSN1545-7214
AutoresAnand Kumar, Andrew B. Newberg, Abass Alavi, Paul Moberg, Jesse A. Berlin, David S. Miller, Elaine Souder, Raquel E. Gur, Gary Gottlieb,
Tópico(s)Functional Brain Connectivity Studies
ResumoThe authors studied 34 subjects with probable dementia of the Alzheimer type (DAT) and 28 healthy, age-matched control subjects, using a 1.5-tesla GE MRI scanner. Absolute volumes of ventricular and sulcal cerebrospinal fluid spaces and volumes, corrected for total intracranial volume, were significantly higher (P < 0.01) in the DAT group, compared to the control group. Right-left measures of hemispheric structural asymmetry were greater in the DAT group, whereas aging alone influenced brain structure in the control group. Also, in the DAT group, certain volumetric measures were significantly correlated with specific clinical indicators of severity of illness and some neuropsychological indices. These data demonstrate widespread structural abnormalities in relatively early DAT and a relationship between brain structure and some measures of cognitive dysfunction. The authors studied 34 subjects with probable dementia of the Alzheimer type (DAT) and 28 healthy, age-matched control subjects, using a 1.5-tesla GE MRI scanner. Absolute volumes of ventricular and sulcal cerebrospinal fluid spaces and volumes, corrected for total intracranial volume, were significantly higher (P < 0.01) in the DAT group, compared to the control group. Right-left measures of hemispheric structural asymmetry were greater in the DAT group, whereas aging alone influenced brain structure in the control group. Also, in the DAT group, certain volumetric measures were significantly correlated with specific clinical indicators of severity of illness and some neuropsychological indices. These data demonstrate widespread structural abnormalities in relatively early DAT and a relationship between brain structure and some measures of cognitive dysfunction. Probable dementia of the Alzheimer type (DAT) is the most common cause of dementia in the Western Hemisphere.1Katzman R Alzheimer's disease.N Engl J Med. 1986; 314: 964-973Crossref PubMed Scopus (844) Google Scholar The primary clinical features of DAT include a decline in memory, language, visuospatial skills, and executive functions. Neuropathologically, DAT is characterized by widespread neuronal atrophy associated with senile plaques and neurofibrillary tangles.1Katzman R Alzheimer's disease.N Engl J Med. 1986; 314: 964-973Crossref PubMed Scopus (844) Google Scholar These neuropathological changes are widespread and involve both gray and white matter.2de la Monte SM Quantitation of cerebral atrophy in preclinical and end-stage Alzheimer's disease.Ann Neurol. 1989; 25: 450-459Crossref PubMed Scopus (209) Google Scholar, 3Tomlinson BE Blessed G Roth M Observations on the brains of non-demented old people.J Neurol Sci. 1968; 7: 331-356Abstract Full Text PDF PubMed Scopus (666) Google Scholar Ventricular dilatation, determined in postmortem studies of the brains of DAT subjects, correlates well with the antemortem cognitive status of subjects.2de la Monte SM Quantitation of cerebral atrophy in preclinical and end-stage Alzheimer's disease.Ann Neurol. 1989; 25: 450-459Crossref PubMed Scopus (209) Google Scholar, 3Tomlinson BE Blessed G Roth M Observations on the brains of non-demented old people.J Neurol Sci. 1968; 7: 331-356Abstract Full Text PDF PubMed Scopus (666) Google Scholar, 4Tomlinson BE Blessed G Roth M Observations on the brains of demented old people.J Neurol Sci. 1970; 11: 205-242Abstract Full Text PDF PubMed Scopus (1391) Google Scholar Although these early studies suggested an association between brain atrophy, ventricular dilatation, and cognitive status, the retrospective nature of the correlations limited interpretation of these data. The advent of computerized tomographic scanning (CT) provided an opportunity to examine neuronal structure in vivo, both qualitatively and quantitatively, in subjects with dementia and in healthy, elderly control subjects.5Nathan RJ, Frumkin K: Cerebral atrophy and independence in the elderly. Proceedings of the American Psychiatric Association, Atlanta, GA, May 8–12, 1978Google Scholar, 6Claveria LE Moseley IF Stevenson JF The clinical significance of cerebral atrophy as shown by CAT.in: DuBoulay GH Moseley IF The First European Seminar on Computed Tomography in Clinical Practice. Springer-Verlag, Berlin, Germany1977: 213-217Crossref Google Scholar, 7Hughes CP Gado M Computed tomography and aging of the brain.Radiology. 1981; 139: 391-396Crossref PubMed Scopus (76) Google Scholar, 8Merskey H Ball MJ Blume WT et al.Relationship between psychological measurements and cerebral organic changes in Alzheimer's disease.Le Journal Canadien Des Sciences Neurologiques. 1980; 7: 45-49PubMed Google Scholar, 9Roberts MA Caird FI Computerized tomography and intellectual impairment in the elderly.J Neurol Neurosurg Psychiatry. 1976; 39: 986-989Crossref PubMed Scopus (63) Google Scholar, 10Stafford JL Albert MS Naeser MA et al.Age-related differences in computed tomographic scan measurements.Arch Neurol. 1988; 45: 409-415Crossref PubMed Scopus (33) Google Scholar, 11deLeon MJ Ferris SH George AH et al.A new method for the CT evaluation of brain atrophy in senile dementia (abstract).International Research Communication, Medical Science. 1979; 7: 404PubMed Google Scholar, 12deLeon MJ Ferris SH Blau I et al.Correlation between computerized tomographic changes and behavioral deficits in senile dementia.Lancet. 1979; 2: 859-860Abstract Scopus (29) Google Scholar, 13deLeon NJ Ferris SH George AG et al.Computed tomographic evaluations of brain behavior relationships in senile dementia of the Alzheimer type.Neurobiol Aging. 1980; 1: 69-79Abstract Full Text PDF PubMed Scopus (91) Google Scholar, 14Earnest MP Heaton HK Wilkinson W et al.Cortical atrophy, ventricular enlargement, and intellectual impairment in the aged.Neurology. 1979; 29: 1138-1143Crossref PubMed Google Scholar, 15Kaszniak AW Garron DC Fox JH et al.Cerebral atrophy, FUG slowing, age, education, and cognitive functioning in suspected dementia.Neurology. 1979; 29: 1273-1279Crossref PubMed Google Scholar Attempts were made to quantitate cerebral atrophy by estimating the volume of cerebrospinal fluid (CSF) within the cranial cavity. Also, the relationship between cognitive status and various measures of neuronal atrophy were examined.5Nathan RJ, Frumkin K: Cerebral atrophy and independence in the elderly. Proceedings of the American Psychiatric Association, Atlanta, GA, May 8–12, 1978Google Scholar, 6Claveria LE Moseley IF Stevenson JF The clinical significance of cerebral atrophy as shown by CAT.in: DuBoulay GH Moseley IF The First European Seminar on Computed Tomography in Clinical Practice. Springer-Verlag, Berlin, Germany1977: 213-217Crossref Google Scholar, 7Hughes CP Gado M Computed tomography and aging of the brain.Radiology. 1981; 139: 391-396Crossref PubMed Scopus (76) Google Scholar, 8Merskey H Ball MJ Blume WT et al.Relationship between psychological measurements and cerebral organic changes in Alzheimer's disease.Le Journal Canadien Des Sciences Neurologiques. 1980; 7: 45-49PubMed Google Scholar, 9Roberts MA Caird FI Computerized tomography and intellectual impairment in the elderly.J Neurol Neurosurg Psychiatry. 1976; 39: 986-989Crossref PubMed Scopus (63) Google Scholar, 10Stafford JL Albert MS Naeser MA et al.Age-related differences in computed tomographic scan measurements.Arch Neurol. 1988; 45: 409-415Crossref PubMed Scopus (33) Google Scholar, 11deLeon MJ Ferris SH George AH et al.A new method for the CT evaluation of brain atrophy in senile dementia (abstract).International Research Communication, Medical Science. 1979; 7: 404PubMed Google Scholar, 12deLeon MJ Ferris SH Blau I et al.Correlation between computerized tomographic changes and behavioral deficits in senile dementia.Lancet. 1979; 2: 859-860Abstract Scopus (29) Google Scholar, 13deLeon NJ Ferris SH George AG et al.Computed tomographic evaluations of brain behavior relationships in senile dementia of the Alzheimer type.Neurobiol Aging. 1980; 1: 69-79Abstract Full Text PDF PubMed Scopus (91) Google Scholar, 14Earnest MP Heaton HK Wilkinson W et al.Cortical atrophy, ventricular enlargement, and intellectual impairment in the aged.Neurology. 1979; 29: 1138-1143Crossref PubMed Google Scholar, 15Kaszniak AW Garron DC Fox JH et al.Cerebral atrophy, FUG slowing, age, education, and cognitive functioning in suspected dementia.Neurology. 1979; 29: 1273-1279Crossref PubMed Google Scholar, 16Hughes CP Gado M Computed tomography and aging of the brain.Radiology. 1981; 139: 391-396Crossref PubMed Google Scholar, 17Jacoby RJ Levy R Computed tomography in the elderly, II: senile dementia: diagnosis and functional impairment.Br J Psychiatry. 1980; 136: 256-269Crossref PubMed Scopus (147) Google Scholar, 18Gado M Hughes CP Danziger W et al.Volumetric measurements of cerebrospinal fluid spaces in demented patients and controls.Radiology. 1982; 144: 535-538Crossref PubMed Scopus (92) Google Scholar, 19George AE deLeon MJ Rosenbloom S et al.Ventricular volume and cognitive deficit: a computed tomographic study.Radiology. 1983; 149: 493-498Crossref PubMed Scopus (49) Google Scholar, 20Pfefferbaum A Sullivan EV Jernigan TL et al.A quantitative analysis of CT and cognitive measures in normal aging and Alzheimer's disease.Psychiatry Res. 1990; 35: 115-136Abstract Full Text PDF PubMed Scopus (38) Google Scholar, 21Creasey H Schwartz M Frederickson H et al.Quantitative computed tomography in dementia of the Alzheimer type.Neurology. 1986; 36: 1563-1568Crossref PubMed Google Scholar Early CT studies showed minimal or no correlation between CT measures of brain atrophy and psychometric indices.5Nathan RJ, Frumkin K: Cerebral atrophy and independence in the elderly. Proceedings of the American Psychiatric Association, Atlanta, GA, May 8–12, 1978Google Scholar, 6Claveria LE Moseley IF Stevenson JF The clinical significance of cerebral atrophy as shown by CAT.in: DuBoulay GH Moseley IF The First European Seminar on Computed Tomography in Clinical Practice. Springer-Verlag, Berlin, Germany1977: 213-217Crossref Google Scholar, 7Hughes CP Gado M Computed tomography and aging of the brain.Radiology. 1981; 139: 391-396Crossref PubMed Scopus (76) Google Scholar, 8Merskey H Ball MJ Blume WT et al.Relationship between psychological measurements and cerebral organic changes in Alzheimer's disease.Le Journal Canadien Des Sciences Neurologiques. 1980; 7: 45-49PubMed Google Scholar More recent CT volumetric studies have more consistently demonstrated significant differences in ventricular volumes between DAT subjects and control subjects.12deLeon MJ Ferris SH Blau I et al.Correlation between computerized tomographic changes and behavioral deficits in senile dementia.Lancet. 1979; 2: 859-860Abstract Scopus (29) Google Scholar, 13deLeon NJ Ferris SH George AG et al.Computed tomographic evaluations of brain behavior relationships in senile dementia of the Alzheimer type.Neurobiol Aging. 1980; 1: 69-79Abstract Full Text PDF PubMed Scopus (91) Google Scholar, 14Earnest MP Heaton HK Wilkinson W et al.Cortical atrophy, ventricular enlargement, and intellectual impairment in the aged.Neurology. 1979; 29: 1138-1143Crossref PubMed Google Scholar, 15Kaszniak AW Garron DC Fox JH et al.Cerebral atrophy, FUG slowing, age, education, and cognitive functioning in suspected dementia.Neurology. 1979; 29: 1273-1279Crossref PubMed Google Scholar, 17Jacoby RJ Levy R Computed tomography in the elderly, II: senile dementia: diagnosis and functional impairment.Br J Psychiatry. 1980; 136: 256-269Crossref PubMed Scopus (147) Google Scholar, 18Gado M Hughes CP Danziger W et al.Volumetric measurements of cerebrospinal fluid spaces in demented patients and controls.Radiology. 1982; 144: 535-538Crossref PubMed Scopus (92) Google Scholar, 19George AE deLeon MJ Rosenbloom S et al.Ventricular volume and cognitive deficit: a computed tomographic study.Radiology. 1983; 149: 493-498Crossref PubMed Scopus (49) Google Scholar, 20Pfefferbaum A Sullivan EV Jernigan TL et al.A quantitative analysis of CT and cognitive measures in normal aging and Alzheimer's disease.Psychiatry Res. 1990; 35: 115-136Abstract Full Text PDF PubMed Scopus (38) Google Scholar, 21Creasey H Schwartz M Frederickson H et al.Quantitative computed tomography in dementia of the Alzheimer type.Neurology. 1986; 36: 1563-1568Crossref PubMed Google Scholar Also, volumetric measures have been shown to correlate well with specific psychometric indices in healthy, elderly subjects and those with DAT.9Roberts MA Caird FI Computerized tomography and intellectual impairment in the elderly.J Neurol Neurosurg Psychiatry. 1976; 39: 986-989Crossref PubMed Scopus (63) Google Scholar, 10Stafford JL Albert MS Naeser MA et al.Age-related differences in computed tomographic scan measurements.Arch Neurol. 1988; 45: 409-415Crossref PubMed Scopus (33) Google Scholar, 19George AE deLeon MJ Rosenbloom S et al.Ventricular volume and cognitive deficit: a computed tomographic study.Radiology. 1983; 149: 493-498Crossref PubMed Scopus (49) Google Scholar, 20Pfefferbaum A Sullivan EV Jernigan TL et al.A quantitative analysis of CT and cognitive measures in normal aging and Alzheimer's disease.Psychiatry Res. 1990; 35: 115-136Abstract Full Text PDF PubMed Scopus (38) Google Scholar, 21Creasey H Schwartz M Frederickson H et al.Quantitative computed tomography in dementia of the Alzheimer type.Neurology. 1986; 36: 1563-1568Crossref PubMed Google Scholar, 22Albert M Naeser MA Levine HL et al.Ventricular size in patients with presenile dementia of the Alzheimer type.Arch Neurol. 1984; 41: 1258-1263Crossref PubMed Scopus (75) Google Scholar Composites of neuropsychological tests as well as individual tests have been shown to correlate significantly with certain (but not all) measures of CSF volume at the level of the lateral ventricles.10Stafford JL Albert MS Naeser MA et al.Age-related differences in computed tomographic scan measurements.Arch Neurol. 1988; 45: 409-415Crossref PubMed Scopus (33) Google Scholar, 19George AE deLeon MJ Rosenbloom S et al.Ventricular volume and cognitive deficit: a computed tomographic study.Radiology. 1983; 149: 493-498Crossref PubMed Scopus (49) Google Scholar, 22Albert M Naeser MA Levine HL et al.Ventricular size in patients with presenile dementia of the Alzheimer type.Arch Neurol. 1984; 41: 1258-1263Crossref PubMed Scopus (75) Google Scholar These findings suggest that a relationship exists between brain structure and cognitive function, especially in subjects with DAT. The exact nature of this relationship, however, remains elusive, as the various studies use different indices of cognitive function and brain structure to examine this relationship. Despite providing the first opportunity to examine neuronal structure in vivo, CT scanning has several limitations that restrict the scope of this technology.10Stafford JL Albert MS Naeser MA et al.Age-related differences in computed tomographic scan measurements.Arch Neurol. 1988; 45: 409-415Crossref PubMed Scopus (33) Google Scholar, 22Albert M Naeser MA Levine HL et al.Ventricular size in patients with presenile dementia of the Alzheimer type.Arch Neurol. 1984; 41: 1258-1263Crossref PubMed Scopus (75) Google Scholar, 23Wyper DJ Pickard JD Matheson M et al.Accuracy of ventricular volume estimation.J Neurol Neurosurg Psychiatry. 1979; 42: 345-350Crossref PubMed Scopus (32) Google Scholar, 24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar, 25Di Chiro G Brooks PA Dubai L et al.The apical artifact: elevated attenuation values towards the apex of the skull.J Comput Assist Tomogr. 1978; 2: 65-70Crossref PubMed Scopus (65) Google Scholar, 26Condon BR Paterson J Wyper D et al.A quantitative index of ventricular and extraventricular intracranial CSF volumes using MR imaging.J Comput Assist Tomogr. 1986; 10: 784-792Crossref PubMed Scopus (42) Google Scholar, 27Penn RD Belanger MG Yasnoff WA Ventricular volume in man computed from CT scans.Ann Neurol. 1978; 3: 216-223Crossref PubMed Scopus (99) Google Scholar Technical factors such as beam hardening artifact, daily fluctuations in CT numbers, and the effect of head size and attenuation on CT numbers place limits on the application of CT scanning to the detailed study of neuronal function.10Stafford JL Albert MS Naeser MA et al.Age-related differences in computed tomographic scan measurements.Arch Neurol. 1988; 45: 409-415Crossref PubMed Scopus (33) Google Scholar, 22Albert M Naeser MA Levine HL et al.Ventricular size in patients with presenile dementia of the Alzheimer type.Arch Neurol. 1984; 41: 1258-1263Crossref PubMed Scopus (75) Google Scholar, 23Wyper DJ Pickard JD Matheson M et al.Accuracy of ventricular volume estimation.J Neurol Neurosurg Psychiatry. 1979; 42: 345-350Crossref PubMed Scopus (32) Google Scholar, 24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar, 25Di Chiro G Brooks PA Dubai L et al.The apical artifact: elevated attenuation values towards the apex of the skull.J Comput Assist Tomogr. 1978; 2: 65-70Crossref PubMed Scopus (65) Google Scholar, 26Condon BR Paterson J Wyper D et al.A quantitative index of ventricular and extraventricular intracranial CSF volumes using MR imaging.J Comput Assist Tomogr. 1986; 10: 784-792Crossref PubMed Scopus (42) Google Scholar Also, ventricular volume estimation, based on manual tracing of ventricular outlines on CT images, vary as much as 30%-100%, thereby reducing the reliability of these measurements.19George AE deLeon MJ Rosenbloom S et al.Ventricular volume and cognitive deficit: a computed tomographic study.Radiology. 1983; 149: 493-498Crossref PubMed Scopus (49) Google Scholar Absence of a clear demarcation between CSF and brain, especially in the cortex, compounded by partial volume averaging, places additional constraints on CT-determined brain volumetric measurements.23Wyper DJ Pickard JD Matheson M et al.Accuracy of ventricular volume estimation.J Neurol Neurosurg Psychiatry. 1979; 42: 345-350Crossref PubMed Scopus (32) Google Scholar, 24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar Magnetic resonance imaging (MRI) is a superior technology that allows excellent visualization of brain anatomy in both normal and pathologic states.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar, 25Di Chiro G Brooks PA Dubai L et al.The apical artifact: elevated attenuation values towards the apex of the skull.J Comput Assist Tomogr. 1978; 2: 65-70Crossref PubMed Scopus (65) Google Scholar, 26Condon BR Paterson J Wyper D et al.A quantitative index of ventricular and extraventricular intracranial CSF volumes using MR imaging.J Comput Assist Tomogr. 1986; 10: 784-792Crossref PubMed Scopus (42) Google Scholar, 28Kohn MI Tanna NK Herman GT et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging.Radiology. 1991; 178: 115-122Crossref PubMed Scopus (256) Google Scholar MRI's improved resolution, together with the complete elimination of the beam hardening artifact, makes it the method of choice for quantitative neuroanatomic studies. Also, MRI provides a much better contrast between gray/white matter and CSF, thereby making it particularly well-suited to taking global and regional brain and CSF volumetric measurements.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar, 28Kohn MI Tanna NK Herman GT et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging.Radiology. 1991; 178: 115-122Crossref PubMed Scopus (256) Google Scholar, 29Jernigan TL Press GA Hesselink JR Methods of measuring brain morphologic features on magnetic resonance images.Arch Neurol. 1990; 47: 27-32Crossref PubMed Scopus (234) Google Scholar, 30Jernigan TL Archibald SL Berhow MT et al.Cerebral structure on MRI, I: localization of age-related changes.Biol Psychiatry. 1991; 29: 55-67Abstract Full Text PDF PubMed Scopus (339) Google Scholar, 31Wahlund CO Agartz I Almqvist Ove et al.The brain in healthy aged individuals: MR imaging.Radiology. 1990; 174: 675-679Crossref PubMed Scopus (80) Google Scholar A segmentation algorithm that uses proton density and T2 pixel values to “segment” brain from CSF was recently developed using MRI in our laboratory.28Kohn MI Tanna NK Herman GT et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging.Radiology. 1991; 178: 115-122Crossref PubMed Scopus (256) Google Scholar The reliability and validity of this technique has been established, and it has been used to study brain atrophy in normal aging and psychiatric conditions such as schizophrenia and DAT.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar, 32Gur RC Mozley PD Resnick SM et al.Gender differences in age effect on brain atrophy measured by magnetic resonance imaging.Proc Natl Acad Sci USA. 1991; 88: 2845-2849Crossref PubMed Scopus (365) Google Scholar, 33Gur RE Mozley PD Resnick SM et al.Magnetic resonance in schizophrenia, I: volumetric analysis of brain and cerebrospinal fluid.Arch Gen Psychiatry. 1991; 48: 407-412Crossref PubMed Scopus (90) Google Scholar In a preliminary study from our laboratory, 16 subjects with DAT and 16 healthy, age-matched control subjects were examined using this technique.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar The DAT group had significantly greater ventricular and sulcal CSF volumes compared to the controls.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar However, only global measures of atrophy were examined in that study, and right-left hemispheric differences in CSF and ventricular volumes as a measure of laterality in DAT and control subjects were not considered.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar Also, no attempt was made to correlate the structural changes in DAT to cognitive measures such as language, visuospatial function, and memory.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar This leaves open the question of the relationship between MRI-determined neuroanatomical changes in DAT and the neuropsychological deficits that characterize the disease. In order to address these questions, the aforementioned study was expanded to include a larger sample of subjects with DAT and healthy, age-matched controls. We were interested in examining ventricular and CSF volumetric measures both globally and hemispherically in subjects with DAT and controls. We were also interested in confirming our earlier finding of increased sulcal and ventricular CSF volumes in DAT subjects when compared to age-matched controls, using a larger patient sample. Also, we wanted to examine the relationship between structural changes and specific cognitive measures in DAT. For example, we were interested in examining the relationship between left-hemisphere CSF (sulcal and ventricular) volumes and tests of language, verbal intelligence, and semantic memory—cognitive functions that are traditionally attributed to the left hemisphere. Similarly, another aspect explored was the relationship between right-hemisphere volumetric measures and cognitive domains such as visuospatial function and visual memory. We hypothesized that increased CSF volumes in the right and left hemispheres would be associated with poor performance on the cognitive functions mediated by the corresponding hemisphere. Our sample consisted of 34 subjects with probable DAT (17 men, 17 women) and 29 healthy, age-matched controls (12 men, 17 women). The DAT group included the 16 subjects who were part of the earlier report from our laboratory. All DAT subjects met NINCDS-ADRDA criteria for probable DAT and were otherwise medically healthy.34McKhann G Drachman D Folstein M et al.Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA workshop under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease.Neurology. 1984; 34: 939-944Crossref PubMed Google Scholar Patients and controls received a complete physical and mental status exam, followed by laboratory testing that included complete and differential blood counts, electrolytes, renal, liver and thyroid screen, serum B12, folate levels, and a syphilis serology test. Patients and controls were free of significant medical, neurologic, and psychiatric illness, such as diabetes, malignancy, stroke, and hepatic, renal, cardiac, or gastrointestinal disease. Subjects with a history of stroke, significant head injury, epilepsy, transient ischemic attacks, neuropathies, and myopathies were excluded from the study, as were those with a prior history of any major psychiatric disorder, such as major depression or substance abuse. These criteria are consistent with inclusion criteria used in earlier reports.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar MRI images were acquired, using a 1.5-tesla GE scanner with a head coil (GE Medical Systems, Milwaukee). Transaxial slices 5.0 mm thick were obtained, with a field of view of 20 cm and a pixel size of 0.781 mm. The slices were contiguous, and the images were displayed with a 256 × 128 matrix. T2-weighted images (TR/TE = 2,500–3,000/80 msec) and proton density images (TR/TE = 2,500–3,000/20-30 msec) were acquired for each patient. No compensation was made for pulsatile flow in these studies. The MR images were analyzed on a Sun Microsystems workstation. The thresholding/segmentation technique that was developed in our laboratory, and previously described in detail,24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar, 28Kohn MI Tanna NK Herman GT et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging.Radiology. 1991; 178: 115-122Crossref PubMed Scopus (256) Google Scholar was used to analyze the MR images. Briefly, thresholds were set for both the proton density and the T2-weighted image. A two-dimensional histogram was obtained, which compared each pixel's proton density and T2-weighted intensity. Regions were then assigned on the histogram to indicate brain and CSF, so that they could be accurately segmented by the program. Regions were drawn around the total brain and the ventricular spaces and divided into right and left sides. Structures from the posterior fossa were excluded in this analysis. Whole-brain CSF (this includes ventricular and sulcal CSF), ventricular (lateral and third ventricle), and sulcal CSF volumes were obtained for both hemispheres, using this method. Details of the image-analysis method and the specific anatomical landmarks used to decide boundaries have been previously described in detail.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar, 32Gur RC Mozley PD Resnick SM et al.Gender differences in age effect on brain atrophy measured by magnetic resonance imaging.Proc Natl Acad Sci USA. 1991; 88: 2845-2849Crossref PubMed Scopus (365) Google Scholar, 33Gur RE Mozley PD Resnick SM et al.Magnetic resonance in schizophrenia, I: volumetric analysis of brain and cerebrospinal fluid.Arch Gen Psychiatry. 1991; 48: 407-412Crossref PubMed Scopus (90) Google Scholar Also, total brain volume, comprising both gray and white matter, and hemispheric brain volumes were calculated. Both absolute and normalized volumetric measures were obtained in both study groups. Normalized values were obtained by dividing the absolute volume of a given region (e.g., right-hemisphere ventricular CSF volume) by the total intracranial volume. This corrects for the effect of head size on brain and CSF volumes, and there-fore provides a more reliable measure of brain and CSF volumes for comparison between groups.24Tanna NK Kohn MI Horwich DN et al.Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PUT data correction for atrophy.Radiology. 1991; 178: 123-130Crossref PubMed Scopus (140) Google Scholar All MRI scans were analyzed by two independent raters blinded to the clinical status of subjects and controls. Both raters were
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