Dementia: Types, Pathology, Clinical Variants, and Biomarkers

Comprehensive vocabulary flashcards covering the clinical subtypes, diagnostic pathways, neuroanatomy, genetics, biomarkers, and neuropathology of major dementias (Alzheimer's disease, Vascular dementia, Frontotemporal dementia, and Lewy body disorders).

Dementia (In-Class Definition)

An umbrella term for the progressive loss of memory and other cognitive thinking abilities severe enough to interfere with an individual's daily life functioning.

Minimal Mental State Examination (MMSE)

A standardized clinical screening assessment utilized to evaluate cognitive status and aid in the diagnosis of cognitive impairment and dementia.

Diagnostic Framework in Dementia

A clinical diagnostic pathway moving sequentially from initial presenting symptoms to the affected brain neuroanatomy, and ultimately to the underlying pathology (such as specific misfolded proteins), which constitutes the definitive 'true' diagnosis.

Amyloid Plaques

Abnormal extracellular clusters of misfolded beta-amyloid proteins that accumulate in the spaces between neurons, disrupting synaptic communication.

Neurofibrillary Tangles

Intracellular twisted aggregates of hyper-phosphorylated tau protein within neuronal cell bodies that distort the microtubule cytoskeleton and compromise cellular structural integrity.

Abnormally Hyper-Phosphorylated Tau (p-tau)

A chemically altered form of tau protein that aggregates in proximity to amyloid plaques, leading to microtubule detachment and neurofibrillary tangle formation.

p-tau217

A specific phosphorylated tau biomarker detectable in blood plasma that measurably increases during Alzheimer's disease progression.

Glymphatic System

The brain's waste clearance network responsible for clearing normal, low levels of age-related protein accumulations such as beta-amyloid plaques and tau tangles.

Typical (Amnestic) Alzheimer's Disease

The classic, late-onset (age 65 and older) clinical presentation of Alzheimer's disease where neurodegeneration initiates in the medial temporal lobe (hippocampus), resulting in recent episodic memory loss as the prominent initial symptom.

Hippocampal Atrophy (Alzheimer's Disease)

Marked bilateral volume reduction and shrinkage within the medial temporal lobe and hippocampus visible on coronal T1 MRI, serving as a primary structural hallmark of Alzheimer's disease.

Beta-Amyloid PET Scan

A molecular neuroimaging modality using specialized radioactive tracers to quantify cortical amyloid accumulation, interpreted clinically as negative (none or sparse tracer retention) versus positive (moderate to frequent tracer retention throughout the isocortex).

APOE Gene Isoforms

Variants of the apolipoprotein E gene mapped to chromosome $19\text{q}13.2$ that regulate lipid and cholesterol transport in the bloodstream, differentiated by amino acid variations at residues 112 and 158.

APOE-ε4 Allele

The APOE genetic variant containing arginine at both residue 112 and residue 158, conferring a substantially elevated genetic risk for developing late-onset Alzheimer's disease.

APOE-ε2 Allele

The APOE genetic variant containing cysteine at both residue 112 and residue 158, associated with a reduced or protective risk profile against Alzheimer's disease.

Frontal Variant of Alzheimer's Disease (fvAD)

An early-onset, non-amnestic clinical presentation of Alzheimer's disease where pathology initially causes frontal lobe atrophy, manifesting as executive dysfunction, behavioral disinhibition, and loss of motivation rather than primary memory decline.

Primary Progressive Aphasia (PPA)

A focal neurodegenerative syndrome characterized by a progressive deterioration of language abilities as the primary and initial clinical deficit, driven by selective degeneration of left hemisphere frontal and temporal networks.

Logopenic Variant of PPA (lvPPA)

A primary progressive aphasia syndrome caused by underlying Alzheimer's pathology (amyloid plaques and neurofibrillary tangles) localized to the left temporoparietal cortex, characterized by hesitant, nonfluent speech due to word-finding difficulties, preserved single-word articulation, and poor sentence repetition.

Frontotemporal Dementia (FTD)

A heterogeneous group of non-Alzheimer neurodegenerative disorders and the most common cause of dementia under age 60, neuropathologically associated with abnormal tau or TDP-43 protein accumulation.

Behavioral Variant Frontotemporal Dementia (bvFTD)

The most prevalent subtype of frontotemporal dementia, characterized by prominent early changes in personality, social disinhibition, apathy, loss of empathy, compulsive collecting, hyperorality/overeating, and severe executive dysfunction stemming from frontal and insular atrophy.

Semantic Variant of PPA (svPPA)

A language presentation of frontotemporal dementia featuring anterior temporal lobe atrophy, manifested by profound anomia, loss of word comprehension, fluent but empty speech, visual object agnosia, and impaired recognition of familiar or famous faces.

Nonfluent/Agrammatic Variant of PPA (nfvPPA)

A language subtype of frontotemporal dementia characterized by effortful, agrammatic speech production and apraxia of speech, driven by atrophy centered in the left posterior inferior frontal cortex (Broca's area).

TDP-43 Pathology

Pathological protein aggregates associated with frontotemporal lobar degeneration that accumulate as cytoplasmic, intranuclear, and neuritic inclusions within both neurons and glial cells (astrocytes, microglia, and oligodendrocytes).

Vascular Dementia

Dementia resulting from cerebrovascular disease (such as arterial occlusion, blood clots, or ischemic strokes) leading to impaired cerebral blood flow; typically presents first with slowed cognitive processing speed and executive impairment rather than episodic memory loss.

Small Subcortical Infarcts (T2 FLAIR)

Areas of cerebral tissue ischemia and diffuse cortical atrophy visualized as white matter hyperintensities on T2-weighted fluid-attenuated inversion recovery MRI, indicative of small vessel cerebrovascular disease.

Binswanger Disease

A subcortical form of vascular dementia occurring in hypertensive individuals, pathologically characterized by diffuse white matter lesions and old cystic subcortical infarctions.

Alpha-Synuclein

A neuronal presynaptic protein that aberrantly misfolds and aggregates into toxic intracellular inclusions termed Lewy bodies in dementia with Lewy bodies and Parkinson's disease.

Dementia with Lewy Bodies (DLB)

A neurodegenerative dementia defined by alpha-synuclein pathology where cognitive decline (fluctuating alertness, early visual hallucinations, visuospatial deficits) precedes or co-occurs within one year of parkinsonian motor symptoms.

Parkinson's Disease Dementia (PDD)

A secondary cognitive disorder sharing alpha-synuclein pathology with DLB, clinically distinguished by the emergence of well-established parkinsonian motor symptoms long before the onset of cognitive decline.

Reticular Formation Involvement in Lewy Body Disease

The early brainstem site of alpha-synuclein accumulation responsible for early autonomic dysregulation, impaired sleep-wake cycles, and fluctuating levels of wakefulness and attention.

REM Sleep Behavior Disorder

A parasomnia involving the physical enactment of vivid dreams due to loss of normal muscle atonia during REM sleep, commonly presenting as an early manifestation of Lewy body dementias.

Cardinal Symptoms of Parkinson's Disease

The classic triad of motor features characteristic of Parkinson's disease, comprising resting tremor, muscle rigidity, and bradykinesia (slowed movement).

Mixed Dementia

The coexistence of two or more independent neuropathological processes simultaneously contributing to cognitive decline (representing approximately $20\%$ of all dementia cases), most commonly Alzheimer's disease combined with vascular dementia.

Alzheimer's Disease Neuropathological Cascade

The macroscopic and microscopic degeneration pattern in Alzheimer's disease, involving progressive cerebral cortical shrinkage, ventricular enlargement, severe hippocampal atrophy, extracellular $A\beta$ plaques, and intracellular tau neurofibrillary tangles.