Dementia Final

Dementia
(Major Neurocognitive Disorders)
By: Yishak Gezahegn (PGY1)
Moderator: Dr. Beakal Amare

(MD, Assistant Professor of Psychiatry)
November 17, 2021

Outline
• Introduction
• History
• Risk Factors
• Etiologies
• Clinical Manifestation
• Diagnosis
• Management
• Dementia Subtypes
11/17/2021 Major Neurocognitive Disorders 2

Introduction
• The word dementia derives from the Latin word dementatus, meaning out of one’s mind.
• It is a disease process marked by progressive cognitive impairment in clear consciousness.
• It is manifested by significant cognitive impairment in one or more of the domains of:
• Complex attention
• Executive function
• Learning and memory
• Language
• Perceptual motor ability
• Social cognition
• Decline from previous level of functioning, not refer to low intellectual functioning or mental
retardation that are developmental and static conditions.
Major vs Minor Neurocognitive Disorder DSM 5
Major Neurocognitive Disorder
A. Evidence of significant cognitive decline from previous level of performance in one or more
cognitive domains based on:
1. Concern of the individual, a knowledgeable informant or the clinician that there has been a
significant decline in cognitive function;
2. A substantial impairment in cognitive performance, preferably documented by standardized
neuropsychological testing or in its absence, another quantified clinical assessment.
B. The cognitive deficits interfere with independence in everyday activities.
C. The cognitive deficits do not occur exclusively in the context of a delirium.
D. The cognitive deficits are not better explained by another mental disorder.
• Specify whether due to:
• AD, FTD, LBD, VD, TBI, HIV, Prion, PD, HD, another medical condition, multiple etiologies, unspecified
• Specify: with or without behavioral disturbance
• Specify current severity:
• Mild: difficulties with instrumental activities of daily living
• Moderate: difficulties with basic activities of daily living
• Severe: Fully dependent.
Basic and Instrumental Activities of Daily Living
Basic Activities of Daily Living Instrumental Activities of Daily Living

Ambulation Transportation
Dressing Using the telephone
Grooming Meal preparation
Bathing Medication management
Feeding Financial management
Toileting Housekeeping, Laundry

Mild Neurocognitive Disorder
A. Evidence of modest cognitive decline from a previous level of performance in one or
more cognitive domains based on:
1. Concern of the individual, a knowledgeable informant, or the clinician that there has been a mild
decline in cognitive function; and
2. A modest impairment in cognitive performance, preferably documented by standardized
neuropsychological testing or in its absence, another quantified clinical assessment.
B. The cognitive deficits do not interfere with capacity for independence in everyday
activities(i.e., complex instrumental activities of daily living are preserved, but greater
effort, compensatory strategies, or accommodation may be required).
C. The cognitive deficits do not occur exclusively in the context of a delirium.
D. The cognitive deficits are not better explained by another mental disorder.
Specify whether due to:
• AD, FTD, LBD, VD, TBI, HIV, Prion, PD, HD, another medical condition, multiple etiologies,
unspecified
Specify:
• With or without behavioral disturbance
History
• Celsus, 1st century AD, first used the term dementia.
• 4th century AD, Oribasius, tried to describe an etiology beyond old age.
• He wrote of a disease of cerebral atrophy that caused loss of intellectual capacity and weakness of movement.
• Jean Esquirol, 19th century, identified three varieties of dementia: acute, chronic and senile.
• 1845, Wilhelm Griesinger, described senile dementia as a disease of the cerebral arteries.
• Emil Kraeplin, narrowed the scope of dementia by differentiating senile dementia from
psychosis, which later came to be known as dementia praecox and finally as schizophrenia.
• In 1907, Alois Alzheimer, was the first to identify specific histopathological changes associated
with progressive degenerative dementia.
Epidemiology
• Age is the leading risk factor for dementia.
• It’s prevalence doubles every 5 years from about

• 1.9 percent at age 65 to 70
• 47.5 percent over age 90
• It is estimated that about 35.6 million people were living with dementia worldwide in 2010.
• By 2050, the number of people worldwide with dementia of the Alzheimer type is projected
to reach 115.4 million.

Risk Factors
• Age
• Female > Male ??
• Hypertension
• High BMI, High cholesterol, DM
• Cardiovascular disease
• Cerebrovascular disease
• Obstructive sleep apnea
• Early life depression
• Excessive alcohol consumption
• ?Smoking (AD and VD vs PD)
• Exercise, Higher education, more social circle (Protective factors)

Etiologies
• Neurodegenerative
• Alzheimer Disease (60-80%)
• Dementia with Lewy Body (Upto 30%)
• Frontotemporal Dementia (2.5% for those >65 and 10% for age <65)
• Parkinson Disease
• Huntington Disease
• Prion Disease
• Vascular(25-50%): Infarction, Binswanger Disease, Hemodynamic insufficiency
• Neurological disease : MS, normal pressure hydrocephalus, brain tumor
• Endocrine: Hypothyroidism, Hypercalcemia, Hypoglycemia
• Nutritional: Vitamin B12 deficiency, Thiamine deficiency, Niacin deficiency,
• Traumatic: subdural hematoma, chronic traumatic encephalopathy
• Infectious: HIV, Syphilis, Cryptococcus
• Metabolic: Hepatic insufficiency, Renal insufficiency, Wilson disease
• Exposure: Alcohol, heavy metal, irradiation, CO, anticholinergic medications

Clinical Features
Cognitive Impairment
• Memory impairment: inability to learn new information or to recall
previously learned information.
• Short-term memory is impaired before long-term memory.
• Forgetting recent events, the date, appointments, misplacing objects.
• Later, long term memory will become impaired

• Language impairment: can manifest as difficulties in receptive or expressive language.
• Word finding difficulties, reduced fluency, word substitutions or mispronouncing

words.
• Difficulties in remembering names of distant friends, acquaintances
• Difficulties maintaining conversations
• Poverty of content with empty speech
• Speech becomes incomprehensible and unintelligible.

• Perceptual-motor impairments: difficulties in visual perception and visuoconstruction,
apraxias and agnosias.
• Apraxia, is impaired ability to carry out motor activities despite intact motor function.
• It may manifest in the earlier stages as difficulty using familiar tools or machines or trouble
performing previously acquired skills.
• In later stages, there may be dressing, bathing, or feeding apraxias that contribute to impairment in
ability to perform activities of daily living.
• Agnosia, is failure to recognize or identify objects despite intact sensory function.

• It may be reflected in the inability to recognize familiar objects, familiar faces or in later stages, one’s
own reflection in the mirror.

• Impairments in complex attention:
• difficulty when there is competing stimuli.
• easily distracted and
• have trouble registering new information;
• thinking may also appear to take longer.
• Impairment in executive functioning:

• Disturbances in planning, organizing, sequencing and abstracting.
• Difficulties in performing complex tasks or problem solving.
• Judgment is often impaired.

• Social cognition: includes the ability to recognize emotions and the ability to
consider another individual’s mental state.
• Impairments in social cognition

• initially difficulty recognizing social cues or emotions in others,
• apathy and disinhibition
• change in personality
• behavioral changes become more overt,
• and showing disinhibited and intrusive behaviors.

Evaluation
• Thorough history from both the patient and a reliable informant.
• Relevant aspects of the history include:

• Onset: insidious or sudden
• Course: gradual or stepwise, progressive or episodic, or fluctuating
• Duration of impairment
• Assessment of each cognitive domain.
• Degree of functional impairment (assessing the executive function or see the basic and
instrumental activities of daily living) `

Evaluation continued….
• A complete physical and neurological examination is necessary.
• The physical examination is targeted toward medical conditions that may cause dementia.
• The neurological examination is necessary to identify focal neurological signs that may point to
specific brain lesions or pathology.
• Mental status examination is useful to assess

• self-care abilities (appearance and grooming),
• behavior (degree of engagement in the interview, demeanor, inappropriate behavior),
• affect (apathy, depression, anxiety),
• speech (language function, fluency, comprehension),
• perception (hallucinations, paranoia, delusions), and
• insight and judgment.

Evaluation continued….
• Bedside cognitive testing is performed to characterize the pattern and extent of cognitive
impairment.
• The most widely employed tool for basic screening and evaluation is the Montreal Cognitive
Assessment (MoCA).
• The MoCA is a 30 point test that can be administered in the office setting in about 10 minutes.
• The test is easily accessible, and available in a number of languages.
• The MoCA has a 90 percent sensitivity of detecting MCI and an 87 percent specificity in
excluding those cognitively intact.

MoCA
Mini Mental State Examination
• A commonly used set of questions for screening cognitive function.
• Not used for diagnosis.
• It only takes 10 minutes.
• It measures orientation, registration, short term memory as well as language functioning.
• The NICE classifies

• 21-24 as mild
• 10-20 as moderate
• <10 as severe
• The MMSE may not be an appropriate assessment if the patient has learning, linguistic/communication or
other disabilities.
Mini Cog Test
Neuropsychiatric Manifestations
• Behavioral disturbance is common in many types of dementia.
• The prevalence of behavioral disturbance increases with advancing dementia.
• Behavioral disturbances include

• Mood changes:
• Major depression (10%), early in the course of dementia
• Depressive symptoms are more common, 50%
• Emotional lability and irritability may be psychological reaction to the awareness of losing one’s
memory
• Suicidal ideation and behavior may also occur: specially in mildly impaired individuals who have
insight into their deficits.
Continued..
• Anxiety (60%)
• Personality changes :
• Disinhibition and impulsivity in FTD
• Amotivation and withdrawal in other types like AD and Vascular dementia
• Pre-existing personality traits may become stronger or exaggerated during the course of the illness.
• Psychosis
• Paranoia: usually belief that belongings are stolen. (poor short term memory or misplacing objects)
• Hallucinations in later stages
• Agitation, aggression and behavioral disturbance
• Sleep disturbances
• Disrupted and fragmented sleep in about half of patients
• Agitation/aggression and
• Other behaviors: wandering

Investigations
• Complete chemistry panel, complete blood count, hepatic function, thyroid stimulating hormone,
vitamin B12, and folate.
• Other laboratory studies that may be indicated depending on the history might include VDRL for
syphilis and HIV.
• CSF
• Structural neuroimaging like CT and MRI
• Molecular and functional imaging like PET amyloid imaging and SPECT
• Brain Biopsy and Autopsy

Differential Diagnosis
• Delirium: Acute, Medical condition/medication as a precipitant, fluctuating level of alertness, attention.
• Mild Neurocognitive Disorder or Mild cognitive impairment: could be prodromal state of dementia but not all
individuals with MCI will go on to develop dementia.
• Other medical conditions
• Medications: those with anticholinergic properties
• Schizophrenia Spectrum: associated with multiple cognitive deficits. But the cognitive deficits are relatively
constant.
• Depressive disorders: Pseudo-dementia
• Factitious disorder or Malingering: the cognitive deficits are inconsistent over time and generally uncharacteristic
of the pattern and course seen in dementia. There is some secondary gain.
• Neurodegenerative disorders
Pseudo-dementia
• Cognitive impairment frequently co-occurs with depressive episodes in late-life.
• The impairment is substantial (not as severe as in dementia though)
• It is present in about 50% of depressed elderly.
• Depression seems to increase the risk for future dementia.
• Although it is not known whether depressed mood represents prodromal dementia or is etiologically
related to future progressive decline.
• Numerous studies have shown that both depression and cognitive impairment in the elderly likely have
shared neurobiological underpinnings.

Course and Prognosis
• Generally, onset is insidious.
• Duration is generally years.
• Progressive cognitive decline and progressive functional impairment.
• Identifying the correctable causes can result in some improvement in symptoms.
• Dementia increases the risk for complications from comorbid medical illnesses
including delirium.
• Dementia eventually leads to death.

Treatment
Multimodal approach:
1. Non pharmacological Treatments
• Psychotherapy:
• therapeutic counseling, CBT,
• Reminiscence therapy
• Behavioral management: e.g. scheduled toileting can reduce frequency of urinary incontinence
• Stimulation Oriented Therapies: enhancing pleasurable activities
• Psychoeducation:
• Course, consequences, treatment, and what to expect so that patients or their families can make arrangements
• Safety Awareness and Management
• Home Safety: accidents, burglary, wandering,
• Medication management
• Legal and Financial Planning: living wills, power of attorney and guardianship
• Caregiver Support: both physically and emotionally demanding
• End of Life issues

Continued…
2. Pharmacological Treatments
• Treatment of Neuropsychiatric Manifestations
a. Psychosis and Behavioral disturbance

1. Non pharmacological:
• Simplifying activities or modifying expectations to the level of the patient
• Modifying the environment to compensate for the patient’s deficits
• Ensuring adequate sleep, nutrition and stimulating activities can help reduce agitation.

Continued…
2. First Generation vs Second Generation Antipsychotics
• Studies of risperidone, olanzapine and aripiprazole have shown modest but clinically significant
improvements in measures of agitation, aggression, psychosis and behavioral disturbances.
• They are first line treatments.
• First generation antipsychotics: were also studied but even though they are effective, adverse effects
were common and drop out rates were high.
• Both first generation and second generation antipsychotics have been associated with increased risk of
cerebrovascular events and mortality, with first generation medications having a slightly higher risk.
• Therefore their use should be carefully considered after nonpharmacological measures have been
implemented, weighing the benefit against the risk.
Continued…
3. Benzodiazepines
• Their use is associated with paradoxical effects, disinhibition, worsening cognition, and
falls.
• They are less effective than antipsychotics in controlling behavior symptoms.
• Their use is largely limited to short term control of acute agitated behavior with short
acting agents such as lorazepam.
4. Anticonvulsants and SSRIs
• They have also been studied in the management of behavioral disturbance in dementia
patients but the result is mixed and there is limited evidence to support their use.

B. Depression
• Several antidepressants have been studied for the treatment of depressive symptoms in patients with
Alzheimer disease.
• SSRIs are the most studied. There is only weak support for their effectiveness in the treatment of
depression in dementia.
• No data clearly favoring any specific antidepressant.
• But Fluoxetine is not generally recommended. (due to it’s very long half life)
C. Sleep Disturbance
• Sleep hygiene: decreasing nocturnal interruptions, like light and sound, coupled with increasing
daytime wakefulness through social and physical activity.
• Benzodiazepines or other sedative hypnotics are not recommended due to their potential for cognitive
and gait impairments.
Dementia Subtypes

Alzheimer Disease
• Alzheimer disease is the most common form of dementia.
• Alois Alzheimer first described the illness in 1906.
• There have been tremendous advances in the last decade in the understanding of
the pathophysiology and genetics of Alzheimer disease.
• However, treatments are limited to symptomatic relief and modest delays of

progression.
• The incidence of Alzheimer disease increases with age.

Etiology
• Multifactorial
• Genetics
• Early Onset Alzheimer

• Mutations in several genes that cause cleavage of amyloid precursor protein (APP) into
Aβ
• Chromosome 21, APP gene
• Chromosome 14, presenilin-1,
• Chromosome 1, presenilin-2

• Late-Onset Alzheimer Disease
• Apolipoprotien E, epsilon 4 allele (APOE4):- the first gene to have an established

relationship late onset Alzheimer disease
• The magnitude of the risk associated with APOE4 may vary by age and ethnicity.
• It is estimated that APOE4 accounts for up to 50% of the genetic contribution to

late onset Alzheimer disease.
• 20 additional genes/loci were recently identified which were associated with late
onset Alzheimer disease.

• Family History
• Patients with a first-degree relative with dementia have a 10 to 30 percent
increased risk of developing the disorder.
• Individuals in families with two or more affected siblings with late-onset AD
have a threefold increased risk of AD compared with the general population

• Acquired Risk Factors
• hypertension
• dyslipidemia
• cerebrovascular disease
• altered glucose metabolism and
• brain trauma

Pathogenesis
• While the pathogenesis of AD remains unclear, all forms of AD appear to share overproduction
and/or decreased clearance of amyloid beta peptides.
• Amyloid beta peptides are produced by the endoproteolytic cleavage of mature protein translated
from the amyloid precursor protein (APP) gene and cleaved by beta-secretase and gamma-
secretase.
• Presenilin forms part of the gamma-secretase complex, and mutations in presenilin 1 (PSEN1) or
presenilin 2 (PSEN2) appear to favor production of amyloid beta overall, or more neurotoxic forms
of amyloid beta (Aβ, senile plaques).

• The pathogenesis of AD also involves a second protein, tau.
• Tau is a microtubule-associated protein that aids in microtubule assembly and

stabilization.
• In AD, tau becomes hyperphosphorylated and aggregates to form paired helical

filament (PHF) tau, a major component of neurofibrillary tangles within the
neuronal cytoplasm.
• The accumulation of this altered protein is toxic to neurons in experimental models.

• Plaques are dense, mostly insoluble deposits of protein and cellular material outside and around
the neurons.
• Plaques are made of beta-amyloid (Ab), a protein fragment snipped from a larger protein called
amyloid precursor protein (APP).
• These fragments clump together and are mixed with other molecules, neurons, and non-nerve cells.
• In AD, plaques develop in the hippocampus, a structure deep in the brain that helps to encode
memories, and in other areas of the cerebral cortex that are used in thinking and making decisions.

• Tangles are insoluble twisted fibers that build up inside the nerve cell.
• Although many older people develop some plaques and tangles, the brains of
people with AD have them to a greater extent, especially in certain regions of the
brain that are important in memory.
• Although NFTs and SPs are characteristic of AD, they are not pathognomonic.
NFTs are found in several other neurodegenerative disorders.

Cholinergic and Glutamatergic neurotransmission in Alzheimer disease
• The cholinergic system is involved in memory function, and cholinergic deficiency has been implicated in the
cognitive decline and behavioral changes of AD.
• Activity of the synthetic enzyme choline acetyltransferase (CAT), the enzyme responsible for the final step of
acetylcholine synthesis is significantly reduced in the cerebral cortex, hippocampus, and amygdala in patients
with AD.
• Because cholinergic dysfunction may contribute to the symptoms of patients with AD, enhancing cholinergic
neurotransmission constitutes a rational basis for symptomatic treatment.
• A dysfunction of glutamatergic neurotransmission, manifested as neuronal excitotoxicity, is hypothesized to be

involved in the etiology of AD. Targeting the glutamatergic system, specially NMDA receptors, offers a novel
approach to treatment.

Macroscopically (Imaging)
• Normal
• Atrophy confined to the hippocampus
• Widened sulci throughout the cortex and increased ventricular size are seen.
• Atrophy in the posterior temporal, parietal and frontal lobes.

• Typically, several years pass between onset of early symptoms and recognition of deficits and
presentation to medical attention.
• After initial presentation, a gradual progressive decline in cognitive function ensues and extends
eventually to all cognitive domains including motor functioning and perception.
• As the illness progresses, there will be greater functional impairment and greater dependency needs.
• In the final stages of Alzheimer disease, parkinsonian symptoms may be present, mobility and gait are
impaired, and the risk of fall is great.
• Eventually patients will be bedridden.
• Swallowing impairments are common. Patients will often succumb to pneumonia or other infections.

Treatment
Cholinesterase inhibitors
• The first class of medications approved by the U.S. FDA for the treatment of
Alzheimer disease was the cholinesterase inhibitors:
• Tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl).
• These agents are reversible inhibitors of the enzyme acetylcholinesterase, which

degrades ACh in the synaptic cleft, thereby increasing the availability of intrasynaptic
ACh.
• They slow cognitive decline in mild to moderate Alzheimer disease.
• Donepezil is the only cholinesterase inhibitor FDA approved for the treatment of
severe Alzheimer disease.
• Common side effects are related to cholinergic excess and include
• nausea and vomiting, decreased appetite and weight, increased gastric acid
secretion,
• muscle cramps,
• bradycardia with syncope, and sleep disturbances.
• They may induce or exacerbate urinary obstruction, worsen asthma or

chronic obstructive pulmonary disease, and cause seizures.
Continued…
• Patients should be titrated gradually to the maximally tolerated dosage as there is a

dose-dependent response.
• If there is a continued rapid decline despite the medication, it can be discontinued.
• However, if there is stabilization of symptoms or slowing of decline, which is a desired

response, the medication should be continued.
• Duration of treatment is unclear.
• Placebo-controlled studies demonstrate efficacy up to 6 months to 2 years depending

on the agent.

Memantine
• Memantine is a noncompetitive NMDA receptor antagonist that may modulate excitatory
signaling and has neuroprotective actions.
• It is FDA approved for use only in moderate to severe Alzheimer disease.
• It has demonstrated efficacy for both cognitive and functional improvement over placebo.
• It is effective and well tolerated when added to the cholinesterase inhibitor.
• There are no data for use longer than 6 months duration.
• It is generally well tolerated
• Infrequent adverse events include confusion, dizziness, headache, sedation, agitation, falls, and
constipation.

Aducanumab (Aduhelm)
• Amid significant controversy, the US Food and Drug Administration (FDA) has approved the anti-
amyloid agent aducanumab (Aduhelm, Biogen/Eisai) for the treatment of Alzheimer's disease
(AD), disregarding the recommendation by its own advisory panel not to approve the drug.
• Aducanumab was approved using the accelerated approval pathway, which can be used to fast-
track a drug that provides a meaningful therapeutic advantage over existing treatments for a
serious or life-threatening illness.
• Administered as IV infusion every 4 weeks and at least 21 days apart.
• Initiate treatment in patients with mild cognitive impairment or mild dementia stage of disease,
the population studied in clinical trials.

Dementia with Lewy Bodies
• The second most common cause of dementia from the neurodegenerative causes.
• The microscopic pathologic hallmark of DLB is the presence of Lewy bodies throughout the neocortex
as well as in the brainstem nuclei and limbic structures.
• On hematoxylin- and eosin-stained sections, these round, eosinophilic, cytoplasmic inclusions can be
seen readily in pigmented neurons within the substantia nigra and locus coeruleus.
• The cortical atrophy is typically less marked than AD but follows a similar pattern, involving frontal,
temporal, and parietal lobes, with relative sparing of occipital cortex.
• Limbic structures, such as the amygdala and cingulate gyrus, however, can show severe atrophy.
• Similar to PD, the substantia nigra and the locus coeruleus can show variable degrees of pallor.

• Core features of DLB
1. Fluctuating cognition with pronounced variations in attention and alertness
2. Recurrent visual hallucinations, which are typically well formed and detailed
3. REM sleep behavior disorder (vivid and often frightening dreams during REM sleep
accompanied by lack of muscle atonia allowing for “acting out of dreams.”)
4. Spontaneous motor features of parkinsonism

• Supportive clinical features
• Severe sensitivity to antipsychotic agents
• Postural instability
• Repeated falls
• Syncope or other transient episodes of unresponsiveness
• Severe autonomic dysfunction (eg, constipation, orthostatic hypotension, urinary incontinence)
• Hypersomnia or Hyposmia
• Hallucinations in other modalities
• Systematized delusions
• Apathy, anxiety, and depression

Diagnostic supportive evidences
• Functional imaging of the dopamine transporter system with SPECT or PET may
be used to assess the nigrostriatal dopaminergic system.
• Low dopamine transporter uptake in the basal ganglia supports the diagnosis of
DLB.
• Prominent posterior slow-wave activity on EEG with periodic fluctuations in the

pre-alpha/theta range
• Polysomnographic confirmation of REM sleep without atonia

Differential Diagnosis
• DLB overlaps with Alzheimer disease both in terms of clinical presentation and
neuropathological changes. The distinction between DLB and Alzheimer disease is complex.
• Functional imaging of cerebral perfusion and cerebral metabolism using SPECT and PET
imaging, respectively, is a better tool for distinguishing between Alzheimer disease and DLB.
• There is also considerable clinical and pathological overlap and comorbidity between DLB
and Parkinson disease.
• The primary diagnosis should be made based on the temporal relationship of the onset of
cognitive and motor symptoms.

• Distinguishing between delirium and DLB can be challenging.
• Delirium and DLB share several common symptoms.

• The fluctuating level of alertness and consciousness in DLB is also a hallmark of delirium.
• Visual hallucinations are also common in both conditions, although they may be less well
formed and less detailed in delirium.
• Delirium, however, should typically have an acute or subacute onset, and a

duration limited to the period of exposure to the underlying causal agent.

• DLB has an insidious and gradual onset, with the mean age at onset being 75.
• DLB usually presents with one of the core features.
• It may have a more rapidly progressing course than Alzheimer disease or vascular
dementia.
• Survival time is usually about 10 years, although it may be as little as 1 to 2 years.
• The course is often marked by psychosis and behavioral disturbances, which

makes management more complicated.
Treatment
• The cholinesterase inhibitors are the mainstay of treatment for the cognitive impairment of DLB.
• A randomized placebo controlled trial showed that donepezil was associated with improvements
in cognition, behavior, and global functioning, as well as reductions in caregiver burden.
• Data in regard to the usage of memantine is mixed.
• First-generation antipsychotics are generally not well tolerated in DLB and should be avoided.
• Olanzapine and Quetiapine: some evidence
• Clonazepam for REM sleep behavior disorder.
• Responses for anti-parkinsonian medications is variable and generally less robust than for those
with PD.

Frontotemporal Dementia
• Dementia associated with atrophy of the frontal and temporal lobes.
• The hallmark of FTD is a progressive change in personality and behavior, with

variable degrees of language and other cognitive impairment.
• It can be a significant clinical challenge to distinguish FTD from primary psychiatric

disorders (specially when it occurs in midlife).
• FTD includes two broadly accepted subgroups:

• Behavioral-variant FTD and
• Language predominant FTD

• Behavioral Variant
• Behavioral disinhibition
• Apathy or inertia
• Loss of sympathy or empathy
• Perseverative, stereotyped or compulsive or ritualistic behavior
• Hyperpolarity and dietary changes
• Language Variant
• Prominent decline in language ability, in the form of speech production, word finding, object
naming, grammar or word comprehension

Etiology
• FTD occurs in both sporadic and familial forms.
• A family history is present in up to approximately 50 percent of cases, typically

with an autosomal dominant pattern of transmission.
• The etiology of the sporadic forms is currently unknown.
• Mutations in one of several genes can result in FTD. (The most commonly
affected gene is C9ORF72)

Imaging
• Currently there are no established biomarkers for the diagnosis of FTD.
• MRI to establish the presence of circumscribed frontal and/or temporal atrophy.
• PET or SPECT to demonstrate selective frontal and/or anterior temporal reduction in blood
flow or metabolism.
• In AD reductions in blood flow and metabolism are most prominent in posterior temporal
and parietal regions.
• Macroscopically, FTD is characterized by focal atrophy of the frontal cortex, the temporal
cortex, or both.
• Atrophy is usually symmetric, though asymmetry is sometimes present.

Course and Treatment
• Overall, individuals with FTD show more rapid cognitive and functional decline
than those individuals with Alzheimer disease.
• Currently there are no treatments for the cognitive deficits associated with FTD,
and no treatments to prevent progression of the underlying pathologies.
• Symptomatic use of second generation antipsychotics, SSRIs, and anticonvulsants

may help agitation, disinhibited, and aggressive behavior.

Dementia in Parkinson Disease
• For an individual to be diagnosed with probable PD with dementia, there must be a
dementia syndrome that developed within the context of PD.
• Up to 80% of individuals with PD will develop dementia.
• On average PD dementia is diagnosed 8-10 years from the onset of PD.
• Risk factors for the development of dementia in PD include age, more severe
Parkinsonism, and MCI at initial diagnosis.
• The cognitive impairment should occur at least 1 year after the symptoms of PD were
first noted.
Treatment
• Acetylcholinesterase inhibitors.
• When psychotic symptoms become problematic, attempts to reduce or discontinue

antiparkinsonian medications, balancing psychotic and motor symptoms are
warranted, with consideration of reduction in L-dopa as a last resort.
• Antipsychotic medications should be used very cautiously.
• Clozapine is the only antipsychotic medication that has been deemed useful for the
treatment of psychosis in PD.

Dementia in Huntington Disease
• Huntington disease is a rare disorder that is characterized by motor, cognitive and psychiatric
symptoms.
• The motor symptoms include chorea and ataxia.
• Individuals may also develop personality changes, depression, blunting of affect, irritability and
psychosis.
• The disease invariably leads to dementia.
• It is an autosomal dominant inherited disease. Family history is important in the diagnosis and it can
be confirmed by genetic testing.
• Atrophy of the caudate is evident on structural imaging, and striatal atrophy may be seen in imaging.
Prognosis and Treatment
• Huntington disease is inevitably fatal.
• Cholinesterase inhibitors have not been shown to have benefit in the treatment
of the cognitive impairment.
• Antipsychotic medications may be used for the treatment of agitation and

psychosis.
• Antidepressants and sedatives can be used for associated mood disorders.

Prion Diseases
• Encompass both sporadically occurring and genetically induced neurodegenerative diseases.
• The DSM criteria for MND due to prion disease include
• Insidious onset with rapid progression of impairment
• Motor features of prion disease
• Bio marker evidence
• Hallmark clinical feature is spongiform degeneration of the cortical gray matter.
• Course is rapidly progressive, with prognosis between 4 and 6 months.
• Treatment is symptomatic. Anti epileptics for seizure control, Clonazepam for myoclonus, and small
doses of antipsychotics.

Vascular Dementia
• It is the second most common cause of dementia.
• Vascular dementia refers to any dementia that is primarily caused by

cerebrovascular disease or impaired cerebral flow.
• It is a syndrome, not a disease.
• The causes of the infarctions can include occlusion of the vessels by

arteriosclerotic plaques or thromboemboli from distant origins (e.g., heart valves).
• An examination of a patient may reveal carotid bruits, funduscopic abnormalities,

or enlarged cardiac chambers.

Evaluation
• Hachinski ischemic score uses information from the past medical history, cognitive course, psychiatric
symptoms, and neurologic examination to predict the likelihood of a vascular contribution to
dementia.
• If present, each of the following features is assigned two points:
• Abrupt onset
• Fluctuating course
• History of Stroke
• Focal neurologic symptoms
• Focal neurologic signs
• The remaining features are each assigned one point:
• Stepwise deterioration
• Nocturnal confusion
• Preservation of personality
• Depression
• Somatic complaints
• Emotional incontinence (pseudobulbar affect)
• Hypertension
• Associated atherosclerosis
• A score of 7 or greater indicates that a vascular contribution is likely.
Treatment
• Risk factor management
• Antihypertensive therapy
• Diabetes management
• Statins
• Antithrombotic therapy
• Cholinesterase inhibitors
• Initiation of cholinesterase inhibitor therapy in patients with VaD who have progressive cognitive decline that
cannot be directly attributed to a clinical stroke, could be helpful.
• Lifestyle interventions
• Exercise
• Nutrition
• Rehabilitation
Summary of the Dementia Subtypes
• Parkinsonism suggests dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD),
progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system
atrophy (MSA).
• Visual hallucinations and rapid eye movement (REM) sleep behavior disorder can be a
prominent early feature of DLB.
• Behavioral abnormalities (including inappropriate behaviors and personality change) suggest

behavioral variant frontotemporal dementia (FTD).
• Rapidly progressive dementia and dementia in younger-age patients could suggest Prion
disease.

References
• Kaplan and Sadock’s Comprehensive Textbook of Psychiatry 10th Edition
• Kaplan and Sadock’s Synopsis of Psychiatry 12th Edition
• DSM 5
• Medscape
• UpToDate

Thank You!

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Dementia

(Major Neurocognitive Disorders)

By: Yishak Gezahegn (PGY1)

Moderator: Dr. Beakal Amare

November 17, 2021

11/17/2021 Major Neurocognitive Disorders 2

• It is a disease process marked by progressive cognitive impairment in clear consciousness.

• It is manifested by significant cognitive impairment in one or more of the domains of:

• Learning and memory

• Perceptual motor ability

Basic Activities of Daily Living Instrumental Activities of Daily Living

11/17/2021 Major Neurocognitive Disorders 5

• It’s prevalence doubles every 5 years from about

• 6.3 percent at age 75 to 80

• 21.7 percent at age 85 to 90

• 47.5 percent over age 90

11/17/2021 Major Neurocognitive Disorders 8

11/17/2021 Major Neurocognitive Disorders 9

11/17/2021 Major Neurocognitive Disorders 10

• Forgetting recent events, the date, appointments, misplacing objects.

• Later, long term memory will become impaired

11/17/2021 Major Neurocognitive Disorders 11

• Word finding difficulties, reduced fluency, word substitutions or mispronouncing

• Difficulties maintaining conversations

• Poverty of content with empty speech

• Speech becomes incomprehensible and unintelligible.

11/17/2021 Major Neurocognitive Disorders 12

• Agnosia, is failure to recognize or identify objects despite intact sensory function.

11/17/2021 Major Neurocognitive Disorders 13

• easily distracted and

• have trouble registering new information;

• thinking may also appear to take longer.

• Impairment in executive functioning:

• Difficulties in performing complex tasks or problem solving.

• Judgment is often impaired.

11/17/2021 Major Neurocognitive Disorders 14

• Impairments in social cognition

• apathy and disinhibition

• behavioral changes become more overt,

• and showing disinhibited and intrusive behaviors.

11/17/2021 Major Neurocognitive Disorders 15

• Relevant aspects of the history include:

• Course: gradual or stepwise, progressive or episodic, or fluctuating

• Assessment of each cognitive domain.

11/17/2021 Major Neurocognitive Disorders 16

• A complete physical and neurological examination is necessary.

• Mental status examination is useful to assess

• behavior (degree of engagement in the interview, demeanor, inappropriate behavior),

• affect (apathy, depression, anxiety),

• speech (language function, fluency, comprehension),

• perception (hallucinations, paranoia, delusions), and

• insight and judgment.

• The test is easily accessible, and available in a number of languages.

11/17/2021 Major Neurocognitive Disorders 19

• Not used for diagnosis.

• It only takes 10 minutes.

• It measures orientation, registration, short term memory as well as language functioning.

• The NICE classifies

• Behavioral disturbance is common in many types of dementia.

• The prevalence of behavioral disturbance increases with advancing dementia.

• Behavioral disturbances include

• Depressive symptoms are more common, 50%

11/17/2021 Major Neurocognitive Disorders 25

• Structural neuroimaging like CT and MRI