Add comprehensive articles on Vascular Dementia and Wallerian Degeneration

- Created a detailed article for Vascular Dementia covering key facts, terminology, imaging findings, differential diagnoses, pathology, clinical issues, and diagnostic checklist. - Developed an extensive article on Wallerian Degeneration including key facts, terminology, imaging features, differential diagnoses, pathology, clinical issues, and diagnostic checklist.
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+---
+title: "Alzheimer Disease"
+docid: "f71f5cf5-b1af-4c6d-b145-b4c10eec7b58"
+breadcrumbs:
+  - "Brain"
+  - "Diagnosis"
+  - "Pathology-Based Diagnoses"
+  - "Acquired Toxic/Metabolic/Degenerative Disorders"
+  - "Dementias and Degenerative Disorders"
+  - "Alzheimer Disease"
+---
+# KEY FACTS
+
+- ## Terminology
+  
+  
+    - Alzheimer disease (AD)
+          - Slowly progressive neurodegenerative disease
+- ## Imaging
+  
+  
+    - Current role of imaging in AD
+          - Exclude other causes of dementia
+          - Identify region-specific patterns of brain volume loss
+          - Identify imaging markers of coexistent disease, such as amyloid angiopathy
+          - Identify early AD for possible innovative therapy
+    - Best imaging = volumetric MR, F-18 FDG PET
+    - Thinned gyri, widened sulci, and enlarged ventricles
+    - Medial temporal lobe particularly hippocampus and entorhinal cortex disproportionately affected
+    - F-18 FDG PET
+          - Early-stage AD: ↓ metabolism in parietotemporal association cortices, posterior cingulate, and precuneus regions
+          - Moderate to severe AD: Additional frontal lobe involvement
+    - Amyloid PET imaging: High sensitivity in detecting amyloid plaques and vascular amyloid in vivo
+- ## Top Differential Diagnoses
+  
+  
+    - Normal aging
+    - Vascular dementia
+    - Normal-pressure hydrocephalus
+    - Frontotemporal lobar degeneration
+    - Dementia with Lewy bodies
+- ## Clinical Issues
+  
+  
+    - Most common cause of dementia > age 65
+    - Age is biggest risk factor
+          - 1-2% prevalence at age 65
+          - Incidence doubles every 5 years after age of 60
+- ## Diagnostic Checklist
+  
+  
+    - Look for reversible causes of dementia
+
+# TERMINOLOGY
+
+- ## Abbreviations
+  
+  
+    - Alzheimer disease (AD)
+- ## Synonyms
+  
+  
+    - Senile/presenile dementia of Alzheimer type
+- ## Definitions
+  
+  
+    - AD dementia is progressive neurodegenerative condition characterized by progressive cognitive decline, memory impairment, and adverse impact on activities of daily living
+    - National Institute on Aging and Alzheimer's Association (NIA-AA) 2011 workgroup recommendations
+          - Phases of AD pathophysiological processes
+                  - Preclinical AD
+                  - Mild cognitive impairment (MCI) in AD
+                  - AD dementia
+    - AD is pathologic process reflected in specific postmortem histopathologic criteria, which is frequently but not necessarily associated with characteristic dementia syndrome
+    - Probable AD dementia: Clinical syndrome meeting core clinical criteria specified in NIA-AA workgroup report
+    - Possible AD dementia: Clinical syndrome meeting core clinical criteria for AD dementia in terms of nature of cognitive deficits for AD dementia, but either 1) has sudden onset of impairment or demonstrates insufficient historical detail or objective documentation of progression, or 2) has mixed etiological presentation due to evidence of vascular or Lewy body pathology
+    - MCI: Clinical syndrome meeting published core clinical criteria for MCI; generally agreed core features include 1) concern for change in cognition, 2) impairment in one or more cognitive domains, and 3) preservation of independence in functional activities, but 4) not demented
+
+# IMAGING
+
+- ## General Features
+  
+  
+    - ### Best diagnostic clue
+      
+      
+          - MR: Temporal/parietal cortical atrophy
+                  - Disproportionate hippocampal volume loss
+          - FDG PET: Regional ↓ glucose metabolism
+                  - Temporoparietal lobes, posterior cingulum
+    - **Current role of imaging in AD**
+          - Exclude other structural abnormalities
+          - Evaluate degree and location of atrophic changes
+          - Evaluate for metabolic abnormalities
+                  - When structural abnormalities absent/uncharacteristic (i.e., early in disease course)
+          - Identify preclinical and MCI in AD for possible innovative therapy
+- ## CT Findings
+  
+  
+    - ### NECT
+      
+      
+          - Screening to exclude potentially reversible or treatable causes of dementia
+          - Medial temporal lobe atrophy in early disease and generalized atrophy in late stages
+- ## MR Findings
+  
+  
+    - Current role of MR
+          - Exclude other causes of dementia
+          - Identify region-specific patterns of brain volume loss
+          - Identify imaging markers of coexistent disease, such as amyloid angiopathy
+    - T1 to assess medial temporal atrophy score and atrophy patterns
+          - High resolution (MPRAGE/SPGR) for volumetric analysis
+          - Thinned gyri, widened sulci, and enlarged ventricles
+          - Medial temporal lobe disproportionately affected
+                  - May help distinguish patients with MCI from normal elderly
+                  - Average hippocampal volume reduction 20-25% in AD and 10-15% in MCI
+    - T2* GRE/SWI for microhemorrhages, amyloid angiopathy
+    - MRS
+          - ↓ NAA and ↑ mI in AD, even in early stage
+          - NAA:mI ratio relatively sensitive and highly specific in differentiating AD from normal elderly
+          - NAA:Cr ratio in posterior cingulate gyri and left occipital cortex predicts conversion of MCI to probable AD
+    - DTI: ↓ FA in multiple regions, especially superior longitudinal fasciculus and splenium
+    - Perfusion MR: ↓ rCBV in temporal, parietal regions
+- ## Nuclear Medicine Findings
+  
+  
+    - F-18 FDG PET
+          - Early-stage AD
+                  - ↓ metabolism in parietotemporal association cortices, posterior cingulate, and precuneus regions
+                  - Most reliable early changes in posterior cingulate
+          - Moderate to severe AD
+                  - Additional frontal lobe involvement
+          - MCI in AD
+                  - Same pattern of ↓ metabolism as AD
+          - Higher accuracy than MR for diagnosing early AD
+    - Amyloid (Aβ) PET imaging
+          - Specifically bind to Aβ plaques and retention of tracer is specific for Aβ neuritic plaque pathology
+                  - F-18 florbetapir, F-18 florbetaben, and F-18 flutemetamol FDA approved for clinical use
+                  - Positive scan shows loss of gray/white matter distinction due to tracer uptake in neocortex
+                  - Negative scan retains gray/white matter distinction
+          - Criteria for appropriate use (AUC) of amyloid PET
+                  - Persistent/progressive unexplained MCI
+                  - Possible AD with unclear presentation
+                  - Atypical early-onset progressive dementia
+          - In patients with MCI fulfilling clinical AUC, Aβ-PET is associated with
+                  - Significant improvement in diagnostic confidence
+                  - High impact on therapeutic management
+    - Tau PET imaging
+          - Currently under development
+          - Signal matches anatomic distribution of neurofibrillary tangles
+          - Earliest detection in entorhinal cortex and hippocampus, later inferior and lateral temporal, followed by parietal and occipital, and finally frontal cortices
+- ## Imaging Recommendations
+  
+  
+    - ### Best imaging tool
+      
+      
+          - Volumetric MR (MPRAGE/SPGR sequences)
+          - F-18 FDG PET
+          - Aβ PET for patients who meet AUC
+    - ### Protocol advice
+      
+      
+          - MPRAGE or SPGR for volumetric measurement
+
+# DIFFERENTIAL DIAGNOSIS
+
+- ## Causes of Reversible Dementia
+  
+  
+    - [Thiamine deficiency, vitamin B12 deficiency, hypothyroidism](/document/alcoholic-encephalopathy/88021852-b73d-4cdf-a719-dd4ae3231e45)
+    - Depression ("pseudodementia")
+    - [Normal-pressure hydrocephalus](/document/normal-pressure-hydrocephalus/ba3f857d-58de-4f21-8463-1631b4cb9972)
+    - [Mass lesions (chronic subdural hematoma, tumor, etc.)](/document/chronic-subdural-hematoma/cc7b52b4-c6a0-4b4e-ae8c-f05bfc5c5cb2)
+- [Vascular Dementia](/document/vascular-dementia/f59dab57-c511-4369-8fcc-592421a4b8d1)
+    - 2nd most common dementia (15-30%)
+    - Parenchymal hyperintensities, focal atrophy (infarcts)
+- [Frontotemporal Lobar Degeneration](/document/frontotemporal-lobar-degeneration/49510d0e-acf7-45cb-9eb1-53f8193b0b6d)
+    - Frontal &/or anterior temporal atrophy
+- [Dementia With Lewy Bodies](/document/dementia-with-lewy-bodies/e8e46d1d-46d2-4e5a-880f-f025a84c5871)
+    - Hypometabolism of entire brain
+- [Corticobasal Degeneration](/document/corticobasal-degeneration/23f97d4e-8724-4229-b9f8-08f63906ebd8)
+    - Prominent extrapyramidal, cortical symptoms
+    - Asymmetric severe frontoparietal atrophy
+- [Creutzfeldt-Jakob Disease](/document/creutzfeldt-jakob-disease-cjd/e1b27954-6591-4bb0-a659-b13790492620)
+    - Dementia with myoclonus, EEG abnormalities
+    - Hyperintensity in anterior basal ganglia, cortex
+- [Cerebral Amyloid Angiopathy](/document/cerebral-amyloid-disease/48e9458e-102f-40bd-8eec-bc0bc97101c6)
+    - Often coexists with AD
+    - Microhemorrhages on T2* GRE/SWI
+
+# PATHOLOGY
+
+- ## General Features
+  
+  
+    - ### Etiology
+      
+      
+          - Extracellular β-amyloid plaques
+                  - Located in cerebral cortex
+          - Intracellular accumulation of neurofibrillary tangles (NTs)
+                  - Initially around hippocampus, later spread to other cortical areas
+    - ### Genetics
+      
+      
+          - Most cases late-onset sporadic AD
+                  - Deterministic genetic mutation not found
+                  - Apolipoprotein E (*ApoE*) ε4 allele is major genetic risk factor
+          - Rare early-onset AD
+                  - Mutations in 1 of 3 genes
+                            - Amyloid precursor protein gene on chromosome 21
+                            - Presenilin-1 (*PSEN1*) gene on chromosome 14
+                            - Presenilin-2 (*PSEN2*) gene on chromosome 1
+- ## Staging, Grading, & Classification
+  
+  
+    - Consortium to Establish a Registry for Alzheimer Disease (CERAD)
+          - Semiquantitative approach counting plaques/tangles
+          - Frequent, moderate, or infrequent
+    - Braak and Braak (B&B)
+          - 6 levels of staging
+                  - Transentorhinal stage (1-2): NTs develop in parahippocampal gyrus (clinically asymptomatic)
+                  - Limbic stage (3-4): NTs dramatically increase in parahippocampal gyrus, begin to develop in hippocampus (mild cognitive impairment)
+                  - Neocortical stage (5-6): NTs develop in temporal and parietal cortex, eventually spread to entire neocortex (severe dementia)
+    - NIA-Reagan
+          - Likelihood high
+                  - CERAD frequent, B&B 5/6
+          - Likelihood intermediate
+                  - CERAD moderate, B&B 3/4
+          - Likelihood low
+                  - CERAD infrequent, B&B 1/2
+- ## Gross Pathologic & Surgical Features
+  
+  
+    - Shrunken gyri, widened sulci
+- ## Microscopic Features
+  
+  
+    - 2 abnormal protein aggregates characterize AD pathologically
+          - Neurofibrillary tangles
+                  - Intracellular aggregates in neurons due to hyperphosphorylation of tau protein
+                  - Begins in entorhinal cortex, progresses to hippocampus, paralimbic system, and adjacent medial-basal temporal lobe
+          - Aβ deposition
+                  - Hallmark of Aβ peptide deposit in AD is neuritic plaque
+                  - Dense Aβ core with inflammatory cells and dystrophic neurites in its periphery
+    - Neurodegeneration: Synapse and neuron loss
+
+# CLINICAL ISSUES
+
+- ## Presentation
+  
+  
+    - ### Most common signs/symptoms
+      
+      
+          - Slowly progressive neurodegenerative disease
+          - Initially affects episodic memory
+                  - Then, at least 1 other area of cognition
+    - ### Clinical profile
+      
+      
+          - Clinical subtypes
+                  - MCI: Early, mild memory impairment; no deficits in cognitive domains other than memory, not impairing daily function
+                  - Possible AD: Dementia features in presence of 2nd disease that could cause memory deficit but is not likely cause
+                  - Probable AD: Memory deficits on neuropsychological testing, progressive worsening of memory and ≥ 2 cognitive functions
+                  - Definite AD: Pathologic diagnosis
+    - 5 major biomarkers for AD
+          - Amyloid accumulation: CSF Aβ 42, Aβ-PET imaging
+          - Neurogeneration or neuronal injury: CSF tau (total and phosphorylated), structural MR, and FDG PET
+- ## Demographics
+  
+  
+    - ### Age
+      
+      
+          - Biggest risk factor
+                  - 1-2% prevalence at age 65
+                  - Incidence doubles every 5 years after age of 60
+    - ### Sex
+      
+      
+          - Women more commonly affected
+    - ### Epidemiology
+      
+      
+          - AD most common neurodegenerative dementia
+          - 5-7 million new AD dementia cases every year
+          - Currently ~ 5.3 million in USA
+                  - 13% of individuals > 65 years and > 50% of individuals > 85 years
+    - Other risk factors
+          - Family history (20%)
+          - Head trauma, metabolic syndrome
+- ## Natural History & Prognosis
+  
+  
+    - Chronic, progressive
+    - Patients live average 8-10 years after diagnosis
+- ## Treatment
+  
+  
+    - No established treatments
+    - May transiently improve cognitive function
+          - Cholinesterase inhibitors, NMDA receptor antagonists
+    - Many current disease-modifying drugs to reduce Aβ
+
+# DIAGNOSTIC CHECKLIST
+
+- ## Consider
+  
+  
+    - Look for
+          - Reversible causes of dementia
+          - Ventricular enlargement, sulcal widening proportionate
+          - ↑ temporal horns of lateral ventricle
+          - Hippocampal, entorhinal cortex volume loss
+- ## Image Interpretation Pearls
+  
+  
+    - MR volumetric analysis helps distinguish MCI in AD from normal elderly subjects, measure change hippocampus/parahippocampal gyri over time
+    - F-18 FDG PET
+          - Helps distinguish AD from frontotemporal dementia
+          - May identify early AD when MR normal
+
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