Neurology -- Correspondence for Gamaldo et al., 67 (8) 1363-1369

Correspondence published:

Effect of a clinical stroke on the risk of dementia in a prospective cohort: Francesco Panza, Cristiano Capurso, Alessia D’Introno, Anna Maria Colacicco, Maria Chirico, Antonio Capurso, Vincenzo Solfrizzi (26 December 2006)

Reply from the Authors: Richard O'Brien (26 December 2006)

Effect of a clinical stroke on the risk of dementia in a prospective cohort 26 December 2006

Francesco Panza,
Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari
Policlinico, Piazza G. Cesare 11, 70124 Bari Italy,
Cristiano Capurso, Alessia D’Introno, Anna Maria Colacicco, Maria Chirico, Antonio Capurso, Vincenzo Solfrizzi
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Re: Effect of a clinical stroke on the risk of dementia in a prospective cohort

geriat.dot{at}geriatria.uniba.it Francesco Panza, et al.

Gamaldo et al [1] reported the results of the Baltimore Longitudinal Study on Aging (BLSA), a prospective community-based study in which clinically overt stroke conferred an increased risk of dementia compared to subjects without stroke. The majority of patients who became demented after a stroke had evidence of mild cognitive impairment (MCI) preceding the stroke. Moreover, a clinically symptomatic stroke was a major risk factor for the progression of MCI to dementia.
The authors discussed these results as consistent with the findings of the Italian Longitudinal Study on Aging (ILSA). In this study, the rate of progression to overt dementia in subjects with MCI was not 100%. This suggests that MCI is an heterogenous condition with a substantial number of prospectively followed individuals who remained cognitively unchanged or improved. [2]
Furthermore, in the ILSA sample, we evaluated 2,963 individuals from a population-based sample and found no association between stroke and incident MCI. However, there was a non-significant trend for stroke as a risk factor of progression of MCI to dementia and among those who progressed to dementia: 60% progressed to Alzheimer’s disease (AD) and 33% to vascular dementia. These findings confirm those of Gamaldo et al suggesting that in a predementia syndrome with a cognitive pattern similar to AD and with a central role for memory decline, stroke may also influence the rate of progression to dementia. Furthermore, in the BLSA, none of the stroke subjects reverted from MCI to normal prior to becoming demented. [1]
One possible limitation of the study by Gamaldo et al was the lack of ascertainment of white matter changes in persons without stroke, as they acknowledged. [1] Considerable evidence has shown that subclinical CVD is strongly associated with dementia in the absence of AD pathology and also may worsen or accelerate cognitive decline in subjects with AD. [3] Alternatively, neuropathologic data on a little sub-sample of the BLSA suggested that either multiple strokes or high AD pathology scores are potential explanations for cognitive dysfunction prior to and following a clinical stroke.
Although it is evident that CVD can be associated with cognitive decline, [3] it did not appear to influence progression to dementia when memory impairment was severe, [4] suggesting that only important cerebrovascular brain injury may have an impact on cognitive function. The lack of effect of cerebrovascular risk factors on subsequent dementia may suggest in this cohort that the presence of stroke would contribute to dementia particularly due to underlying AD pathology rather that subclinical CVD. [1] However, a recent neuropathologic study showed that large vessel CVD but not cerebral infarcts or small vessel CVD was related to increased frequency of senile plaques [5] suggesting that ischemia or cerebrovascular risk factors, but not stroke itself, may cause AD pathology.
References
1. Gamaldo A, Moghekar A, Kilada S, Resnick SM, Zonderman AB, O’Brien R. Effect of a clinical stroke on the risk of dementia in a prospective cohort. Neurology 2006;67:1363–1369.
2. Solfrizzi V, Panza F, Colacicco AM, et al. for the Italian Longitudinal Study on Aging Working Group. Vascular risk factors, incidence of MCI, and rates of progression to dementia. Neurology 2004;63:1882-1891.
3. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215–1222.
4. DeCarli C, Mungas D, Harvey D, et al. Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia. Neurology 2004;63:220-227.
5. Honig LS, Kukull W, Mayeux R. Atherosclerosis and AD: analysis of data from the US National Alzheimer’s Coordinating Center. Neurology 2005;64:494-500.
Disclosure: The authors report no conflicts of interest.

Reply from the Authors 26 December 2006

Richard O'Brien,
Johns Hopkins Bayview Medical Ctr
Mason F. Lord Center Tower, Suite 5100, 5200 Eastern Ave, Baltimore, MD 21224
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Re: Reply from the Authors

robrien{at}jhmi.edu Richard O'Brien

We thank Panza et al for their thoughtful comments. We agree with them about the limitations of our study concerning white matter disease and hope to correct it in the future as the BLSA has added a neuroimaging component including post mortem MRIs.
To answer whether only important cerebrovascular brain injury may have an impact on cognitive function, we have unpublished data on microscopic strokes and asymptomatic stokes that suggests any cortical stroke regardless of size or symptoms is important. We agree that the question of whether stroke is the actual cause of dementia or is a marker of another unknown cause is of paramount importance and hope, with Dr Panza's group, to further investigate this issue.
Disclosure: The author reports no conflicts of interest.