A brief discussion about Neurocognitive disorders. NCD are on the rise especially due to the ageing population and good treatment modalities leading to less mortality. The burden of NCD is to increase with time especially due to the little interventions available

1. NEUROCOGNITIVE DISORDER
Dr. kaggwa mark Mohan

2. Epidemiology

3. Women and men comparison of NCD

4. Epidemiology in Africa
The overall prevalence of dementia in adults older than
50 years in Africa was estimated to be about 2.4%
Prevalence was the highest among females aged 80 and
over (19.7%) and there was little variation between
regions.
Alzheimer disease was the most prevalent cause of
dementia (57.1%) followed by vascular dementia (26.9%).
The main risk factors were increasing age, female sex,
cardiovascular disease and HIV

5. Uganda prevalence
• 13.2% of Uganda above the age of 60 have dementia

6. Risk factors of NCD
1. Demographic factors
2. Genetic factors
3. Medical factors
4. Psychiatric factors
5. Head injury
6. Life style and environmental factors

7. Protective factors for NCD
1. Education and cognitive factors
2. Pharmacological factors
3. Lifestyle factors

8. Types of NCD
Dementia/major neurocognitive impairment
acquired cognitive impairment has become severe enough to
compromise social and/or occupational functioning.
Mild cognitive impairment (MCI)
state intermediate between normal cognition and dementia, with
essentially preserved functional abilities

9. NCD as diagnosed by DSM V
Diagnostic
criteria
Major NCD Mild NCD
A Significant decline in 1 or more
cognitive domains, based on:
Modest cognitive decline in one or more
domains, based on:
1. Concerns about significant decline, expressed by individual or reliable
informants, or observed by clinician
2. Substantial impairment, documented by objective cognitive assessment
B Interference with independence in
everyday activities.
No interference with independence in
everyday activities, although these
activities may require more time and
effort, accommodation, or
compensatory strategies

10. C Not exclusively during delirium.
D Not better explained by another mental disorder.
E Specify one or more etiologic subtypes, “due to”
Alzheimer’s disease
Cerebrovascular disease (Vascular Neurocognitive Disorder)
Frontotemporal Lobar Degeneration (Frontotemporal Neurocognitive Disorder)
Dementia with Lewy Bodies (Neurocognitive Disorder with Lewy Bodies)
Parkinson’s disease
Huntington’s disease
Traumatic Brain Injury
HIV Infection
Prion Disease
Another medical condition
Multiple etiologies

11. Functional limitations associated with impairment in
different cognitive domains
Cognitive domain Examples of changes in everyday activities
Complex attention Normal tasks take longer, especially when there are competing stimuli; easily distracted;
tasks need to be simplified; difficulty holding information in mind to do mental
calculations or dial a phone number
Executive functioning Difficulty with multi-stage tasks, planning, organizing, multi-tasking, following directions,
keeping up with shifting conversations
Learning and memory Difficulty recalling recent events, repeating self, misplacing objects, losing track of
actions already performed, increasing reliance on lists, reminders
Language Word-finding difficulty, use of general phrases or wrong words, grammatical errors,
difficulty with comprehension of others’ language or written material
Perceptual-
motor/visuospatial
function
Getting lost in familiar places, more use of notes and maps, difficulty using familiar tools
and appliances
Social cognition Disinhibition or apathy, loss of empathy, inappropriate behavior, loss of judgment

12. Examples of objective cognitive assessment
Cognitive
domains
Objective Assessment
Complex Attention  Maintenance of attention, e.g., press a button every
time a tone is heard, over a period of time
 Selective attention, e.g., hear numbers and letters, but
count only the letters
 Divided attention, e.g., tap rapidly while learning a
story.
 Processing speed: carry out any timed task.

14. Executive
Functioning
Planning: e.g., maze puzzles, interpret sequential pictures or
arrange objects in sequence
Decision making with competing alternatives, e.g., simulated
gambling.
Working memory: hold information for a brief period and
manipulate it, e.g. repeat a list of numbers backward
Feedback utilization: Use feedback on errors to infer rules to
carry out tasks.
Inhibition: Override habits; choose the correct but more
complex and less obvious solution, e.g., read printed names of
colors rather than naming the color in which they are printed
Cognitive flexibility: Shift between sets, concepts, tasks, rules,
e.g., alternate between numbers and letters.

15. Learning and
Memory
Immediate memory: Repeat a list of words or digits.
Recent memory:
Free recall: recall as many items as possible from,
e.g., a list of words, or a story, or a diagram.
Cued recall: with examiner providing cues, e.g.,
“recall as many food items as you can from the list.”
Recognition: with examiner asking, e.g., “was there
an apple on the list?”
Semantic memory: recall well-known facts
Autobiographical memory: recall personal events.
Implicit (procedural) memory: recall skills to carry out
procedures.

16. Language  Expressive language: confrontation naming of e.g., objects or
pictures; fluency for words in a given category (e.g. animals) or
beginning with a given letter, as many as possible in one
minute.
 Grammar and syntax: omitting or incorrectly using articles,
prepositions, helper verbs.
 Receptive language: comprehend /define words, carry out
simple commands.
Perceptu
omotor
functioni
ng
 Visuoconstructional: e.g., Draw, copy, assemble blocks.
 Perceptuomotor: e.g., Insert blocks or pegs into appropriate
slots.
 Praxis: Mime gestures such as “salute” or actions such as “use
hammer.”
 Gnosis: e.g., recognize faces and colors.

17. Social cognition  Recognize emotions: Identify pictures showing e.g.,
happy, sad, scared, angry faces.
 Theory of mind: Consider another person’s
thoughts, intentions when looking at story cards,
e.g., “why is the boy sad?”

19. Other investigation
• Graduate record examination
• Functional capacity assessment
• Clinical dementia rating
• Laboratory tests
• CT scan
• MRI
• EEG
• LP
• Urine screen – drugs
• Screen for systemic illness e.g SLE
• Cerebral biopsy

21. Classification of
dementia
&
Common causes
AD
DLB
FTLD
Vascular Dementia
Prevalence
Late onset (above 65)
for all types
Between 21 & 65 e.g.
HIV, substance, head
injury, vascular, MS etc.
Age of onset
Gait apraxia
Myoclonus
Peripheral neuropathy
Chorea
Accompanying
physical
manifestations
Autosomal dominant
(HD)
Autosomal recessive
(Wilson disease)
Others (AD, CJD, &
FTLD)
Genetic
Depression
Medication
Hypothyroidism
Metabolic diseases
B12 deficiency
Reversibility
Cortical vs subcortical
Cortical area

23. ALZHEIMER’S DISEASE
A ‘‘definite’’ diagnosis of Alzheimer’s
disease, the illness that most
commonly causes dementia, requires
histologic examination of brain tissue.
A ‘‘probable’’ diagnosis, which is
accepted for clinical purposes and is
consistent with psychiatric criteria, is
acceptable if adults have
1. the insidious onset of a
progressively worsening
dementia
2. clinical and laboratory
evaluations that exclude
alternative neurologic and
systemic illnesses.
Clinical features
 Cognitive impairment
 Neuropsychiatric
manifestation
 Physical signs

26. ATROPHY IN DEMENTIA
Alzheimer's disease
AD has more atrophy than
any other type of dementia
Primary affected cortical
areas
Parietal temporal junction
Limbic system
Hippocampus
Locus ceruleus
Entire olfactory nerve
Areas spared by atrophy
Visual
Motor
Sensory
Effects of atrophy
Dilatation of 3rd ventricles
Anterior horn of the
lateral ventricle maintain a
concave shape (in HD
dementia it is convex)

27. Trisomy 21 dementia (Alzheimer's disease)
Almost all individuals with trisomy 21, if they live to 40 years, develop an
Alzheimer-like dementia superimposed on their mental retardation.
Their brains show Alzheimer-like changes:
Atrophy
Cholinergic depletion
Amyloid plaques
Neurofibrillary tangles
Loss of neurons in the nucleus basalis.
Imaging (CT, MRI, and PET studies) show Alzheimer-like changes.
Note
Even women who give birth to a child with trisomy 21 have a five-fold increase in
Alzheimer’s disease.
Defected chromosome 21 is involved in formation of alpha-beta plaques

28. Dementia Lewy body
The second most common neurodegenerative dementia
The underlying disease is primarily characterized by:
alpha-synuclein misfolding (stain with a-synuclein antibodies)
aggregation within the pathognomonic Lewy bodies (found PD).
Onset of symptoms is between the 6th and 9th decades,
Average survival is 5–7 years
Insidious onset and gradual progression
The cognitive deficits are most prominent in the domains of
attention, visuospatial and executive functioning(may fluctuate)
Has more chAT loss than Alzheimer's dementia

29. Additional core features
of DLB
fluctuating cognition
recurrent visual hallucinations
They are very sensitive to
antipsychotics and they pose
little effects
Parkinsonism
Ant parkinsonism drugs have
very little benefit

30. Difference btn DLB & PD
In DLB, cognitive impairment precedes the onset of
parkinsonism, while in the latter, the cognitive
impairment occurs in the context of established
Parkinson’s disease.

31. Suggestive features of DLB
 REM sleep behavior
disorder
 Severe neuroleptic
sensitivity
 Low dopamine transporter
(DaT) uptake in basal ganglia
demonstrated by SPECT or
PET imaging
 Repeated falls
 Syncope
 Transient and unexplained
loss of consciousness
 Severe autonomic
dysfunction
 Hallucinations in other
modalities
 Systematized delusions
Depression

32. Neuroimaging
 Generalized low uptake on SPECT and
fluorodeoxyglucose PET with reduced occipital
activity also suggests DLB.
Additional testing supportive of DLB include
low uptake MIBG myocardial scintigraphy,
suggesting synaptic denervation,
prominent slow wave activity on EEG with temporal lobe
transient sharp waves

34. Neurocognitive Disorders due to Parkinson’s
Disease
 These disorders are diagnosed when there is gradual
cognitive decline in the presence of a well-established
diagnosis of Parkinson’s disease.
 Over the course of their disease, approximately 75% of
individuals with Parkinson’s disease will develop a major
neurocognitive disorder.
 The pattern of cognitive deficits is variable but often affects
the executive, memory, and visuospatial domains, with a
slowing of information processing that suggests a “subcortical”
picture.

35. Associated features
Psychiatric symptoms such
as:
depressed
anxious mood
apathy
hallucinations
Delusions
personality change
REM sleep behavior
disorder
Excessive daytime
sleepiness

36. Neurocognitive Disorder due to Huntington’s
Disease
HD caused by an autosomal dominant mutation consisting of
CAG repeats on Chromosome 4.
The neurotoxic Huntingtin (HTT) protein begins by damaging the
striatum of the basal ganglia but eventually affects the entire
brain.
Although adult onset HD usually manifests in the 4th or 5th
decades
Patients have a median survival of 15 –20 years after diagnosis,
and can thus preset to geriatric services.

37. Neurocognitive Disorder due to Huntington’s
Disease
A few patients develop their first symptoms at older
ages in the absence of a family history.
Progressive cognitive impairment to eventual
dementia is inevitable.
A family history of the disease should alert clinicians
to the possibility, and genetic testing for the HTT
mutation is diagnostic

38. Course of HD dementia
•Early stages
• Cognitive deficits (executive function)
• Behavioral symptoms (depression, anxiety, apathy, obsessive-
compulsive symptoms, and psychosis)
•Late stages
• The motor abnormalities (bradykinesia and chorea),
•Note
• Clinical diagnosis is rarely made on the basis of cognitive
symptoms alone.

39. Frontotemporal lobar degeneration (Fronto-temporal
Dementia)
Third most prevalent degenerative dementia
Characterized by prominent atrophy of the frontal and temporal lobes
The predominant neuropathological proteins
Inclusions of hyperphosphorylated tau
ubiquitin protein
mean onset in the 6th decade (younger age of onset compared to other types)
Common cause of early-onset dementia although 20–25% of
individuals with this disorder are over age 65
The duration of survival is 6–11 years after symptom onset, and 3–4
years after diagnosis
With insidious onset and gradual progression

40. Clinical subtypes
1.Behavioral Variant
changes in personality and behavior are most prominent
loss of interest in personal affairs and responsibilities, social
withdrawal, loss of awareness of personal hygiene, and socially
disinhibited behavior.
Perseverative or compulsive motor behaviors, as well as
hyperorality and dietary changes may also be evident.
These patients are often initially seen in psychiatric settings
and can be misdiagnosed as major depressive or bipolar
disorder.

41. Clinical subtypes
1.Language Variants:
I. Semantic type
 appears as a fluent aphasia with impoverished content and paraphasic
errors, with intact syntax and prosody
 emotional blunting, loss of empathy, and rigid behaviors may also be
seen,
II.Progressive Nonfluent Aphasia,
III.Logopenic subtype.

42. Other presentations
•Bradykinetic (slow) movement
•Repetitive (perseverated) movements
•Absent (akinetic)
•Apraxic (Walking becomes awkward and uncertain)
•Absence of voluntary movement
•Absence of speaking and expression (akinetic mutism)
•Patients’ have viscous thinking and bradykinesia combine to
cause psychomotor retardation
•Bladder and bowel incontinence
•Unrestrained sexual urges

43. Causes
•TBI (Traumatic Brain Injury)
• Invasive glioblastoma multiforme
• Metastatic tumors
•Metachromatic leukodystrophy,
• Multiple sclerosis plaques
•Ruptured anterior cerebral artery
• Infarction of both anterior cerebral arteries
• Picks diseases
•Genetical causes

44. Genetics
Mutations have been associated with genes encoding proteins
affecting a number of fundamental cellular functions,
including:
 microtubule-associated protein tau (MAPT)
granulin (GRN)
C9ORF72
transactive response DNA- binding protein of 43 kDa
valosin-containing protein
chromatin modifying protein 2B
fused in sarcoma protein.

45. Neuroimaging
Structural MRI or CT can show
distinct patterns of regional
cortical atrophy which correlate
with the clinical variants of FTD
(poor sensitivity and specificity).
•PET and SPECT often show
hypometabolism in frontal lobes
but relatively normal metabolism
in parietal and occipital lobes.

46. Vascular Dementia
(Vascular Neurocognitive Disorder, arteriosclerotic dementia, multi-infarct dementia, vascular
cognitive impairment, vascular cognitive disorder)
Major and Mild Vascular Neurocognitive Disorders
The cognitive deficits are principally attributed to
cerebrovascular disease
Second most common cause of dementia (20%)
Frequently present in combination with AD (“mixed dementia”)
It can result from both large and small vessel disease, with the
location of the lesions more important than the volume of
destruction (infarcts = large, multiple lacunar, Binswanger’s disease {white matter})
Given the variability of lesions and locations, the presenting
symptoms and time course are often variable

47. Intro…
The progression of the
neurocognitive decline can
be in an acute stepwise
pattern, show a more
gradual pattern, or can be
fluctuating or rapid in its
course
•Focal neurological signs
dominate the cognitive
impairment (dysarthria,
hemiparesis, hemianopsia, and ataxia)

48. Diagnosis and presentation
There should either be:
 A clear history of stroke or
Transient ischemic attacks temporally related to the cognitive decline, or
Neurological deficits consistent with sequelae of previous strokes
Cognitive decline is usually seen in the domains of complex attention and
executive functions.
Gait disturbance
urinary symptoms
personality or mood changes (including emotional lability)
The depression may have a late-life presentation coupled with
psychomotor slowing and executive dysfunction, the so called vascular
depression

49. Neuroimaging
CT or MRI
evidence of significant
parenchymal injury attributable
to cerebrovascular disease
Including
one or more large vessel
infarcts,
a single large or strategically
located infarct or hemorrhage,
extensive lacunar infarcts
outside the brainstem,
extensive white matter
lesions

51. Genetics
Rare autosomal dominant cerebrovascular disorders
CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts
and leukoencephalopathy)
A form of hereditary stroke caused by Notch-3 mutations on Chromosome 19.
Management
Control the vascular disease
If comorbid with AD treat with cholinesterase inhibitors
Manage any complication such as stroke, movement
disorders and others

52. Wernicke-Korsakoff Syndrome Dementia
Commonly due to excessive chronic alcohol consumption
Other causes – starvation, dialysis, chemotherapy, gastric surgeries, eating disorders
Symptoms
confabulation and global confusion
Amnesia (retrograde for facts and anterograde) – Anterior thalamic nucleus damage
Ataxia (peripheral neuropathy and cerebellar vermis atrophy)
Ocular motility abnormality (conjugate gaze paresis, abducens nerve paresis, and
nystagmus)
Imaging (CT & MRI) & EEG may be normal
petechial hemorrhages develop in the mamillar y bodies and
structures surrounding the third ventricle and aqueduct of Sylvius
(periaqueductal gray matter)
Treatment – thiamine

53. Other Causes of Dementia in Alcoholics
TBI – accidents
Subdural hematoma – atrophy
Laennec’s cirrhosis –GIT bleeding, hepatic encephalitis
Marchiafava-Bignami syndrome - ‘‘split brain syndrome’’
degeneration of the corpus callosum
Prone to seizures
Fetal alcohol syndrome
Prone to dementia and Mental retardation when adults

54. Medication-Induced Dementia
Medication-induced cognitive impairment remains one of the
few correctable causes of dementia or delirium.
Common drugs medicines— opioids, antiepileptic drugs, antiparkinson agents,
steroids, cimetidine, and psychotropic
Even medicines instilled into the eye may be absorbed into the
systemic circulation and cause mental changes.
Also, seemingly innocuous over-the-counter medicines, such
as St. John’s wort, may directly produce a mental aberration or
cause an adverse interaction that produces one.

55. Neurocognitive Disorder due to Prion Disease
Human transmission has been reported due to:
 infected growth hormone injection and corneal transplantation
cross-species transmission is exemplified by bovine spongiform
encephalopathy (“mad cow disease.”)
Other causes: kuru - Fatal familial insomnia, Mink - transmissible mink encephalopathy,
These illnesses progress rapidly and combine neurocognitive
decline and motor features such as myoclonus and ataxia
They are encoded on chromosome 20
Prions resist routine sterilization, heat, formaldehyde, and
treatments that hydrolyze nucleic acids
However, because they are protein-based, prions are susceptible to
procedures that denature proteins, such as exposure to proteases.

56. CJD
Variant CJD may present with low mood, withdrawal, and
anxiety
Typically diagnosed in their seventh and eighth decades
Rapidly progressive (survival typically under one year)
Diagnosis
can only be confirmed by biopsy or autopsy
MRI scanning with diffusion weighted imaging or fluid-attenuated inversion
recovery may show multifocal gray matter hyperintensities in the subcortical
and cortical areas
Tau or 14-3-3 protein may be found in the cerebrospinal fluid
characteristic triphasic waves on EEG
Genetic testing may be useful in the 15% of cases who have a family history
suggesting an autosomal dominant mutation

57. Other causes of NCD

58. Treatment
1. Etiology specific treatment - Not yet available
2. Symptomatic treatment
A. Cholinesterase inhibitors
B. NMDA receptor agonists
C. Serotonergic agents
D. Dopamine blocking agents
E. Benzodiazepines
3. Supportive treatment

59. A. Cholinesterase inhibitors
Increase cholinergic transmission at the synaptic cleft,
potentially benefiting patients with cholinergic deficits
as in AD, DLB.
The currently available drugs (all equally effective):
donepezil,
Rivastigmine
galantamine
 Rivastigmine is also approved for dementia in PD.

60. A. Cholinesterase inhibitors
In frontotemporal dementia, there is no convincing
evidence of benefits from these drugs, and there are
reports that they worsen behavior symptoms.
Cholinesterase inhibitors also help in reducing certain
neuropsychologic symptoms such as depression,
psychosis, and anxiety

61. A. Cholinesterase inhibitors
There is inadequate evidence on the use of
cholinesterase inhibitors in other neurocognitive
disorders.
a systematic review has found minimal evidence of
benefit from these drugs in mild cognitive impairment,
either with symptom relief or delay in progression to
dementia.
Side effects include:
Abdominal cramps (increased parasympathetic activities)

62. B. NMDA receptor antagonist
 Memantine, is approved for the treatment of moderate
to severe dementia due to AD.
It is believed to be neuroprotective against excitoxicity in
the cortex and hippocampus.
An advantage of memantine is that it is well tolerated.
In frontotemporal dementia, memantine has shown mixed
results.
Worsen delusions and hallucinations in DLB

63. C. Serotonergic agents
SSRI antidepressants can produce benefits for
behavioral /psychiatric symptoms in frontotemporal
dementia, without concomitant improvements in
cognition.

64. D. Dopamine blocking agents
Neuroleptic (antipsychotic) drugs should be prescribed in
dementia with due attention to the risk of adverse
cerebrovascular events.
They should be avoided or used with extreme caution in
patients with DLB, given their sensitivity to these agents.
When necessary the second-generation antipsychotics are
preferred.
If the patient is taking a dopaminergic (anti-parkinsonian) drug,
lowering its dose would be the preferred first step before
introducing a dopamine-blocking agent

65. E. Benzodiazepines
In general, benzodiazepines are to be avoided in the
neurocognitive disorders because of the risk of
paradoxical agitation as well as of falls and further
diminished cognition.
An exception may be the treatment of REM Sleep
Behavior Disorder in DLB.

66. Behavioral modifications
•Creating a safe environment
•Creating a schedule for patient activities
General rule of prescription
Target one symptom and begin treatment with small doses of a
single medicine and then proceed to an effective dose.

67. Drugs to avoid
• TCA
• Cause orthostatic hypotension & confusion
Note
• Psychopharmacology only provides a modest relief