An overview of Alzheimers disease and other major dementias

1. Alzheimers Disease and
other Dementias

2. Outline
• Introduction
• Functional Anatomy
• Approach
• History
• Physical + Neurological Exam
• Lab
• Alzheimers Disease
• Intro
• Epidemiology
• Pathology
• Genetics
• Clinical Features
• Treatment
• DDx
• Vascular Dementia
• FTD, PSP and CB
• Dementia with Lewy Bodies
• Other causes

3. Dementias - Introduction
• It is defined as an acquired deterioration in cognitive abilities that impairs the successful
performance of activities of daily living.
• Memory is the most common cognitive ability lost with dementia; 10% of persons >70 and 20–
40% of individuals >85 have clinically identifiable memory loss.
• In addition to memory, other mental faculties are also affected in dementia; these include
• Language
• visuospatial ability
• Calculation
• judgment, and problem solving.
• Neuropsychiatric and social deficits also develop in many dementia syndromes, resulting in
• depression, withdrawal, hallucinations, delusions, agitation, insomnia, and disinhibition.
• Usually progressive, but some dementing illnesses are static and unchanging or fluctuate
dramatically from day to day.
• Affects >4 million Americans
• Total health care cost of >$100 billion annually.

5. Dementias – Functional Anatomy
• Dementia results from the disruption of cerebral neuronal circuits
• The quantity of neuronal loss and the location of affected regions are
factors that combine to cause the specific disorder .
• Behavior and mood are modulated by noradrenergic, serotonergic, and
dopaminergic pathways
• Acetylcholine seems to be particularly important for memory.
• Therefore, the loss of cholinergic neurons in Alzheimer's disease (AD) may
underlie the memory impairment
• Patients with non-AD dementias, the loss of serotonergic and glutaminergic
neurons causes primarily behavioral symptoms, leaving memory relatively
spared.

7. • Subcortical structures
• include the caudate, putamen, thalamus, and substantia nigra
• modulate cognition and behavior in ways that are not yet well
understood.
• Therefore
• AD primarily presents as memory loss and is often associated with aphasia
or other disturbances of language.
• In subcortical dementias are less likely to begin with memory problems
and more likely to have difficulties with attention, judgment, awareness,
and behavior.

8. Neuroanatomy
• Frontal lobe
• Controlling responses to input
from the rest of the CNS
• Voluntary movement
• Emotion
• Planning and execution of
behavior
• Intellect
• Memory
• Speech
• Writing
• Parietal Lobe
• Interprets sensations of
tactile stimulation, e.g.
pain, temperature,
touch, size, shape, and
body part awareness.

9. Neuroanatomy
• Temporal Lobe
• Understanding sounds
• Understanding speech
• Emotion
• Memory
• Occipital Lobe
• Understanding visual images
• Understanding the meaning of
the written word.

10. Neuroanatomy
•Hippocampus
•Plays a crucial role in both the encoding and retrieval of
information.
•Damage to the hippocampus produces global retrograde
amnesia, which is the inability to retain newly learned
information.

11. Dementias
• The single strongest risk factor for dementia is increasing age.
• Dementia may be a normal aging process
• Yet some centenarians have intact memory function and no evidence
of clinically significant dementia.
• Whether dementia is an inevitable consequence of normal human
aging remains controversial.

12. Approach - History
• Three major issues should be kept in the forefront:
(1) What is the most accurate diagnosis?
(2) Is there a treatable or reversible component to the dementia?
(3) Can the physician help to alleviate the burden on caregivers?

13. • Onset and Duration
• Tempo of progression of the dementia.
• An acute or subacute onset of confusion may represent
delirium and should trigger the search for intoxication,
infection, or metabolic derangement.
• An elderly person with slowly progressive memory loss over
several years is likely to suffer from AD.
• Nearly 75% of AD patients begin with memory symptoms,
but other early symptoms include difficulty with managing
money, driving, shopping, following instructions, finding
words, or navigating.

14. • A change in personality, disinhibition, and gain of weight or food
obsession suggests FTD, not AD.
• FTD is also suggested by the finding of apathy, loss of executive
function, or progressive abnormalities in speech, or by a relative
sparing of memory or spatial abilities.
• The diagnosis of DLB is suggested by the early presence of visual
hallucinations; parkinsonism; delirium; REM sleep disorder (the
merging of dream-states into wakefulness); or Capgras' syndrome, the
delusion that a familiar person has been replaced by an impostor.

15. • A history of sudden stroke with irregular stepwise progression suggests
multi-infarct dementia.
• Multi-infarct dementia is also commonly seen in the setting of
hypertension, atrial fibrillation, peripheral vascular disease, and diabetes.
• In patients suffering from cerebrovascular disease, it can be difficult to
determine whether the dementia is due to AD, multi-infarct dementia, or a
mixture of the two as many of the risk factors for vascular dementia,
including diabetes, high cholesterol, elevated homocysteine and low
exercise, are also risk factors for AD.
• Rapid progression of the dementia in association with motor rigidity and
myoclonus suggests CJD.
• Seizures may indicate strokes or neoplasm.

16. • Gait disturbance is commonly seen with multi-infarct dementia, PD, or
normal-pressure hydrocephalus (NPH).
• Multiple sex partners or intravenous drug use should trigger a search for
central nervous system (CNS) infection, especially for HIV.
• A history of recurrent head trauma could indicate chronic subdural
hematoma or NPH.
• Alcoholism may suggest malnutrition and thiamine deficiency.
• A remote history of gastric surgery resulting in loss of intrinsic factor can
bring about vitamin B12 deficiency.
• Certain occupations such as working in a battery or chemical factory might
indicate heavy metal intoxication.
• Careful review of medication intake, especially of sedatives and
tranquilizers, may raise the issue of chronic drug intoxication.
• A positive family of dementia is found in HD and in forms of familial
Alzheimer's disease (FAD), FTD, or prion disorders.
• The recent death of a loved one, or depressive signs such as insomnia or
weight loss, raises the possibility of pseudodementia due to depression.

17. Approach – Physical and Neurological Exam
• A thorough general and neurologic examination is essential to document
dementia
• Clues suggesting a systemic disease that might be responsible for the cognitive
disorder.
• AD does not affect motor systems until later in the course
• In DLB, initial symptoms may be the new onset of a parkinsonian syndrome
(resting tremor, cogwheel rigidity, bradykinesia, festinating gait) with the
dementia following later, or vice versa.
• Corticobasal degeneration (CBD) is associated with dystonia, asymmetric
extrapyramidal, pyramidal, or sensory deficits or myoclonus.
• Progressive supranuclear palsy (PSP) is associated with unexplained falls, axial
rigidity, dysphagia, and vertical gaze deficits.

18. • CJD is suggested by the presence of diffuse rigidity, an akinetic state, and
myoclonus.
• Hemiparesis or other focal neurologic deficits may occur in multi-infarct dementia
or brain tumor.
• Dementia with a myelopathy and peripheral neuropathy suggests vitamin B12
deficiency.
• A peripheral neuropathy could also indicate an underlying vitamin deficiency or
heavy metal intoxication.
• Dry, cool skin, hair loss, and bradycardia suggest hypothyroidism. Confusion
associated with repetitive stereotyped movements may indicate ongoing seizure
activity.
• Hearing impairment or visual loss may produce confusion and disorientation
misinterpreted as dementia.

19. • Brief screening tools such as the mini-mental state examination
(MMSE) help to confirm the presence of cognitive impairment and to
follow the progression of dementia
• In AD the deficits involve episodic memory, category generation
("name as many animals as you can in one minute"), and
visuoconstructive ability.
• In FTD, the earliest deficits often involve frontal executive or language
(speech or naming) function.
• DLB patients have more severe deficits in visuospatial function but do
better on episodic memory tasks than patients with AD.
• Patients with vascular dementia often demonstrate a mixture of
frontal executive and visuospatial deficits.

21. • A functional assessment should also be performed
• determine the day-to-day impact of the disorder
• Neuropsychiatric assessment is important for diagnosis, prognosis,
and treatment.
• In the early stages of AD, mild depressive features, social withdrawal,
and denial of illness are the most prominent psychiatric changes.
• However, patients often maintain their social skills into the middle
stages of the illness, when delusions, agitation, and sleep disturbance
become more common.
• In FTD, dramatic personality change, apathy, overeating, repetitive
compulsions, disinhibition, euphoria, and loss of empathy are
common.
• DLB shows visual hallucinations, delusions related to personal
identity, and day-to-day fluctuation. Vascular dementia can present
with psychiatric symptoms such as depression, delusions,
disinhibition, or apathy.

24. Alzheimers - Intro
• Approximately 10% of all persons over the age of 70 have
significant memory loss
• > half the cause is AD.
• Significant costs
• annual total cost of caring for a single AD patient in an advanced stage of
the disease is >$50,000.
• The disease also exacts a heavy emotional toll on family members and
caregivers.
• AD can occur in any decade of adulthood
• But it is the most common cause of dementia in the elderly.
• AD most often presents with subtle onset of memory loss followed
by a slowly progressive dementia that has a course of several
years.

25. Epidemiology – risk factors
• Age – most important risk factor
• The frequency of AD increases with
each decade of adult life, reaching 20–
40% of the population over the age of
85.
• A positive family history of dementia
suggests a genetic cause of AD.
• Female gender may also be a risk
factor independent of the greater
longevity of women.
• ?? Head trauma
• AD is more common in groups with very low
educational attainment??
• Environmental (aluminum, mercury, and
viruses)
• NSAIDS ?? Protective
• Vascular disease, in particular stroke, seems
to lower the threshold for the clinical
expression of AD.
• Diabetes increases the risk of AD threefold.
• Elevated homocysteine and cholesterol levels;
hypertension; diminished serum levels of folic
acid; low dietary intake of fruits, vegetables,
and red wine; and low levels of exercise are
all being explored as potential risk factors for
AD.

26. What cause neuronal death in AD?
• The mechanism is not clearly known
• but it is proposed that some neuronal death is due to
accumulation of both beta amyloid plaques and
Neurofibrillary Tangles in the brain

27. Cont…..
• Amyloid Plaques:
• Formed from β-amyloid; fragments from a larger protein
called amyloid precursor protein (APP), a transmembrane
protein that penetrates through the neuron's membrane
• APP is critical to neuron growth, survival and post-injury
repair.
• In Alzheimer's disease, an unknown process causes APP to
be divided into smaller fragments by enzymes through
proteolysis.

28. Cont….
• One of these fragments gives rise to fibrils of beta-amyloid,
which form clumps that deposit outside neurons in dense
formations known as amyloid plaques.
• Accumulation of these plaques are said to be associated
with neuronal death

32. Cont…..
• Neurofibrillary tangles:
• AD is also considered a tauopathy due to abnormal
aggregation of the tau protein.
• Every neuron has a cytoskeleton, an internal support
structure partly made up of structures called microtubules.

33. Cont….
• These microtubules act like tracks, guiding nutrients and
molecules from the body of the cell to the ends of the axon
and back.
• A protein called tau stabilizes the microtubules when
phosphorylated, and is therefore called a microtubule-
associated protein
• In AD, tau undergoes chemical changes, becoming
hyperphosphorylated; sticky together forming
neurofibrillary tangles and disintegrating the neuron's
transport system → neuronal death

36. cont…..

37. Cont..
• AD has been identified as a protein misfolding disease
(proteopathy), caused by accumulation of abnormally folded
A-beta and tau proteins in the brain
• AD, is also associated with a decrease in the cerebral
cortical levels of several proteins and neurotransmitters,
especially acetylcholine; there is reduction in nor
epinephrine levels also in brainstem nuclei.

38. Genetics
• Several genetic factors play important roles in the pathogenesis of at least some cases of
AD.
• One is the APP gene on chromosome 21. Adults with trisomy 21 (Down's syndrome)
consistently develop the typical neuropathologic hallmarks of AD if they survive beyond
age 40. Many develop a progressive dementia superimposed on their baseline mental
retardation.
• APP is a membrane-spanning protein that is subsequently processed into smaller units,
including A amyloid that is deposited in neuritic plaques. A peptide results from cleavage
of APP by and secretases (Fig. 365-4).
• Presumably the extra dose of the APP gene on chromosome 21 is the initiating cause of
AD in adult Down's syndrome and results in an excess of cerebral amyloid.
• Furthermore, a few families with early onset FAD have been discovered to have point
mutations in the APP gene. Although very rare, these families were the first examples of
a single-gene autosomal dominant genetic transmission of AD.

39. Clinical Features - Early
• The cognitive changes with AD tend to follow a characteristic pattern, beginning
with memory impairment and spreading to language and visuospatial deficits.
• However, ~20% of AD patients present with nonmemory complaints such as
word-finding, organizational, or navigational difficulty.
• In the early stages of the disease, the memory loss may go unrecognized or be
ascribed to benign forgetfulness. Once the memory loss begins to affect day-to-
day activities or falls below 1.5 standard deviations from normal on standardized
memory tasks, the disease is defined as MCI.
• Approximately 50% of MCI individuals will progress to AD within 5 years.
• Slowly the cognitive problems begin to interfere with daily activities, such as
keeping track of finances, following instructions on the job, driving, shopping, and
housekeeping.
• Some patients are unaware of these difficulties (anosognosia), while others have
considerable insight.

40. • Change of environment may be bewildering, and the patient may become lost on walks
or while driving an automobile.
• In the middle stages of AD, the patient is unable to work, is easily lost and confused, and
requires daily supervision.
• Social graces, routine behavior, and superficial conversation may be surprisingly intact.
• Language becomes impaired—first naming, then comprehension, and finally fluency.
• In some patients, aphasia is an early and prominent feature.
• Word finding difficulties and circumlocution may be a problem even when formal testing
demonstrates intact naming and fluency.
• Apraxia emerges, and patients have trouble performing sequential motor tasks.
Visuospatial deficits begin to interfere with dressing, eating, solving simple puzzles, and
copying geometric figures. Patients may be unable to do simple calculations or tell time.

41. Clinical Features - Late
• In the late stages of the disease, some persons remain ambulatory but wander aimlessly.
• Loss of judgment, reason, and cognitive abilities is inevitable.
• Delusions are common and usually simple in quality, such as delusions of theft, infidelity, or
misidentification.
• Approximately 10% of AD patients develop Capgras' syndrome, believing that a caregiver has
been replaced by an impostor.
• In contrast to DLB, where Capgras' syndrome is an early feature, in AD this syndrome emerges
later in the course of the illness.
• Loss of inhibitions and aggression may occur and alternate with passivity and withdrawal.
• Sleep-wake patterns are prone to disruption, and nighttime wandering becomes disturbing to the
household.
• Some patients develop a shuffling gait with generalized muscle rigidity associated with slowness
and awkwardness of movement.
• Patients often look parkinsonian but rarely have a rapid, rhythmic, resting tremor.

42. Clinical Features – End Stage
• In end-stage AD, patients become rigid, mute, incontinent, and bedridden.
• Help may be needed with the simplest tasks, such as eating, dressing, and toilet function.
• They may show hyperactive tendon reflexes.
• Myoclonic jerks (sudden brief contractions of various muscles or the whole body) may
occur spontaneously or in response to physical or auditory stimulation. 7
• Myoclonus raises the possibility of CJD, but the course of AD is much more prolonged.
• Generalized seizures may also occur.
• Often death results from malnutrition, secondary infections, pulmonary emboli, or heart
disease.
• The typical duration of AD is 8–10 years, but the course can range from 1 to 25 years.
• For unknown reasons, some AD patients show a steady downhill decline in function,
while others have prolonged plateaus without major deterioration.

43. Treatment
• The primary focus is on long-term amelioration of associated behavioral and
neurologic problems.
• Building rapport with caregivers is essential to successful management.
• In the early stages of AD, memory aids such as notebooks and posted daily
reminders can be helpful.
• Common sense and clinical studies show that family members should emphasize
activities that are pleasant and deemphasize those that are unpleasant.
• Kitchens, bathrooms, and bedrooms need to be made safe, and eventually
patients must stop driving.
• Loss of independence and change of environment may worsen confusion,
agitation, and anger.
• Communication and repeated calm reassurance are necessary.
• Caregiver "burnout" is common, often resulting in nursing home placement of
the patient, and respite breaks for the caregiver help to maintain successful long-
term management of the patient.

44. • Donepezil, rivastigmine, galantamine, memantine, and tacrine are the drugs presently approved by the Food
and Drug Administration (FDA) for treatment of AD.
• Due to hepatotoxicity, tacrine is no longer used.
• The pharmacologic action of donepezil, rivastigmine, and galantamine is inhibition of cholinesterase, with a
resulting increase in cerebral levels of acetylcholine.
• Memantine appears to act by blocking overexcited N-methyl-D-aspartate (NMDA) channels.
• Double-blind, placebo-controlled, crossover studies with cholinesterase inhibitors and memantine have
shown them to be associated with improved caregiver ratings of patients' functioning and with an apparent
decreased rate of decline in cognitive test scores over periods of up to 3 years.
• The average patient on an anticholinesterase compound maintains his or her MMSE score for close to a year,
whereas a placebo-treated patient declines 2–3 points over the same time period.
• Memantine, used in conjunction with cholinesterase inhibitors or by itself, seems to slow cognitive
deterioration in patients with moderate to severe AD and is not approved for mild AD.
• These compounds have only modest efficacy for AD and offer even less benefit in the late stages.
• All the cholinesterase inhibitors are relatively easy to administer, and their major side effects are
gastrointestinal symptoms (nausea, diarrhea, cramps), altered sleep with bad dreams, bradycardia (usually
benign), and sometimes muscle cramps.

45. • In a prospective observational study, the use of estrogen replacement
therapy appeared to protect—by about 50%—against development of
AD in women.
• This study seemed to confirm the results of two earlier case-
controlled studies. Sadly, a prospective placebo-controlled study of a
combined estrogen-progesterone therapy for asymptomatic
postmenopausal women increased, rather than decreased, the
prevalence of dementia.
• This study markedly dampened enthusiasm for hormone treatments
for the prevention of dementia. Additionally, no benefit has been
found in the treatment of AD with estrogen.

46. • In patients with moderately advanced AD, a prospective trial of the
antioxidants selegiline, -tocopherol (vitamin E), or both, slowed
institutionalization and progression to death.
• Because vitamin E has less potential for toxicity than selegiline and is
cheaper, the doses used in this study of 1000 IU twice daily are
offered to many patients with AD.
• However, the beneficial effects of vitamin E remain controversial, and
most investigators no longer give it in these high doses because of
potential cardiovascular complications.

47. • A randomized, double-blind, placebo-controlled trial of an extract of
Ginkgo biloba found modest improvement in cognitive function in
subjects with AD and vascular dementia.
• This study requires confirmation before Ginkgo biloba is used as a
treatment for dementia because there was a high subject dropout
rate and no improvement on a clinician's judgment scale.
• A comprehensive 6-year multicenter prevention study using Ginkgo
biloba is underway.

48. • Vaccination against A42 has proved highly efficacious in mouse
models of AD; it helped to clear amyloid from the brain and prevent
further accumulation of amyloid.
• However, in human trials this approach led to life-threatening
complications, including meningoencephalitis.
• Modifications of the vaccine approach using passive immunization
with monoclonal antibodies are currently being evaluated in phase 3
trials.
• Another experimental approach to the treatment of AD has been the
use of β and γ secretase inhibitors that diminish the production of
A42.

49. • Several retrospective studies suggest that nonsteroidal anti-
inflammatory agents and statins (HMG-CoA reductase inhibitors) may
have a protective effect on dementia, and controlled prospective
studies are being conducted.
• Similarly, prospective studies with the goal of lowering serum
homocysteine levels are underway, suggesting an association of
elevated homocysteine with dementia progression based on
epidemiologic studies.
• Finally, there is now a strong interest in the relationship between
diabetes and AD, and insulin-regulating studies are being conducted.

50. • Mild to moderate depression is common in the early stages of AD and responds
to antidepressants or cholinesterase inhibitors.
• Selective serotonin reuptake inhibitors (SSRIs) are commonly used due to their
low anticholinergic side effects.
• Generalized seizures should be treated with an appropriate anticonvulsant, such
as phenytoin or carbamazepine.
• Agitation, insomnia, hallucinations, and belligerence are especially troublesome
characteristics of some AD patients, and these behaviors can lead to nursing
home placement.
• The newer generation of atypical antipsychotics, such as risperidone, quetiapine,
and olanzapine, are being used in low doses to treat these neuropsychiatric
symptoms.
• The few controlled studies comparing drugs against behavioral intervention in the
treatment of agitation suggest mild efficacy with significant side effects related to
sleep, gait, and cardiovascular complications. All of the antipsychotics carry a
black-box warning and should be used with caution.
• However, careful, daily, nonpharmacologic behavior management is often not
available, rendering medications necessary.

51. Vascular Dementia
• Dementia associated with cerebral vascular disease can be divided into two general categories
• multi-infarct dementia
• diffuse white matter disease (also called Binswanger's disease).
• Cerebral vascular disease appears to be a more common cause of dementia in Asia than in Europe
and North America.
• Individuals who have had several strokes may develop chronic cognitive deficits, commonly called
multi-infarct dementia.
• The strokes may be large or small (sometimes lacunar) and usually involve several different brain
regions. The occurrence of dementia depends partly on the total volume of damaged cortex, but
it is also more common in individuals with left-hemisphere lesions, independent of any language
disturbance.
• Patients typically report a history of discrete episodes of sudden neurologic deterioration.
• Many multi-infarct dementia patients have a history of hypertension, diabetes, coronary artery
disease, or other manifestations of widespread atherosclerosis.
• Physical examination usually shows focal neurologic deficits such as hemiparesis, a unilateral
Babinski reflex, a visual field defect, or pseudobulbar palsy.
• Recurrent strokes result in a stepwise progression of disease. Neuroimaging studies show multiple
areas of infarction. Thus, the history and neuroimaging findings differentiate this condition from

52. • Some individuals with dementia are discovered on MRI to have bilateral abnormalities of subcortical white
matter, termed diffuse white matter disease, often occurring in association with lacunar infarctions
• The dementia may be insidious in onset and progress slowly, features that distinguish it from multi-infarct
dementia, but other patients show a stepwise deterioration more typical of multi-infarct dementia.
• Early symptoms are mild confusion, apathy, changes in personality, depression, psychosis, memory, and
spatial or executive deficits.
• Marked difficulties in judgment and orientation and dependence on others for daily activities develop later.
Euphoria, elation, depression, or aggressive behaviors are common as the disease progresses. Both
pyramidal and cerebellar signs may be present in the same patient. A gait disorder is present in at least half
of these patients.
• With advanced disease, urinary incontinence and dysarthria with or without other pseudobulbar features
(e.g., dysphagia, emotional lability) are frequent. Seizures and myoclonic jerks appear in a minority of
patients. This disorder appears to result from chronic ischemia due to occlusive disease of small, penetrating
cerebral arteries and arterioles (microangiopathy). Any disease-causing stenosis of small cerebral vessels
may be the critical underlying factor, though most typically hypertension is the main cause. The term
Binswanger's disease should be used with caution, because it does not really identify a single entity.

53. Frontotemporal Dementia
• Fifth to seventh decades, and in this age group it is nearly as common
as AD.
• M > F
• Unlike AD, behavioral symptoms predominate in the early stages of
FTD.
• The most common genetic mutations that cause an autosomal
dominant form of FTD involve the tau or progranulin genes, both on
chromosome 17.
• Tau mutations lead to a change in the alternate splicing of tau or
cause loss of function in the tau molecule.

54. • In FTD, early symptoms are divided among cognitive, behavioral, and
sometimes motor abnormalities, reflecting degeneration of the
anterior frontal and temporal regions, basal ganglia, and motor
neurons.
• Cognitive testing typically reveals spared memory but impaired
planning, judgment, or language. Poor business decisions and
difficulty organizing work tasks are common, and speech and
language deficits often emerge.
• Patients with FTD often show an absence of insight into their
condition. Common behavioral deficits include apathy, disinhibition,
weight gain, food fetishes, compulsions, and euphoria.

55. • Findings at the bedside are dictated by the anatomic localization of the
disorder.
• Asymmetric left-frontal cases present with nonfluent aphasias
• while left anterior temporal degeneration is characterized by loss of words
and concepts related to language (semantic dementia).
• Memory and visuospatial skills are relatively spared in most FTD patients.
• There is a striking overlap among FTD, PSP, CBD, and motor neuron disease;
ophthalmoplegia, dystonia, swallowing symptoms, and fasciculations are
common at presentation of FTD or emerge during the course of the illness.

56. • The distinguishing anatomic hallmark of FTD is a marked lobar
atrophy of temporal and/or frontal lobes, which can be visualized by
neuroimaging studies and is readily apparent at autopsy
• The atrophy is sometimes asymmetric and may involve the basal
ganglia.

57. • In contrast to AD, the cholinergic system is relatively spared in FTD,
whereas serotonergic and glutaminergic neurons are depleted in
many patients.

58. • The burden on caregivers of FTD patients is extremely high.
• Treatment is symptomatic, and there are currently no therapies
known to slow progression or improve cognitive symptoms.
• Many of the behaviors that accompany FTD, such as depression,
hyperorality, compulsions, and irritability, can be ameliorated with
serotonin-modifying antidepressants.

59. Dementia with Lewy Bodies
• The parkinsonian dementia syndromes are under increasing study, with many cases
unified by the presence of Lewy bodies in both the substantia nigra and the cortex at
pathology.
• The clinical syndrome is characterized by visual hallucinations, parkinsonism, fluctuating
alertness, falls, and often REM sleep behavior disorder.
• Dementia can precede or follow the appearance of parkinsonism.
• Hence, one pathway to DLB occurs in patients with longstanding PD without cognitive
impairment who slowly develop a dementia that is associated with visual hallucinations,
parkinsonism, and fluctuating alertness.
• In others, the dementia and neuropsychiatric syndrome precede the parkinsonism.
• Despite the fluctuating pattern, the clinical features persist over a long period of time,
unlike delirium, which resolves following correction of the underlying precipitant.
• Cognitively, DLB patients tend to have relatively better memory but more severe
visuospatial deficits than individuals with AD.

60. • The key neuropathologic feature is the presence of Lewy bodies
throughout the cortex, amygdala, cingulate cortex, and substantia
nigra.
• Lewy bodies are intraneuronal cytoplasmic inclusions that stain with
periodic acid–Schiff (PAS) and ubiquitin.

61. • Due to the overlap with AD and the cholinergic deficit in DLB,
anticholinesterase compounds may be helpful.
• Exercise programs maximize the motor function of these patients.
Similarly, antidepressants are often necessary to treat the depressive
syndromes that accompany DLB.
• Atypical antipsychotics in low doses are sometimes needed to
alleviate psychosis, although even low doses can increase
extrapyramidal syndromes and may rarely lead to death.
• As noted above, patients with DLB are extremely sensitive to
dopaminergic medications, which must be carefully titrated;
tolerability may be improved by concomitant AD medications.

62. Other Causes
• Prion Diseases
• Huntingtons Disease
• Normal Pressure Hydrocephalus

63. Its about memory