Task 7. Diagnosis of dementia

What is dementia?

A syndrome of acquired intellectural impairment of sufficient severity to interfere with social or occupational functioning cause by brain dysfunction

Dementia diagnosis is a syndrommal diagnosis, not a clear biological marker to distinguish the type of dementia, you have to differ based on the evolution of the clinical symptoms.

Essential symptoms: an acquired impairment in short and long-term memory, associated with impairment in abstract thinking, impaired judgment, other disturbances of higher cortical function, or personality changes. The disturbance is severe enough to interfere with work or usual social activities or relationships with others. The diagnosis of dementia is not made if these symptoms occur in the presence of delirium. (Robillard).

Subtypes of dementia

AD: The primary cinical manifestation of AD is a progressive global dementia symdrome that usually begins in later life (60-70)

Huntington Dementia :an inherited, autosomal dominant disease that that results in the midlife (e.g. ages 30-40) development of movement disorder (e.g. chorea, dysarthria, gait disturbance, oculomotor dysfunction), behavioral changes (e.g. depression, irritability, anxiety) and dementia ,

Dementia with Lewy Bodies (DLB): a clinic-pathologic condition characterized by a dementia syndrome that occurs in the presence of cell loss and the deposition of Lewy bodies. in a subcortical pattern similar to that of Parkinson’s disease, the presence of Lewy bodies is diffusely distributed throughout the limibic system and neocortex, and in many cases AD pathology that occurs in the same general distribution throughout the brain as in “pure” AD. There is a widespread depletion of cortical choline acetyltransferase in the neocortex and striatum and a disruption of dopaminergic input to the striatum due to the loss of pigmented substantia nigra neurons.


Frontotemporal dementia (FTD): : a clinic-pathologic condition characterized by deterioration of personality and cognition associated with prominent frontal and temporal lobar atrophy. A number of conditions fall under the rubric of FTD including Pick’s disease, familial chromosome 17-linked frontal lobe dementia, dementia lacking distinctive histopathology, semantic dementia, and primary progressive aphasia.

Vascular dementia: cumulative decline in cognitive functioning secondary to multiple or strategically placed infarctions, ischemic injury, or hemorrhagic lesions. The clinical and neuropathologic presentation is quite heterogeneous, and a variety of conditions fall under the general rubric of VaD. These conditions generally fall into three categories

Assessment

Progressive and fatal neurodegenerative disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavioural disturbances

Core symptoms: prominent amnesia with additional deficits in language and semantic knowledge, abstract reasoning, executive functions, attention, and visuospatial abilities.

Semantic knowledge: deficits that manifiests as a loss of general knowledge and impairment of language abilities (e.g. aphasia). They often impaired tests of naming, berbal fluency, and semantic categorization. They also have a reduced ability to recall overlearned facts.

Executive functioning : EF deficits responsible for (especially) concurrent mentla infomation, concept formation, problem solving, and cue-directed behavior occur early in AD.

Amnesia: episodic memory impairment is usually the earliest and most salient aspect of AD dementia syndrome. A number of characteristics that are quite effective in differentiating between mildly demented AD patients an normal older adults: (1) impaired on measures of delayed recall, (2) recognition testing do not make more accesible the to-be-remembered information (3) AD patients exhibit and abnormal serial position effect (attenuation of primacy effect (4) semantic encoding is less effective in improving episodic memory performance (5) enhance tendency to produce intrusion errors on both verbal and nonverbal memory tests- -decreased inhibitory processing-

Attention ; (less salient in early stages): deficits are usually evident on dual-processing tasks, tasks that require the disengagement and shifting of attention, and WM tasks that are dependent upon the control of attentional resources.

Visuospatial abilities (less salient in early stages): deficits usually affect visuoconstructional abilities assessed by the Block Design Test, the Clock Drawing Test, and complex figure copying (e.g. apraxia), and visuoperceptual abilities tapped by tests such as Judgment of Line Orientation or the Money Road Map Test.



Functional disturbances: patients progress from the loss of higher-level activities of daily living (e.g. check writing, use of public transportation) through abnormalities of basic activities of daily living (e.g. eating, grooming) as the disease enters advanced phases.

Behavioral disturbances:: progress over the course of the illness. Mood change and apathy commonly develop early and continue for the duration of the disease. Psychosis and agitation are characteristic of the middle and later phases of the disease.


These deficits arise primarily from a progressive deterioration of the neostriatum (caudate nucleus and putamen) that disrupts frontostriatal loops, which are believed to provide subcortical influences on both motor control and higher cognitive function (subcortical dementia syndrome)

Core symptoms: slowness of thought, impaired attention, EF, poor learning, visuoperceptual and constructional deficits, and personality changes such as apathy and depression

Core symptoms: parkinsonian symptoms, fluctuating cognition with pronounced variations in attention and alertness and recurrent well-formed and detailed visual hallucinations. Supportive symptoms are REM sleep behavior disorder and severe neuroleptic sensitivity. The time sequence in which symptoms of DLB appear is key to differentiation from Parkinson’s Disease with Dementia (PDD); dementia appears after a number of years (10 years) of parkinsonian symptoms in PDD, whereas parkinsonian symptoms are central to the initial diagnosis of DLB.

Subtypes

Core symptoms: although each of these variants has a unique clinical presentation, the most common variant of FTD typically begins with the insidious onset of personality and behavioral changes (e.g. inappropriate social conduct, apathy, disinhibition, perseverative behavior, loss of insight, hyperorality, decreased speech output) that are accompanied or soon followed by cognitive deficits that include alterations in EF, attention, and/or language, often with relative sparing of visuospatial abilities and memory.



Semantic dementia: there is a breakdown in the conceptual database that underlies language production and comprehension (progressive fluent aphasia). They have asymmetric anterolateral temporal atrophy with relative sparing of hippocampal formations, typically worse on the left side.

Progressive nonfluent aphasia: the phonologic and syntactic components of language are affected in association with left perisylvian atrophy.

Frontal variant FTD: changes in social behaviour and personality predominate, reflects orbitobasal frontal lobe focus of the pathology.

(b) Dementia due to strategically placed infarction (e.g. left angular gyrus damage related to infarction of the posterior branch of the medial cerebral artery).

(c) Subcortical ischemic vascular dementia due to subcortical small vessel disease that results in multiple lacunar strokes, leukoaraiosis (Binswanger’s disease).

(a) Multi-infarct dementia associated with multiple large cortical infarctions.

Core symptom: dysexecutive syndrome. Progression in stepwise fashion, slow insidious progress is recognized.

Laboratory studies are necessary to identify causes of dementia and coexisting conditions that are common in the elderly. Thyroid-function tests and measurement of vitamin B12 level are required to identify specific alternative causes of dementia. A complete blood count and liver-function tests should be performed. Neuroimaging plays an important role in the diagnosis of AD and is particularly helpful in excluding alternative causes of dementia. Currently recommended are CT and MRI at least once in the course of dementia. PET or single-photon-emission CT may be helpful in the differential diagnosis of disorders associated with dementia. A very important tool is also neuropsychological assessment for understanding cognitive profiles ==> DIAGNOSIS OF DEMENTIA REMAINS MAINLY CLINICAL.

Diagnosis of AD: most often based on the criteria developed by the National Institute of Neurologic and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA), according to which the diagnosis is classified as:

(b) Probable (typical clinical syndrome without histologic confirmation).

(c) Possible (atypical clinical features but not alternative diagnosis apparent; no histologic confirmation).

(a) Definite (clinical diagnosis with histologic confirmation)

Typical sensitivity and specificity values for the diagnosis of probable AD with the use of these criteria are .65 and .75, respectively. “Mild AD” is defined by a MMSE score of less than 25.

Mild Cognitive Impairment (MCI): memory impairment beyond that expected for age and education, yet not demented. But this definition is hard to apply in a clinical setting. A high proportion of these patients go on to AD.

Young old AD patients and very-old AD differences: young-old AD patients are generally more impaired than the very-old AD patients and show a typical AD profile. In contrast, the very-old AD patients exhibit a similar level of impairment across al cognitive domains so that their deficit profile lacks the disproportionate saliency of memory and EF deficits typical for the disease. Thus, normal aging can significantly affect the severity and pattern of neuropsychological deficits associated with early AD and reduce the saliency of the deficit profile as a diagnostic marker of the disease

Differential Diagnosis:

AD vs DLB

AD vs FTD; Most patients with FTD fulfil also criteria for AD (= low specificity) -buscar


  • FTD greater deficit EF than in other cognitive abilities, whereas AD executive dysfunction is proportion to deficits in language and visuospatial abilites (and less prominent than episodic memory deficit)
  • FTD worse on word-generation tasks sensitive to frontal lobe dysfunction, whereas better on tests of memory and visuospatial abilities that are sensitive to medial temporal and parietal association cortices
  • FTD worse in letter fluency, AD in semantic fluency

AD vs HD

AD vs VaD:

Risk and protective factors of dementia:

Treatment

(a) Severe deficits in episodic memory (AD) versus mild-to-moderate memory impairment that appears to result form a general deficit in the ability to initiate and carry out systematic retrieval of successfully stored information (HD). => equivalent memory deficits when asses during free recall, but in recognition is less impaired in HD.

AD faster forgettin over delay interval and decline in structure and organization of semantic knowledge.

HD more pronnounced attentional deficits, decline in shifting/ allocating attention -when its must be internally regulated

Initial mild WM deficits and pronounced WM deficits later on (AD) versus early affected WM (HD).

Impaired visuoconstructional ability that requires extrapersonal orientation (e.g. copying) (AD) versus impaired on visuospatial tasks that require personal orientation (HD).

a general pattern of greater visuospatial, attention, and EF impairment in DLB than AD, and greater memory impairment in AD than DLB is seen. Consideration of these patters of deficits (particularly those of visuospatial abilities) may have important clinical utility in distinguishing between AD and DLB in mildly demented patients. (hallucinations?)

AD and DLB can also coexist, which is hard (impossible) to diagnose with high specificity. More tangle pathology (higher Braak stage) led to less visual hallucinations, DLB diagnostic accuracy was higher for lower tangle pathology. (chequar lo ultimo)

71% of AD patients exhibited a profile with memory impairment more prominent than executive dysfunction, whereas only 45% of patients with subcortical VaD exhibited a profile with
more prominent executive dysfunction than memory impairment

Pure VaD or pure AD is rare. Integrative approach is proposed, which would take into account the neuropsychological profile, neuroimaging, and vascular risk factors.

Head injury is an important risk factor for AD: the risk is doubled for individuals with a history of a single head injury that led to loss of consciousness or hospitalization

Genetics: AD development is increased by a positive family history in a first-degree relative and specific point mutations on the amyloid precursor protein gene of chromosome 21 as well as presenilin gene mutations on chromosomes’ 1 and 14 are deterministic gene mutations for AD. Also, the APOE e4 allele located on chromosome 19 has been identified as the single most important susceptibility gene for the disease

Age is the single most important risk factor for AD (prevalence rises between the ages of 65 and 85).

Gene-environment interactions: interaction between the APOE e4 allele and head injury leads to a tenfold increase in the risk of developing AD in people with both risk factors.

Protective factors

Occupational work complexity

Mentally and socially integrated lifestyle in late life

Higher education

Exercise and cardiorespiratory fitness (long-term benefits): physical activity has been shown to reduce the risk for dementia and improve cognition.

Key characteristics: dysexecutive syndrome, insidious onset and step-wise progression (but depends on type of stroke)

Key characteristics: insidious onset of personality and behavioural changes that are accompanied/soon followed by cognitive deficits often with relative sparing of visuospatial abilities and memory.

Time course

Early: Episodic memory, EF (set-shifting), semantic knowledge with a gradual onset. - Mood, apathy (continue throughout the disease) - Loss of higher-level activities of daily living

Later: Attention, visuospatial abilities - Psychosis, agitation, basic daily life problems - Abnormalities of basic activities of daily living

Very late Motor and sensory deficit

Sensitivity = number of positives correctly identified as such

Specificity = number of negatives correctly identified as such

Gender: women have a slightly higher risk, but also live longer

Vascular diseases: hypertension, heart disease, stroke

Brain areas: Medial temporal lobe (early), association cortices

Brain areas: subcortical: brain stem, limbic system, neocortex

Brain areas: Frontal, temporal

MMSE is used to indicate whether extensive testing is needed. Neuroimaging is just to rule out other disorders

DLB: motor features of Parkinsonism, visual hallucinations and fluctuating cognition

Wilson: examine change in cognitive function during the prodromal phase of AD and before the onset of mild cognitive impairment, a common AD precursor

Participants had an annual clinical evaluation consisting of medical history, complete neurological examination, cognitive performance testing. An experienced clinician diagnosed dementia, AD and MCI (amnestic and nonamnestic)

  • Cognitive decline increased sharply about 5-6 years before dementia was diagnosed, and showed a modest increase 4-6 years before MCI was diagnosed
  • dementia in AD is preceded by many years of progressively accelerating cognitive decline
  • Prodromal period for amnestic MCI begins 1-2 years earlier than nonamnestic and is characterized by more rapid cognitive decline
  • Prodromal cognitive decline in AD varies across cognitive domains (semantic and working memory preceded other domains)

Dementia due to AD is preceded about 5-6 years of accelerated decline in multiple cognitive functions. Little decline is evident in persons who do not develop AD