Review of Differential Diagnoses in cases of Dementia

Kaye, J.A. (1998). Diagnostic challenges in dementia. Neurology, 51 (Supplement 1), S45-S52.

The prevalence of cognitive impairment consistent with dementia doubles every five years (p. S45). At age 65 1% of the population will have dementia; 50% of those living into their 10th decade may have cognitive impairment (p. S45).

Diagnostic Challenges

Dementias that present with clinical or laboratory evidence of potentially significant medical disorders (such as thyroid deficiency or vitamin B₁₂ deficiency) are relatively easy to detect.

Two general situations create more problems in differential diagnosis of dementia:

1. dementias without distinctive neurologic signs or evidence of medical or neurologic disease (e.g., Alzheimer's disease, frontotemporal dementias)

2. dementias with neurologic signs without obvious significant medical disorders (e.g., parkinsonian dementias, vascular dementia)

I. Differentiation of expected changes associated with aging from an early dementia consistent with Alzheimer's disease (AD).

The perception of failing memory is common among the elderly with 25 to 30% of nondemented, healthy elderly complaining of memory impairment (p. S46 with ref.)

features of cognitive performance that characterize typical aging and are not considered pathologic:

1. a general decline in speed of processing over all domains of cognitive functioning is seen; accuracy of responses, however, is not usually affected.

2. verbal abilities (vocabulary, information store, comprehension) reach a peck in 3rd decade and are stable into the 9th decade.

3. most types of memory remain relatively stable over lifespan. Includes immediate or primary (digit or letter span),

long term or remote, new learning or recent (secondary memory is relatively resistant to aging, although not to the same degree. ( p. S46)

Depression as differential diagnosis.

II. Frontotemporal dementias (FTD)

Bizarre or puzzling behaviors in presence of seemingly preserved cognitive functions early in course. Onset often/usually before 7th decade. Classically referred to as Pick's disease: describes the clinically distinct patients with socially inappropriate behaviors, disinhibition, aphasia, and abulia, but with relatively preserved constructional, calculating, and memory function. Autopsy shows characteristic localized atrophy of frontal and anterior temporal lobes. These cases are part of a spectrum of FTDs.

Disorders considered in clinicopathologic spectrum of FTD:

Pick's disease

Dementia lacking distinctive pathology

Progressive aphasia with dementia

Primary progressive apraxia in Pick's disease

Familial progressive subcortical gliosis

Frontal lobe dementia and motor neuron disease

Frontotemporal dementia and parkinsonism linked to

chromosome 17

FTDs cover a distinct but broad spectrum of clinical dementias. The Lund and Manchester consensus statement on criteria for FTD provide for current clinical diagnosis.

core diagnostic features consist of behavior disorder of insidious onset and slow progression with loss of personal (hygiene & grooming) and social (tact, manners) awareness, disinhibition, impulsivity, inflexibility and rigidity, and various repetitive or stereotyped behaviors. May be hyperoral, overeating or obsessively focusing on particular foods, in some cases placing or packing nonfood objects in the mouth. Patients may appear to need to touch or manipulate everything in their reach.

Coupled with behavior changes are affective symptoms with depression, anxiety, fixed ideas, and somatic preoccupations or delusions. As syndrome progresses, speech output tends to decrease or become restricted and stereotyped. Eventual echolalia or muteness may develop.

Often have well-preserved spatial orientation and praxis.

(p. S47)

Key features of FTD:

Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester groups. J Neurol Neurosurg Psychiatry. 1994; 57; 416-418.

Onset is insidious, with slow progression

Dominant deficits in behavior and conduct appearing early

in course

Loss of personal awareness (neglect of hygiene and grooming)

Loss of social graces and awareness

Disinhibition (sexually provocative or demanding, inappropriate jocularity)

Impulsivity, distractibility

Hyperorality (dietary changes, excessive eating, smoking, or alcohol consumption

Withdrawal from social contact

Stereotyped or perseverative behaviors (wandering, repetitive clapping, humming or singing, ritualistic toileting, dressing)

Speech output changes

Progressive reduction of speech (late mutism)

Stereotypy of speech (few repeated phrases or themes)

Echolalia

Physical signs

Early or prominent primitive or "frontal" reflexes

Early incontinence

Late akinesia, rigidity, tremor

Deficits in social comportment, behavior, judgment, or language are out of proportion to memory deficit

III. Dementia and parkinsonism

Parkinsonian signs occur in up to 30% of AD cases by time patients are severely impaired (p. S48 with ref). Dementia occurs in up to 30% of cases of idiopathic Parkinson's disease. A common element is concomitant occurrence of AD pathology (neuritic plaques and neurofibrillary tangles) and Lewy bodies. Not clear that Lewy body itself is sufficient to cause dementia. Cases of "diffuse" Lewy body dementia without neuritic plaques or neurofibrillary tangles have been observed. Wide variability in cortical and subcortical distribution and type of neurodegenerative lesions has lead to a number of interpretations and terminologies for these parkinsonian dementia syndromes: AD with Parkinson's disease changes, Lewy body variant of AD, diffuse Lewy body disease, and senile dementia of the Lewy body type.

Recent consensus conference developed framework for this spectrum of disorders. Recommended the term "dementia with Lewy bodies (DLB)." (p. S48)

Key or core features include parkinsonism, visual hallucinations, and fluctuating cognition with variations in alertness and attention. Parkinsonism accompanying this syndrome is usually mild at onset. When mental status changes precede the parkinsonian signs, the diagnosis of DLB is more likely than when the dementia syndrome follows the onset of parkinsonism. The current convention is that if the motor signs precede the dementia by 12 months, these cases are designated Parkinson's disease with dementia.

Memory deficit is not prominent and lies more in retrieval than in acquisition or consolidation (p. S49). Because memory and language function not usually disrupted early in DLB, screening batteries (such as MMSE) may be insensitive.

Fluctuation in cognitive function associated with DLB is more than the commonly observed "good day--bad day dichotomy." Fluctuations are characteristically more pronounced and are associated with variations in attention and alertness.

Consensus criteria for the clinical diagnosis of probable and possible dementia with Lewy bodies (DLB)

McKeith, L.G., Galasko, D., Kosaka, K., et al. (1996). Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology, 47, 1113-1124.

The central feature required for a diagnosis of DLB is progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function. Prominent or persistent memory impairment may not necessarily occur in the early stages but is usually evident with progression. Deficits on tests of attention and of frontal-subcortical skills and visuospatial ability may be especially prominent.

Two of the following core features are essential for a diagnosis of probable DLB, and one is essential for possible DLB

Fluctuating cognition with pronounced variations in attention and alertness

Recurrent visual hallucinations that are typically well formed and detailed

Spontaneous motor features of parkinsonism

Features supportive of the diagnosis are

Repeated falls

Syncope

Transient loss of consciousness

Neuroleptic sensitivity

Systematized delusions

Hallucinations in other modalities

A diagnosis of DLB is less likely in presence of

Stroke disease, evident as focal neurologic signs or on brain imaging

Evidence on physical examination and investigation of any physical illness or other brain disorder sufficient to account for the clinical picture

IV. Vascular dementias

Diagnosis of vascular or stroke-related dementia (VAD) is difficult diagnostic challenge. Cerebrovascular disease is common in the age groups most susceptible to dementia and, like AD, increases in frequency with age (S49).

Clinical criteria for VAD include the California Alzheimer Disease Diagnostic and Treatment Centers criteria

and the NINDS-AIREN criteria.

History of abrupt onset coinciding with a stroke is helpful in suggesting VAD. Some symptomatic improvement after the event or a "plateau" period is also of diagnostic value. More definitive is a history of stair-step progression of the dementia, which may be difficult to obtain in retrospect but, if present, is particularly helpful.

Chui, H.C., Victoroff, J.I., Margolin, D., Jagust, W., Shankle, R., Katzman, R. (1992). Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers. Neurology, 42, 473-480.

Vascular dementia criteria from the NINDS-AIREN Workshop

Roman G.C., Tatemichi, T.K., Erkinjuntti, T. et al. (1993). Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology, 43, 250-260.

Dementia: loss of memory and at least two other cognitive domains that cause impaired functioning in daily living

Cerebrovascular disease is present with

Focal neurologic signs

Imaging evidence of cerebrovascular disease (may be large vessel or small vessel infarctions, single infarct in strategic location, or diffuse and extensive white matter changes)

Dementia is correlated with cerebrovascular disease by:

Temporal association (within 3 months)

Sudden or stepwise deterioration

Features consistent with the diagnosis of VAD

Early gait disturbance

History of unsteadiness or frequent falls

Early urinary symptoms without urologic disease

Pseudobulbar palsy

Personality and mood changes