Vascular Dementia & Fronto-Temporal Dementia

Chapter 20, Lecture 10

Vascular dementia prevalence in Netherlands

22% of dementias (Franke 2018); pure VaD and pure AD mostly in relatively young patients; mixed etiology far more likely in patients over 75

VaD pathology types

(1) One or more strategic strokes ("multi-infarct dementia"); (2) Small Vessel Disease (SVD) — umbrella for small vessel abnormalities causing widespread WM lesions ("white matter changes" on MRI)

VaD course

Can start suddenly (strategic/multiple minor strokes) OR slowly (small vessel disease); severity and localisation create very heterogeneous clinical picture

Post-stroke dementia

Within 3–12 months after stroke, approximately 25% of patients are classified with major NCD/dementia

VaD cognitive profile — most distinctive feature

Mental and psychomotor slowing — differentiates from AD

VaD cognitive profile — primary deficits

Problems with initiating, planning, and mental flexibility (executive function primarily affected)

VaD cognitive profile — relatively intact

Memory and language (contrast with AD where these are primary)

VaD other symptoms

Personality change, denial, loss of insight, motor symptoms (gait, balance, slowness of thought)

VaD risk factors

Age over 65, HTN, high cholesterol, smoking, obesity, diabetes, cardiac history, TIA/stroke history (similar to heart disease and stroke risk factors)

AD vs VaD cognitive contrast

AD: memory and language decline first; VaD: slowing and EF decline first, memory relatively spared

FTD spectrum definition

Wide spectrum of clinical and pathological neurodegenerative diseases; also includes ALS, Corticobasal syndrome (CBS), and Progressive Supranuclear Palsy (PSP)

FTD epidemiology

10–20% of all dementias; 60% bvFTD and 30% svPPA; 75% early onset (under 65), most 45–65 years at first symptoms; disease duration 2–20 years; death often indirect (pneumonia, heart failure, malnutrition)

FTD diagnostic limitations

No biomarker diagnostic test; no curative treatment

FTD misdiagnosis rate

40% misdiagnosis rate; initially wrongly diagnosed as autism, depression, OCD, ADHD, or late-onset schizophrenia; biomarkers (CSF/PET amyloid) needed to differentiate from atypical AD behavioural variant

bvFTD diagnostic criteria

Progressive deterioration of behaviour/cognition; 75% disinhibition, 85% apathy, 80% eating behaviour changes; NP profile shows EF and social cognition severely impaired; memory and visuospatial relatively spared

FTD neuroimaging

Strongly asymmetric frontal and temporal atrophy (AD is more symmetrical); bvFTD shows prefrontal and orbitofrontal atrophy; PPA shows left-sided greater than right-sided atrophy

svPPA (Semantic variant PPA) speech profile

Fluent, grammatically correct but empty content; poor word-finding and naming; loss of word meaning

nfvPPA (Non-fluent variant PPA) speech profile

Slow, effortful speech; errors in speech sounds; reduced rhythm and prosody; shorter sentences; maintains naming and word comprehension (unlike svPPA)

LvPPA (Logopenic variant PPA) profile

Language and communication problems first; memory and EF affected later; 75% have underlying AD pathology

Neural tube formation timing

Starts 21 days post-conception; neural tube develops into human brain in approximately 100 days

Brain differentiation (3–14 weeks)

Forebrain, midbrain, and hindbrain differentiate

Neurogenesis and migration (6–28 weeks)

Neural stem cells from neural tube produce neurons and glial cells; neurons migrate from subventricular zone along radial glia to cortical destination

Cortical layering direction

Built inside-out — layer VI forms first, layer I forms last

Subventricular zone

Acts as a map of the cortex; cells are guided to corresponding cortical areas

Brain folding timing

Sulci and gyri appear from 28 weeks; overproduction followed by apoptosis (programmed cell death)

Postnatal dendrite development

Starts prenatally; continues long after birth at micrometers per day

Postnatal axon development

Grows at 1 mm/day; faster axons reach targets first and direct dendrite growth and synapse formation

Synaptogenesis and pruning

Synaptic overproduction followed by pruning, continuing into early adulthood

Myelination sequence

Sensorimotor cortex → parietal/temporal → prefrontal cortex last (not complete until age 20+)

Plasticity during neurogenesis

Recovery is almost complete even with severe damage

Plasticity during neuronal migration

Permanent damage regardless of size or location

Plasticity after migration

Nearly complete recovery of cognitive functions; motor functions less so

Growing into deficits

Children may appear recovered early; compensating brain regions can no longer do so as cognitive demands increase with development → deficits emerge later

Kennard principle

States that early brain injury leads to better outcome — this principle is OUTDATED

SES and brain development (Rakesh et al. 2023)

Lower family income leads to reduced cortical and subcortical volumes at all ages; yearly word exposure is 11.0 million (high SES) vs 3.2 million (low SES)

SES mechanisms for brain development

Parental education, child health, school quality, language exposure, adversity (threat, deprivation, unpredictability)

Korom et al. 2021 finding

High-risk group (child protective services) showed reduced cortical thickness leading to increased anxiety and depression

Right hemispherectomy case (Lec 10)

A child with chronic encephalitis and seizures underwent right hemispherectomy and showed good cognitive recovery — extreme example of early brain plasticity

FTD spectrum — other disorders belonging to it

ALS (Amyotrophic Lateral Sclerosis), Corticobasal Syndrome (CBS), and Progressive Supranuclear Palsy (PSP) all belong to the FTD spectrum

FTD cause of death

Often indirect — pneumonia, heart failure, malnutrition

FTD — no biomarker test

There is currently no biomarker diagnostic test for FTD (unlike AD where CSF/PET amyloid can be used)

bvFTD — specific symptom percentages

75% disinhibition; 85% apathy; 80% eating behaviour changes

bvFTD NP profile specifics

EF and social cognition are severely impaired; memory and visuospatial are relatively SPARED

FTD neuroimaging asymmetry

Strongly asymmetric frontal and temporal atrophy in FTD (contrast with AD which is more symmetrical); bvFTD shows prefrontal and orbitofrontal atrophy specifically

svPPA — what is preserved

Word comprehension and naming are LOST (contrast with nfvPPA where these are maintained)

nfvPPA — what is preserved

Naming and word comprehension are maintained (contrast with svPPA where these are lost)

PPA — defining feature

Language problems are the most prominent symptom and the principal cause of impaired daily activities in all PPA subtypes

LvPPA — AD pathology link

75% of logopenic PPA cases have underlying AD pathology; this is why it is also classified under atypical AD

VaD — why heterogeneous picture

Severity and localisation of vascular damage vary widely between patients → very heterogeneous clinical presentations

VaD treatment

Vascular risk factor management to prevent further strokes; no curative treatment

VaD — pure vs mixed etiology age pattern

Pure VaD and pure AD occur mostly in relatively younger patients; mixed etiology is far more likely in patients over 75

VaD personality and insight changes

Personality change, denial, and loss of insight can be present alongside cognitive and motor features