NEUROIMAGING OF THE AGING BRAIN

doi:10.1016/S0733-8619(05)70082-7

Neurologic Clinics

Volume 16, Issue 3, 1 August 1998, Pages 581-598

https://doi.org/10.1016/S0733-8619(05)70082-7 Get rights and content

The elderly now constitute a very rapidly growing proportion of the population. It has been estimated that by the year 2020, more than 30% of the population in the United States will be more than 55 years of age.¹ This demographic change necessitates imaging analysts to be aware of the imaging changes seen in normal aging of the brain. Meaningful interpretation of brain imaging studies necessitates understanding of the appearance of “normal” physiologic changes and the variety of neurodegenerative disorders that present in brain images of late middle-aged and elderly patients.

Advances in brain imaging technology have resulted in a growing understanding of the imaging appearance of the aging process, although exact mechanisms are not well understood. In the brain, the normal aging process and some of the neurodegenerative disorders share the same imaging findings, although those associated with the neurodegenerative disorders occur more prematurely. Sulcal and ventricular enlargement seen on computed tomography (CT) or magnetic resonance (MR) images, periventricular and subcortical hyperintensities on MR images, and iron accumulation in certain areas of the brain are considered to represent neurodegenerative changes in neurologically intact elderly people. Significant gender differences exist in age-related brain degeneration.⁸²

Section snippets

WHITE MATTER CHANGES ON MR IMAGES

Some white matter hyperintensities are considered physiologic and are seen in young individuals. In young individuals, triangular hyperintensities in the terminal area of myelination above and posterior to the trigones of the lateral ventricles is a normal finding (Fig. 1). These hyperintensities are seen normally up to the second decade but occasionally up to the fourth decade.⁹⁹ In all ages the posterior aspect of the posterior limb of the internal capsule, the small Virchow-Robin (VR)

PERIVENTRICULAR AND DEEP WHITE MATTER HYPERINTENSITIES

Punctate, less than 5-mm hyperintensities on T2-weighted images are a frequent finding on the MR images of the elderly. These increase in frequency from 11% in the fourth decade to 65% in the seventh decade.⁴⁰ The histologic correlates of these punctate lesions consist of a spectrum of processes. Minor perivascular damage, but not infarction, is the most likely etiology for these high signal foci.43, 91 These lesions are seen around arteries and veins. Enlarged perivascular space and ectatic

SUBCORTICAL WHITE MATTER CHANGES

Subcortical arteriosclerotic encephalopathy (SAE), synonymous with Binswanger's disease (first described in 1894 by Otto Binswanger), has experienced a renaissance with the advent of CT and MR imaging. It has been claimed that irregular areas of T2 hyperintensity in the periventricular region and centrum semiovale represent Binswanger's disease in the proper clinical setting. This observation, however, has limited clinical utility since alteration of the white matter signal is common in both

VIRCHOW-ROBIN SPACE

VR space, or perivascular space, is an invagination of the subarachnoid space surrounding a vessel going into the brain. VR spaces surround arteries, veins, arterioles, and venules. They are found in the inferior third of the basal ganglia, perforating the anterior commissure, and paralleling the lenticulostriate arteries (see Fig. 2). They are also found in the high convexity and in midbrain (see Fig. 3). Although more rare in the centrum semiovale, they are more frequently seen in the

MRI SIGNAL CHANGES OF EXTRAPYRAMIDAL NUCLEI DUE TO IRON DEPOSITION

Signal intensity changes of gray matter nuclei with normal aging are well-documented.³¹ Although the cause of this age-related signal change seen on T2-weighted image (T2 shortening) is controversial, iron deposition most likely accounts for these observations in the aging brain.³³ Age-related increase in brain iron demonstrated in postmortem studies of healthy individuals correspond to the age-related T2 shortening observed on MR imaging.2, 54, 79 The association between increased tissue iron

ATROPHY

Normal aging beginning around the fifth to sixth decade shows enlargement of the CSF spaces due to age-related neuronal loss.⁸³ This volume loss of the brain is called atrophy (Fig. 10). Most early changes are seen in the posterior fossa, especially in the vermis. By the early sixth decade, the third ventricle begins to enlarge. Enlargement of cortical sulci and cisterns is part of the normal aging process (Fig. 11). The normal brain ventricular volume is 20 to 25 mL; however, atrophy increases

ALZHEIMER'S DISEASE

AD is the most common dementing disorder of the elderly.⁹⁴ It affects 50% of individuals older than 85 years.³⁹ In the past, neuroimaging of the suspected AD patients was limited to exclusion of other pathology such as neoplastic lesions and subdural hematomas and verification of atrophy and/or presence of white matter changes. Currently, the radiologic diagnosis of AD is becoming increasingly a diagnosis of inclusion. CT studies in patients suspected of having AD showed weak correlation

PARKINSON'S DISEASE

Parkinson's disease (PD) is a common disorder affecting approximately 1% of population over age 50 years.⁵⁹ PD shares many of the same imaging findings as AD; however, in many patients with PD, the MR image will appear normal for age. Decreased T2 signal in the putamen and caudate may be seen in up to 40% of individuals with PD. PD is a primary disorder of pars compacta of substantia nigra. MR imaging may show decreased width of pars compacta in both PD patients and patients with striatonigral

SUMMARY

With advancing age, periventricular, subcortical, and deep white matter signal alterations occur that cannot be categorized into specific disease entities. These signal changes are seen as low density on CT or high signal on proton density and T2-weighted MR images. Clinical correlation ranges from normal cognition to mild slowing of mental processing speed. Association of these white matter changes with AD is controversial. Differentiation between white matter high signal foci and disease

References (101)

De LeonM.J. et al.
Correlations between computerized tomographic changes and behavioural deficits in senile dementia [letter]
Lancet
(1979)
De LeonM.J. et al.
Early marker for Alzheimer's disease: The atrophic hippocampus [letter]
Lancet
(1989)
B.M. Hubbard et al.
A quantitative study of cerebral atrophy in old age and senile dementia
J Neurol Sci
(1981)
T. Jernigan et al.
Cerebral structure on MRI, Part I: Localization of age-related changes
Biol Psychiatry
(1991)
K.O. Lim et al.
In vivo quantification of the limbic system using MRI: Effects of normal aging
Psychiatry Res
(1990)
J.L. Price et al.
The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease
Neurobiol Aging
(1991)
D.C. Steffens et al.
Magnetic resonance imaging changes in putamen nuclei iron content and distribution in normal subjects
Psychiatry Research: Neuroimaging Section
(1996)
E.V. Sullivan et al.
Age-related decline in MRI volumes of temporal lobe gray matter but not hippocampus
Neurobiology of Aging
(1995)
C. Ansberry
Day-Care centers for elderly spring up as alternative to costly nursing homes
Wall Street Journal
(December 8; 1986)
S. Aoki et al.
Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5T
Radiology
(1989)

I. Awad et al.

Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. I. Correlation with age and cerebrovascular risk factors

Stroke

(1986)

I. Awad et al.

Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. II. Postmortem pathological correlation

Stroke

(1986)

I. Awad et al.

Incidental lesions noted on magnetic resonance imaging of the brain: Prevalence and clinical significance in various age groups

Neurosurgery

(1987)

G. Bartzokis et al.

In vivo MR evaluation of age-related increases in brain iron

AJNR Am J Neuroradiol

(1994)

D.A. Bennett et al.

Clinical diagnosis of Binswanger's disease

J Neurol Neurosurg Psychiatry

(1990)

A. Bizzi et al.

Role of iron and ferritin in MR imaging of the brain: A study in primates at different field strengths

Radiology

(1990)

D.D. Blatter et al.

Quantitative volumetric analysis of brain MR: Normative database spanning 5 decades of life

AJNR Am J Neuroradiol

(1995)

W. Bradley et al.

Patchy periventricular white matter lesions in the elderly: A common observation during NMR imaging

Magn Reson Med

(1984)

B. Braffman et al.

Brain MR: Pathologic correlation with gross and histopathology. 1. Lacunar infarction and Virchow-Robin spaces

AJNR Am J Neuroradiol

(1988)

B. Braffman et al.

Brain MR: Pathologic correlation with gross and histopathology. 2. Hyperintense white matter foci in the elderly

AJNR Am J Neuroradiol

(1988)

M. Brant-Zawadzki et al.

MR imaging of the aging brain: Patchy white matter lesions and dementia

AJNR Am J Neuroradiol

(1985)

A. Brun et al.

Subcortical pathology of Alzheimer's disease

Adv Neurol

(1990)

R.N. Bryan et al.

Infarctlike lesions in the brain: Prevalence and anatomic characteristics at MR imaging of the elderly—data from the cardiovascular health study

Radiology

(1997)

A. Cajade-Law et al.

Vascular causes of white matter disease

Neuroimaging Clinics of North America

(1993)

L. Caplan et al.

Clinical features of subcortical arteriosclerotic encephalopathy (Binswanger's disease)

Neurology

(1978)

Carr CA, Guimaraes AR, Growdon JH, et al: Combining proton MRS and MRI morphometry increases accuracy in the diagnosis...

M. Chimowitz et al.

Periventricular lesions on MRI. Facts and theories

Stroke

(1989)

M.I. Chimowitz et al.

Further observations on the pathology of subcortical lesions identified on magnetic resonance imaging

Arch Neurol

(1992)

M.I. Chimowitz et al.

Periventricular lesions of MRI. Facts and theories

Curr Conc Cerebrovasc Dis Stroke

(1989)

C.E. Coffey et al.

Quantitative cerebral anatomy of the aging human brain: A cross-sectional study using magnetic resonance imaging

Neurology

(1992)

J.R. Connor et al.

A histochemical study of iron, transferin, and ferritin in Alzheimer's disease brains

J Neurosci Res

(1992)

ConvitA. et al.

Age-related changes in brain: 1. Magnetic resonance imaging measures of temporal lobe volumes in normal subjects

Psychiatr Q

(1995)

P.E. Cowell et al.

Sex differences in aging of the human frontal and temporal lobes

J Neurosci

(1994)

C. DeCarli et al.

The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults

Neurology

(1995)

De ReuckJ. et al.

Periventricular atherosclerotic leukoencephalopathy

Neurology

(1972)

R. Dietrich et al.

Iron accumulation in the basal ganglia following severe ischemic-anoxic insults in children

Radiology

(1988)

B.P. Drayer

Imaging of the aging brain. I. Normal findings

Radiology

(1988)

B.P. Drayer

Imaging of the aging brain. II. Pathologic conditions

Radiology

(1988)

B. Drayer et al.

Magnetic resonance imaging of brain iron

AJNR Am J Neuroradiol

(1986)

B. Drayer et al.

Parkinson plus syndrome: Diagnosis using high field MR imaging of brain iron

Radiology

(1986)

M. Durand-Fardel

Traite du ramollissement du cerveau

T. Erkinjuntti et al.

Temporal lobe atrophy on magnetic resonance imaging in the diagnosis of early Alzheimer's disease

Arch Neurol

(1993)

T. Erkinjuntti et al.

Do white matter changes on MRI and CT differentiate vascular demetia from Alzheimer's disease?

J Neurol Neurosurg Psychiatry

(1987)

M.S. Edwards

Comment

Neurosurgery

(1987)

D.A. Evans et al.

Prevalence of Alzheimer's disease in a community population of older persons: Higher than previously reported

JAMA

(1990)

F. Fazekas

Magnetic resonance signal abnormalities in asymptomatic individuals: Their incidence and functional correlates

Eur Neurol

(1989)

F. Fazekas et al.

MR signal abnormalities at 1.5T in Alzheimer's dementia and normal aging

AJNR Am J Neuroradiol

(1987)

F. Fazekas et al.

White matter signal abnormalities in normal individuals: Correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors

Stroke

(1988)

F. Fazekas et al.

The morphologic correlate of incidental punctate MR white matter hyperintensities

AJNR Am J Neuroradiol

(1991)

M. Gado et al.

Volumetric measurements of the cerebrospinal fluid spaces in demented subjects and controls

Radiology

(1982)

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Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness
2010, Neurobiology of Aging
Citation Excerpt :
Studies using T2-weighted MRI have documented signal changes that are believed to arise from an accumulation of heavy metals in the striatum with increasing age (Ketonen, 1998). Iron deposition in neural tissue has been associated with neurodegenerative disorders, such as Parkinson's disease (Ke and Ming Qian, 2003; Zecca et al., 2004), and there is some evidence that a notable amount of buildup also occurs in subcortical GM structures during the course of healthy aging (Bartzokis et al., 1994, 2007; Hallgren and Sourander, 1958; Ketonen, 1998). While the mechanism by which iron deposition would cause a change in the FA metric is not entirely understood, a well-documented decrease or shortening of the T2 signal has been linked to heavy metal accumulation in the putamen in the sixth decade of life (Ketonen, 1998).
It is well established that healthy aging is accompanied by structural changes in many brain regions and functional decline in a number of cognitive domains. The goal of this study was to determine (1) whether the regional distribution of age-related brain changes is similar in gray matter (GM) and white matter (WM) regions, or whether these two tissue types are affected differently by aging, and (2) whether measures of cognitive performance are more closely linked to alterations in the cerebral cortex or in the underlying WM in older adults (OA). To address these questions, we collected high-resolution magnetic resonance imaging (MRI) data from a large sample of healthy young adults (YA; aged 18–28) and OA (aged 61–86 years). In addition, the OA completed a series of tasks selected to assess cognition in three domains: cognitive control, episodic memory, and semantic memory. Using advanced techniques for measuring cortical thickness and WM integrity, we found that healthy aging was accompanied by deterioration of both GM and WM, but with distinct patterns of change: Cortical thinning occurred primarily in primary sensory and motor cortices, whereas WM changes were localized to regions underlying association cortices. Further, in OA, we found a striking pattern of region-specific correlations between measures of cognitive performance and WM integrity, but not cortical thickness. Specifically, cognitive control correlated with integrity of frontal lobe WM, whereas episodic memory was related to integrity of temporal and parietal lobe WM. Thus, age-related impairments in specific cognitive capacities may arise from degenerative processes that affect the underlying connections of their respective neural networks.
An MRI study of age-related white and gray matter volume changes in the rhesus monkey
2008, Neurobiology of Aging
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To our knowledge, the present study uniquely examines ROI volume changes of the entire rhesus monkey forebrain, brainstem and cerebellum as a function of age group. The overall decrease from young to old age in the standardized volumes of total forebrain (5.01%), forebrain parenchyma (5.24%), forebrain white matter (11.53%), forebrain gray matter (2.08%), caudate nucleus (11.79%) and globus pallidus (18.26%) that we found have been similarly reported by many human aging studies (Andersen et al., 1999; Bartzokis et al., 2001; Ge et al., 2002; Gunning-Dixon et al., 1998; Guttmann et al., 1998; Jernigan et al., 1991; Ketonen, 1998; Kohn et al., 1991; Krishnan et al., 1990; Matochik et al., 2000; Meier-Ruge et al., 1992; Murphy et al., 1992; Raz et al., 1995, 2003; Resnick et al., 2003; Salat et al., 1999). Forebrain white matter and forebrain gray matter volume changes in the monkey closely matches the results of Guttmann et al. (1998) and Ge et al. (2002) in humans.
We applied the automated MRI segmentation technique Template Driven Segmentation (TDS) to dual-echo spin echo (DE SE) images of eight young (5–12 years), six middle-aged (16–19 years) and eight old (24–30 years) rhesus monkeys. We analyzed standardized mean volumes for 18 anatomically defined regions of interest (ROI's) and found an overall decrease from young to old age in the total forebrain (5.01%), forebrain parenchyma (5.24%), forebrain white matter (11.53%), forebrain gray matter (2.08%), caudate nucleus (11.79%) and globus pallidus (18.26%). Corresponding behavioral data for five of the young, five of the middle-aged and seven of the old subjects on the Delayed Non-matching to Sample (DNMS) task, the Delayed-recognition Span Task (DRST) and the Cognitive Impairment Index (CII) were also analyzed. We found that none of the cognitive measures were related to ROI volume changes in our sample size of monkeys.
Tremor/ataxia syndrome and fragile X premutation: Diagnostic caveats
2007, Journal of Clinical Neuroscience
Citation Excerpt :
This is especially relevant in Case 2, where massive periventricular white matter changes were not associated with either increased T2-weighted signal intensity of the middle cerebellar peduncles or tremor/ataxia symptoms. Furthermore, this individual had a history of untreated hypertension, one of the risk factors associated with these types of MRI changes.20 However, the relatively young age of this individual, no history of either ischaemic cerebrovascular or heart disease, or inflammatory process, the severity of MRI changes combined with elevated levels of mRNA, as well as the presence of anxiety and autonomic dysfunction earlier reported in the FXTAS patients,5 all suggest that fragile X premutation is the most likely factor causing, or contributing to the MRI changes observed in Case 2.
The fragile X-associated tremor/ataxia syndrome (FXTAS) is a newly discovered late-onset neurodegenerative disorder caused by a premutation in the FMR1 X-linked gene. We present examples of a discrepancy between obvious brain changes observed on MRI, and minimal clinical neurological manifestations in three older carriers of this premutation. This discrepancy occurred in three of nine carriers ascertained in an unbiased manner. If the systematic follow-up studies of adult carriers confirm this trend, this will have an impact on early diagnosis of neurological involvement and possible prevention. If MRI changes precede clinical manifestation of FXTAS this may explain the low detection rate of fragile X carriers among patients with neurological syndromes associated with tremor/ataxia.
Increased risk of death in community-dwelling older people with white matter hyperintensities on MRI
2006, Journal of the Neurological Sciences
Previous studies in subjects with a history of stroke have shown that white matter hyperintensities (WMH) on MRI are associated with increased risk of death. However, it has not been determined whether WMH are independently related to death in community-dwelling older people without stroke.
In a sample of community-dwelling people over 75 years with no history of stroke or other neurological diseases, WMH on brain MRI T2-weighted sequences were classified as grade 0, grade 1, or grade 2. Grade 2 WMH were identified in 36 subjects. Age- and sex-matched grade 0 and grade 1 WMH groups were selected for comparison to the grade 2 WMH group. All subjects underwent an initial clinical evaluation and were followed for a median of 11.8 years (interquartile range = 10.7 to 12.2 years). Cox proportional-hazards analysis was used to determine the independent association between WMH and time to death from any cause.
In an unadjusted analysis, grade 2 WMH was associated with death from any cause (hazard ratio = 1.98; 95% confidence interval = 1.06, 3.70). After adjustment for hypertension, high cholesterol, diabetes, and coronary artery disease, grade 2 WMH remained significantly associated with death (hazard ratio = 2.31; 95% confidence interval = 1.21, 4.40) in these age- and sex-matched groups.
Severe WMH increase the risk of death, even in community-dwelling elderly without stroke or other neurological disease, independent of other covariates including hypertension, age, and coronary artery disease.
Brain atrophy in long-term abstinent alcoholics who demonstrate impairment on a simulated gambling task
2006, NeuroImage
We recently demonstrated impairment on the Simulated Gambling Task (SGT) in long-term abstinent alcoholics (AbsAlc). Brain regions that have been shown to be necessary for intact SGT performance are the ventromedial prefrontal cortex (VMPFC) and the amygdala; patients with VMPFC or amygdalar damage demonstrate SGT impairments similar to those of substance abusing populations. We examined these brain regions, using T1-weighted MRIs, in the 101 participants from our previous study using voxel-based morphometry (VBM). VBM was performed using a modification we developed [Fein, G., Landman, B., Tran, H., Barakos, J., Moon, K., Di Sclafani, V., Shumway, R., 2006. Statistical parametric mapping of brain morphology: sensitivity is dramatically increased by using brain-extracted images as inputs. Neuroimage] of Baron's procedure, [Baron, J.C., Chetelat, G., Desgranges, B., Perchey, G., Landeau, B., de la Sayette, V., Eustache, F., 2001. In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease. Neuroimage 14 (2), 298–309], in which we use skull-stripped images as input. We also restricted the analysis to a ROI consisting of the amygdala and VMPFC as defined by the Talairach Daemon resource. Compared to the controls, the AbsAlc participants had significant foci of reduced gray matter density within the amygdala. Thus, SGT decision-making deficits are associated with reduced gray matter in the amygdala, a brain region previously implicated in similar decision-making impairments in neurological samples. This structurally based abnormality may be the result of long-term alcohol abuse or dependence, or it may reflect a pre-existing factor that predisposes one to severe alcoholism. From an image analysis perspective, this work demonstrates the increased sensitivity that results from using skull-stripped inputs and from restricting the analysis to a ROI. Without both of these methodological advances, no statistically significant finding would have been forthcoming from this work.
Longitudinal Progression of Subclinical Structural Brain Disease in Normal Aging
2004, American Journal of Geriatric Psychiatry
The authors describe four types of brain structural change in “normal aging:” cortical atrophy, central atrophy, deep white-matter hyperintensities (DWMH), and periventricular hyperintensities (PVH). Cross-sectional investigations have reported that greater volumes of these forms of “subclinical structural brain disease” (SSBD) were found with increasing age. Greater volumes were also associated with poorer cognition, even though subjects performed within the normal range. The natural history of these forms of SSBD and their functional impact are not well established.
Twenty-nine normal subjects, ages 60–89, were examined longitudinally by volumetric magnetic resonance imagery, with two assessments performed at least 2 years apart; 26 also completed neuropsychological testing to evaluate processing speed, executive functions, language, and other cognitive functions. Associations between structure and function were evaluated with regression models.
For most subjects, the volumes for signs of all types of SSBD were found to have increased; for many subjects, increases were small, and a few showed no change or small decreases. PVH and DWMH increases were predicted by baseline cerebrovascular risk factors. Cognitive test performance changed little over time for these normal subjects.
SSBD volumes increased for most subjects over time, with small average increases for most types. Pretreatment cerebrovascular risk factors were associated with greater increases of PVH and DWMH, suggesting that progression of these types of SSBD may be amenable to intervention.

View all citing articles on Scopus

: Address reprint requests to Leena M. Ketonen, MD, PhD, Department of Radiology, University of Texas Medical Branch, 301 University Blvd, Rt. 0709, 237 Clinical Sciences Bldg, Galveston, TX 77555-0709

^*: Department of Radiology, University of Texas Medical Branch at Galveston, Galveston, Texas

View full text

NEUROIMAGING OF THE AGING BRAIN

Section snippets

WHITE MATTER CHANGES ON MR IMAGES

PERIVENTRICULAR AND DEEP WHITE MATTER HYPERINTENSITIES

SUBCORTICAL WHITE MATTER CHANGES

VIRCHOW-ROBIN SPACE

MRI SIGNAL CHANGES OF EXTRAPYRAMIDAL NUCLEI DUE TO IRON DEPOSITION

ATROPHY

ALZHEIMER'S DISEASE

PARKINSON'S DISEASE

SUMMARY

Lancet

Lancet

J Neurol Sci

Biol Psychiatry

Psychiatry Res

Neurobiol Aging

Psychiatry Research: Neuroimaging Section

Neurobiology of Aging

Day-Care centers for elderly spring up as alternative to costly nursing homes

Wall Street Journal

Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5T

Radiology

Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. I. Correlation with age and cerebrovascular risk factors

Stroke

Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. II. Postmortem pathological correlation

Stroke

Incidental lesions noted on magnetic resonance imaging of the brain: Prevalence and clinical significance in various age groups

Neurosurgery

In vivo MR evaluation of age-related increases in brain iron

AJNR Am J Neuroradiol

Clinical diagnosis of Binswanger's disease

J Neurol Neurosurg Psychiatry

Role of iron and ferritin in MR imaging of the brain: A study in primates at different field strengths

Radiology

Quantitative volumetric analysis of brain MR: Normative database spanning 5 decades of life

AJNR Am J Neuroradiol

Patchy periventricular white matter lesions in the elderly: A common observation during NMR imaging

Magn Reson Med

Brain MR: Pathologic correlation with gross and histopathology. 1. Lacunar infarction and Virchow-Robin spaces

AJNR Am J Neuroradiol

Brain MR: Pathologic correlation with gross and histopathology. 2. Hyperintense white matter foci in the elderly

AJNR Am J Neuroradiol

MR imaging of the aging brain: Patchy white matter lesions and dementia

AJNR Am J Neuroradiol

Subcortical pathology of Alzheimer's disease

Adv Neurol

Infarctlike lesions in the brain: Prevalence and anatomic characteristics at MR imaging of the elderly—data from the cardiovascular health study

Radiology

Vascular causes of white matter disease

Neuroimaging Clinics of North America

Clinical features of subcortical arteriosclerotic encephalopathy (Binswanger's disease)

Neurology

Periventricular lesions on MRI. Facts and theories

Stroke

Further observations on the pathology of subcortical lesions identified on magnetic resonance imaging

Arch Neurol

Periventricular lesions of MRI. Facts and theories

Curr Conc Cerebrovasc Dis Stroke

Quantitative cerebral anatomy of the aging human brain: A cross-sectional study using magnetic resonance imaging

Neurology

A histochemical study of iron, transferin, and ferritin in Alzheimer's disease brains

J Neurosci Res

Age-related changes in brain: 1. Magnetic resonance imaging measures of temporal lobe volumes in normal subjects

Psychiatr Q

Sex differences in aging of the human frontal and temporal lobes

J Neurosci

The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults

Neurology

Periventricular atherosclerotic leukoencephalopathy

Neurology

Iron accumulation in the basal ganglia following severe ischemic-anoxic insults in children

Radiology

Imaging of the aging brain. I. Normal findings

Radiology

Imaging of the aging brain. II. Pathologic conditions

Radiology

Magnetic resonance imaging of brain iron

AJNR Am J Neuroradiol

Parkinson plus syndrome: Diagnosis using high field MR imaging of brain iron