518 lines
36 KiB
Markdown
518 lines
36 KiB
Markdown
---
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title: "Normal Aging Brain"
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docid: "2a315550-b2ea-4afe-a2ef-f93a2209f276"
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authors:
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- key: "a25c450b-3d34-4f64-bba3-cc0834813df6"
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value: "Miral D. Jhaveri, MD, MBA"
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breadcrumbs:
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-
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name: "Brain"
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slug: "brain"
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treeNodeId: "6d8829f1-14d7-45af-8675-255189aa526a"
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-
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name: "Diagnosis"
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slug: "diagnosis"
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treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
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-
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name: "Pathology-Based Diagnoses"
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slug: "pathology-based-diagnoses"
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treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
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-
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name: "Acquired Toxic/Metabolic/Degenerative Disorders"
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slug: "acquired-toxicmetabolicdegenerativ-"
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treeNodeId: "ba3cfeaf-64d9-4117-91e8-d2ce58783fc5"
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-
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name: "Dementias and Degenerative Disorders"
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slug: "dementias-and-degenerative-disorde-"
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treeNodeId: "6381104d-7a4c-4be5-bb19-3cd90837d547"
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-
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name: "Normal Aging Brain"
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slug: "normal-aging-brain"
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treeNodeId: null
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category: "Brain"
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cmeTopicId: "5933cd1e-de83-43b9-b172-894d762b8787"
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documentVersionId: "7789baf5-4f7f-4519-b217-90bd5c560838"
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imageCount: 31
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lastUpdated: "09/29/20"
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pageDescription: "Normal Aging Brain"
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pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Acquired Toxic/Metabolic/Degenerative Disorders, Dementias and Degenerative Disorders, Normal Aging Brain"
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pageTitle: "Normal Aging Brain | STATdx"
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enhancedTitle: "Normal Aging Brain"
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type: "DX"
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references: true
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breadcrumbs:
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- "Brain"
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- "Diagnosis"
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- "Pathology-Based Diagnoses"
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- "Acquired Toxic/Metabolic/Degenerative Disorders"
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- "Dementias and Degenerative Disorders"
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- "Normal Aging Brain"
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---
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# KEY FACTS
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- ## Terminology
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- ↓ overall brain volume with advancing age
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- Reflected in relative ↑ CSF spaces
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- ## Imaging
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- Broad spectrum of "normal" on imaging in elderly
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- "Successfully aging brain"
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- Smooth, thin, periventricular, high signal rim on FLAIR is normal
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- White matter hyperintensities (WMHs) absent/few
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- ↓ total brain volume
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- Selective atrophy of white matter (not gray matter) predominates
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- ± punctate hippocampal Ca⁺⁺
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- Enlarged perivascular (Virchow-Robin) spaces
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- WMHs ↑ in number/size after 50 years
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- Focal high signal intensity in splenium of corpus callosum
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- GRE/SWI
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- Increasing mineralization of basal ganglia with age
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- "Black line" in visual, motor/sensory cortex
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- Microbleeds are relatively common in aging patients
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- Lower prevalence than in cerebral amyloid disease & Alzheimer disease
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- ## Top Differential Diagnoses
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- Mild cognitive impairment
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- Alzheimer disease
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- Sporadic subcortical arteriosclerotic encephalopathy
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- Vascular dementia
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- Frontotemporal lobar degeneration
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- ## Clinical Issues
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- WMHs correlate with age, silent stroke, hypertension, female sex
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- ## Diagnostic Checklist
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- Cannot predict cognitive function from CT/MR
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- If brain volume loss appears disproportionate to age, look for potential neurodegenerative or systemic causes
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# TERMINOLOGY
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- ## Definitions
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- ↓ overall brain volume with advancing age
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- Reflected in relative ↑ CSF spaces
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# IMAGING
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- ## General Features
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- ### Best diagnostic clue
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- "Successfully aging brain"
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- Thin, periventricular, high-signal rim
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- Absent/few white matter hyperintensities (WMHs)
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- Mild shrinkage of selected cerebellar regions
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- ### Location
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- Selective atrophy of white matter (WM) predominates, not gray matter (GM)
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- Striatum (primarily caudate nucleus, putamen)
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- ### Size
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- ↓ total brain volume
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- Absolute striatal size
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- Caudate ↓ linearly with age
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- Putamen remains relatively stable
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- Relative striatal size (ratio of absolute size:total brain volume)
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- Caudate remains relatively stable
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- Putamen ↑ linearly with age
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- ### Morphology
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- Brain tissue ↓, CSF volume ↑
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- Reflects overall WM volume loss > focal WMHs
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- Rounded appearance of dilated ventricles, sulci ↑
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- Strong correlation between WM volume and CSF volume: Measure of overall brain atrophy
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- ## CT Findings
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- ### NECT
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- Enlarged ventricles, widened cortical sulci
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- Patchy periventricular low densities
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- ± symmetrical, punctate calcifications in globi pallidi (GP)
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- ± curvilinear vascular Ca⁺⁺
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- ± punctate hippocampal Ca⁺⁺
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- ### CECT
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- No parenchymal enhancement
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- ## MR Findings
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- ### T1WI
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- Mild but symmetric ventricular enlargement, proportionate prominence of subarachnoid spaces
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- Mild but significant age-related shrinkage of
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- Posterior vermis (lobules 6, 7, and 8-10)
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- Cerebellar hemispheres
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- Apparent age invariance of anterior vermis, ventral pons
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- Enlarged perivascular (Virchow-Robin) spaces
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- Common in aging, considered reflection of cerebral small vessel disease
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- Isointense to CSF on all sequences
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- Conform to course of penetrating arteries
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- Round/oval/curvilinear
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- Smooth, well-defined margins
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- Bilateral, often symmetrical; usually no mass effect
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- ↑ in number, size (> 2 mm) with age
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- Can be found in most areas
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- Midbrain, hippocampi, basal ganglia (BG), & centrum semiovale
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- Tend to cluster around anterior commissure
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- Inferior 1/3 of putamen, external capsule
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- ### T2WI
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- Focal/confluent periventricular WMHs
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- Number/size ↑ after 50 years; ~ universal after 65 years
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- Only rough correlation with cognitive function
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- Significant overlap with dementias
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- Infarct-like T2-hyperintense lesions
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- Seen in 1/3 of asymptomatic patients > 65 years
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- 70% < 10 mm
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- Mostly in BG, thalami
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- Probably represent clinically silent lacunar infarcts
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- ### FLAIR
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- Smooth, thin, periventricular hyperintense rim is normal
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- Focal high signal intensity in splenium of corpus callosum
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- BG and thalamic foci
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- Perivascular spaces suppress
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- Lacunar infarcts hyperintense
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- ### T2* GRE
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- SWI: Increasing mineralization of BG with age
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- Normal in GP, abnormal in thalamus
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- Can see linear "waves" or conglomerate mineralization in GP
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- Putaminal hypointensity less prominent until 8th decade
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- Microbleeds are common in aging brain
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- SWI demonstrates microbleeds in 20% of patients > 60 years and in 60-70% of patients > 80 years
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- Microbleeds are relatively common in aging patients
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- Lower prevalence than in cerebral amyloid disease & Alzheimer disease
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- BG, brainstem, and cerebellar microbleeds indicative of chronic hypertensive encephalopathy
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- Lobar and cortical microbleeds typical of amyloid angiopathy
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- SWI: "Black line" in visual, motor/sensory cortex
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- Common, normal in older patients
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- ### DWI
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- Small but significant ↑ water diffusibility
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- ADC ↑
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- DTI: Loss of fractional anisotropy in normal-appearing WM
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- ### T1WI C+
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- Age-related WMHs do not enhance
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- If enhancing, consider acute/subacute lacunar infarct or metastases
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- ### MRS
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- Metabolite distribution varies among different brain regions
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- Choline (Cho) content ↑ with aging
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- Creatine (Cr) ↑ with aging
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- N-acetyl aspartate (NAA) ↓ in cortex, centrum semiovale, temporal lobes
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- ## Nuclear Medicine Findings
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- ### PET
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- Metabolic alterations common
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- Global, regional changes in cerebral blood flow (CBF)
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- Gradual ↓ in regional CBF of GM, WM
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- Particularly in frontal lobes
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- Age-related shift from anterior to posterior cortical metabolism
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- Putamen receives primarily posterior cortical input
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- Caudate receives relatively more anterior cortical input
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- Relative glucose metabolic rate (rGMR) measured by FDG PET
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- With age, rGMR ↑ in putamen and ↓ in caudate
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- ↓ pre-/postsynaptic dopamine markers in BG
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- Tc-99m HMPAO SPECT, Xe-133 inhalation show regional, global reduction in CBF
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- ## Imaging Recommendations
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- ### Best imaging tool
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- MR with FLAIR, DWI, T2* GRE/SWI
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# DIFFERENTIAL DIAGNOSIS
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- ## Mild Cognitive Impairment
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- Overlap with normal on standard imaging studies
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- Associated with ↓ size and number of regions of brain activation in response to memory tasks despite normal-appearing brain on conventional MR
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- Higher calculated hippocampal ADCs (not visible)
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- Subtle hypoperfusion, hypometabolism in parahippocampal regions, cingulum, thalamus
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- ↓ NAA
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- [Alzheimer Disease](/document/alzheimer-disease/f71f5cf5-b1af-4c6d-b145-b4c10eec7b58)
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- Parietal and temporal cortical atrophy
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- Striking volume loss in hippocampi, entorhinal cortex
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- Often coexisting microvascular disease, WMHs
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- Striking temporoparietal hypometabolism, hypoperfusion
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- ↓ NAA, ↑ myoinositol (mI)
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- [Sporadic Subcortical Arteriosclerotic Encephalopathy](/document/chronic-hypertensive-encephalopathy/1afc1f3f-203d-4cdf-8d49-2283cb13d6db)
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- Associated with hypertension
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- Numerous WMHs (overlap with normal)
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- Multiple lacunar infarcts
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- Lenticular nuclei, pons, thalamus, internal capsule, and caudate nuclei
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- Diffuse, confluent regions of periventricular WM involvement (leukoaraiosis)
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- [Vascular Dementia](/document/vascular-dementia/f59dab57-c511-4369-8fcc-592421a4b8d1)
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- Hyperintense lesions on T2WI and focal atrophy suggestive of chronic infarcts
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- [Frontotemporal Lobar Degeneration](/document/frontotemporal-lobar-degeneration/49510d0e-acf7-45cb-9eb1-53f8193b0b6d)
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- Asymmetric frontal, anterior temporal atrophy
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- T2 hyperintensity in frontotemporal WM
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- Dilated subarachnoid space over frontal lobes signifying atrophy
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- ↓ metabolic activity in frontotemporal cortices
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# PATHOLOGY
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- ## General Features
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- ### Etiology
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- Previous conception of aging: Substantial cortical neuronal loss with age
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- New: Predominant neuroanatomic changes
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- WM alterations, subcortical neuronal loss
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- Reduction in cell size > cell number
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- Neuronal dysfunction rather than loss of neurons/synapses
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- ↓ neuronal viability or function associated with accelerated membrane degradation &/or ↑ glial cell numbers
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- Loss of synapses and dendritic pruning in selected areas rather than globally
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- Some investigators consider accumulation of neurofibrillary tangles (NFTs) may be responsible for memory loss associated with aging
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- ### Genetics
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- Clearly affect aging of brain
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- Apolipoprotein E (*APOE*) and 6 novel risk-associated single nucleotide polymorphisms (SNPs) on chromosome 17q25 associated with brain pathology in aging
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- ## Gross Pathologic & Surgical Features
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- Widened sulci, proportionate large ventricles
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- Minor thinning of cortical mantle, predominant changes in subcortical WM
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- ## Microscopic Features
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- Degeneration of neurons and oligodendrocytes
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- ↓ myelinated fibers in subcortical WM
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- ↑ extracellular space, gliosis
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- Iron deposition in GP, putamen
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- WM capillaries lose pericytes, have thinner endothelium
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- Dilated perivascular spaces of Virchow-Robin
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- Extension of subarachnoid space that accompanies penetrating vessels into brain to level of capillaries
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- Senile plaques
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- Extracellular amyloid deposits in cerebral GM
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- Lewy bodies
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- Intraneuronal clumps of α-synuclein and ubiquitin proteins
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- Found in 5-10% of cognitively intact individuals
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- NFTs
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- Tau phosphorylation, mitochondrial dysfunction may precede full NFT formation
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- NFTs appear in small numbers in entorhinal and transentorhinal cortices early in aging (patients ~ 60 years)
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- NFTs may induce neural dysfunction, destruction of synapses, and, eventually, neuronal death
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# CLINICAL ISSUES
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- ## Presentation
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- ### Most common signs/symptoms
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- Normal cognitive function
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- Mild cognitive impairment correlates with ↑ risk of Alzheimer disease
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- ## Demographics
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- ### Age
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- > 60 years
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- ### Sex
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- Differences in striatal size
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- Relatively constant across lifespan in men
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- Variable across lifespan in women: Smaller in women aged 50-70 years than in men
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- Differences in rGMR
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- Caudate: Higher rGMR in women than men
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- Putamen: Equal rGMR in women and men
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- Greater dopamine transporters in caudate in women
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- ### Epidemiology
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- WMHs correlate with age, silent stroke, hypertension, female sex
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- ## Natural History & Prognosis
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- Parenchymal volume ↓, CSF spaces ↑ progressively
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- WMHs progressively ↑ with age
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# DIAGNOSTIC CHECKLIST
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- ## Consider
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- Striatum may mediate age-associated cognitive decline
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- ↓ volume, functional activity with age
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- ## Image Interpretation Pearls
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- Broad spectrum of "normal" on imaging in elderly
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- Cannot predict cognitive function from CT/MR
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- If brain volume loss appears disproportionate to age, look for potential neurodegenerative or systemic causes
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a71a0c8f-d105-4815-9edf-3fc113d5acc4
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## References
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# Selected References
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1. [Dubost F et al: Enlarged perivascular spaces in brain MRI: automated quantification in four regions. Neuroimage. 185:534-44, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30326293%5Bpmid%5D)
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1. [Jonkman LE et al: Normal Aging Brain Collection Amsterdam (NABCA): a comprehensive collection of postmortem high-field imaging, neuropathological and morphometric datasets of non-neurological controls. Neuroimage Clin. 22:101698, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30711684%5Bpmid%5D)
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1. [Walker L et al: Neurodegenerative diseases and ageing. Subcell Biochem. 91:75-106, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30888650%5Bpmid%5D)
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1. [de Brouwer EJM et al: Hippocampal calcifications: risk factors and association with cognitive function. Radiology. 288(3):815-20, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29893650%5Bpmid%5D)
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1. [Haller S et al: Cerebral microbleeds: imaging and clinical significance. Radiology. 287(1):11-28, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29558307%5Bpmid%5D)
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1. [Xekardaki A et al: Neuropathological changes in aging brain. Adv Exp Med Biol. 821:11-7, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25416106%5Bpmid%5D)
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1. [van Velsen EF et al: Brain cortical thickness in the general elderly population: the Rotterdam Scan Study. Neurosci Lett. 550:189-94, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23831346%5Bpmid%5D)
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1. [Poels MM et al: Arterial stiffness and cerebral small vessel disease: the Rotterdam Scan Study. Stroke. 43(10):2637-42, 2012](http://www.ncbi.nlm.nih.gov/pubmed/?term=22879099%5Bpmid%5D)
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1. [Ikram MA et al: The Rotterdam Scan Study: design and update up to 2012. Eur J Epidemiol. 26(10):811-24, 2011](http://www.ncbi.nlm.nih.gov/pubmed/?term=22002080%5Bpmid%5D)
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1. [Poels MM et al: Incidence of cerebral microbleeds in the general population: the Rotterdam Scan Study. Stroke. 42(3):656-61, 2011](http://www.ncbi.nlm.nih.gov/pubmed/?term=21307170%5Bpmid%5D)
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1. [Ni JM et al: Regional diffusion changes of cerebral grey matter during normal aging--a fluid-inversion prepared diffusion imaging study. Eur J Radiol. 75(2):134-8, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=19443158%5Bpmid%5D)
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1. [Williams LR et al: Clinical correlates of cerebral white matter hyperintensities in cognitively normal older adults. Arch Gerontol Geriatr. 50(2):127-31, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=19356807%5Bpmid%5D)
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1. [Salat DH et al: Regional white matter volume differences in nondemented aging and Alzheimer's disease. Neuroimage. 44(4):1247-58, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19027860%5Bpmid%5D)
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1. [Galluzzi S et al: Aging. Neurol Sci. 29 Suppl 3:296-300, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18941717%5Bpmid%5D)
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1. [Gruber S et al: Metabolic changes in the normal ageing brain: consistent findings from short and long echo time proton spectroscopy. Eur J Radiol. 68(2):320-7, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=17964104%5Bpmid%5D)
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1. [Harder SL et al: Mineralization of the deep gray matter with age: a retrospective review with susceptibility-weighted MR imaging. AJNR Am J Neuroradiol. 29(1):176-83, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=17989376%5Bpmid%5D)
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1. [Kövari E et al: Cortical microinfarcts and demyelination significantly affect cognition in brain aging. Stroke. 35(2):410-4, 2004](http://www.ncbi.nlm.nih.gov/pubmed/?term=14707236%5Bpmid%5D)
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1. [Brickman AM et al: Striatal size, glucose metabolic rate, and verbal learning in normal aging. Brain Res Cogn Brain Res. 17(1):106-16, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12763197%5Bpmid%5D)
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## Images
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### Selected Images
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*Axial graphic depicts a normally aging brain in an 80-year-old patient. Note the widening of sulci & ventricles in the absence of any brain parenchymal abnormalities.*
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*Axial graphic depicts a normally aging brain in an 80-year-old patient. Note the widening of sulci & ventricles in the absence of any brain parenchymal abnormalities.*
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*Axial graphic depicts a normally aging brain in an 80-year-old patient. Note the widening of sulci & ventricles in the absence of any brain parenchymal abnormalities.*
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*Axial graphic depicts a normally aging brain in an 80-year-old patient. Note the widening of sulci & ventricles in the absence of any brain parenchymal abnormalities.*
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*Axial graphic depicts a normally aging brain in an 80-year-old patient. Note the widening of sulci & ventricles in the absence of any brain parenchymal abnormalities.*
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*Axial FLAIR MR in a 78-year-old man shows prominence of the ventricles & sulci due to age-related volume loss. Smooth, thin, periventricular hyperintense rim <img src='img/arrows/CC.png'/> & subtle hyperintensity in the splenium <img src='img/arrows/CS.png'/> of corpus callosum is common & normal. In addition, there are few white matter FLAIR hyperintensities <img src='img/arrows/CO.png'/>.*
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*Axial NECT in a 83-year-old man demonstrates mild sulcal enlargement <img src='img/arrows/CC.png'/> & mild ventriculomegaly <img src='img/arrows/CS.png'/>. The white matter appears relatively normal with subtle periventricular hypodensities.*
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*Axial T2 MR in a 84-year-old woman demonstrates numerous enlarged perivascular spaces in the centrum semiovale bilaterally <img src='img/arrows/CC.png'/>. Note prominence of the cortical sulci due to age-related volume loss. Enlarged perivascular spaces are commonly seen in the midbrain, hippocampi, basal ganglia, & centrum semiovale.*
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*Axial NECT in a 82-year-old patient shows subtle calcifications in the region of the hippocampal formations bilaterally <img src='img/arrows/CC.png'/>.*
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*Sagittal NECT in the same patient demonstrates punctate calcification in the region of the tail of the hippocampus <img src='img/arrows/CS.png'/>. Note normal calcification <img src='img/arrows/CO.png'/> in the choroid plexus within the atrium of the lateral ventricle. Hippocampal calcifications are seen with greater prevalence over the age of 50.*
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*Axial SWI MR in a 76-year-old patient demonstrates horizontal linear "waves" of mineralization in the globus pallidi <img src='img/arrows/CC.png'/>, a normal finding in the aging brain. There is less prominent hypointensity in the putamina due to iron deposition.*
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*Axial SWI MR in an 85-year-old patient demonstrates marked fairly symmetric hypointensity in the basal ganglia <img src='img/arrows/CO.png'/> related to normal mineralization with age. Putaminal hypointensity on SWI is less prominent until 8th decade.*
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*Axial SWI MR in an 83-year-old woman demonstrates linear hypointensity along the cortical motor area <img src='img/arrows/CC.png'/> referred to as cortical pencil lining. This relates to natural age-related iron accumulation in healthy brains.*
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*Axial T2 MR in 82-year-old man demonstrates enlarged perivascular spaces <img src='img/arrows/CS.png'/> in the basal ganglia bilaterally giving a cribriform appearance. With advancing age, perivascular spaces are found with increasing frequency & larger apparent size (> 2 mm).*
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### Additional Images
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*Axial T2WI MR shows atrophy & white matter changes of aging <img src='img/arrows/WS.png'/>.*
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*Axial T2* SWI MR reveals normal mineralization of the red nucleus <img src='img/arrows/WS.png'/>, substantia nigra <img src='img/arrows/BS.png'/>, & fasciculi nigrae <img src='img/arrows/WC.png'/>.*
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*Axial FLAIR MR in an elderly patient shows dilated ventricles, wide cortical sulci, & periventricular white matter hyperintensity.*
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*Coronal T2WI MR in an elderly patient shows marked hypointensity in both lenticular nuclei & wide cortical sulci.*
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*Coronal T2WI MR in the same individual shows hypointense putamina & normal hippocampal size despite loss of brain cortex.*
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*Axial PD FSE intermediate MR in a 79-year-old patient without cognitive impairment shows mild periventricular white matter hyperintensities.*
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*FDG PET in a normal 83-year-old shows normal metabolism in the brain cortex, basal ganglia, & thalami. (Courtesy N. Foster, MD & the University of Michigan PET Center.)*
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*FDG PET in the same patient shows essentially normal glucose metabolism (depicted in red & yellow) in the cerebral cortex, except for small regions of decreased metabolism.*
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*Axial FLAIR shows mild periventricular hyperintensity <img src='img/arrows/WS.png'/> & mild enlargement of the ventricles & sulci in a 65-year-old man. No focal hyperintensities are seen in the hemispheric white matter; cortical thickness & signal intensity are normal.*
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*Axial T2* SWI MR demonstrates hypointensity in the lentiform nuclei, particularly related to the globus pallidi <img src='img/arrows/WS.png'/>.*
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*Axial FLAIR MR demonstrates confluent hyperintense white matter changes <img src='img/arrows/WS.png'/> that may occur during normal aging.*
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*Axial FLAIR MR in the same patient demonstrates prominent subcortical white matter hyperintensity <img src='img/arrows/WS.png'/>.*
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*Axial FLAIR MR in a 79-year-old man shows enlargement of ventricles & sulci due to age-related volume loss. Smooth, thin, periventricular hyperintense rim <img src='img/arrows/CC.png'/> & subtle hyperintensity in the splenium <img src='img/arrows/CS.png'/> of corpus callosum is common & normal.*
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*Axial SWI in a 67-year-old woman shows striking hypointensity in the globi pallidi <img src='img/arrows/CC.png'/> with less prominent hypointensity in the putamina <img src='img/arrows/CS.png'/> due to iron deposition.*
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*Axial NECT in an 85-year-old patient without cognitive impairment shows wide sulci & lateral ventricles, as well as moderate periventricular hypodense white matter.*
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*Axial T2* SWI MR demonstrates marked hypointensity in the basal ganglia <img src='img/arrows/WC.png'/> related to normal mineralization with age.*
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*Axial T2* SWI MR demonstrates marked hypointensity in the basal ganglia <img src='img/arrows/BC.png'/> related to normal mineralization with age.*
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*Axial T2* SWI MR demonstrates horizontal linear "waves" of mineralization in the globus pallidi <img src='img/arrows/BS.png'/>, a normal finding in the aging brain.*
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*Axial FLAIR in a 72-year-old man shows scattered white matter hyperintensities <img src='img/arrows/CS.png'/>. Aging brains may demonstrate a few scattered nonconfluent white matter hyperintensities. Increased prevalence of white matter hyperintensities with cardiovascular risk factors such as diabetes & hyperlipidemia is shown.*
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*Axial FLAIR in the same patient shows additional subcortical white matter hyperintensities <img src='img/arrows/CS.png'/>.*
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*Axial NECT demonstrates mild sulcal enlargement & mild ventriculomegaly in a 70-year-old patient. The white matter appears completely normal, without periventricular hypodensities or white matter lacunar infarcts.*
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