The Dementias: Neuropsychiatric Syndromes of the 21st Century

The Parkinson disease spectrum disorders are a variable group of late-life–onset neuropsychiatric disorders, in which psychomotor slowing, rigidity, tremor, and gait ataxia are clinical features along with cognitive loss. Diagnostic accuracy remains difficult for these syndromes because not all parkinsonian syndromes are associated with cognitive impairment, and not all Parkinson disease spectrum disorders demonstrate motor features of parkinsonism, at least early in their course.⁸

The major Parkinson disease spectrum dis-orders associated with cognitive impairment include:

• Idiopathic Parkinson disease.
• Dementia with Lewy bodies.
• Multisystem atrophy.

The pattern of cognitive impairments in these disorders tends to affect frontal-executive, and visuospatial functions in its milder versions, but the impairment syndrome can progress to a full cortical dementia syndrome, with memory loss, apraxias, and aphasias. The neuropathologies underlying these syndromes are variable, but fundamentally, these are the Lewy body disorders. These disorders have patterns of intraneuronal eosinophilic inclusions that contain a-synuclein, a chaperone protein found in neuronal synapses.

Dementia with Lewy bodies is the archetype cognitive loss syndrome in this group of disorders, and may account for the 3% to 5% of patients who attend memory disorder clinics. The clinical features of dementia with Lewy bodies include a cortical dementia, atypical parkinsonism, visual hallucinations, delusions, depression, fluctuations in consciousness and cognition, adverse reactions to low-dose psychotropic medications, and falls. The isolated onset of rapid eye movement sleep disorders, and delusional states in elderly persons may be clinical harbingers of this syndrome. In Parkinson disease with cognitive loss, in contrast with dementia with Lewy bodies, there is a several-year prodrome of more typical parkinsonism (asymmetric tremor; levodopa(Drug information on levodopa) responsiveness) before cognitive deficits appear. Current diagnostic criteria for dementia with Lewy bodies are presented in Table 3.⁹

Patients who have dementia with Lewy bodies have reduced cortical choline acetyltransferase activity in the neocortex, and they respond to cholinesterase inhibitors at least as well as patients with AD.¹⁰ In addition, these patients have loss of nigrostriatal neurons and parkinsonian features, so they sometimes respond to levodopa therapy. Occasionally, there is a Lazarus-like response in these patients who have dementia with Lewy bodies to a regimen such as donepezil(Drug information on donepezil) 10 mg daily plus levodopa/carbidopa 25/100 mg 3 times a day. As in all the neurodegenerative disorders, the syndrome inevitably progresses, and when it does, it may proceed more quickly than the AD syndromes.

The vascular syndromes

Older patients with generalized vascular disease tend to exhibit a mixed neuropsychiatric syndrome characterized by focal neurological findings, such as dysarthria, ataxia, hyperreflexia, hemiparesis, and cognitive impairment. Most of these patients have vascular risk factors, such as hypertension, diabetes, smoking, elevated lipids, inactivity, and obesity. The pattern of cognitive impairments in these patients tends to differ from that of AD patients. It is characterized by abnormalities in abstraction, psychomotor speed, flexibility, and working memory.¹¹ These patients have abnormal brain imaging, with diffuse cortical atrophy, and extensive subcortical white matter damage. At autopsy, intercurrent, significant AD neuropathology as well as vascular disease is often found.¹²

There are several sets of criteria for the diagnosis of vascular dementia.^1,13,14 The criteria that we use in the Memory Disorders Clinic at the Cleveland Clinic require that impairment of cognitive function in 2 domains be present as measured objectively; memory need not be 1 of these domains. We require that objective findings of vascular disease be present on neurological examination, and that there be some clinical relationship between the cognitive deterioration and presumed vascular disease. We accept the probable versus possible distinction, depending on whether structural neuroimaging confirms cerebral strokes (probable) or is either unavailable or nonconfirmatory (possible). It does not seem to us that a cognitive deficit syndrome that arises from a single clinical stroke should qualify as vascular dementia.

Vascular dementia is defined as cognitive decline from a previously higher level of functioning and manifested by impairment of 2 cognitive domains (eg, orientation, language, attention, visuospatial function, executive function, motor control, praxis, calculation abilities, or others). The presence of these cognitive deficits should be indicated in the clinical history and confirmed by cognitive testing. In the judgment of the examiner, the cognitive deficits should be of sufficient severity to interfere with vocational or social function, beyond the physical effects of stroke alone.

In addition, the presence of neurovascular disease, as indicated by such focal signs on neurological examination as hemiparesis, lower facial weakness, Babinski sign, sensory deficits, hemianopsia, or dysarthria, is an indication for vascular dementia. For probable vascular dementia, confirmatory neuroimaging is required. If neuroimaging is unavailable, or nonconfirmatory of vascular disease, the diagnosis of possible vascular dementia should be made.

Finally, a relationship between the vascular disease and the dementia syndrome should be evident, as manifested by a temporal relationship between a stroke or series of strokes and loss of cognitive function, or a fluctuating and stepwise progression of cognitive deficits in the presence of neurovascular disease.

There is evidence from the Mayo Clinic that persons with vascular dementia do not survive as long as patients with AD.¹⁵ Retrospectively, median survival from onset was 3.3 years for the vascular dementia group, and 7.1 years for those with all other dementias combined.

The primary therapies for vascular dementia are those directed at the underlying vascular disease: risk factor management, secondary prevention of thromboembolic stroke, and vascular surgical procedures as needed. There are findings from controlled studies that indicate that cholin-esterase inhibitors may be of benefit.¹⁶ One wonders about these studies, however, because of questions about inclusion criteria based on imaging and the possibility that many of the study participants had AD.

Nondegenerative nonvascular syndromes

Another large group of cognitive impairment syndromes that are seen in memory disorder clinics can be termed nondegenerative nonvascular disorders (Table 4). Prevalence rates for these disorders may vary substantially based on selection pressures that operate locally for cognitive disorder programs. In the Mayo Clinic series cited earlier, these disorders represented 5% of dementia cases with onset after age 70, but 30% of cases with clinical onset before age 70.¹⁵ For most of these nondegenerative nonvascular syndromes, formal diagnostic criteria do not exist, and diagnoses are reached only after significant neuropsychiatric investigation.

Many of these disorders occur in people who have general psychiatric disorders, for which we have proposed the term “psychodementia.”¹⁷ Such patients may constitute 10% or more of referrals to memory disorder clinics. When we were at Texas Tech, we used the following diagnostic criteria for “psychodementia”:

• Subjective complaint of memory impairment with or without complaints of change in other cognitive domains.
• Evidence of impaired cognitive performance against standardized norms in at least one cognitive domain on neuropsychological tests.
• Temporally associated general psychiatric disorder that, in the judgment of the clinician, causally explains the cognitive impairment syndrome.

Summary

The age-related cognitive disorders constitute a vast, medically unexplored area of behavioral syndromes that deprive millions of people of the serenity and satisfaction to which they are entitled in their later years. These disorders have become treatable, but for evolving treatment programs to become successful, there will have to be a much broader and committed participation by psychiatry as a medical specialty, and by psychiatrists as individuals. We hope that the clinical issues outlined in this article will serve as an invitation for this process to begin.

Earn CME Credit