Dementia

Dr.Jaidaa Mekky
A.Prof of Neuropsychiatry
Sleep Medicine Consultant

Progressive deterioration of intellect, behavior and personality as
a consequence of diffuse disease of the brain hemispheres,
maximally affecting the cerebral cortex and hippocampus.
Dementia is a symptom of disease rather than a single disease
entity!!!

 Memory must be impaired to make the diagnosis of
dementia.
 Loss of memory for recent events is the earlist feature of
dementia.
 Subsequent symptoms include abnormal behavior, loss of
intellect, mood changes, and difficulty coping with ordinary
routes.
 Insight may be retained initially, but is then usually lost.
 Ultimately, there is loss of self-care, wandering,
incontinence, and often paranoia.

Dementia has to be distinguished from delirium which is an acute disturbance of
cerebral function with impaired conscious level, hallucinations and autonomic
overactivity as a consequence of toxic, metabolic or infective conditions.
Depression can mimic the initial phases of dementia and it is termed
’pseudodementia’ (which is amenable to antidepressant medication).

Dementia may occur at any age but is more common in the elderly,
accounting for 40% of long-term psychiatric in-patients over the age
of 65 years.
The prevalence in persons aged between 50 and 70 years is about
1% and in those approaching 90 years reaches 50%.
An annual incidence rate is 190/100 000 persons.

Clinical course:
The rate of progression depends upon the
underlying cause.
The duration of history helps establish the cause of dementia: Alzheimer‘s
disease is slowly progressive over years, whereas encephalitis may be rapid over
weeks.
Dementia due to cerebrovascular disease appears to occur ’stroke by stroke‘.

 Alzheimer‘s disease (~60% of all dementias)
 Cerebrovascular (multiinfarct state, subcortical small
vessel, amyloid angiopathy,…) (~20%)
 Neurodegenerative (DLB, Pick‘s disease, Huntington‘s chorea, Parkinson‘s disease)
 Infectious (Creutzfeld-Jakob disease, HIV infection, progressive multifocal
leucoencephalopathy)
TREATABLE!
 Normal pressure hydrocephalus
 Nutritional (thiamine deficiency in alcoholics!, B12 deficiency, folate deficiency)
 Metabolic (hepatic disease, thyroid d., parathyroid d., Cushing‘s syndrome)
 Chronic inflammatory (MS, …)
 Trauma (head injury, ’Punch drunk‘ syndrome)
 Tumour (e.g. subfrontal meningioma)

Neuropathology of Dementia Disorders
2013

Figure 1 Clinicopathological spectrum of neurodegenerative proteinopathies
Elahi, F. M. & Miller, B. L. (2017) A clinicopathological approach to the diagnosis of dementia
Nat. Rev. Neurol. doi:10.1038/nrneurol.2017.96

 Mild changes in memory and rate of information processing
 Not progressive
 Does not interfere with daily function or independence

Mild cognitive impairment (MCI)
 MCI is a relatively recent term, used to describe people who have
some problems with their memory but do not actually have
dementia.
 Some people (80%?) will be in the early stages of Alzheimer’s
disease or another dementia. Others, however, will have MCI as a
result of stress, anxiety, depression, physical illness or just an ‘off
day’.
 It is estimated that 15% of the population may be experiencing
MCI.
 Currently extensive research on MCI is ongoing.
 At the moment there is not enough evidence to recommend any
specific treatments.

 12% of people over age 70
 Usually memory affected
 Does not significantly interfere
with daily function
 3 times increased risk of
developing AD
 10–15% /year will develop
dementia

https://www.medscape.com/viewarticle/580765_3

Whole-brain Functional Networks in Cognitively Normal, Mild Cognitive Impairment, and
Alzheimer’s Disease
Eun Hyun Seo, Dong Young Lee, Jong-Min Lee, Jun-Sung Park, Bo Kyung Sohn, Dong Soo Lee ,
Young Min Choe, Jong Inn Woo
Published: January 15, 2013

Age
Family hx of AD or Parkinson’s (10-30% risk of AD in
patients with first degree relative)
Head trauma
Depression (early marker for dementia)
Low educational attainment
hyperlipidemia
diabetes
HTN !!!

Gender (confounding in literature – women more
likely to live longer, be older….)
Down’s syndrome

1. Memory impairment
2. At least one of the following:
 Aphasia
 Apraxia
 Agnosia
 Disturbance in executive functioning
3. Disturbance in 1 and 2 interferes with daily function or
independence
4. Does not occur exclusively during delirium

 ADLs: bathing, toileting, transfer, dressing, eating
 IADLs (executive functioning):
 Maintaining household
 Shopping
 Transportation
 Finances

 The commonest cause of dementia.
 The disorder rarely occurs under the age of 45 years.
 The incidence increases with age.
 Up to 30% of cases are familial (the loci were found on
chromosome 21 and 19).
 Family hx (especially for early types)
 Pathology – the presence of senile plaques and neurofibrillary tangles in
the brain.
 Diagnosis of AD may be established during life by early
memory failure, slow progression and exclusion of other
causes.

Onset usually near age 65; older age, more likely diagnosis
Absence of focal neurological signs (but significant overlap in the
elderly with hx of CVAs…)
Aphasia, apraxia, agnosia
Normal/nonspecific EEG
MRI: bilateral hippocampal atrophy (suggestive)

 Role of the Hippocampus
 Patient HM with surgery for seizures to remove bilateral medial temporal lobes resulting in
severe anterograde amnesia
 Formation of new memories
 Spatial navigation
 Early evidence for damage in this area

Depression occurs in 1/3
Delusions and hallucinations in 1/3
Extracellular deposition of amyloid-beta protein, intracellular
neurofibrillary tangles, and loss of neurons at autopsy
Clinical diagnosis: 87% of diagnosed AD confirmed pathologically
(but high pretest probability increases predictive value of clinical
diagnosis!!!)

 This is an overdiagnosed condition which accounts for less than 10% of cases
of dementia.
 MID is caused by multiple strokes - SILENT STROKES
 Dementia occurs ’stroke by stroke‘, with progressive focal loss of function.
 Clinical features of stroke profile – hypertension, diabetes, etc. – are present.
More often in males.
 Diagnosis is obtained from the history and
confirmed by CT or MRI scan (the presence
of multiple areas of infarction).
 Treatment: Maintain adequate blood pressure control,
anti-platelet aggregants (aspirin).

Onset of cognitive deficits associated with a stroke (but often no
clear hx of CVA but multiple small, undiagnosed CVAs)
Abrupt onset of symptoms with stepwise deterioration
 +Findings on neurological examination
Infarcts on cerebral imaging (but ct/mri findings often have no clear
relationship)

Most patients previously categorized as either Alzheimer’s type or
vascular type dementias probably have BOTH
Likelihood of AD and vascular disease significantly increases with
age, therefore likelihood of both does as well
Vascular risk factors predispose to AD -- ?does it allow the
symptoms of AD to be unmasked earlier??

 30% with PD may develop dementia; Risk Factors:
 Age over 70
 Depression
 Confusion/psychosis on levodopa
 Facial masking upon presentation
 Hallucinations and delusions
 May be exacerbated by treatment
 Usually occurs 10 y after the PD onset

Dementia with Lewy bodies (DLB)
 One of the most common types of progressive dementia.
 Progressive cognitive decline, combined with three additional defining
features:
 (1) pronounced “fluctuations” in alertness and attention;
 (2) recurrent visual hallucinations,
 (3) parkinsonian motor symptoms, such as rigidity and the loss of
spontaneous movement.

 The symptoms of DLB are caused by the build-up of Lewy bodies – accumulated bits of alpha-
synuclein protein - inside the nuclei of neurons in areas of the brain that control particular
aspects of memory and motor control. Lewy bodies are often also found in the brains of people
with Parkinson's and Alzheimer’s diseases.These findings suggest that either DLB is related to
these other causes of dementia or that an individual can have both diseases at the same time.
 DLB usually occurs sporadically, in people with no known family history of the disease.
However, rare familial cases have occasionally been reported.

 Cortical Lewy Bodies on path
 10–20% of dementias
 Compare to PD: Lewy Bodies in substantia nigra
 Overlap with AD and PD
 40% patients with AD have LBs on path

 Visual hallucinations (early)
 Parkinsonism
 Cognitive fluctuations
 Dysautonomia
 Sleep disorders
 Neuroleptic sensitivity
 Memory changes later in course

 Visual hallucinations
 2/3 of patients with DLB
 Rare in AD
 May precede other symptoms of DLB
 Psychosis, paranoia and other psychiatric
manifestations early in course
 Cognitive Fluctuations
 60–80%
 Episodic
 Loss of consciousness, staring spells, more
confused or delirious like behavior
 Days of long naps
 Significant impact on functional status

 Parkinsonism
 70–90%
 More bilateral and symmetric than with PD
 Tremor less common
 Bradykinesia, rigidity, gait changes
 Sleep disorders
 REM sleep behavior disorder/parasomnia
 Acting out of dreams: REM dreams
without usual muscle atonia
 85% of patients with DLB
 May precede other symptoms by years

 More progressive course than AD or Vascular dementia
 Possibly better response to cholinergic drugs than AD or vascular dementias
 ?response of psychiatric type symptoms to cholinergic agents/cholinesterase inhibitors
DLB: Neuroleptic Hypersensitivity
 30–50% of patients
 May induce Parkinsonian symptoms or cognitive changes that are not reversible, leading to
rapid decline in overall status
 NOT dose related
 Slightly less likely with newer atypical antipsychotics, but can STILL happen

 This progressive condition accounts for 5% of all dementias.
 Usually sporadic, it more commonly affect women between 40 and 60 years.
 Personality and behaviour are initially more affected than memory.
 Frontal lobe dysfunction predominates with apathy, lack of initiative and personality changes.
 CT or MRI scans show frontal (and/or temporal) atrophy, often asymmetrical.
 SPECT reveal anterior hypoperfusion, EEG is usually normal.
 The disorder is characterized pathologically by argyrophylic inclusion bodies within the
cytoplasm of cells of the frontotemporal cortex.
 There is no treatment, death occuring within 2-3 years of the onset.

 Impairment of executive function
 Initiation
 Goal setting
 Planning
 Disinhibited/inappropriate behavior (90%)
 Cognitive testing may be normal; memory loss NOT prominent early
feature
 5–10% cases of dementia
 Onset usually 45–65 (rare after age 75)
 Familial: 20–40%

 This condition is one of a group of disorders characterized
by asymmetrical cortical degeneration.
 Dominant hemisphere perisylvian atrophy is associated with
loss of language, which, after many years, becomes a more
widespread dementia.
 Pathologically non-specific cell loss, Pick’s pathology or
spongiform changes are described.
 MRI and SPECT confirm focal changes.

 Uncommon
 Vertical supranuclear palsy with downward gaze abnormalities
 Postural instability
 Falls (especially with stairs)
 “Surprised look”
 Difficulty with spilling food/drink

Subtype of frontal lobe dementia
Pick bodies (silver staining intracytoplasmic inclusions in
neocortex and hippocampus)
?Serotonergic deficit?
Language abnormalities and behavioral disturbances
 Logorrhea (abundant unfocused speech)
 Echolalia (spontaneous repetition of words/phrases)
 Palilalia (compulsive repetition of phrases)
 Fluent or non-fluent forms

Patients slowly develop non-fluent, anomic aphasia with hesitant,
effortful speech
Repetition, reading, writing also impaired; comprehension initially
preserved
Slow progression, initially memory preserved but 75% eventually
develop non-language deficits; most patients eventually become
mute
Average age of onset = 60
Subset of FTD

= term applied to the triad of:
1. Dementia
2. Gait disturbance
3. Urinary incontinence
occuring in conjunction with hydrocephalus and normal CSF pressure.
Two types:
- NPH with a preceding cause (SAH, meningitis, trauma,
radiation-induced).
- NPH with no known preceding cause – idiopathic (50%).

Aetiology is unclear.
It is presumed that at some preceding period, impedence to normal CSF
flow causes raised intraventricular pressure and ventricular dilatation.
Compensatory mechanisms permit a reduction in CSF pressure yet the
ventricular dilatation persists and causes symptoms.

Diagnosis is based on clinical picture plus CT scan/MRI evidence of ventricular enlargement.
NPH must be differentiated from pts whose ventricular enlargement is merely the result of
shrinkage of the surrounding brain, e.g. AD. These pts do not respond to CSF shunting,
whereas a proportion of NPH pts (but not all) show a definitive improvement with ventriculo-
peritoneal shunting.

Gait
 Early Feature
 Most responsive to shunting
 Magnetic/gait apraxia/frontal “ataxia”
Cognitive
 Psychomotor slowing, apathy, decreased attention
Urinary
 Urgency or incontinence

Hydrocephalus in absence of papilledema, with normal CSF
pressure
Begins as transient/intermittent increased CSF pressure, leading to
ventricular enlargement; ventricular enlargement leads to
normalization of CSF pressure
Thought to be due to decreased CSF absorption at arachnoid villi
Causes: SAH, tumors, CVA

 Diagnosis: initially on neuroimaging
 Ventricular enlargement our of proportion to sulcal
atrophy
 Miller Fisher test: objective gait assessment before
and after removal of 30 cc CSF
 Radioisotope diffusion studies of CSF
 MRI: turbulent flow in posterior third ventricle and
within aqueduct of sylvius
 MRI flow imaging
 SPECT (Single Photon emission CT): decreased
blood flow in frontal and periventricular areas

 Limited data
 Gait may be most responsive
 Predictors of better outcome:
 Lack of significant dementia
 Known etiology (prior SAH)
 New (< 6 months) symptoms
 Prominence of gait abnormality

 Approximately two-thirds of persons with AIDS develop
dementia, mostly due to AIDS dementia complex.
 In some patients HIV is found in the CNS at postmortem. In
others an immune mechanism or an unidentified pathogen is
blamed.
 Dementia is initially of a "subcortical " type.
 CT - atrophy; MRI - increased T2 signal from white matter.
 Treatment with Zidovudine (AZT) halts and partially revers
neuropsychological deficit.

 Reduction of intellectual function is common after severe head injury.
 Chronic subdural haematoma can also present as progressive dementia,
especially in the elderly.
 Punch-drunk encephalopathy (dementia pugilistica) is the cumulative result of
repeated cerebral trauma. It occurs in both amateur and professional boxers and
it manifests by dysarthria, ataxia and expy signs associated with ’subcortical‘
dementia. There is no treatment for this progressive syndrome.

 Dementia rarely may be due to intracranial tumour, especially when tumours
occur in certain anatomical sites.
 Mental or behavioral changes occur in 50-70% of all brain tumours as distinct
from dementia which is associated with frontal lobe tumours, III ventricle
tumours and corpus callosum tumours.
 Cognitive impairment also occurs as a non metastatic complication of systemic
malignancy.

 Rapid onset and deterioration
 Motor deficits
 Seizures
 Slowing and periodic complexes on EEG
 Myotonic activity

 Medications
 Alcohol
 Metabolic (b12, thyroid, hyponatremia, hypercalcemia, hepatic and renal dysfunction)
 Depression? (likely marker though…)
 CNS neoplasms, chronic subdural
 NPH

Investigation
 Blood tests (to exclude hypothyroidism,FBS, Lipid profile ,
vitamin B12, thiamine and folate deficiency, Lyme disease, HIV
infection, metabolic disorders and inflammatory diseases).
 Liver and renal function
 Lumbar puncture
 ECG , Echocardiogram
 CRP, ESR
 Serum Na,K, Ca
 Cranial imaging (CT or/and MRI) (to exclude NPH)
 PET and SPECT
 EEG (slowing in AD, normal in pseudodementia, periodic
complexes in CJD)
 Genetic testing (rarely – Huntington mutation, apolipoprotein E4
mutation in AD)
 Brain biopsy (if treatable cause is suspected)

 schematic approach to history taking and involving clinical history assessments that assay
cognition, function abilities, and behavior.
 An informant generally provides these data components due to the limited reliability of a
patient with impaired memory and insight

 The Ascertain Dementia 8 (AD8), an 8-item measure of informant-reported changes
in cognitive functioning, is a well-validated and widely used historical cognitive
screening instrument
 The AD8 content includes memory, orientation, and other faculties, including
executive, motivation, praxis, and functional ability(eg,managing money).
 A score of 2 or higher (out of 8 total items) on the AD8 is highly predictive of
dementia

MENTAL STATUS EXAMINATION
The mental status examination is the part of the neurologic examination that assesses current mental
capacity through evaluation of appearance, mood, perceptions (eg, delusions, hallucinations), and all
aspects of cognition (eg, attention, orientation, memory).
Several standardized mental status examinations enable quantification of cognitive impairment,
typically yielding a single composite score that reflects disease severity. For example, the Montreal
Cognitive Assessment, a brief 30-point screening instrument, was developed and
validated to identify patients with mild cognitive impairment, a clinical state that often progresses to
dementia.

 24/30 suggestive of dementia (sens 87%, spec 82%)
 Not sensitive for MCI
 Spuriously low in people with low educational level, low SES, poor language skills,
illiteracy, impaired vision
 Not sensitive in people with higher educational background

No on serial sevens (months backwards, name backwards…
assessment of attention)
Assess literacy prior
Assess for dominant hand prior to handing paper over
Do not over lead
3-item repetition, repeat all 3 then have patients repeat; 3-stage
command, repeat all 3 parts of command and then have patient
do…

 Clockface
 Short assessments with good validity: 3-item recall and clockface
 Neurological exam (focality, frontal release signs such as grasp, jawjerk;
apraxia, cogwheeling, eye movements)
 Lab testing and neuroimaging

• Tests such as the MMSE, however, are not particularly sensitive indicators of
early disease manifestations. Therefore, in some instances, the behavioral
neurologist will need to assess skills such as episodic memory, working memory,
executive functions, language, and visuospatial abilities in greater detail
• The Perhaps the most widely used measure in behavioral neurology
and dementia is the Mini-Mental State Examination (MMSE).Typically
taking about 10 minutes.
• The MMSE evaluates orientation to time and place, registration,a
ttention, working memory, recall, language, and visuoconstruction. This
30- point scale was originally designed to facilitate differential diagnosis
of hospitalized psychiatric patients but is now routinely used to assess
cognitive abilities in a broad range of diagnoses

 Working memory is a functional system that works
to register, recall, and mentally manipulate information within short-term
memory and it is a common substrate to patients’ difficulty with
multitasking.
 Digit span tests are widely used, with the forward digit span component
used to assess immediate auditory memory, and the backward span
component evaluating working memory (ie, the capacity to juggle
information mentally). Research has shown that on average, people
can keep 7 ± 2 items in their short term memory.
 Working memory is assessed on MMSE when the patient spells world
backward.
 Reciting months of the year in reverse.

Mental flexibility:
The Trail Making Test is a widely administered test of attention and
cognitive flexibility.
In Part A of the test, patients connect a series ofnumbered circles
distributed arbitrarily on a page.
In Part B, the patients are to serially alternate between connecting
numbers and letters (eg, 1 to A to 2 to B, etc) that also are arranged
arbitrarily on a page. The scores are the time taken to complete each part.
This test is particularly sensitive to the progressive cognitive
decline in dementia. Elderly persons who perform poorly on Part B are
likely to have problems with complex activities of daily living.

Inhibition:
Response inhibition requires the patient to suppress an overlearned
response or a salient environmental stimulus.
Stroop interference tests are widely used to assess inhibition. In
this paradigm, patients are shown a series of color names printed in
a dissonant color of ink (eg, the word red printed in blue ink). The
patient has to inhibit the overlearned tendency to read the words
and instead name the color of the ink in which the words are printed.

Fluency:
can be assessed by having the patient generate words beginning with
specified letters (eg, F-A-S) or belonging to semantic categories (eg,
animals) in a specified time period, usually 1 minute for each letter or
category.
Relative difficulty with semantic categories often suggests AV or SV,
whereas relative difficulty with letter prompts (phonemic cueing) suggests
frontal and/or subcortical deficits.
Nonverbal fluency tasks eg, design fluency) typically present patients with
numerous boxes containing dots and require them to generate as many
novel designs as possible by connecting the dots following specified rules.

Abstract reasoning:
Abstract reasoning can be evaluated by asking patients to describe
conceptual similarities or differences between word pairs (eg, dog—
lion), give opposites (eg, healthy— sick), or interpret proverbs .
When asked to describe how a dog and a lion are alike, a patient
with poor abstract reasoning might provide a very concrete answer,
such as they both have four legs, fur, or a tail; a more correct,
conceptual response is that they are both animals or mammals.
For interpreting proverbs, the patient should describe the essence
or meaning of the proverb. A patient with EF Problems often
provides a rather concrete response.

• Several aspects of language should be screened during
neurocognitive testing, including articulatory agility, repetition of
high-frequency and low-frequency word combinations (eg, ‘‘No
ifs, ands, or buts,’’ )
• comprehension of single words (give the subject simple
commands, such as, ‘‘Show me your chin,’’ or have the patient
say the word that a picture is illustrating), comprehension of
complex syntax (eg, ‘‘Put your left hand on your right ear”,
reading of regular and irregular words and naming (the Boston
naming test).
• Reading and writing should also be assessed.
Language:

Visuospatial Abilities:
Constructional tasks are extremely useful in detecting organic brain disease and should be included
in every neurocognitive assessment.
Constructional abilities require complex nonverbal cognitive functions and rely on a multifaceted
network of brain regions, including parietal, frontal, and occipital cortex.
Parietal cortex in particular is critical for the integration of visual/spatial information.
Design copying (eg, interlocking pentagons or hexagons, cube, clock, Rey-Osterrieth complex
figure, or modified Rey-Osterrieth complex figure is commonly used to examine visuoconstructional
abilities at the bedside.
Careful observation of how patients approach their copy can be an extremely useful part of the
evaluation. For example, working from right to left, omitting parts of the left side , directional
confusion and missing the overall configuration ,all could point out to right hemisphere injury
Another useful test for neglect, and one that may help differentiate it from a visual-field defect, is to
show patients a page with the letter C drawn in various orientations and ask them to complete the
C into an O.

Functional status refers to the capacity to carry out instrumental
activities of daily living, such as food preparation, medication
management, driving, housekeeping, financial management, and
shopping.
It can be informally assessed by asking patients if they are
having difficulty carrying out these daily activities.
Functional abilities can also be assessed by having caregivers
complete questionnaires, such as the Functional Activities
Questionnaire and the Clinical Dementia Rating scale
Components of the neurocognitive assessment that bear the
strongest relationship to functional abilities are memory and EF.

 Depression anxiety psychosis common
 Apathy agitation disinhibition typical for dementia and traumatic brain injury
 Mood pseudodementia
 Assessment of depression

Cholinesterase inhibitor
1 systematic review with 5 RCTs, 1434 people, 1–39 weeks
No difference in overall clinical improvement
Some clinically insignificant improvement in cognition
Significant risk of LFT abnormalities: NOT USED

 Aricept
 Cholinesterse inhibitor
 Easy titration (start 5/day, then 10)
 Side effects: GI (nausea, diarrhea)
 Can be associated with bradycardia
 Main effect seems to be lessening of rate of decline, delayed time to needing nursing
home/more intensive care

NEJM April 2003
Moderate to severe AD (MMSE 3–14)
N-methyl D aspartate (NMDA) receptor antagonist; theory that
overstimulation of NMDA receptor by glutamate leads to
progressive neurodegenerative damage
28-week, double blinded, placebo controlled study; 126 in each
group; 67% female, mean age 76, mean MMSE 7.9

 Found less decline in ADL scores, less decline in MMSE (-.5 instead of –1.2)
 Problem: significant drop outs (overall 28% dropout rate) in both groups; data analyzed did
not account for drop outs, followed those “at risk”

Rivastigmine
Galantamine
Cholinesterase inhibitors
?more side effects, more titration required
Future directions:
 Prevention of delirium in at-risk patients (cholinergic theory of delirium)
 Behavioral effects in those with severe dementia?
 Treatment of Lewy Body dementia
 Treatment of mixed Vascular/AD dementia

 Unclear benefit
 Less than 10mg day, selective MAO B inhibitor
 Small studies, not very conclusive

NEJM 1997: selegiline, Vit E, both , placebo for tx of AD
Double blind, placebo controlled, RCT with mod AD; 341
patients
Primary outcome: time to death, institutionalization, loss of
ADLS, severe dementia
Baseline MMSE higher in placebo group
No difference in Primary outcomes; adjusted for MMSE
differences at baseline and found delay in time to NH from
670 days with Vit E to 440 days with placebo

 1 systematic review of 9 double blind RCTs with AD, vascular, or mixed dementia
 Heterogeneity, short durations
 High withdrawal rates; best studies have shown no significant change in clinician’s global
impression scores
 NO good evidence to support estrogens or NSAIDS

 Behavioral/agitation:
 Nonpharmacologic strategies
 Reasons for NH placement:
 Agitation
 Incontinence
 Falls
 Caregiver stress

HTN and DM linked to ALL types dementia
Studies of treating systolic hypertension in the elderly
(SHEPS and others): decreased risk of development of
cognitive impairment in patients in treatment group
Decreased risk included vascular AND Alzheimer type
dementias
Cholinesterase inhibitors seem to work as well (or as poorly)
for both vascular and Alzheimer type of dementias
What is the link? Both common, ?unmasking?

 Conflicting data
 Retrospective studies suggest decreased risk in those patients who are treated with statins
 PROSPER study
 6000 patients age 70–80 with vascular risk factors given pravastatin or placebo
 3 year: no effect on cognitive function
 ?Long enough follow up?

 Delirium Treat underlying medical condition, If medication is needed, consider typical antipsychoc.
 Depression
Without psychosis: antidepressant With psychosis: antidepressant plus antipsychotic, or ECT
 Psychosis
Acute: atypical antipsychotic Long-term: atypical antipsychotic
 Anxiety
Acute: benzodiazepine such as lorazepam or oxazepam Long-term: buspirone
 Insomnia
Acute: trazodone ,consider or zolpidem Long-trm: trazodone
 “Sundowning”
Acute: trazodone Long-term: trazodone; typical or atypical antipsychotic.
 Aggression or anger
Severe Acute: typical or atypical antipsychotic
Long-term: divalproex sodium (Depakote) or atypical antipsychotic
Mild Acute: trazodone
Long-term: divalproex sodium, SSRI, trazodone, or buspirone
 Osteoarthritic pain Long-term: tricyclic antidepressant, SSRI, or trazodone

Antipsychotic drugs
 Haloperidol (Haldol), fluphenazine ,thiothixene, Trifluoperazine (Stelazine)
Dosage: varies by agent
Comments: anticipated extrapyramidal symptoms; if these symptoms occur, decrease
dosage or switch to another agent;
be cautious with the use of benztropine (Cogentin) or trihexyphenidyl (Artane).

Atypical antipsychotic agents
Recommended uses: control of problematic delusions, hallucinations, severe psychomotor agitation,
and combativeness
General cautions: diminished risk of developing extrapyramidal symptoms and tardive dyskinesia
compared with typical antipsychotic agents
Risperidone (Risperdal)
Initial dosage: 0.25 mg per day at bedtime; maximum: 2 to 3 mg per day, usually twice daily in
divided doses
Olanzapine (Zyprexa)
Initial dosage: 2.5 mg per day at bedtime; maximum: 10 mg per day, usually twice daily in divided
doses
Quetiapine (Seroquel)
Initial dosage: 12.5 mg twice daily; maximum: 200 mg twice daily

 Risperidone (0.5 BID)
 Olanzepine (zyprexa): 2.5–5 mg/day
 Quetiapine (seroquel)
 Rapid titration, use in PD
 12.5–200 mg/day
 Clozapine
 Use in PD (least risk of tremor)
 Agranulocytosis and limited use
 Ziprasidone (geodon)
 QT prolongation

Side Effects:
 Sedation
 Anticholinergic effects
 Prolonged QT
 Edema
 Orthostasis
 Weight gain
 Confusion
Warnings:
 FDA black box warning for increased mortality (OR 1.5–1.7), and increased
?increased stroke risk

Mood-stabilizing (antiagitation)
drugs
 Recommended uses: control of problematic delusions, hallucinations, severe
psychomotor agitation, and combativeness; useful alternatives to antipsychotic agents
for control of severe agitated, repetitive, and combative behaviors
Carbamazepine (Tegretol)
 Initial dosage: 100 mg twice daily; titrate to therapeutic blood level (4 to 8 mcg per mL)
 Comments: monitor complete blood cell count and liver enzyme levels regularly;
carbamazepine has problematic side effects.
Divalproex sodium (Depakote)
 Initial dosage: 125 mg twice daily; titrate to therapeutic blood level (40 to 90 mcg per
mL)
 Comments: generally better tolerated than other mood stabilizers; monitor liver enzyme
levels; monitor platelets, prothrombin time, and partial thromboplastin time as
indicated.

Anixolytic medications
 Benzodiazepines
 Recommended uses: management of insomnia, anxiety, and agitation
 General cautions: regular use can lead to tolerance, addiction, depression, and cognitive
impairment; paradoxic agitation occurs in about 10% of patients treated with
benzodiazepines; infrequent, low doses of agents with a short half-life are least
problematic.
 Lorazepam (Ativan), oxazepam (Serax), temazepam (Restoril), zolpidem (Ambien),
triazolam (Halcion)
Nonbenzodiazepines
 Buspirone (BuSpar)
 Initial dosage: 5 mg twice daily; maximum: 20 mg three times daily
 Comments: useful only in patients with mild to moderate agitation; may take 2 to 4
weeks to become effectiv

Antidepressant drugs
 General cautions: selection of an antidepressant is usually based on previous
treatment response, tolerance, and the advantage of potential side effects (e.g.,
sedation versus activation);
 a full therapeutic trial requires at least 4 to 8 weeks; as a rule, dosage is increased
using increments of initial dose every 5 to 7 days until therapeutic benefits or
significant side effects become apparent; after 9 months, dosage reduction is used
to reassess the need to medicate; discontinuing an antidepressant over 10 to 14
days limits withdrawal symptoms.
 NOTE: Patients with depression and psychosis require concomitant antipsychotic
medication.

 Desipramine (Norpramin)
 Initial dosage: 10 t 25 mg in the morning; maximum: 150 mg in the morning
 Comments: tends to be activating (i.e., reduces apathy); lower risk for cardiotoxic,
hypotensive, and anticholinergic effects; may cause tachycardia; blood levels may be
helpful-
 Nortriptyline (Pamelor) desipramine,
 Initial dosage: 10 mg at bedtime; anticipated dosage range: 10 to 40 mg per day (given
twice daily)
 Comments: tolerance profile is similar to that for but nortriptyline tends to be more
sedating; may be useful in patients with agitated depression and insomnia; therapeutic
blood level “window” of 50 to 150 ng per mL (190 to 570 nmol per L)

 Nefazodone (Serzone)
 Initial dosage: 50 mg twice daily; maximum: 150 to 300 mg twice daily
 Comments: effective, especially in patients with associated anxiety; reduce dose of
coadministered alprazolam (Xanax) or triazolam by 50%; monitor for hepatotoxicity.
 Bupropion (Wellbutrin)
 Initial dosage: 37.5 mg every morning, then increase by 37.5 every 3 days; maximum:
150 mg twice daily
 Comments: activating; possible rapid improvement of energy level; should not be used
in agitated patients and those with seizure disorders; to minimize risk of insomnia, give
second dose before 3 p.m.
 Mirtazapine (Remeron)
 Initial dosage: 7.5 mg at bedtime; maximum: 30 mg at bedtime
 Comments: potent and well tolerated; promotes sleep, appetite, and weight gain

.
 Fuoxetine (Prozac)
 Initial dosage: 10 mg every other morning; maximum: 20 mg every morning
 Paroxetine (Paxil)
 Initial dosage: 10 mg per day; maximum: 40 mg per day (morning or evening)
 Comments: less activating but more anticholinergic than other SSRIs
 Sertraline (Zoloft)
 Initial dosage: 25 to 50 mg per day; maximum: 200 mg per day (morning or evening)
 Comments: well tolerated; compared with other SSRIs, sertraline has less effect on metabolism of other medications.
 Citalopram (Celexa)
 Initial dosage: 10 mg per day; maximum: 40 mg per day
 Comments: well tolerated; some patients experience nausea and sleep disturbances.
 Fluvoxamine (Luvox)
 Initial dosage: 50 mg twice daily; maximum: 150 mg twice daily
 Comments: exercise caution when using fluvoxamine with alprazolam or triazolam.
 Venlafaxine (Effexor)
 Initial dosage: 37.5 mg twice daily; maximum: 225 mg per day in divided doses

 Lithium
 Recommended uses: for anticycling; can also be used to augment antidepressant drugs
 General cautions: at higher lithium dosages, elderly patients are prone to develop neurotoxicity.
 Initial dosage: 150 mg per day
 Comments: blood levels of 0.2 to 0.6 mEq per L (0.2 to0.6 mmol per L) are generally adequate and
are usuallyachieved with dosage of 150 to 300 mg per day.
 Electroconvulsive therapy
 Recommended uses: may be required in patients who are at risk of injuring or starving themselves,
patients who are severely psychotic, and patients who cannot tolerate or do not respond to antide
pressants

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