[1] 6w Cortical vs Subcortical Dementia Neuropsychological Differences

[1] 188w \s=b\The distinction between cortical and subcortical syndromes of dementia is controversial. Clinical reports suggest that subcortical syndromes (eg, Parkin- son's disease) involve less severe intel- lectual and memory dysfunction and lack the aphasia, agnosia, and apraxia typical of the cortical dementias (eg, dementia of the Alzheimer type). A recent neuropsy- chological investigation using a standard- ized procedure failed to confirm the distinction. We examined patients with Alzheimer's disease, patients with Parkin- son's disease, and normal controls by using a neuropsychological procedure specifically designed to quantitatively evaluate the proposed clinical differ- ences. The results differentiated these dementia syndromes, and the pattern of performance was consistent with the cor- tical-subcortical hypothesis. (Arch Neurol 1986;43:392-394) T~\ementia is classically associated with degenerative disorders of the cerebral cortex, and dementia of the Alzheimer type (DAT) is the most common example. Dementia is also seen in neurologic disorders that involve predominately subcortical structures such as the basal ganglia and brain stem; progressive supranu- clear palsy,1 Huntington's disease (HD),2 and Parkinson's disease (PD)3 5 are examples. The nature of the dif- ferences, if any, between cortical and subcortical dementia syndromes is controversial.Cortical and subcortical dementia

[1] 289w Performances of patient and con¬ trol groups were analyzed by analysis of variance and planned comparisons (Newman-Keuls) to detect specific group differences. Patients and con¬ trols were comparable in age (F [2,69] = 0.79) and years of formal edu¬ cation (F [2,69] = 0.09). Of the 16 measures, only Registration (F [2,69] = 2.4) and Digit Span (F [2,69] = 2.67) resulted in a nonsignifi¬ cant overall difference between groups. Since these procedures are basically measures of attentiveness, all further group differences are prob¬ ably not the result of the patient's failure to attend or to concentrate on the task at hand. For ease of communication, the pat¬ tern of results is divided into two categories, qualitative and quantita¬ tive differences. Qualitative differ¬ ences refer to instances where perfor¬ mance of patients with PD was not significantly different from that of normal controls, but both groups per¬ formed significantly better than patients with DAT. This pattern occurred for the following subtests: Verbal Fluency, Naming, Vocabulary, Orientation, Apraxia, and Trails A. Quantitative differences ocurred when both patient groups achieved significantly lower scores relative to controls, but patients with DAT were significantly more impaired relative to patients with PD. This pattern occurred on the following subtests: Mini-Mental State Examination (to¬ tal), Paired-Associate Memory, and Visuospatial performance. Finally, patient groups with DAT and PD both achieved higher scores on the Depres¬ sion scale relative to controls. A graphic illustration of the pattern of results is presented in the Figure and the Table . COMMENT This research was an attempt to evaluate dementia by using a specific series of neuropsychological tests designed to quantify the proposed clinical differences between cortical (DAT) and subcortical (PD) forms of dementia. The results support a dis¬ tinction.

[2] 98w Dementia in patients with PD was characterized by mild impairment of memory and visuospatial function but no impairment of language or evi¬ dence of apraxia. Significant depres¬ sion was also present. The pattern of performance for patients with DAT was markedly different. Overall men¬ tal functioning, memory performance, and visuospatial skills were more severely impaired relative to patients with PD. There was significant dis¬ turbance on all language-related tasks and evidence of apraxia. Depres¬ sion was also evident. In summary, the results suggest qualitative as well as quantitative differences in the dementia syndromes associated with PD and DAT.

[3] 193w Our findings are in conflict with conclusions derived from previous neuropsychological research examin¬ ing the cortical-subcortical distinc¬ tion of dementia. Mayeux and asso- ciates11<p282) compared patients with DAT, HD, and PD and concluded that "the clinical aspects of dementia are similar in patients with DAT, HD, and PD." This conclusion is contrary to a vast literature on the clinical distinctions between these dementing syndromes summarized by Ben- son5(ppi89 wo). «it js obvious that the clin¬ ical features alone provide a clear distinction between the two types of dementia.... On the basis of the striking clinical differences, accep¬ tance of the two distinct types of dementia would appear mandatory." Why this discrepancy? Mayeux et al11 used a lengthened version of the Mini- Mental State Examination,12 a mea¬ sure not specifically designed to detect differences between dementing syndromes. Our research evaluated dementia in patients with PD and DAT by a procedure designed to examine specific clinical symptoms. Perhaps a simpler interpretation of the findings of Mayeux et al would be that the Mini-Mental State Examina¬ tion is a useful bedside procedure to assess severity of dementia but is not sufficiently sensitive to differentiate dementing syndromes.

[4] 96w There is no question that similari¬ ties do exist in the dementia of PD and DAT. Pathologic similarities have also been noted, such as a similar pattern of cortical degeneration in PD and DAT910 and evidence of subcortical degeneration in patients with both disorders.23 In fact, some researchers suggest that this type of evidence argues against the cortical-subcorti- cal distinction of dementia. However, this distinction is a clinical and not a precise anatomic one, and the entire concept cannot be dismissed simply on the basis of a literal interpretation of a probably unfortunate choice of terms.

[5] 140w Another argument raised concern¬ ing the cortical-subcortical distinc¬ tion is whether the intellectual decline associated with PD can be considered a true example of demen¬ tia. According to Cummings and Ben¬ son, 7(pl) dementia may be defined as "an acquired persistent impairment of intellectual function with compro¬ mise in at least three of the following spheres of mental activity: language, memory, visuospatial skills, emotion or personality, and cognition (abstrac¬ tion, calculation, judgment, etc)." In our study, patients with PD were impaired relative to controls on mea¬ sures of memory, visuospatial skills, and depression, thereby meeting the definition of the dementia syndrome. The primary controversy surround¬ ing the cortical-subcortical distinc¬ tion is whether the clinical manifesta¬ tions of these dementing syndromes are quantitatively different examples of the same syndrome, or whether they are qualitatively unique. Our results support the latter distinction.

[6] 68w Certain features of dementia are invariant in both disorders, but these impairments are more severe in patients with DAT. Striking qualita¬ tive differences also exist, and these are easily identified using procedures specifically designed to evaluate these symptoms. In conclusion, it would appear there are overlapping patho¬ logic and clinical features in the dementia of DAT and PD, but there is no doubt these are distinct clinical disorders.

[1] 291w Fourteen patients who met currently accepted criteria1314 for DAT were exam¬ ined. Other possible sources of dementia were excluded by appropriate laboratory evaluation that included computed tomog¬ raphy and electroencephalography. The modified Hachinski Ischemie Rating Scale" was also used to aid in excluding multi-infarct dementia. This patient group had a mean age of 65.3 years and 14.9 years of formal education. All patients met the definition of dementia as proposed by Cummings and Benson.' Thirty-eight patients with idiopathic PD were examined. All patients were receiving some form of medication to alleviate clini¬ cal symptoms, but none had undergone thalamotomy. This group had a mean age of 64.9 years and 14.7 years of formal Accepted for publication Nov 6, 1985. From the Department of Neurology, Ohio State University College of Medicine, Colum- on Neuropsychological Measures* Measure Control, Mean ± SD PD, Mean ± SD DAT, Mean ± SD Group Differences Age, yr 61.65 ± 11.1 64.95 ±9.7 65.29±10.3 0.79 Education, yr 15±2.9 14.68±2.8 NS Mini-Mental State 29.65±0.6t 27.16±3.8* 18.54±6.2 Orientation 10±0 9.5 ±1.5* 5.9±2.8 28.73 .01 Registration 3±0 2.9±0.16 Calculation 4.7±0.6t 3.7 ±1.4* 1.7± 1.7 Recall 3±0 2.8±0.68* 1.1 ± 1.23 Language 9±0t 8.4 ±1.0* 18.66 .01 Vocabulary 10±0 9.9 ±0.39* 10.59 .01 Naming 9.9±0.3 9.5 ±0.86* Fluency 13.1 ±4.56* Digit Span 6.8± 1.6 5.7±1.9 NS Paired Associates 16.1 ±3.1t 12.5±3.9* 5.6±2.9 37.56 .01 Apraxia 5±0 4.9±0.39* 23.39 .01 Visuospatial 5.2±0.7t 4.2 ± 1.3* Trails A (s) 37.7± 15.3 65.9 ±49.9* 218.7± 1.6 Depression 30.2 ± 7.9t 40.8 ±9.4 37.6± 10.6 8.59 *PD indicates Parkinson \P < .05, control vs PD. *P < .05, PD vs DAT. s disease; DAT, dementia of the Alzheimer type; NS, not significant. education. All patients met the definition of dementia as proposed by Cummings and Benson.'

[2] 134w Twenty normal controls with no known neurologic disorders or history of alcohol¬ ism were also examined. Many of these subjects were spouses of patients in either of the two patient groups. This group had a mean age of 61. Language.-Verbal fluency16 was tested by asking subjects to generate as many words as possible that begin with s or in 60 s. Significant impairment on this test may indicate impaired search of verbal (lexical) long-term memory. Vocabulary" was assessed by presenting each subject with ten sheets containing four outline drawings of common objects and asking the subject to point to the object named by the experimenter. In the naming task, sub¬ jects were to name ten outline drawings of common objects. Significant impairment on these tests suggest the presence of visual agnosia, anomia, or both.

[3] 89w Memory.-Immediate memory was as¬ sessed by the digit span procedure.18 Sub¬ jects were to repeat sets of numbers increasing in length in the same order in which they were presented. Acquisition memory was assessed using the pairedassociate technique in which a list of ten word pairs (six easy and four hard) were read to the subject, and the task was to provide the appropriate second item when given the first. Significant failure on this test may indicate impairment of attention (digit span) or impairment of short-term memory (paired associates).

[4] 23w Apraxia.-Subjects performed five com¬ mon motor sequences (eg, threading a nee¬ dle)." Inability to perform these actions was considered indicative of ideomotor apraxia.

[5] 35w Visuospatial Ability.-Subjects were pre¬ sented with a systematic visual array with a blank area and with six alternatives, of which only one completed the pattern.20 Impairment on this test was thought to indicate visuospatial dysfunction.

[6] 39w Trail Making Task A.-Subjects were to connect circles in ascending order (one through 25) as quickly as possible.21 Fail¬ ure to complete this task resulted in a maximum score of 300 s. This task assessed sequencing and visuomotor ability.

[7] 15w Zung Self-rated Depression Scale.-Sub¬ jects were to complete a questionnaire that quantifies level of depression.22

[1] 285w syndromes have been clinically de¬ scribed as quite different.6 '8 The pro¬ gressive intellectual and memory dys¬ function of DAT may be more severe and progress more rapidly than that of the subcortical syndromes. In addi¬ tion, the hallmarks of cortical demen¬ tia, aphasia, agnosia, and apraxia, are typically absent in subcortical disor¬ ders. Patients with subcortical dis¬ eases are described as apathetic and often depressed, whereas patients with DAT often lack insight and tend not to be depressed. Finally, subcorti- cal disorders often are linked with movement disorders, such as the rigidity and bradykinesia of PD or the chorea of HD. Despite these well-described clini¬ cal distinctions, some researchers question the validity of the entire concept of a subcortical dementia. Of the proposed subcortical dementia syndromes, PD may be the most con¬ troversial. Recent research has sug¬ gested that the mental deterioration seen in PD may result from cortical degeneration superimposed on the subcortical degeneration responsible for the motor disturbance. Neuro- pathologic reports have noted that the pattern of cortical degeneration seen in DAT (senile plaques and neurofi- brillary tangles) can also be present in patients with PD.910 Neuropsychologi¬ cal studies have also suggested that the clinical aspects of dementia in patients with DAT and PD are simi¬ lar. Mayeux and associates" compared performance on a lengthened version of the Mini-Mental State Examina¬ tion12 and found no systematic pattern of deficits associated with these disor¬ ders. However, the procedure used was designed to confirm the presence and assess the severity of dementia and was not intended to evaluate spe¬ cific differences between dementing disorders. It is possible that both groups of patients achieved low scores on this mental status scale for differ¬ ent reasons.

[2] 48w We examined the possible distinc¬ tion between cortical and subcortical dementia by using a neuropsychologi¬ cal test battery that was specifically designed to evaluate the proposed clinical differences. This battery included measures of overall mental function, memory, language, apraxia, attention, and visuospatial skills, and a scale for depression.