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Dementia screening
and diagnosis
Presented by
Heba Mohamed Tawfik
Senior lecturer and Consultant of
Geriatrics and Gerontology,
Psychogeriatric diploma
Faculty of Medicine, Ain-Shams
University December 2020

Criteria for diagnosing
different dementia subtypes

Criteria for all-cause dementia: Core clinical criteria (NINCDS-
ADRDA criteria, 2011)
Dementia is diagnosed when there are cognitive or behavioural symptoms
that:
1. Interfere with the ability to function at work or at usual activities; and
2. Represent a decline from previous levels of functioning; and
3. Are not explained by delirium or major psychiatric disorder;
4. Cognitive impairment is detected and diagnosed through a combination
of
(1)History-taking from the patient and a knowledgeable informant and
(2) An objective cognitive assessment, either a “bedside” mental status
examination or neuropsychological testing.
Neuropsychological testing should be performed when history and bedside
mental status examination cannot provide a confident diagnosis.

5. The cognitive or behavioural impairment involves a minimum of two of the following
domains:
a. Impaired ability to acquire and remember new information, symptoms include: repetitive
questions or conversations, misplacing personal belongings, forgetting events or
appointments, getting lost on a familiar route.
b. Impaired reasoning and handling of complex tasks, poor judgment, symptoms include:
poor understanding of safety risks, inability to manage finances, poor decision-making ability,
inability to plan complex or sequential activities.
c. Impaired visuospatial abilities, symptoms include: inability to recognize faces or common
objects or to find objects in direct view despite good acuity, inability to orient clothing to the
body.
d. Impaired language functions (speaking, reading, writing),symptoms include: difficulty
thinking of common words while speaking, hesitations, spelling and writing errors.
e. Changes in personality, behaviour, symptoms include: mood fluctuations such as
agitation, impaired motivation or initiative, apathy, loss of drive, social withdrawal, decreased
interest in previous activities, loss of empathy, compulsive or obsessive behaviours, socially
unacceptable behaviours.

Alzheimer’s disease (AD) [NINCDS-ADRDA
criteria, 2011]
Probable AD dementia: Core clinical criteria is
diagnosed when the patient
Meets criteria for dementia described earlier, and in
addition, has the following:
A. Insidious onset: Symptoms have a gradual onset over
months to years
B. Clear-cut history of worsening of cognition by report or
observation; and
C. The initial and most prominent cognitive deficits are
evident on history and examination in one of the following
categories:
1. Amnestic presentation: It is the most common
presentation of AD dementia. The deficits should include
impairment in learning and recall of recently learned
information. There should also be evidence of cognitive
dysfunction in at least one other cognitive domain, as the
following:

2. Non-amnestic presentations:
• Language presentation: The most prominent
deficits are in word-finding, but deficits in other
cognitive domains should be present.
• Visuospatial presentation: The most prominent
deficits are in spatial cognition, including object
agnosia, impaired face recognition,
simultanagnosia, and alexia. Deficits in other
cognitive domains should be present.
• Executive dysfunction: The most prominent
deficits are impaired reasoning, judgment, and
problem solving. Deficits in other cognitive
domains should be present.

D. The diagnosis of probable AD dementia should not be
applied when there is evidence of
(a) Substantial concomitant cerebrovascular disease,
defined by a history of a stroke temporally related to the
onset or worsening of cognitive impairment; or the
presence of multiple or extensive infarcts or severe white
matter hyperintensity burden; or
(b) Core features of Dementia with Lewy bodies other
than dementia itself; or
(c) Prominent features of behavioral variant
frontotemporal dementia; or
(d) Prominent features of semantic variant primary
progressive aphasia or nonfluent/ agrammatic variant
primary progressive aphasia; or
(e) evidence for another concurrent, active neurological
disease, or a non-neurological medical comorbidity or use
of medication that could have a substantial effect on
cognition.

Possible AD dementia: Core clinical criteria
A diagnosis of possible AD dementia should be made in either of the circumstances mentioned below
1. Atypical course
Atypical course meets the core clinical criteria in terms of the nature of the cognitive deficits for AD dementia,
but either has a sudden onset of cognitive impairment or demonstrates insufficient historical detail or
objective cognitive documentation of progressive decline,
Or
2. Etiologically mixed presentation
Etiologically mixed presentation meets all core clinical criteria for AD dementia but has evidence of
(a) Concomitant cerebrovascular disease, defined by a history of stroke temporally related to the onset or
worsening of cognitive impairment; or the presence of multiple or extensive infarcts or severe white
matter hyperintensity burden; or
(b) Features of Dementia with Lewy bodies other than the dementia itself; or
(c) Evidence for another neurological disease or a non-neurological medical comorbidity or medication use
that could have a substantial effect on cognition

Classification of
vascular cognitive
impairment
Grinberg et al., 2010, Jellinger, 2008, Chui et al., 2007

Other classification of vascular dementia [according to Vascular Impairment of
Cognition Classification Consensus Study (VICCCS) ]
Four major subtypes are present
1-Post-stroke dementia (PSD), defined as dementia manifesting within 6 months
after a stroke;
2-Subcortical ischemic vascular dementia (SIVaD);
3-Multi-infarct (cortical) dementia; and
4-Mixed dementia [further labelled according to the presumed predominant cause
of dementia ( VaD-AD or AD-VaD)]
MRI is crucial for diagnosis of vascular dementia

Newcastle categorisation of
vascular dementia (VaD)
LVD= large vessel disease
MID= multi-infarct dementia
SVD= small vessel disease
SIVD=subcortical ischemic vascular dementia
Kalaria, 2016

Classification of VaD according to major morphologic lesions
(Jellinger, 2013)

Different diagnostic criteria for vascular dementia
Eizaguirre et al., 2017

Core elements of the diagnostic Criteria for Vascular Cognitive Disorders: Statement from
VasCog (2014)
Dementia (i.e., major cognitive disorder)
(A) Acquired decline from a previous level of performance in ≥1 cognitive domains as
evidenced:
(a) Concerns of a patient, knowledgeable informant, or a clinician
(b) Evidence of deficits on objective cognitive assessment based on a validated measure
of neurocognitive function in ≥1 cognitive domains. For dementia typically ≥2 SDs below
norms
(B) For dementia, the cognitive deficits are sufficient to interfere with independence (e.g.,
at a minimum requiring assistance with instrumental activities of daily living, i.e., more
complex tasks such as managing finances or medications)

Evidence for predominantly vascular etiology of cognitive impairment
(A) One of the following clinical features
(1) The onset of the cognitive deficits is temporally related to ≥1 cerebrovascular events.
(2) Evidence for decline is prominent in speed of information processing, complex
attention, and/or frontal-executive functioning in the absence of history of a stroke or
transient ischemic attack.
One of the following features is additionally present:
(a) Early presence of a gait disturbance (small-step gait or Marche a petits pas, or
magnetic, apraxic–ataxic
(b) Parkinsonian gait; this may also manifest as unsteadiness and frequent, unprovoked
falls
(c) Early urinary frequency, urgency, and other urinary symptoms not explained by
urologic disease
(d) Personality and mood changes: abulia, depression, or emotional incontinence

(B) Presence of significant neuroimaging (MRI or CT) evidence of
cerebrovascular disease (one of the following)
(1) ≥2 large vessel infarcts are generally necessary for VaD (or Major VCD)
(2) An extensive or strategically placed single infarct, typically in the
thalamus or basal ganglia may be sufficient for VaD (or Major VCD)
(3) Multiple lacunar infarcts outside the brainstem; 1–2 lacunes may be
sufficient if strategically placed or in combination with extensive white
matter lesions
(4) Extensive and confluent white matter lesions
(5) Strategically placed intracerebral hemorrhage, or ≥2 intracerebral
hemorrhages

Exclusion criteria
(1) History (a) Early onset of memory deficit and progressive worsening of memory and other
cognitive functions such as language (transcortical sensory aphasia), motor skills (apraxia), and
perception (agnosia) in the absence of corresponding focal lesions on brain imaging or history of
vascular events.
(b) Early and prominent parkinsonian features suggestive of Lewy body disease
(c) History strongly suggestive of another primary neurological disorder such as multiple sclerosis
(d) Encephalitis, toxic or metabolic disorder, etc., sufficient to explain the cognitive impairment
(2) Neuroimaging
(a) Absent or minimal cerebrovascular lesions on CT or MRI
(3) Other medical disorders severe enough to account for memory and related symptoms
(4) For research: The presence of biomarkers for Alzheimer disease (cerebrospinal Ab and pTau
levels or amyloid imaging at accepted thresholds) exclude diagnosis of probable VCD, and indicate
AD with CVD

• Cognitive symptoms in VCI are often accompanied by behavioural
changes that can sometimes even be the most prominent
manifestations of vascular damage.
• Behavioural changes that should be addressed include change in
personality, apathy or disinhibition, and depressive symptoms.

Examples of dementia due to strategic infarction
Thalamic dementia (anterior thalamic nuclei)
Decreased or fluctuating level of consciousness is a distinctive finding at
the start.
The main feature is loss of long-term anterograde memory with a less
marked loss in long-term retrograde memory.
Short-term memory are largely preserved.
Associated with:
Disorientation, agitation, aggressiveness, apathy, and dysexecutive
syndrome
Extensive infarct in the dominant tubero-thalamic territory gives rise to anomic
aphasia, and acalculia. Lesion to the non-dominant hemisphere will result in visual
memory impairment.

Infarcts in the dominant angular gyrus cause Gerstmann
syndrome
Tetrad of typical symptoms:
 Not recognising the fingers on both hands (finger agnosia),
 Confusing the left and right sides of the body,
 Losing the ability to calculate(dyscalculia),
 Losing ability to write (dysgraphia).
These symptoms may be associated with:
alexia, visual hemianopsia, severe left-sided neglect, and anomic aphasia

Binswanger's Disease (subcortical arteriosclerotic
encephalopathy)
 There is diffuse ischemic damage to the cerebral white matter along with a scattering
of lacunar infarcts.
Deep gray matter structures are also affected to a variable extent.
Nearly all reported patients have had hypertension.
Affected persons develop an insidious dementia with prominent neuropsychiatric
features, focal neurologic signs, gait disorder, and incontinence.
MRI scans have shown marked leukoencephalopathy, and the severity of clinical
involvement is generally commensurate with the degree of white matter abnormality.
The pathophysiology involves ischemic demyelination as a result of hypoperfusion of
the cerebral white matter.
Treatment is limited to prevention of disease progression by attention to
cerebrovascular risk factors; specific pharmacologic treatment targeted to cholinergic
and other systems has been considered, but its efficacy is unknown.

Criteria for DLB
McKeith IG. et al.,2017.

Criteria for DLB
(continue)
McKeith IG. et al.,2017.

Parkinson plus syndrome
Corticobasal degeneration (CBD) shares some clinical and pathologic
overlap with PSP but is much less common.
In addition to progressive asymmetric parkinsonism and early falls,
CBD most frequently presents with dystonia, myoclonus, alien
limb phenomena, and dementia. Cortical sensory deficits are
frequently found, including astereognosis and agraphesthesia with
eyes closed, despite having apparently normal somatic sensation
Miller-Patterson et al., 2020

Dementia screening and diagnosis

How to differentiate between
different dementia subtypes in
clinical practice?????

Cognitive profile of different forms of dementia in relation to Alzheimer’s
disease
1- Memory in AD
 The earliest and most common clinical manifestation of AD is impairment in episodic
memory (Greater than other forms of dementia)
 Diminished ability to encode new material into long-term memory, both leading to:
Affection of both recall and recognition of verbal and visual material
Prominent recency effects (i.e., recall of only the last few words presented)
Frequent intrusion errors (i.e., responding with semantically related words rather
than items on the target list in free recall),
 Lack of benefit noted with cuing.
 Intact immediate and procedural memory in early stages only

Posterior cortical atrophy (PCA) [an atypical
variant of AD]
Characterized by:
A disproportionate deficit in visuo-perceptual
and spatial skills, with milder deficits in
memory and executive functions

In LBD
 The deficit here is in retrieval rather than encoding
 Memory deficit in pure LBD usually appears later in the disease course
However
LBD tends to co-occur with AD in 80% of cases, with only 20% having pure
LBD.
SO
Patients with pure LBD have better verbal memory skills than those with
pure AD or mixed LBD/AD
Patients with pure AD and mixed LBD/AD show equivalent degrees of
impairment on verbal memory testing.
Mixed LBD/AD have an additive effect on visual memory skills

In FTD
A- bv FTD
 There is progressive deterioration of personality
 And relative preservation of episodic memory and
no semantic memory impairment
However
Revised diagnostic guidelines for bvFTD in 2011
published that there is possible variations in
symptoms at initial presentation and ‘Severe
amnesia’ became no longer an exclusion criteria
for bvFTD.
10% of confirmed cases have reported memory
problems at the time of presentation with some
showing severe amnesia

B-Semantic variant-primary
progressive aphasia (SV-PPA)
Patients have relatively preserved episodic
memory and autobiographical memory, with a
rather selective loss of semantic memory.
C-Progressive non-fluent aphasia
(PNFA)
Produces a severe disruption of speech output
(not typically seen in early AD), accompanied
by mild episodic and semantic memory
deficits

In Vascular dementia
In cortical
 Abrupt onset , a stepwise deterioration and a fluctuating
course of cognitive function temporally related to stroke
Mild episodic memory impairment
Some cortical symptoms, such as aphasia, apraxia,
agnosia and visuospatial difficulty.
Some degree of executive dysfunction
In subcortical
 Presentation more variable, with no consistent pattern
of symptom onset or progression.
Primary deficits in executive functions and speed of
information processing
Secondary deficits in episodic memory.

Memory impairment in VaD is characterized by :
Impaired recall
Relatively intact recognition
A greater benefit from cues than AD
But higher rates of disturbances on visual
memory

2- Visuospatial Problems
 Visuo-spatial problems are often among the first
symptoms noted in AD.
 Patients with bvFTD have better visuospatial skills.
However visuospatial tasks requiring executive
function, (e.g. trail-making) are impaired at an early
stage, but block designs may be preserved..
 Pronounced and early visuospatial difficulties is a
consistent finding in LBD. Patients show greater
difficulties on tests of visuospatial processing relative
to AD patients.

Alzheimer’s association,
accessed 2020

Cognitive profile
of different
dementia subtypes
Karantzoulis and Galvin, 2011

Based on modified neuropsychiatric inventory categories

Screening for dementia
The US Preventive Services Task
Force has recommended against
screening people aged over 65
for mild to moderate cognitive
impairment, saying that the
evidence is insufficient to assess
the balance of its benefits and
harms

How to diagnose
History of dementia +FH
Mode of onset
Progression
Fluctuation

Cognitive domains to ask about
Memory
Attention
Executive functions
Calculation
Visuo-spatial problems
Language
If there is a deficit ask if affecting function
or not (ADL and IADL)

Ask about behavioural problems
Apathy
Disinhibition
Delusions and hallucinations
Agitation and aggression
Wandering
obsessive-compulsive behaviours
+
Sleep disturbances
+
Assess anxiety and depression
Ask about autonomic dysfunction/ urinary and
stool incontinence

DSM V criteria for dementia diagnosis,
2013, American academy of family
physicians 2018

Algorithm for diagnosing dementia
American academy of family physicians 2018

Normal MRI findings
(A) The left MRI image is a normal FLAIR image
in a 30 year old man and the right image is the
typical appearance in eighth decade
(B)Normal 18F-FDG PET shows high uptake in
gray matter structures.
(C) Normal amyloid PET scan with the
radiotracer 18F-florbetapir shows typical white
matter uptake but no evidence of elevated
cortical binding
Nasrallah and Wolk, 2014

Radiological criteria
of vascular dementia
(Roman et al., 1993, van Straaten et al., 2003)

Approach to signal change in
various dementia subtypes
Harper et al., 2014

Approach to cortical
atrophy in various
dementia subtypes
Harper et al., 2014

MRI imaging in AD
T2 weighted MRI coronal section perpendicular to the long axis of the
hippocampus is important to detect changes in mesial temporal lobe
hippocampus
entorhinal
perirhinal cortex

(a) Is normal and (b) for a patient with cognitive impairment, the blue arrow
represents the entorhinal and the red one represents perirhinal cortex (Patel
et al., 2020)
The PRC is involved in some complex memory functions as object
recognition, sensory representation, and spatial orientation. Damage
to PRC results in deficits in object recognition memory, complex visual
discrimination, and attention to visual stimuli. The It represents a
component of the ventral visual stream
The ERC serves as the major interface between the hippocampus and
sensory cortices. Its close connection with cortical regions involved in
the processing of visual and spatial information suggests that the ERC
is an important substrate for visuo-spatial functioning . Also,
hippocampal memory function depends on an intact ERC.
(Vismer et al., 2015)

Braak staging of AD
Six stages of disease propagation
with respect to the location of the
tangle-bearing neurons and the
severity of changes
(trans-entorhinal stages I–II: which
are clinically silent cases;
limbic stages III–IV: incipient
Alzheimer's disease;
And neocortical stages V–VI: fully
developed Alzheimer's disease)

PET scan in a patient
with Alzheimer’s disease
Sagittal T1 weighted MRI in (a) and sagittal 18f-FDG- PET in (b) in AD
patient showing atrophy and decrease activity in precuneus respectively
and normal uptake of frontal and occipital regions.
Patel et al., 2020

PET scan in a patient
with advanced
Alzheimer’s disease
(a) Is a patient without dementia (b) is Alzheimer’s
disease patient in advanced stage with diffuse
cortical atrophy sparing sensori-motor area.
Patel et al., 2020

PET scan in LBD
Sparing of posterior cingulate gyrus is characteristic for
LBD (Patel et al., 2020)

References
• McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer's disease: Recommendations from the
National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May. 7(3):263-9.
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: American Psychiatric Association; 2013.
• Grinberg L, Heinsen H. Toward a pathological definition of vas-cular dementia. J Neurol Sci. 2010;299:136—8.
• Chui HC, Brown NN. Vascular cognitive impairment. Continuum Lifelong Learning Neurol. 2007;13:109—43.
• Kalaria RN. Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer’s disease. Acta Neuropathol. 2016; 131:659–685.
• Jellinger KA. Morphologic diagnosis of ‘‘vascular dementia’’—–a critical update. J Neurol Sci. 2008;270:1—12.
• Jellinger KA. The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol (Berl). 2007 Apr. 113(4):349-88.
• Jellinger KA. Pathology and pathogenesis of vascular cognitive impairment—a critical update. Front. Aging Neurosci., 10 April 2013 | https://doi.org/10.3389/fnagi.2013.00017.
• Iadecola C, Duering M, Hachinski V , Joutel A, Pendlebury ST, Schneider JA, Dichgans M. Vascular Cognitive Impairment and Dementia: JACC Scientific Expert
Panel. J Am Coll Cardiol. 2019 July 02; 73(25): 3326–3344. doi:10.1016/j.jacc.2019.04.034.
• Eizaguirre NO, RementeriaGP, González-TorresMÁ, Gaviria M. Updates in vascular dementia. Heart Mind 2017;1:22-35.
• Rodríguez García PL and Rodríguez García D. Diagnosis of vascular cognitive impairment and its main categories. Neurología. 2015;30:223—239.
• Gorelick PB, Scuteri A, Black SE, et al; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing,
Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and
dementia: a statement for healthcare professionals from the american heart association/ american stroke association. Stroke. 2011;42:2672–2713. doi: 10.1161/
STR.0b013e3182299496.
• P. Sachdev, R. Kalaria, J. O'Brien, I. Skoog, S. Alladi, S.E. Black, D. Blacker, D.G. Blazer, C. Chen, H. Chui, M. Ganguli, K. Jellinger, D.V. Jeste, F. Pasquier, J. Paulsen, N.
Prins, K. Rockwood, G. Roman, P. Scheltens, Diagnostic criteria for vascular cognitive disorders: a VASCOG statement, Alzheimer Dis. Assoc. Disord. 28 (2014) 206–
218.
• Filley CM, in Encyclopedia of the Human Brain, 2002.
• McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium
on DLB International Workshop. Neurology 1996; 47:1113–1124.

• McKeith IG, Dickson DW, Lowe J, et al. Dementia with Lewy bodies: diagnosis and management: third report of the DLB Consortium. Neurology 2005;65:1863–
1872.
• McKeith, IG. et al "Diagnosis and management of dementia with Lewy bodies." Neurology 89.1 (2017): 88-100.
• Miller-Patterson C., Krobot K.E., Burton E.A., Smith L.J. (2020) Parkinson-Plus Syndromes. In: Weissbrod P., Francis D. (eds) Neurologic and Neurodegenerative
Diseases of the Larynx. Springer, Cham. https://doi.org/10.1007/978-3-030-28852-5_13
• Karantzoulis S & Galvin JE. Distinguishing Alzheimer’s disease from other major forms of dementia, Expert Review of Neurotherapeutics 2011; 11:11, 1579-1591.
• Rascovsky K, Hodges JR, Knopman D et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134, 2456–
2477.
• Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ 2015;350:h369.
• https://www.alz.org/media/Documents/inbrief-differentiating-dementias.pdf
• Shaik SS and Varma AR. Differentiating the dementias: a neurological approach. Progress in Neurology and Psychiatry, 2012.
• Torjesen I. Dementia: US recommends against screening over 65s because of insufficient evidence. BMJ 2020;368:m750.
• Falk N, Cole A, Meredith TJ. Evaluation of Suspected Dementia. Am Fam Physician 2018 Mar 15;97(6):398-405.
• Elahi FM and Miller BL. A clinicopathological approach to the diagnosis of dementia. Nat Rev Neurol. 2017 Aug; 13(8): 457–476.
• Hugo J, Ganguli M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clin Geriatr Med. 2014;30(3):421-442.
• Nasrallah IM and Wolk DA. Multimodality Imaging of Alzheimer Disease and Other Neurodegenerative Dementias. J Nucl Med. 2014 December ; 55(12): 2003–
2011.
• Harper L, Barkhof F, Scheltens P, Schott JM, Fox NC. An algorithmic approach to structural imaging in dementia. J Neurol Neurosurg Psychiatry 2014;85:692–698.
• Braak H and Braak E. Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiol Aging May-Jun 1995;16(3):271-8; discussion 278-84.
• Vismer MS, Forcelli PA, Skopin MD, Gale K and Koubeissi MZ. The piriform, perirhinal, and entorhinal cortex in seizure generation. Front. Neural Circuits, 29 May
2015.
• Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.
Neurology 1993;43:250–60.
• van Straaten EC, Scheltens P, Knol DL, et al. Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study. Stroke
2003;34:1907–12.
• Patel KP, Wymer DT, Bhatia VK, Duara R, Rajadhyaksha CD. Multimodality Imaging of Dementia: Clinical Importance and Role of Integrated Anatomic and Molecular
Imaging. RadioGraphics 2020; 40(1): 200-222.

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Dementia screening and diagnosis

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