A LZ H EIM ER S D IS EA S E

A N D O TH ER D EM EN TIA S
Aileen Costa-Merioles, MD, FPCP
Internal Medicine Specialist

Alzheim ers D isease

Alzheim ers D isease

most common cause of dementia in

the elderly
Insidious loss of episodic memory
followed by a slowly progressive
dementia that evolves over years
Typical duration 8-10 years

Alzheim ers D isease

Brain Imaging--atrophy that begins in

the medial temporal lobes before

spreading to lateral and medial
parietal and temporal lobes and
lateral frontal cortex

Alzheim ers D isease

Microscopic -- neuritic

plaques containing
amyloid beta (A),
neurofibrillary tangles
(NFTs) composed of
hyperphosphorylated
tau filaments, and A
accumulation of in
blood vessel walls in
cortex and
leptomeninges

Alzheim ers D isease

major genetic risk for AD is

apolipoprotein 4 (Apo 4)

EPID EM IO LO GY
most important risk factors for AD

are old age and a positive family

history
Female sex -- women who carry an
Apo 4 allele
history of head trauma with
concussion
Diabetes

CLIN ICAL M AN IFESTATIO N S

memory impairment and progressing to

language and visuospatial deficits

word-finding, organizational, or
navigational difficulty (20% of AD cases)
upstream visual processing dysfunction
progressive logopenic aphasia
asymmetric akineticrigid-dystonic
(corticobasal) syndrome or a
dysexecutive frontal variant of AD

STAG ES O F AD
Early stage typical amnestic AD
cognitive problems begin to interfere

with daily activities

STAG ES O F AD
middle stages -- the patient is unable

to work, is easily lost and confused,

and requires daily supervision.
Language becomes impaired
Apraxia
Visuospatial deficits

STAG ES O F AD
late stages wandering aimlessly
Loss of judgment and reasoning
Delusions
Capgras syndrome (10% of AD

cases)
shuffling gait with generalized
muscle rigidity associated with
slowness and awkwardness of
movement

STAG ES O F AD
end stages -- AD patients become

rigid, mute, incontinent, and

bedridden
Hyperactive tendon reflexes and
myoclonic jerks
Death results from malnutrition,
secondary infections, pulmonary
emboli, heart disease, or, most
commonly, aspiration

pathology

treatm ent
Inhibition of the cholinesterases,

primarily acetylcholinesterase, with a

resulting increase in cerebral
acetylcholine levels
Donepezil (target dose, 10 mg daily)
rivastigmine (target dose,6 mg twice
daily or 9.5-mg patch daily)
galantamine (target dose 24 mg
daily, extended-release)

treatm ent
act by blocking overexcited N-

methyl-d-aspartate (NMDA)
glutamate receptors
memantine (target dose, 10 mg
twice daily)

treatm ent
Ginkgo biloba
Modest improvement in cognitive

function in subjects with AD and

vascular dementia
6-year multicenter prevention study
found no slowing of progression of
dementia in the treated group

Vascular D em entia

VASCU LAR D EM EN TIA

Dementia associated with

cerebrovascular disease
two general categories:
multi-infarct dementia
diffuse white matter disease
leukoaraiosis, subcortical arteriosclerotic
leukoencephalopathy, or Binswangers
disease

M AN IFESTATIO N
chronic cognitive deficits, commonly

called multi-infarct dementia

occurrence of dementia depends
partly on the total volume of
damaged cortex

M AN IFESTATIO N
PE --focal neurologic

deficits such as
hemiparesis, a
unilateral Babinski
sign, a visual field
defect, or
pseudobulbar palsy
Neuroimaging --

multiple areas of
infarction

TREATM EN T
preventing new ischemic injury by

stabilizing or removing the

underlying causes, such as
hypertension, diabetes, smoking, or
lack of exercise

FRO N TO TEM PO RAL LO BAR

D EG EN ERATIO N SPECTRU M

FRO N TO TEM PO RAL LO BAR

D EG EN ERATIO N SPECTRU M
group of clinical syndromes united by

underlying frontotemporal lobar

Degeneration (FTLD) pathology
fifth to seventh decades

core clinicalsyndrom es

behavioralvariant (bvFTD )
most common FTD syndrome
social and emotional systems

dysfunction manifests as apathy,

disinhibition, compulsivity, loss of
empathy, and overeating

sem antic variant

primary progressive aphasia (PPA),
slowly lose the ability to decode

word, object, person-specific, and

emotion meaning, whereas patients
with the

nonfl
uent/agram m atic variant
primary progressive aphasia (PPA),
develop profound inability to produce

words, often with prominent motor

speech impairment

D IAG N O STICS
gross pathologic hallmark of FTLD is

a focal atrophy of frontal, insular,

and/or temporal cortex
cholinergic system is relatively
spared in FTD
Microscopic --gliosis,
microvacuolation, and neuronal loss

PARKIN SO N S D ISEASE
D EM EN TIA AN D D EM EN TIA
W ITH LEW Y
BO D IES

PD D AN D D LB
DLB clinical syndrome:
visual hallucinations, parkinsonism,

fluctuating alertness, falls, and often

rapid eye movement (REM) sleep
behavior disorder
Parkinsons disease dementia (PDD)
dementia that is associated with
visual hallucinations and fluctuating
alertness

PD D AN D D LB
Both PDD and DLB
Involves brainstem pathology below

the substantia nigra including

constipation, orthostatic
lightheadedness

PD D AN D D LB
first manifestation of illness:
Delirium
precipitated by an infection, new

medicine, or other systemic

disturbance

D LB
key neuropathologic feature is the

presence of Lewy bodies and Lewy

neurites throughout specific
brainstem nuclei, substantia nigra,
amygdala, cingulate gyrus, and,
ultimately, the neocortex
Lewy bodies are intraneuronal

cytoplasmic inclusions that stain with

periodic acidSchiff (PAS) and

TREATM EN T
DLB
dopaminergic medications
cholinesterase inhibitors
reducing hallucinosis, stabilizing

delusional symptoms

Exercise programs
Antidepressants
Atypical antipsychotics

O TH ER CAU SES O F D EM EN TIA

Prion diseases such as Creutzfeldt-Jakob disease (CJD)
rapidly progressive disorder
dementia, focal cortical signs, rigidity, and myoclonus, causing death <1 year

after first symptoms appear

Huntingtons disease (HD)

Chorea, behavioral disturbance, and executive impairment
Delusions and obsessive-compulsive behavior

Normal-pressure hydrocephalus (NPH)

abnormal gait (ataxic or apractic), dementia, and urinary urgency or
incontinence
Intracranial hypotension
sagging brain syndrome

headache, often exacerbated by coughing or a Valsalva maneuver or by

moving from lying to standing

progressive bvFTD-like syndrome

O TH ER CAU SES O F D EM EN TIA

Chronic alcoholism
dementia and seizures with degeneration of the

corpus callosum - primarily in male Italian red wine

drinkers (Marchiafava-Bignami disease)

Thiamine (vitamin B1) deficiency

Wernickes encephalopathy
Korsakoffs syndrome

Vitamin B12 deficiency

Deficiency of nicotinic acid (pellagra)

O TH ER CAU SES O F D EM EN TIA

CNS infections
Chronic meningitis
Advanced HIV

Primary and metastatic neoplasms of the CNS

occult carcinoma

nonconvulsive seizure disorder

confusion, clouding of consciousness, and garbled speech

Isolated vasculitis of the CNS

chronic encephalopathy

O TH ER CAU SES O F D EM EN TIA

Chronic metal exposure
Chronic lead poisoning
Chronic mercury poisoning

punch-drunk syndrome or dementia pugilistica

chronic traumatic encephalopathy

(CTE)

Chronic subdural hematoma

Transient global amnesia (TGA)
sudden onset of a severe episodic memory deficit

O TH ER CAU SES O F D EM EN TIA

ALS/parkinsonian/dementia complex of Guam
adult-onset leukodystrophies, lysosomal storage diseases
Metachromatic leukodystrophy (MLD)

Progressive psychiatric or dementia syndrome associated with

extensive, confluent frontal white matter abnormality

Psychogenic amnesia
deliberate avoidance of unpleasant memories, outright
malingering, or unconscious repression
Psychiatric diseases
chronic drug or medication use